Trial Outcomes & Findings for Imipenem/Cilastatin-XNW4107 Versus Imipenem/Cilastatin/Relebactam for Treatment of Participants With Bacterial Pneumonia (XNW4107-302, REITAB-2) (NCT NCT05204563)

NCT ID: NCT05204563

Last Updated: 2025-11-06

Results Overview

The all-cause mortality rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 450 participants
• Primary outcome timeframe: Day 14
• Results posted on: 2025-11-06

Participant Flow

Participants with a clinical diagnosis of hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP) who met all eligibility criteria, and were assessed by the investigator as requiring 7 up to 14 days of intravenous (IV) antibiotic treatment in the hospital were randomized.

Participant milestones

Measure	Imipenem/Cilastatin and XNW4107 Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.	Imipenem/Cilastatin/Relebactam Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.
Overall Study STARTED	300	150
Overall Study Received at Least 1 Dose	299	150
Overall Study COMPLETED	261	139
Overall Study NOT COMPLETED	39	11

Reasons for withdrawal

Measure	Imipenem/Cilastatin and XNW4107 Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.	Imipenem/Cilastatin/Relebactam Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.
Overall Study Other than Specified	2	1
Overall Study Death	18	4
Overall Study Lost to Follow-up	6	3
Overall Study Withdrawal by Subject	12	3
Overall Study Enrolled, Not Treated	1	0

Baseline Characteristics

Imipenem/Cilastatin-XNW4107 Versus Imipenem/Cilastatin/Relebactam for Treatment of Participants With Bacterial Pneumonia (XNW4107-302, REITAB-2)

Baseline characteristics by cohort

Measure	Imipenem/Cilastatin and XNW4107 n=300 Participants Participants received imipenem/cilastatin via intravenous (IV) infusion and XNW4107 via injection during the treatment period of up to 14 days.	Imipenem/Cilastatin/Relebactam n=150 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Total n=450 Participants Total of all reporting groups
Age, Customized In utero	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Age, Customized Preterm newborn infants (gestational age < 37 wks)	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Age, Customized Newborns (0-27 days)	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Age, Customized Infants and toddlers (28 days-23 months)	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Age, Customized Children (2-11 years)	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Age, Customized Adolescents (12-17 years)	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Age, Customized Adults (18-64 years)	168 Participants n=49 Participants	86 Participants n=50 Participants	254 Participants n=50 Participants
Age, Customized From 65-84 years	121 Participants n=49 Participants	61 Participants n=50 Participants	182 Participants n=50 Participants
Age, Customized 85 years and over	11 Participants n=49 Participants	3 Participants n=50 Participants	14 Participants n=50 Participants
Sex: Female, Male Female	86 Participants n=49 Participants	50 Participants n=50 Participants	136 Participants n=50 Participants
Sex: Female, Male Male	214 Participants n=49 Participants	100 Participants n=50 Participants	314 Participants n=50 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	300 Participants n=49 Participants	150 Participants n=50 Participants	450 Participants n=50 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Race/Ethnicity, Customized Asian	296 Participants n=49 Participants	149 Participants n=50 Participants	445 Participants n=50 Participants
Race/Ethnicity, Customized White	4 Participants n=49 Participants	1 Participants n=50 Participants	5 Participants n=50 Participants

PRIMARY outcome

Timeframe: Day 14

Population: Measured in the Modified Intent-To-Treat (MITT) population, which included all participants from the Intent-to-Treat (ITT) who received at least 1 dose of study drug.

The all-cause mortality rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=150 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=299 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Day 14 All-cause Mortality Rate	2.7 percentage of participants	3.0 percentage of participants

SECONDARY outcome

Timeframe: Day 28

Population: Measured in the MITT, which included all participants from the ITT who received at least 1 dose of study drug.

The all-cause mortality rate at Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 28.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=150 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=299 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Day 28 All-cause Mortality Rate	3.3 percentage of participants	7.7 percentage of participants

SECONDARY outcome

Timeframe: Day 14, Day 28

Population: Measured in the microbiologic (micro)-MITT population, which included all participants from the MITT who had a Gram-negative pathogen identified at baseline and the pathogen was susceptible to the investigational medicinal product and comparator.

The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=57 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=113 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Day 14 and Day 28 All-cause Mortality Rate in the Micro-MITT Population Day 28	1.8 percentage of participants	6.2 percentage of participants
Day 14 and Day 28 All-cause Mortality Rate in the Micro-MITT Population Day 14	0 percentage of participants	3.5 percentage of participants

SECONDARY outcome

Timeframe: Day 14, Day 28

Population: Measured in the Extended micro-MITT population, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which was susceptible to either the investigational medicinal product or comparator.

