Trial Outcomes & Findings for A Study of Auxora in Patients With Severe COVID-19 Pneumonia (NCT NCT04345614)

Last Updated: 2025-09-18

Results Overview

Defined as the number of days hospitalized but not requiring supplemental oxygen or ongoing medical care, or; discharged and requiring supplemental oxygen, or; discharged, not requiring supplemental oxygen.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

314 participants

Primary outcome timeframe

From start of first infusion of study drug to day 60

Results posted on

2025-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	Auxora (Part 1) Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Overall Study STARTED	20	10	143	141
Overall Study Part 1: Low -Flow Oxygen Therapy Part 2: PaO2/FiO2 </= 200	17	9	130	131
Overall Study COMPLETED	20	10	143	141
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=130 Participants Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=131 Participants Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Total n=287 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 12.47 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	61.0 years STANDARD_DEVIATION 13.32 • n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	59.4 years STANDARD_DEVIATION 12.1 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	60.4 years STANDARD_DEVIATION 12.3 • n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	59.9 years STANDARD_DEVIATION 12.2 • n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Sex: Female, Male Female	10 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	4 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	46 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	39 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	99 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Sex: Female, Male Male	7 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	5 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	84 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	92 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	188 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	45 Participants n=5 Participants	58 Participants n=4 Participants	106 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	6 Participants n=7 Participants	82 Participants n=5 Participants	72 Participants n=4 Participants	174 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants	5 Participants n=4 Participants	15 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	19 Participants n=5 Participants	12 Participants n=4 Participants	41 Participants n=21 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	5 Participants n=7 Participants	85 Participants n=5 Participants	98 Participants n=4 Participants	196 Participants n=21 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	16 Participants n=5 Participants	15 Participants n=4 Participants	33 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	17 participants n=5 Participants	9 participants n=7 Participants	130 participants n=5 Participants	131 participants n=4 Participants	287 participants n=21 Participants
65+years of age	4 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	4 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	45 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	47 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	100 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Body Mass Index	34.4 kg/m^2 STANDARD_DEVIATION 13.5 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	33.1 kg/m^2 STANDARD_DEVIATION 8.58 • n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	32.8 kg/m^2 STANDARD_DEVIATION 8.8 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	32.0 kg/m^2 STANDARD_DEVIATION 7.0 • n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	32.4 kg/m^2 STANDARD_DEVIATION 8.0 • n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Time from symptom onset	11.1 Days STANDARD_DEVIATION 7.13 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	6.9 Days STANDARD_DEVIATION 2.59 • n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	12.2 Days STANDARD_DEVIATION 5.8 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	12.0 Days STANDARD_DEVIATION 5.9 • n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	12.1 Days STANDARD_DEVIATION 5.8 • n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
High-flow nasal cannula use (HFNC)	0 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	0 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	81 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	82 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	163 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Baseline imputed PaO2/FiO2 value	177.5 Ratio STANDARD_DEVIATION 74.03 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	167.6 Ratio STANDARD_DEVIATION 77.60 • n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	109.7 Ratio STANDARD_DEVIATION 36.8 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	105.1 Ratio STANDARD_DEVIATION 32.8 • n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	107.4 Ratio STANDARD_DEVIATION 34.8 • n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Baseline imputed PaO2/FiO2=/<100	4 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	2 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	59 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	58 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	123 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Baseline imputed PaO2/FiO2 101-200	6 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	4 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	71 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	73 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	154 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
C-reactive protein (CRP)	99.9 mg/L STANDARD_DEVIATION 68.34 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	124.3 mg/L STANDARD_DEVIATION 59.28 • n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	93.1 mg/L STANDARD_DEVIATION 71.2 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	92.5 mg/L STANDARD_DEVIATION 67.6 • n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	92.8 mg/L STANDARD_DEVIATION 69.2 • n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Ferritin	709.1 ng/mL STANDARD_DEVIATION 553.09 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	771.6 ng/mL STANDARD_DEVIATION 741.57 • n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	1027 ng/mL STANDARD_DEVIATION 907 • n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	1050 ng/mL STANDARD_DEVIATION 869 • n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	1039 ng/mL STANDARD_DEVIATION 886 • n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Hypertension	8 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	4 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	84 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	80 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	176 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Diabetes	8 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	2 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	52 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	57 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	119 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Hyperlipidemia	2 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	0 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	50 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	51 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	103 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
Former smoker	5 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	2 Participants n=7 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	39 Participants n=5 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	34 Participants n=4 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set	80 Participants n=21 Participants • For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set

