Trial Outcomes & Findings for An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Subjects With Alagille Syndrome (ALGS) (NCT NCT02047318)

NCT ID: NCT02047318

Last Updated: 2021-11-19

Results Overview

The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

MRX baseline to Week 48

Results posted on

2021-11-19

Participant Flow

All participants within the study were enrolled from the lead-in Study LUM001-302, where they received various doses of maralixibat (LUM001, MRX) or placebo. Within this study, after a short dose escalation period, participants received MRX 280 ug/kg/day, which consisted of the majority of their exposure within the study. As such, summaries are presented as a single arm, MRX.

Participant milestones

Participant milestones
Measure	LUM001 (Maralixibat) LUM001 also known as Maralixibat (MRX) administered orally up to twice each day
Core Study Period STARTED	19
Core Study Period Received MRX 14 ug/kg/Day	6
Core Study Period Received MRX 35 ug/kg/Day	6
Core Study Period Received MRX 70 ug/kg/Day	6
Core Study Period Received MRX 140 ug/kg/Day	11
Core Study Period Received MRX 280 ug/kg/Day	19
Core Study Period COMPLETED	7
Core Study Period NOT COMPLETED	12
52-week Follow-up Treatment Period STARTED	6
52-week Follow-up Treatment Period COMPLETED	6
52-week Follow-up Treatment Period NOT COMPLETED	0
Long-term Follow-up Treatment Period STARTED	7
Long-term Follow-up Treatment Period Received MRX 280 ug/kg/Day	7
Long-term Follow-up Treatment Period Received 420 ug/kg/Day	5
Long-term Follow-up Treatment Period Received 560 ug/kg/Day	5
Long-term Follow-up Treatment Period COMPLETED	6
Long-term Follow-up Treatment Period NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	LUM001 (Maralixibat) LUM001 also known as Maralixibat (MRX) administered orally up to twice each day
Core Study Period Did not consent to 52-week follow- up	8
Core Study Period Adverse Event	1
Core Study Period Withdrawal by caregiver	3
Long-term Follow-up Treatment Period consent withdrawn by subject	1

Baseline Characteristics

An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Subjects With Alagille Syndrome (ALGS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Core Study Period n=19 Participants In the lead-in Study LUM001-302, participants were randomized to receive either placebo or active drug (MRX). The last observation obtained before first dose of MRX (either for participants who received MRX in Study LUM001-302 or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302. The core study period of Study LUM001-303 was from Day 1 to Week 72. It encompassed: - a 4-week double-blind dose-escalation period - an 8-week dose-optimization period - a 60-week stable dosing period. Participants could consent to continued long-term follow-up. The furthest analysis timepoint reached by any participant was Week 336. All participants received MRX.
Age, Customized <2 years	3 Subjects n=5 Participants
Age, Customized 2 to 4 years	6 Subjects n=5 Participants
Age, Customized 5 to 8 years	5 Subjects n=5 Participants
Age, Customized 9 to 12 years	2 Subjects n=5 Participants
Age, Customized 13 to 18 years	3 Subjects n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: MRX baseline to Week 48

Population: Data collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline to Week 48 in Fasting sBA Levels	261.96 μmol/L Standard Deviation 206.839	128.32 μmol/L Standard Deviation 101.742

SECONDARY outcome

Timeframe: MRX baseline to End of Treatment (maximum exposure was 336 weeks)

Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from all 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

This secondary efficacy endpoint is the mean change from MRX baseline over time in fasting sBA levels. Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Fasting sBA Levels	261.96 μmol/L Standard Deviation 206.839	118.32 μmol/L Standard Deviation 76.140

SECONDARY outcome

Timeframe: MRX baseline to Week 48

Population: Values were collected from 19 participants at MRX baseline. Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

This secondary efficacy endpoint is the change from MRX baseline to Week 48 in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline to Week 48 in Pruritus	2.435 scores on a scale Standard Deviation 0.7952	1.307 scores on a scale Standard Deviation 0.6995

SECONDARY outcome

Timeframe: MRX baseline to End of Treatment (maximum exposure was 336 weeks)

Population: Data collected from 19 participants at MRX baseline Data collected at Week 278 from all 6 participants who contributed values at MRX baseline. Week 278 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