The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=78 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=153 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Day 14 and Day 28 All-cause Mortality Rate in the Extended Micro-MITT Day 14	2.6 percentage of participants	3.3 percentage of participants
Day 14 and Day 28 All-cause Mortality Rate in the Extended Micro-MITT Day 28	3.8 percentage of participants	7.2 percentage of participants

SECONDARY outcome

Timeframe: Day 14, Day 28

Population: Measured in the CE population, which included all participants from the MITT who received at least 72 hours of IV study treatment, had an appropriate diagnosis of hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP), had no important protocol deviations that affected the assessment of clinical outcome, and had no missing nor indeterminate assessment of clinical outcome.

The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=120 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=233 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Day 14 and Day 28 All-cause Mortality Rate in the Clinically Evaluable (CE) Population Day 14	2.5 percentage of participants	1.7 percentage of participants
Day 14 and Day 28 All-cause Mortality Rate in the Clinically Evaluable (CE) Population Day 28	3.3 percentage of participants	5.6 percentage of participants

SECONDARY outcome

Timeframe: Day 14, Day 28

Population: Measured in the ME population, which included all participants from the micro-MITT who received at least 72 hours of IV study treatment, had an appropriate diagnosis of HABP/VABP, had no important protocol deviations that affected the assessment of microbiological outcome, and had no missing nor indeterminate assessment of microbiological outcome. 'n' = participants evaluable at specified timepoint.

The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=51 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=96 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Day 14 and Day 28 All-cause Mortality Rate in the Microbiologically Evaluable (ME) Population Day 14	0 percentage of participants	2.1 percentage of participants
Day 14 and Day 28 All-cause Mortality Rate in the Microbiologically Evaluable (ME) Population Day 28	2.0 percentage of participants	3.1 percentage of participants

SECONDARY outcome

Timeframe: Day 14, Day 28

Population: Measured in the CR-MITT Population, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which is resistant to any carbapenem.

The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=23 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=53 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Day 14 and Day 28 All-cause Mortality Rate in the Carbapenem-resistant MITT (CR-MITT) Population Day 14	8.7 percentage of participants	1.9 percentage of participants
Day 14 and Day 28 All-cause Mortality Rate in the Carbapenem-resistant MITT (CR-MITT) Population Day 28	8.7 percentage of participants	1.9 percentage of participants

SECONDARY outcome

Timeframe: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

Population: Measured in the MITT, which included all participants from the ITT who received at least 1 dose of study drug.

Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For end of treatment (EOT) or test-of-cure (TOC) visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=150 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=299 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the MITT Population Day 4	56.0 percentage of participants	59.2 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the MITT Population EOT (up to Day 14)	71.3 percentage of participants	74.6 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the MITT Population TOC (Day 21)	63.3 percentage of participants	62.9 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the MITT Population LFU (Day 28)	56.7 percentage of participants	58.9 percentage of participants

SECONDARY outcome

Timeframe: Day 4, EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the micro-MITT, which included all participants from the MITT who had a Gram-negative pathogen identified at baseline and the pathogen was susceptible to the investigational medicinal product and comparator.

Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=57 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=113 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Micro-MITT Population Day 4	56.1 percentage of participants	54.0 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Micro-MITT Population EOT (up to Day 14)	71.9 percentage of participants	84.1 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Micro-MITT Population TOC (Day 21)	61.4 percentage of participants	66.4 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Micro-MITT Population LFU (Day 28)	54.4 percentage of participants	62.8 percentage of participants

SECONDARY outcome

Timeframe: Day 4, EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the Extended micro-MITT, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which was susceptible to either the investigational medicinal product or comparator.

Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=78 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=153 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Extended Micro-MITT Day 4	56.4 percentage of participants	56.2 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Extended Micro-MITT EOT (up to Day 14)	73.1 percentage of participants	81.0 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Extended Micro-MITT TOC (Day 21)	57.7 percentage of participants	65.4 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Extended Micro-MITT LFU (Day 28)	51.3 percentage of participants	60.8 percentage of participants

SECONDARY outcome

Timeframe: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

Population: Measured in the CE population, which included all participants from the MITT who received at least 72 hours of IV study treatment, had an appropriate diagnosis of hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP), had no important protocol deviations that affected the assessment of clinical outcome, and had no missing nor indeterminate assessment of clinical outcome.

Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=120 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=233 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CE Population Day 4	63.3 percentage of participants	65.7 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CE Population EOT (up to Day 14)	83.3 percentage of participants	85.0 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CE Population TOC (Day 21)	75.0 percentage of participants	75.5 percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CE Population LFU (Day 28)	68.3 percentage of participants	70.8 percentage of participants

SECONDARY outcome

Timeframe: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

Population: Measured in the ME population, which included all participants from the micro-MITT who received at least 72 hours of IV study treatment, had an appropriate diagnosis of HABP/VABP, had no important protocol deviations that affected the assessment of microbiological outcome, and had no missing nor indeterminate assessment of microbiological outcome.

Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=51 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=96 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the ME Population Day 4	60.8 Percentage of participants	57.3 Percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the ME Population EOT (up to Day 14)	80.4 Percentage of participants	88.5 Percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the ME Population TOC (Day 21)	68.6 Percentage of participants	76.0 Percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the ME Population LFU (Day 28)	60.8 Percentage of participants	71.9 Percentage of participants

SECONDARY outcome

Timeframe: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

Population: Measured in the CR-MITT Population, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which is resistant to any carbapenem.

Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=23 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=53 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CR-MITT Population Day 4	56.5 Percentage of participants	60.4 Percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CR-MITT Population EOT (up to Day 14)	60.9 Percentage of participants	79.2 Percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CR-MITT Population TOC (Day 21)	43.5 Percentage of participants	64.2 Percentage of participants
The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CR-MITT Population LFU (Day 28)	39.1 Percentage of participants	50.9 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the micro-MITT, which included all participants from the MITT who had a Gram-negative pathogen identified at baseline and the pathogen was susceptible to the investigational medicinal product and comparator.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=57 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=113 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success in the Micro-MITT Population EOT (up to Day 14)	70.2 percentage of participants	81.4 percentage of participants
The Percentage of Participants With Microbiological Success in the Micro-MITT Population TOC (Day 21)	50.9 percentage of participants	57.5 percentage of participants
The Percentage of Participants With Microbiological Success in the Micro-MITT Population LFU (Day 28)	43.9 percentage of participants	52.2 percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the Extended micro-MITT, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which was susceptible to either the investigational medicinal product or comparator.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=78 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=153 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success in the Extended Micro-MITT Population EOT (up to Day 14)	65.4 Percentage of participants	75.8 Percentage of participants
The Percentage of Participants With Microbiological Success in the Extended Micro-MITT Population TOC (Day 21)	47.4 Percentage of participants	52.9 Percentage of participants
The Percentage of Participants With Microbiological Success in the Extended Micro-MITT Population LFU (Day 28)	42.3 Percentage of participants	46.4 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the CR-MITT Population, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which is resistant to any carbapenem.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=23 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=53 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success in the CR-MITT Population TOC (Day 21)	26.1 Percentage of participants	28.3 Percentage of participants
The Percentage of Participants With Microbiological Success in the CR-MITT Population LFU (Day 28)	26.1 Percentage of participants	17.0 Percentage of participants
The Percentage of Participants With Microbiological Success in the CR-MITT Population EOT (up to Day 14)	34.8 Percentage of participants	56.6 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the ME population, which included all participants from the micro-MITT who received at least 72 hours of IV study treatment, had an appropriate diagnosis of HABP/VABP, had no important protocol deviations that affected the assessment of microbiological outcome, and had no missing nor indeterminate assessment of microbiological outcome.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=51 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=96 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success in the ME Population EOT (up to Day 14)	78.4 Percentage of participants	85.4 Percentage of participants
The Percentage of Participants With Microbiological Success in the ME Population TOC (Day 21)	56.9 Percentage of participants	65.6 Percentage of participants
The Percentage of Participants With Microbiological Success in the ME Population LFU (Day 28)	49.0 Percentage of participants	58.3 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the micro-MITT, which included all participants from the MITT who had a Gram-negative pathogen identified at baseline and the pathogen was susceptible to the investigational medicinal product and comparator. Overall number of participants analysed=participants evaluable for the endpoint, n=number evaluable at the specified timepoint.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=37 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=76 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Enterobacter cloacae complex LFU (Day 28)	100.0 Percentage of participants	40.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Klebsiella aerogenes EOT (up to Day 14)	100.0 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Klebsiella aerogenes TOC (Day 21)	33.3 Percentage of participants	33.3 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Klebsiella aerogenes LFU (Day 28)	33.3 Percentage of participants	33.3 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Escherichia coli EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Escherichia coli TOC (Day 21)	100.0 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Escherichia coli LFU (Day 28)	100.0 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population K.pneumoniae complex EOT (up to Day 14)	64.9 Percentage of participants	88.2 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population K.pneumoniae complex TOC (Day 21)	54.1 Percentage of participants	61.8 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population K.pneumoniae complex LFU (Day 28)	45.9 Percentage of participants	57.9 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Pseudomonas aeruginosa EOT (up to Day 14)	45.5 Percentage of participants	68.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Pseudomonas aeruginosa TOC (Day 21)	27.3 Percentage of participants	36.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Pseudomonas aeruginosa LFU (Day 28)	27.3 Percentage of participants	28.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population A.calco/baumannii complex EOT (up to Day 14)	72.7 Percentage of participants	72.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population A.calco/baumannii complex TOC (Day 21)	72.7 Percentage of participants	72.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population A.calco/baumannii complex LFU (Day 28)	63.6 Percentage of participants	72.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Enterobacter cloacae complex EOT (up to Day 14)	100.0 Percentage of participants	60.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Enterobacter cloacae complex TOC (Day 21)	100.0 Percentage of participants	40.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Citrobacter koseri EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Citrobacter koseri TOC (Day 21)	50.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Citrobacter koseri LFU (Day 28)	50.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Acinetobacter junii EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Acinetobacter junii TOC (Day 21)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Acinetobacter junii LFU (Day 28)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Klebsiella oxytoca EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Klebsiella oxytoca TOC (Day 21)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Klebsiella oxytoca LFU (Day 28)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Citrobacter freundii complex EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Citrobacter freundii complex TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Citrobacter freundii complex LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Serratia marcescens EOT (up to Day 14)	0.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Serratia marcescens TOC (Day 21)	100.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population Serratia marcescens LFU (Day 28)	0.0 Percentage of participants	—