PRIMARY outcome

Timeframe: From start of first infusion of study drug to day 60

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=130 Participants Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=131 Participants Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Days From the Start of the First Infusion of Study Drug (SFISD) to Recovery	5 Days Interval 3.0 to 10.0	12 Days Interval 2.0 to 12.0	7.0 Days Interval 6.0 to 9.0	10.0 Days Interval 7.0 to 14.0	—	—	—	—

SECONDARY outcome

Timeframe: Day 30

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=130 Participants Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=131 Participants Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Participants Who Have Died at Day 30 (Mortality)	2 Participants	2 Participants	10 Participants	23 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Day 60

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=130 Participants Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=131 Participants Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Participants Who Have Died at Day 60 (Mortality)	2 Participants	2 Participants	18 Participants	27 Participants	—	—	—	—

SECONDARY outcome

Timeframe: From start of first infusion of study drug and up to Day 28

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Participants Requiring Invasive Mechanical Ventilation or Dying (Part 1)	4 Participants	5 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: from start of first infusion of study drug and up to day day 60

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=130 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=131 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Proportion of Patients Requiring Invasive Mechanical Ventilation or Dying (Part 2)	.23 Proportion of Participants Interval 0.17 to 0.31	.31 Proportion of Participants Interval 0.24 to 0.39	—	—	—	—	—	—

SECONDARY outcome

Timeframe: from start of first infusion of study drug and up to day Day 60

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=130 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=131 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Proportion of Patients Requiring Invasive Mechanical Ventilation (Part 2)	0.19 Proportion of participants Interval 0.13 to 0.28	0.28 Proportion of participants Interval 0.21 to 0.37	—	—	—	—	—	—

SECONDARY outcome

Timeframe: from start of first infusion of study drug and up to day 28

The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Improvement in 8-point Ordinal Scale (Part 1)	6.3 score on a scale Standard Deviation 2.39	4.6 score on a scale Standard Deviation 2.92	—	—	—	—	—	—

SECONDARY outcome

Timeframe: from start of first infusion of study drug hrough Day 60

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=130 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=131 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=122 Participants Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=129 Participants Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 n=124 Participants Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 n=129 Participants Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 n=124 Participants Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 n=129 Participants Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 1	0 Participants	0 Participants	5 Participants	8 Participants	10 Participants	23 Participants	18 Participants	27 Participants
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 3	81 Participants	82 Participants	17 Participants	16 Participants	5 Participants	3 Participants	0 Participants	0 Participants
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 2	0 Participants	0 Participants	11 Participants	23 Participants	11 Participants	8 Participants	3 Participants	5 Participants
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 4	49 Participants	49 Participants	6 Participants	7 Participants	2 Participants	2 Participants	0 Participants	0 Participants
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 6	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	2 Participants	5 Participants
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 7	0 Participants	0 Participants	38 Participants	39 Participants	24 Participants	33 Participants	32 Participants	33 Participants
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) 8	0 Participants	0 Participants	45 Participants	36 Participants	71 Participants	58 Participants	69 Participants	59 Participants

SECONDARY outcome

Timeframe: From start of first infusion of study drug through Day 28

Measures of PaO2/FiO2 ratio

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Change in PaO2/FiO2 (Part 1)	66.94 ratio of the arterial partial pressure o Standard Deviation 152.673	153.31 ratio of the arterial partial pressure o Standard Deviation 153.258	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From start of first infusion of study drug through Discharge up to 28 days

Time to discharge alive from hospital

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Days in the Hospital(Part 1)	5 Days Interval 3.0 to 10.0	12 Days Interval 2.0 to Not enough events to determine upper CI value	—	—	—	—	—	—

SECONDARY outcome

Timeframe: from admission into the hospital until discharge from the hospital up to 60 days

Population: Number of days in the hospital during the first 28 days of the study with a baseline imputed PaO2/FiO2 \</= 200

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=130 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=131 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Days in the Hospital (Part 2)	13.65 Days Interval 11.92 to 15.38	15.29 Days Interval 13.57 to 17.01	—	—	—	—	—	—

SECONDARY outcome

Timeframe: from admission into ICU until discharge from ICU up to 60 days

Population: Number of ICU days during the first 28 days of the study in patients with a baseline imputed PaO2/FiO2 \</= 200

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=130 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=131 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Days in the Intensive Care Unit (ICU) (Part 2)	6.88 Days Interval 4.92 to 8.85	8.36 Days Interval 6.4 to 10.32	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From randomization through Day 28