This secondary efficacy endpoint is the change from MRX baseline over time in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Pruritus	2.435 scores on a scale Standard Deviation 0.7952	0.952 scores on a scale Standard Deviation 0.4302

SECONDARY outcome

Timeframe: MRX baseline to Week 48

Population: Mean MRX baseline scores were calculated from the 5 participants assigned placebo in LUM001-302 who had a baseline value in study LUM001-303. Those assigned to MRX within study LUM001-302 did not have this data collected at baseline. Mean MRX Week 48 scores were calculated from 17 participants. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the participant's lesions interfere or limit his or her activities. Clinician xanthoma severity scores range from 0 to 4, with a xanthoma score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants who were assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=5 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score	0.4 scores on a scale Standard Deviation 0.55	0.2 scores on a scale Standard Deviation 0.73

SECONDARY outcome

Timeframe: MRX baseline to End of Treatment (maximum exposure was 336 weeks)

Population: Mean MRX baseline scores were calculated from the 5 participants assigned placebo in LUM001-302.Mean Week 252 scores were calculated from 6 participants. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

This secondary efficacy endpoint is the mean change from MRX baseline over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants) in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the lesions interfere or limit activities. Clinician xanthoma severity scores range from 0 to 4, with a score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=5 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score	0.4 scores on a scale Standard Deviation 0.55	0.2 scores on a scale Standard Deviation 0.41

SECONDARY outcome

Timeframe: MRX baseline to Week 48

Population: Data collected from 19 participants at MRX baseline. \[Data collected at Week 48 from 17 of the 19 participants who contributed values at MRX baseline. Since all participants escalated to MRX 280 ug/kg/day by Week 48, the summary is presented as a single arm.

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase	601.5 U/L Standard Deviation 232.54	596.2 U/L Standard Deviation 185.20

SECONDARY outcome

Timeframe: MRX baseline to end of treatment (maximum exposure was 336 weeks)

Population: Data collected from 19 participants at MRX baseline. Data collected at Week 252 from 6 participants who contributed values at MRX baseline. Week 252 was chosen as this was the latest timepoint with more than 5 participants reporting data and was considered representative of values near the end of treatment. Since all participants escalated to MRX 280 ug/kg/day, the summary is presented as a single arm.

This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Alkaline Phosphatase	601.5 U/L Standard Deviation 232.54	430.5 U/L Standard Deviation 223.56

SECONDARY outcome

Timeframe: MRX baseline to Week 48

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline to Week 48 in Alanine Aminotransferase	130.7 U/L Standard Deviation 59.12	174.5 U/L Standard Deviation 97.28

SECONDARY outcome

Timeframe: MRX baseline to End of Treatment (maximum exposure was 336 weeks)

This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Alanine Aminotransferase	130.7 U/L Standard Deviation 59.12	175.3 U/L Standard Deviation 101.17

SECONDARY outcome

Timeframe: MRX baseline to Week 48

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline to Week 48 in Aspartate Aminotransferase	127.6 U/L Standard Deviation 60.03	142.4 U/L Standard Deviation 78.94

SECONDARY outcome

Timeframe: MRX baseline to End of treatment (maximum exposure was 336 weeks)

This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Aspartate Aminotransferase	127.6 U/L Standard Deviation 60.03	145.0 U/L Standard Deviation 56.50

SECONDARY outcome

Timeframe: MRX baseline to Week 48

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase	476.9 U/L Standard Deviation 376.85	440.5 U/L Standard Deviation 230.60

SECONDARY outcome

Timeframe: MRX baseline to End of Treatment (maximum exposure was 336 weeks)

This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Gamma Glutamyltransferase	476.9 U/L Standard Deviation 376.85	377.5 U/L Standard Deviation 163.10

SECONDARY outcome

Timeframe: MRX baseline to Week 48

This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=17 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline to Week 48 in Total and Direct Bilirubin Total bilirubin	4.47 mg/dL Standard Deviation 4.837	4.25 mg/dL Standard Deviation 5.384
Change From MRX Baseline to Week 48 in Total and Direct Bilirubin Direct bilirubin	3.80 mg/dL Standard Deviation 3.858	3.21 mg/dL Standard Deviation 3.656

SECONDARY outcome

Timeframe: MRX baseline to End of Treatment (maximum exposure was 336 weeks)

This secondary efficacy endpoint is the mean change from MRX baseline over time in total bilirubin and direct bilirubin. Results reported here are the long-term results.