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the Extended micro-MITT, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which was susceptible to either the investigational medicinal product or comparator. Overall number of participants analysed=participants evaluable for the endpoint, n=number evaluable at the specified timepoint.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=43 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=89 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population K.pneumoniae complex EOT (up to Day 14)	67.4 Percentage of participants	85.4 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population K.pneumoniae complex TOC (Day 21)	58.1 Percentage of participants	58.4 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population K.pneumoniae complex LFU (Day 28)	51.2 Percentage of participants	53.9 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population A.calco/baumannii complex EOT (up to Day 14)	56.5 Percentage of participants	75.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population A.calco/baumannii complex TOC (Day 21)	47.8 Percentage of participants	57.1 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population A.calco/baumannii complex LFU (Day 28)	43.5 Percentage of participants	46.4 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Pseudomonas aeruginosa EOT (up to Day 14)	50.0 Percentage of participants	59.4 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Pseudomonas aeruginosa TOC (Day 21)	28.6 Percentage of participants	34.4 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Pseudomonas aeruginosa LFU (Day 28)	28.6 Percentage of participants	28.1 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Burkholderia cepacia complex EOT (up to Day 14)	100.0 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Burkholderia cepacia complex TOC (Day 21)	66.7 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Burkholderia cepacia complex LFU (Day 28)	66.7 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Klebsiella aerogenes EOT (Up to Day 14)	100.0 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Klebsiella aerogenes TOC (Day 21)	33.3 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Klebsiella aerogenes LFU (Day 28)	33.3 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Enterobacter cloacae complex EOT (up to Day 14)	100.0 Percentage of participants	60.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Enterobacter cloacae complex TOC (Day 21)	100.0 Percentage of participants	40.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Enterobacter cloacae complex LFU (Day 28)	66.7 Percentage of participants	40.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Escherichia coli EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Escherichia coli TOC (Day 21)	100.0 Percentage of participants	75.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Klebsiella oxytoca LFU (Day 28)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Citrobacter freundii complex EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Citrobacter freundii complex TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Citrobacter freundii complex LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Klebsiella oxytoca EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Escherichia coli LFU (Day 28)	100.0 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Haemophilus influenzae EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Haemophilus influenzae TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Haemophilus influenzae LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Citrobacter koseri EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Citrobacter koseri TOC (Day 21)	50.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Citrobacter koseri LFU (Day 28)	50.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Proteus mirabilis EOT (up to Day 14)	0.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Proteus mirabilis TOC (Day 21)	0.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Proteus mirabilis LFU (Day 28)	0.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Acinetobacter junii EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Acinetobacter junii TOC (Day 21)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Acinetobacter junii LFU (Day 28)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Klebsiella oxytoca TOC (Day 21)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Serratia marcescens EOT (up to Day 14)	0.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Serratia marcescens TOC (Day 21)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Serratia marcescens LFU (Day 28)	0.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Morganella morganii EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Morganella morganii TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Morganella morganii LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Pseudomonas otitidis EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Pseudomonas otitidis TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Pseudomonas otitidis LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Ralstonia pickettii EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Ralstonia pickettii TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Ralstonia pickettii LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Sphingomonas species EOT (up to Day 14)	100.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Sphingomonas species TOC (Day 21)	100.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Sphingomonas species LFU (Day 28)	100.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Stenotrophomonas maltophilia EOT (up to Day 14)	0.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Stenotrophomonas maltophilia TOC (Day 21)	0.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population Stenotrophomonas maltophilia LFU (Day 28)	0.0 Percentage of participants	—