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Days Alive and Free of Mechanical Ventilation (Part 1)	22.9 Days Standard Deviation 10.3	12.9 Days Standard Deviation 14.3	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From start of first infusion of study drug through Day 28

Recovery is defined as a 6, 7, or 8 on the 8 point ordinal scale

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=17 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=9 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Number of Participants Considered Recovered (Part 1)	14 Participants	4 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From start of first infusion of study drug through 72 hours

Population: Patients with a viable PK sample at 72 hours

Concentration measured using a validated assay

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=71 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
CM4620-IE Plasma Concentration (Part 2)	165.2 ng/mL Standard Deviation 91.9	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From start of first infusion of study drugand through day 60

Population: For Part 1 of the study, all 30 treated patients were included in the Safety Analysis Set. In Part 2, 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set

Outcome measures

Outcome measures
Measure	Auxora (Part 1) n=20 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=10 Participants Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=141 Participants Patients were randomized 1:1 to receive either Auxora or placebo Auxora: Auxora was given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora were administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=140 Participants Patients were randomized 1:1 to receive either Auxora or placebo Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 30 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.	Auxora Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo Day 60 Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) Patients with at least 1 TEAE	75.0 percentage of patients	80.0 percentage of patients	64.5 percentage of patients	61.4 percentage of patients	—	—	—	—
Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) Mild TEAE	20.0 percentage of patients	20.0 percentage of patients	29.8 percentage of patients	17.9 percentage of patients	—	—	—	—
Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) Moderate TEAE	25.0 percentage of patients	10.0 percentage of patients	10.6 percentage of patients	8.6 percentage of patients	—	—	—	—
Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) Severe TEAE	25.0 percentage of patients	10.0 percentage of patients	24.1 percentage of patients	35 percentage of patients	—	—	—	—
Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) Patients with at least one treatment related TEAE	15.0 percentage of patients	0.0 percentage of patients	25.5 percentage of patients	12.9 percentage of patients	—	—	—	—

Adverse Events

Auxora (Part 1)

Serious events: 6 serious events

Other events: 15 other events

Deaths: 2 deaths

Standard of Care (Part 1)

Serious events: 5 serious events

Other events: 8 other events

Deaths: 2 deaths

Auxora (Part 2)

Serious events: 34 serious events

Other events: 69 other events

Deaths: 18 deaths

Placebo (Part 2)

Serious events: 49 serious events

Other events: 68 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Additional Information

Sudarshan Hebbar, MD

CalciMedica, Inc.

Phone: 8168387105

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Auxora (Part 1) n=20 participants at risk Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=10 participants at risk Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=141 participants at risk Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=140 participants at risk Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Blood and lymphatic system disorders Anaemia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Blood and lymphatic system disorders Leukocytosis	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Cardiac disorders Atrial Fibrillation	5.0% 1/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Cardiac disorders Cardiac arrest	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	4.3% 6/141 • Adverse event (AE) data were collected from randomization through Day 60	4.3% 6/140 • Adverse event (AE) data were collected from randomization through Day 60
Cardiac disorders Cardio-Respiratory Arrest	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Cardiac disorders Conduction Disorder	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Cardiac disorders Coronary Artery Occlusion	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Cardiac disorders Pulseless Electrical Activity	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Cardiac disorders Sinus Tachycardia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Gastrointestinal disorders Ileus	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Bacterial Pneumonia	10.0% 2/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Klebsiella Bacteraemia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Pneumonia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	4.3% 6/141 • Adverse event (AE) data were collected from randomization through Day 60	5.0% 7/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Pneumonia Klebsiella	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Pneumonia Staphylococcal	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Pseudomonal Bacteraemia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Sepsis	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Septic shock	15.0% 3/20 • Adverse event (AE) data were collected from randomization through Day 60	20.0% 2/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	5.7% 8/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Staphylococcal Bacteraemia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Staphylococcal Infection	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Infections and infestations Viral Sepsis	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Injury, poisoning and procedural complications Fall	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Investigations Alanine Aminotransferase Increased	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Investigations Aspartate Aminotransferase Increased	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Investigations Decreased Oxygen Saturation	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Investigations Increased Liver Function Test	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Nervous system disorders Brain Injury	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Nervous system disorders Cerebral Haemorrhage	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Nervous system disorders Cerebrovascular Accident	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Renal and urinary disorders Acute Kidney Injury	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	2.9% 4/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders ARDS	10.0% 2/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	5.0% 7/141 • Adverse event (AE) data were collected from randomization through Day 60	7.9% 11/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	2.9% 4/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Organising Pneumonia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	2.8% 4/141 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Pneumothorax Spontaneous	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	2.1% 3/141 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Respiratory, thoracic and mediastinal disorders Respiratory failure	15.0% 3/20 • Adverse event (AE) data were collected from randomization through Day 60	20.0% 2/10 • Adverse event (AE) data were collected from randomization through Day 60	15.6% 22/141 • Adverse event (AE) data were collected from randomization through Day 60	18.6% 26/140 • Adverse event (AE) data were collected from randomization through Day 60
Vascular disorders Deep Vein Thrombosis	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	2.1% 3/140 • Adverse event (AE) data were collected from randomization through Day 60
Vascular disorders Orthostatic Hypotension	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Vascular disorders Shock	5.0% 1/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	2.1% 3/140 • Adverse event (AE) data were collected from randomization through Day 60