Outcome measures

Outcome measures
Measure	Core Study Period: MRX Baseline Values n=19 Participants These are the MRX baseline values for participants. The last observation obtained before the first dose of MRX (whether before receiving MRX in Study LUM001-302 for participants who received MRX in Study LUM001-302, or in Study LUM001-303 for participants who received placebo in Study LUM001-302) was used as the MRX baseline observation for all calculations of change from MRX baseline. For participants who were assigned MRX in Study LUM001-302, results at each post-baseline analysis visit included up to 13 more weeks of treatment than participants who were assigned placebo in Study LUM001-302.	Core Study Period: Week 48 Values n=6 Participants These are the Week 48 values for participants. These participants are also represented in the Core study period: MRX baseline values group; the analyses look at the change from MRX baseline to Week 48 in the same participants.
Change From MRX Baseline Over Time in Total and Direct Bilirubin Total bilirubin	4.47 mg/dL Standard Deviation 4.837	5.05 mg/dL Standard Deviation 6.449
Change From MRX Baseline Over Time in Total and Direct Bilirubin Direct bilirubin	3.80 mg/dL Standard Deviation 3.858	3.53 mg/dL Standard Deviation 3.727

Adverse Events

14 Microgram Per Kilogram Per Day (mcg/kg/Day)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

35 Microgram Per Kilogram Per Day (mcg/kg/Day)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

70 Microgram Per Kilogram Per Day (mcg/kg/Day)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

140 Microgram Per Kilogram Per Day (mcg/kg/Day)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

280 Microgram Per Kilogram Per Day (mcg/kg/Day)

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

420 Microgram Per Kilogram Per Day (mcg/kg/Day)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

560 Microgram Per Kilogram Per Day (mcg/kg/Day)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

LUM001 MRX Treatment

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	14 Microgram Per Kilogram Per Day (mcg/kg/Day) n=6 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated starting at 14 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 14 mcg/kg/day.	35 Microgram Per Kilogram Per Day (mcg/kg/Day) n=10 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 14 to 35 for one week. This reporting group includes the period of time that participants received 35 mcg/kg/day.	70 Microgram Per Kilogram Per Day (mcg/kg/Day) n=10 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 35 to 70 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 70 mcg/kg/day.	140 Microgram Per Kilogram Per Day (mcg/kg/Day) n=13 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 70 to 140 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 140 mcg/kg/day.	280 Microgram Per Kilogram Per Day (mcg/kg/Day) n=19 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 140 to 280 microgram per kilogram per day (mcg/kg/day) for 8-week dose optimization period and during the stable dosing period for up to 124 weeks. Participants who received MRX in the predecessor study LUM001-302 started on their dose from Week 13 of that study (280 mcg/kg/day or highest tolerated dose). This reporting group includes the period of time that participants received 280 mcg/kg/day.	420 Microgram Per Kilogram Per Day (mcg/kg/Day) n=5 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Based on efficacy and safety assessments, participants could receive BID dosing after week 136, starting at 420 microgram per kilogram per day (mcg/kg/day) for 4-week dose escalation period. This reporting group includes the period of time that participants received 420 mcg/kg/day.	560 Microgram Per Kilogram Per Day (mcg/kg/Day) n=5 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants on BID dosing could have their dose escalated from 480 to 560 microgram per kilogram per day (mcg/kg/day) for the remainder of the study. This reporting group includes the period of time that participants received 560 mcg/kg/day.	LUM001 MRX Treatment n=19 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 14, 35, 70, and 140 microgram per kilogram per day (mcg/kg/day) for 4-week dose escalation period. Participants who received maralixibat during study LUM001-302, underwent a mock dose escalation and remained on the dose received at the end of study LUM001-302. During 8-weeks of dose optimization period, drug was adjusted in titrated manner up to 280 mcg/kg/day or highest tolerated dose and dosing was continued to complete the stable dosing and safety monitoring periods for up to 136 weeks of cumulative MRX exposure in this study at this dose level. In the long-term extension, participants could receive BID dosing up to 560 mcg/kg/day for the remainder of the study for up to 336 weeks of cumulative MRX exposure in this study. This reporting group includes all doses of MRX.
Cardiac disorders Bradycardia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Cardiac disorders Pericardial effusion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Cardiac disorders Right ventricular failure	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Ear and labyrinth disorders Ear haemorrhage	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
General disorders Pyrexia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Gastrointestinal infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Lower respiratory tract infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Gastrointestinal stoma output decreased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations International normalised ratio increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Fibrinous bronchitis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Surgical and medical procedures Medical device change	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Vascular disorders Hypotension	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.