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the ME population, which included all participants from the micro-MITT who received at least 72 hours of IV study treatment, had an appropriate diagnosis of HABP/VABP, had no important protocol deviations that affected the assessment of microbiological outcome, and had no missing nor indeterminate assessment of microbiological outcome. Overall number of participants analysed=participants evaluable for the endpoint, n=number evaluable at the specified timepoint.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=33 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=64 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Pseudomonas aeruginosa LFU (Day 28)	30.0 Percentage of participants	31.8 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population A.calco/baumannii complex EOT (up to Day 14)	88.9 Percentage of participants	80.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population A.calco/baumannii complex TOC (Day 21)	88.9 Percentage of participants	80.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population A.calco/baumannii complex LFU (Day 28)	77.8 Percentage of participants	80.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Klebsiella aerogenes EOT (up to Day 14)	100.0 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Klebsiella aerogenes TOC (Day 21)	33.3 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Klebsiella aerogenes LFU (Day 28)	33.3 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Enterobacter cloacae complex EOT (up to Day 14)	100.0 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Enterobacter cloacae complex TOC (Day 21)	100.0 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Enterobacter cloacae complex LFU (Day 28)	100.0 Percentage of participants	50.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Escherichia coli EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Escherichia coli TOC (Day 21)	100.0 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Escherichia coli LFU (Day 28)	100.0 Percentage of participants	66.7 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Citrobacter koseri EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Citrobacter koseri TOC (Day 21)	50.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Citrobacter koseri LFU (Day 28)	50.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Acinetobacter junii EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Acinetobacter junii TOC (Day 21)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Acinetobacter junii LFU (Day 28)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Klebsiella oxytoca EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Klebsiella oxytoca TOC (Day 21)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Klebsiella oxytoca LFU (Day 28)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Citrobacter freundii complex EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Citrobacter freundii complex TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Citrobacter freundii complex LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Serratia marcescens EOT (up to Day 14)	0.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Serratia marcescens TOC (Day 21)	100.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Serratia marcescens LFU (Day 28)	0.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population K.pneumoniae complex EOT (up to Day 14)	72.7 Percentage of participants	93.8 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population K.pneumoniae complex TOC (Day 21)	60.6 Percentage of participants	70.3 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population K.pneumoniae complex LFU (Day 28)	51.5 Percentage of participants	64.1 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Pseudomonas aeruginosa EOT (up to Day 14)	50.0 Percentage of participants	68.2 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the ME Population Pseudomonas aeruginosa TOC (Day 21)	30.0 Percentage of participants	40.9 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the CR-MITT Population, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which is resistant to any carbapenem. Overall number of participants analysed=participants evaluable for the endpoint, n=number evaluable at the specified timepoint.

Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=16 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=26 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population A.calco/baumannii complex EOT (up to Day 14)	31.3 Percentage of participants	61.5 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population A.calco/baumannii complex TOC (Day 21)	18.8 Percentage of participants	30.8 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population A.calco/baumannii complex LFU (Day 28)	18.8 Percentage of participants	19.2 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Klebsiella pneumoniae complex EOT (up to Day 14)	71.4 Percentage of participants	63.2 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Klebsiella pneumoniae complex TOC (Day 21)	71.4 Percentage of participants	31.6 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Klebsiella pneumoniae complex LFU (Day 28)	71.4 Percentage of participants	26.3 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Pseudomonas aeruginosa EOT (up to Day 14)	33.3 Percentage of participants	53.8 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Pseudomonas aeruginosa TOC (Day 21)	33.3 Percentage of participants	30.8 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Pseudomonas aeruginosa LFU (Day 28)	33.3 Percentage of participants	15.4 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Proteus mirabilis EOT (up to Day 14)	0.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Proteus mirabilis TOC (Day 21)	0.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Proteus mirabilis LFU (Day 28)	0.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Escherichia coli EOT (up to Day 14)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Escherichia coli TOC (Day 21)	100.0 Percentage of participants	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Escherichia coli LFU (Day 28)	100.0 Percentage of participants	0.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Haemophilus influenzae EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Haemophilus influenzae TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Haemophilus influenzae LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Burkholderia cepacia complex EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Burkholderia cepacia complex TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Burkholderia cepacia complex LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Citrobacter freundii complex EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Citrobacter freundii complex TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Citrobacter freundii complex LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Enterobacter cloacae complex EOT (up to Day 14)	100.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Enterobacter cloacae complex TOC (Day 21)	100.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Enterobacter cloacae complex LFU (Day 28)	0.0 Percentage of participants	—
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Pseudomonas otitidis EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Pseudomonas otitidis TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Pseudomonas otitidis LFU (Day 28)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Ralstonia pickettii EOT (up to Day 14)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Ralstonia pickettii TOC (Day 21)	—	100.0 Percentage of participants
The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population Ralstonia pickettii LFU (Day 28)	—	100.0 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the micro-MITT, which included all participants from the MITT who had a Gram-negative pathogen identified at baseline and the pathogen was susceptible to the investigational medicinal product and comparator.

Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=57 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=113 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Overall Success in the Micro-MITT Population EOT (up to Day 14)	64.9 percentage of participants	75.2 percentage of participants
The Percentage of Participants With Overall Success in the Micro-MITT Population TOC (Day 21)	47.4 percentage of participants	50.4 percentage of participants
The Percentage of Participants With Overall Success in the Micro-MITT Population LFU (Day 28)	40.4 percentage of participants	47.8 percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the Extended micro-MITT, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which was susceptible to either the investigational medicinal product or comparator.

Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=78 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=153 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Overall Success in the Extended Micro-MITT Population EOT (up to Day 14)	61.5 Percentage of participants	68.6 Percentage of participants
The Percentage of Participants With Overall Success in the Extended Micro-MITT Population TOC (Day 21)	44.9 Percentage of participants	45.8 Percentage of participants
The Percentage of Participants With Overall Success in the Extended Micro-MITT Population LFU (Day 28)	39.7 Percentage of participants	42.5 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the ME population, which included all participants from the micro-MITT who received at least 72 hours of IV study treatment, had an appropriate diagnosis of HABP/VABP, had no important protocol deviations that affected the assessment of microbiological outcome, and had no missing nor indeterminate assessment of microbiological outcome.

Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=51 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=96 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Overall Success in the ME Population EOT (up to Day 14)	72.5 Percentage of participants	78.1 Percentage of participants
The Percentage of Participants With Overall Success in the ME Population TOC (Day 21)	52.9 Percentage of participants	57.3 Percentage of participants
The Percentage of Participants With Overall Success in the ME Population LFU (Day 28)	45.1 Percentage of participants	54.2 Percentage of participants

SECONDARY outcome

Timeframe: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

Population: Measured in the CR-MITT Population, which included all participants from the MITT who had a baseline Gram-negative pathogen identified which is resistant to any carbapenem.

Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=23 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=53 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
The Percentage of Participants With Overall Success in the CR-MITT Population EOT (up to Day 14)	34.8 Percentage of participants	47.2 Percentage of participants
The Percentage of Participants With Overall Success in the CR-MITT Population TOC (Day 21)	26.1 Percentage of participants	22.6 Percentage of participants
The Percentage of Participants With Overall Success in the CR-MITT Population LFU (Day 28)	26.1 Percentage of participants	17.0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 to Day 28

Population: Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.