Measure	Auxora (Part 1) n=20 participants at risk Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours	Standard of Care (Part 1) n=10 participants at risk Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.	Auxora (Part 2) n=141 participants at risk Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.	Placebo (Part 2) n=140 participants at risk Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours.
Metabolism and nutrition disorders Blood triglycerides increased	5.0% 1/20 • Adverse event (AE) data were collected from randomization through Day 60	20.0% 2/10 • Adverse event (AE) data were collected from randomization through Day 60	11.3% 16/141 • Adverse event (AE) data were collected from randomization through Day 60	3.6% 5/140 • Adverse event (AE) data were collected from randomization through Day 60
Metabolism and nutrition disorders Hyperglycemia	15.0% 3/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	7.8% 11/141 • Adverse event (AE) data were collected from randomization through Day 60	7.9% 11/140 • Adverse event (AE) data were collected from randomization through Day 60
Renal and urinary disorders Acute kidney injury	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	5.7% 8/141 • Adverse event (AE) data were collected from randomization through Day 60	8.6% 12/140 • Adverse event (AE) data were collected from randomization through Day 60
Investigations Increased transaminases	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	5.7% 8/141 • Adverse event (AE) data were collected from randomization through Day 60	3.6% 5/140 • Adverse event (AE) data were collected from randomization through Day 60
Vascular disorders DVT	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	3.5% 5/141 • Adverse event (AE) data were collected from randomization through Day 60	2.9% 4/140 • Adverse event (AE) data were collected from randomization through Day 60
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	2.8% 4/141 • Adverse event (AE) data were collected from randomization through Day 60	4.3% 6/140 • Adverse event (AE) data were collected from randomization through Day 60
Blood and lymphatic system disorders Anemia	10.0% 2/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	5.7% 8/140 • Adverse event (AE) data were collected from randomization through Day 60
Metabolism and nutrition disorders Hypoglycaemia	15.0% 3/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	2.1% 3/140 • Adverse event (AE) data were collected from randomization through Day 60
Investigations Blood Alkaline Phosphatase Increased	10.0% 2/20 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Investigations Blood Creatine Phosphokinase Increased	10.0% 2/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Vascular disorders Hypotension	10.0% 2/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
General disorders Abdominal Pain	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	2.8% 4/141 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/140 • Adverse event (AE) data were collected from randomization through Day 60
General disorders Chills	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Gastrointestinal disorders Constipation	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	2.1% 3/140 • Adverse event (AE) data were collected from randomization through Day 60
Gastrointestinal disorders Decubitus Ulcer	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60
Nervous system disorders Dizziness	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Nervous system disorders Encephalopathy	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/140 • Adverse event (AE) data were collected from randomization through Day 60
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	20.0% 2/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/140 • Adverse event (AE) data were collected from randomization through Day 60
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/141 • Adverse event (AE) data were collected from randomization through Day 60	1.4% 2/140 • Adverse event (AE) data were collected from randomization through Day 60
Blood and lymphatic system disorders Normocytic Anaemia	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/141 • Adverse event (AE) data were collected from randomization through Day 60	0.71% 1/140 • Adverse event (AE) data were collected from randomization through Day 60
Nervous system disorders Seizure	0.00% 0/20 • Adverse event (AE) data were collected from randomization through Day 60	10.0% 1/10 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/141 • Adverse event (AE) data were collected from randomization through Day 60	0.00% 0/140 • Adverse event (AE) data were collected from randomization through Day 60