Other adverse events

Other adverse events
Measure	14 Microgram Per Kilogram Per Day (mcg/kg/Day) n=6 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated starting at 14 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 14 mcg/kg/day.	35 Microgram Per Kilogram Per Day (mcg/kg/Day) n=10 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 14 to 35 for one week. This reporting group includes the period of time that participants received 35 mcg/kg/day.	70 Microgram Per Kilogram Per Day (mcg/kg/Day) n=10 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 35 to 70 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 70 mcg/kg/day.	140 Microgram Per Kilogram Per Day (mcg/kg/Day) n=13 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 70 to 140 microgram per kilogram per day (mcg/kg/day) for one week. This reporting group includes the period of time that participants received 140 mcg/kg/day.	280 Microgram Per Kilogram Per Day (mcg/kg/Day) n=19 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 140 to 280 microgram per kilogram per day (mcg/kg/day) for 8-week dose optimization period and during the stable dosing period for up to 124 weeks. Participants who received MRX in the predecessor study LUM001-302 started on their dose from Week 13 of that study (280 mcg/kg/day or highest tolerated dose). This reporting group includes the period of time that participants received 280 mcg/kg/day.	420 Microgram Per Kilogram Per Day (mcg/kg/Day) n=5 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Based on efficacy and safety assessments, participants could receive BID dosing after week 136, starting at 420 microgram per kilogram per day (mcg/kg/day) for 4-week dose escalation period. This reporting group includes the period of time that participants received 420 mcg/kg/day.	560 Microgram Per Kilogram Per Day (mcg/kg/Day) n=5 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants on BID dosing could have their dose escalated from 480 to 560 microgram per kilogram per day (mcg/kg/day) for the remainder of the study. This reporting group includes the period of time that participants received 560 mcg/kg/day.	LUM001 MRX Treatment n=19 participants at risk Participants received LUM001 (also known as Maralixibat or MRX) as an oral solution once daily based on participant's weight. Participants who received placebo in the predecessor study LUM001-302 had their dose escalated from 14, 35, 70, and 140 microgram per kilogram per day (mcg/kg/day) for 4-week dose escalation period. Participants who received maralixibat during study LUM001-302, underwent a mock dose escalation and remained on the dose received at the end of study LUM001-302. During 8-weeks of dose optimization period, drug was adjusted in titrated manner up to 280 mcg/kg/day or highest tolerated dose and dosing was continued to complete the stable dosing and safety monitoring periods for up to 136 weeks of cumulative MRX exposure in this study at this dose level. In the long-term extension, participants could receive BID dosing up to 560 mcg/kg/day for the remainder of the study for up to 336 weeks of cumulative MRX exposure in this study. This reporting group includes all doses of MRX.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Ear and labyrinth disorders Ear pain	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 4 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Ear and labyrinth disorders Ear pruritus	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Abdominal distension	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 2/10 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	30.8% 4/13 • Number of events 7 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	52.6% 10/19 • Number of events 26 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	57.9% 11/19 • Number of events 40 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Abnormal faeces	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Chapped lips	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Constipation	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Dental caries	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.4% 2/13 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	36.8% 7/19 • Number of events 9 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	60.0% 3/5 • Number of events 5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	57.9% 11/19 • Number of events 18 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Faeces discoloured	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Flatulence	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Gingival bleeding	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Haematochezia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Inguinal hernia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Lip haemorrhage	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Malabsorption	16.7% 1/6 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Melaena	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Nausea	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Teething	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	26.3% 5/19 • Number of events 7 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	26.3% 5/19 • Number of events 7 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
General disorders Chest pain	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
General disorders Fatigue	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 4 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
General disorders Feeling abnormal	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
General disorders Feeling hot	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
General disorders Influenza like illness	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
General disorders Pyrexia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.4% 2/13 • Number of events 4 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	31.6% 6/19 • Number of events 8 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	42.1% 8/19 • Number of events 15 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Hepatobiliary disorders Biliary tract disorder	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Hepatobiliary disorders Hepatic lesion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Hepatobiliary disorders Jaundice	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Immune system disorders Seasonal allergy	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Clostridium difficile infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Ear infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 8 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	26.3% 5/19 • Number of events 9 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Epstein-Barr virus infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Gastroenteritis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Gastrointestinal infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Hepatitis infectious mononucleosis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Impetigo	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Nasopharyngitis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.4% 2/13 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	36.8% 7/19 • Number of events 18 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	80.0% 4/5 • Number of events 16 