A TEAE was defined as any untoward medical occurrence after first dose associated with the use of a drug in humans, whether or not considered drug-related. An SAE was defined as any adverse event (AE) occurring at any dose that met one or more of the following criteria: resulted in death, was life-threatening, required participant hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, a congenital anomaly or birth defect or an important medical event.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam n=150 Participants Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=299 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAE	147 Participants	286 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAE	10 Participants	34 Participants

SECONDARY outcome

Timeframe: Predose, 5-25 minutes post-dose, and 2-3 hours post-dose on Day 4, 5, or 6

Population: Measured in the pharmacokinetic (PK) population, which included all participants from the safety population during the study with at least 1 reportable concentration of XNW4107, imipenem, or cilastatin. As pre-specified, data for PK was collected and reported only for the study drug treatment group (Imipenem/Cilastatin and XNW4107).

Blood samples were taken for analysis of XNW4107, imipenem, and cilastatin concentrations. The data at each time point was calculated as an average across Days 4, 5 and 6.

Outcome measures

Measure	Imipenem/Cilastatin/Relebactam Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.	Imipenem/Cilastatin and XNW4107 n=286 Participants Participants received imipenem/cilastatin via IV infusion and XNW4107 via injection during the treatment period of up to 14 days.
Blood XNW4107, Imipenem, and Cilastatin Concentrations XNW4107 Day (D)4/D5/D6 Pre-dose	—	3840 nanograms per milliliter (ng/ml) Standard Deviation 3330
Blood XNW4107, Imipenem, and Cilastatin Concentrations XNW4107 D4/D5/D6 5-25min post dose	—	16000 nanograms per milliliter (ng/ml) Standard Deviation 6030
Blood XNW4107, Imipenem, and Cilastatin Concentrations XNW4107 D4/D5/D6 2-3hour post dose	—	7320 nanograms per milliliter (ng/ml) Standard Deviation 3890
Blood XNW4107, Imipenem, and Cilastatin Concentrations Imipenem D4/D5/D6 Pre-dose	—	1770 nanograms per milliliter (ng/ml) Standard Deviation 2050
Blood XNW4107, Imipenem, and Cilastatin Concentrations Imipenem D4/D5/D6 5-25min post dose	—	22900 nanograms per milliliter (ng/ml) Standard Deviation 9310
Blood XNW4107, Imipenem, and Cilastatin Concentrations Imipenem D4/D5/D6 2-3hour post dose	—	5970 nanograms per milliliter (ng/ml) Standard Deviation 2980
Blood XNW4107, Imipenem, and Cilastatin Concentrations Cilastatin D4/D5/D6 Pre-dose	—	1910 nanograms per milliliter (ng/ml) Standard Deviation 3350
Blood XNW4107, Imipenem, and Cilastatin Concentrations Cilastatin D4/D5/D6 5-25min post dose	—	24200 nanograms per milliliter (ng/ml) Standard Deviation 10100
Blood XNW4107, Imipenem, and Cilastatin Concentrations Cilastatin D4/D5/D6 2-3hour post dose	—	5610 nanograms per milliliter (ng/ml) Standard Deviation 4720

Adverse Events

Imipenem/Cilastatin and XNW4107

Serious events: 34 serious events

Other events: 260 other events

Deaths: 23 deaths

Imipenem/Cilastatin/Relebactam

Serious events: 10 serious events

Other events: 136 other events

Deaths: 5 deaths

Serious adverse events

Measure	Imipenem/Cilastatin and XNW4107 n=299 participants at risk Participants received imipenem/cilastatin via intravenous (IV) infusion and XNW4107 via injection during the treatment period of up to 14 days.	Imipenem/Cilastatin/Relebactam n=150 participants at risk Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.3% 4/299 • Number of events 6 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Cerebral haemorrhage	0.67% 2/299 • Number of events 2 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Haemorrhage intracranial	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Ruptured cerebral aneurysm	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Injury, poisoning and procedural complications Thermal burn	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Cardiac disorders Atrial fibrillation	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Cardiac disorders Cardiac arrest	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Cardiac disorders Cardiogenic shock	0.33% 1/299 • Number of events 2 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Cardiac disorders Ventricular fibrillation	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Gastrointestinal disorders Gastric mucosal lesion	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Infections and infestations Haematological infection	0.33% 1/299 • Number of events 2 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Infections and infestations Pneumonia viral	0.33% 1/299 • Number of events 2 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Eye disorders Mydriasis	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Investigations Alanine aminotransferase increased	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.0% 3/299 • Number of events 3 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Intraventricular haemorrhage	0.33% 1/299 • Number of events 3 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Brain oedema	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Brain stem syndrome	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Cerebrospinal fluid leakage	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Nervous system disorders Cerebral infarction	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
General disorders and administration site conditions Death	2.0% 6/299 • Number of events 6 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
General disorders and administration site conditions Multiple organ dysfunction syndrome	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
General disorders and administration site conditions Sudden cardiac death	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Injury, poisoning and procedural complications Brain herniation	0.67% 2/299 • Number of events 2 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	1.3% 2/150 • Number of events 3 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Injury, poisoning and procedural complications Post concussion syndrome	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Gastrointestinal disorders Haematochezia	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Gastrointestinal disorders Melaena	0.33% 1/299 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.00% 0/150 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Investigations Aspartate aminotransferase increased	0.00% 0/299 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	0.67% 1/150 • Number of events 1 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.

Other adverse events

Measure	Imipenem/Cilastatin and XNW4107 n=299 participants at risk Participants received imipenem/cilastatin via intravenous (IV) infusion and XNW4107 via injection during the treatment period of up to 14 days.	Imipenem/Cilastatin/Relebactam n=150 participants at risk Participants received imipenem/cilastatin/relebactam via IV infusion during the treatment period of up to 14 days.
Metabolism and nutrition disorders Hypoalbuminaemia	9.0% 27/299 • Number of events 44 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	8.7% 13/150 • Number of events 20 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Metabolism and nutrition disorders Hypernatraemia	5.4% 16/299 • Number of events 26 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	6.7% 10/150 • Number of events 24 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Vascular disorders Deep vein thrombosis	7.7% 23/299 • Number of events 28 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	12.0% 18/150 • Number of events 20 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Metabolism and nutrition disorders Hyponatraemia	32.4% 97/299 • Number of events 198 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	35.3% 53/150 • Number of events 101 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Metabolism and nutrition disorders Hypokalaemia	36.5% 109/299 • Number of events 185 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	24.0% 36/150 • Number of events 61 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Metabolism and nutrition disorders Hypoproteinaemia	25.4% 76/299 • Number of events 106 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	14.7% 22/150 • Number of events 37 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Metabolism and nutrition disorders Hypocalcaemia	16.7% 50/299 • Number of events 94 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	8.7% 13/150 • Number of events 23 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Metabolism and nutrition disorders Hypochloraemia	9.7% 29/299 • Number of events 48 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	9.3% 14/150 • Number of events 19 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Blood and lymphatic system disorders Anaemia	41.1% 123/299 • Number of events 234 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	34.0% 51/150 • Number of events 98 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Gastrointestinal disorders Constipation	16.7% 50/299 • Number of events 67 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	18.7% 28/150 • Number of events 52 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Gastrointestinal disorders Diarrhoea	17.1% 51/299 • Number of events 60 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	17.3% 26/150 • Number of events 27 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Gastrointestinal disorders Vomiting	7.4% 22/299 • Number of events 25 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	6.0% 9/150 • Number of events 10 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Investigations Alanine aminotransferase increased	20.1% 60/299 • Number of events 110 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	26.7% 40/150 • Number of events 74 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Investigations Aspartate aminotransferase increased	18.7% 56/299 • Number of events 106 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	24.7% 37/150 • Number of events 93 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Investigations Gamma-glutamyltransferase increased	10.0% 30/299 • Number of events 46 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	9.3% 14/150 • Number of events 25 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Investigations Blood alkaline phosphatase increased	5.0% 15/299 • Number of events 20 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	6.7% 10/150 • Number of events 15 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Vascular disorders Venous thrombosis limb	10.0% 30/299 • Number of events 35 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	8.0% 12/150 • Number of events 17 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Infections and infestations Urinary tract infection	16.7% 50/299 • Number of events 58 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	15.3% 23/150 • Number of events 29 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Respiratory, thoracic and mediastinal disorders Hiccups	7.4% 22/299 • Number of events 30 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	3.3% 5/150 • Number of events 9 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Skin and subcutaneous tissue disorders Rash	5.4% 16/299 • Number of events 16 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	5.3% 8/150 • Number of events 9 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.
Metabolism and nutrition disorders Hyperlipidaemia	5.7% 17/299 • Number of events 27 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.	5.3% 8/150 • Number of events 10 • Day 1 to Day 28 Measured in the safety population, which included all participants who received at least 1 dose of study drug during the study. Participants were analyzed according to the treatment received during the study.

Additional Information

Evopoint Biosciences

Evopoint Biosciences USA, Inc.

Phone: 646-750-2661

Email: info@evopointbio.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place