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	42.1% 8/19 • Number of events 36 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Oral herpes	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 4 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 4 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Otitis media	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Tonsillitis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	60.0% 3/5 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 8 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	23.1% 3/13 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	52.6% 10/19 • Number of events 25 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	57.9% 11/19 • Number of events 28 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Varicella	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Anaemia postoperative	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Concussion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Contusion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Drain site complication	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Fall	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Head injury	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Joint injury	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Limb crushing injury	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Limb injury	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Post procedural fever	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Scratch	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 4 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Stoma site erythema	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Stoma site pain	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Stress fracture	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Vaccination complication	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Injury, poisoning and procedural complications Wound haemorrhage	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.4% 2/13 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 7 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Bilirubin urine present	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Blood bilirubin increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Blood parathyroid hormone increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Body temperature increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations International normalised ratio increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Intracardiac pressure increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Urobilinogen urine increased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Vitamin D decreased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Investigations Vitamin E decreased	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Musculoskeletal and connective tissue disorders Bone metabolism disorder	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 7 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 8 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Disturbance in attention	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Dizziness	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Headache	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 7 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	40.0% 2/5 • Number of events 6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	31.6% 6/19 • Number of events 13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Lethargy	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	40.0% 2/5 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	21.1% 4/19 • Number of events 6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Poor quality sleep	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Seizure	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Somnolence	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Nervous system disorders Taste disorder	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Product Issues Device occlusion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Psychiatric disorders Breath holding	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Psychiatric disorders Enuresis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Psychiatric disorders Restlessness	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Psychiatric disorders Sleep disorder	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Renal and urinary disorders Dysuria	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Renal and urinary disorders Pollakiuria	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Renal and urinary disorders Urinary incontinence	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Reproductive system and breast disorders Amenorrhoea	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	30.8% 4/13 • Number of events 4 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	42.1% 8/19 • Number of events 16 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	52.6% 10/19 • Number of events 21 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 8 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 8 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	15.8% 3/19 • Number of events 16 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Fibrinous bronchitis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	31.6% 6/19 • Number of events 6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	60.0% 3/5 • Number of events 10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	36.8% 7/19 • Number of events 18 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 3 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Acne	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.0% 1/10 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	10.5% 2/19 • Number of events 2 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Skin and subcutaneous tissue disorders Xanthelasma	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Vascular disorders Hypertension	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Vascular disorders Hypotension	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.
Vascular disorders Thrombosis	0.00% 0/6 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/10 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/13 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/19 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	0.00% 0/5 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.	5.3% 1/19 • Number of events 1 • Treatment-emergent adverse events are AEs with a start date on or after the first dose of study drug and with a start date prior to the last dose of study drug plus 14 days. Maximum exposure was 336 weeks. After a short dose escalation period (at dose levels less than 280 ug/kg/day), participants received MRX 280 ug/kg/day. An increase to BID dosing up to 560 mcg/kg/day was permitted during the long-term extension. The majority of exposure within the study was at 280 mcg/kg/day. 4 participants started on 140 mcg/kg/day or higher but had a dose interruption and went through dose escalation from 35 mcg/kg/day up to 280 mcg/kg/day. Thus, the counts for AE are higher than the core period.

Additional Information

Mirum Clinical Trials

Mirum Pharmaceuticals

Phone: 650-667-4085

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER