All results were summarized descriptively by treatment arm and expressed as proportions, along with corresponding 95%CI of the difference between response rates, and p-values using Cochran-Mantel-Haenszel (CMH). The 95% CI will be constructed using the normal approximation method. Respiratory failure was defined as subjects who were on invasive mechanical ventilation; received oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) noninvasive positive pressure ventilation or extracorporeal membrane oxygenation; or had a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation).Subjects who died prior to the study timepoint (Day 7 or Day 28) were imputed based on the worst outcome.

The Full Analysis (FA) Population included subjects who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. The FA Population was a subset of the ITT Population which was defined as all subjects randomized. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. Count of participants who were alive and free of respiratory failure on Days 7 and 28 were included in analyses.

Mean Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, D-Dimer) at Day 7 and 28 in the Full Analysis Set

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included subjects who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. The summaries of the mean change from baseline analyses included those participants who had post-baseline D-Dimer values available on Days 7 and 28.

Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, CRP ) at Day 7 and 28 in the Full Analysis Set

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included subjects who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. The summaries of the mean change from baseline analyses included those participants who had post-baseline CRP values available on Days 7 and 28.

Analysis of the proportion of participants who improve by >=2 categories on the NIAID 8-point scale from baseline to Day 7. % = 100 x n/N', where N' = number of participants with a non-missing values at baseline and the specified post-baseline visit. Baseline is defined as the last measurement prior to the first dose of study drug.

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. The count of participants who had NIAID 8-point scale results at the Day 7 and Day 28 timepoints were included in the analyses.

The number of participants who were discharged and free of respiratory failure at Day 7 and Day 28 were summarized by treatment arm and pooled razuprotafib (10 and 20 mg) group.

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. The count of participants who were discharged and free of respiratory failure at the Day 7 and Day 28 timepoints.

Analysis of Number of Participants Alive and Not Requiring Invasive Mechanical Ventilation at Any Time Through Day 28 in the Full Analysis Set

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. The count of participants who had post-baseline data and were alive and not requiring mechanical ventilation were included in the analysis.

The clinical status of the participants was assessed within 1 hr prior to each dose of study drug, using the NIAID 8-point ordinal scale until Day 28. After the treatment period, clinical status will be assessed once daily until Day 18, unless discharged. If the subject is discharged alive prior to Day 28, clinical status was assessed at the post-treatment observation period telephone visits only. Grade 6=hospitalized, not requiring oxygen and no longer requires ongoing medical care; Grade 7 = not hospitalized, limitation on activities and/or requiring home oxygen; and Grade 8 = not hospitalized, no limitations on activities.

Intent-to-Treat (ITT) Population: The ITT Population was defined as all subjects randomized. Participants in this population were analyzed according to the treatment group to which they were assigned at randomization. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. The number of participants included in the analyses had post-baseline data through the end of the study.

Analysis of the change in PaO2:FiO2 ratio from baseline to Day 7 (or discharge) and baseline to Day 28 (or discharge) in the intent-to-treat population. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline PaO2;FiO2 ratio value was not provided for the pooled Razuprotafib group.

Intent-to-Treat (ITT) Population: The ITT Population was defined as all subjects randomized. Participants in this population were analyzed according to the treatment group to which they were assigned at randomization. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. The summaries of the mean changes from baseline included only those participants with available data.

Analysis of length of hospitalization and not requiring invasive mechanical ventilation from baseline to Day 7 and Day 28 in the intent-to-treat population. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. The summaries of the mean number of days from baseline included only those participants with available data. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline values were not provided.The length of hospitalization was to include all days that the participant was admitted to the hospital. For participants who were discharged and readmitted to the hospital, the length of hospitalization was to include the days after readmission. Hospitalization days were counted in 24-hour periods; any partial days were counted as a whole day.

Intent-to-Treat (ITT) Population: The ITT Population was defined as all subjects randomized. Participants in this population were analyzed according to the treatment group to which they were assigned at randomization. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. Those participants who had post-baseline values on Day 7 and 28 were included in the analyses.

Analysis of length of hospitalization from baseline to day 7 and day 28 (or death) in the intent-to-treat population. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline values were not provided. The length of hospitalization was to include all days that the participant was admitted to the hospital. For participants who were discharged and readmitted to the hospital, the length of hospitalization was to include the days after readmission. Hospitalization days were counted in 24-hour periods; any partial days were counted as a whole day.

Intent-to-Treat (ITT) Population: The ITT Population was defined as all subjects randomized. Participants in this population were analyzed according to the treatment group to which they were assigned at randomization. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. Participants who had post-baseline data on Days 7 and 28 (or death) were included in the analyses.

Analysis of number of participants who worsen by >= 2 categories on the NIAID 8-point ordinal scale from baseline to Day 7 in the Full Analysis Population. % = 100 x n/N', where N' = number of participants with non-missing values at baseline and the specified post-baseline visit. Participants who died prior to the Day 7 or Day 28 were imputed as 1.

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. Those participants who had post-baseline data on Days 7 and 28 were included in the analyses.

Summary of number and percent of subjects in each category (ie, categories 1 to 8) of the NIAID 8-Point Ordinal Scale at baseline, Day 7 and Day 28. The NIAID 8-point ordinal scale includes the following grades:

1. Death;
2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);
3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices;
4. Hospitalized, requiring supplemental oxygen;
5. Hospitalized, not requiring supplementation oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
7. Not hospitalized, limitation on activities and/or requiring home oxygen; and
8. Not hospitalized, no limitations on activities.

Intent-to-Treat (ITT) Population: The ITT Population was defined as all subjects randomized. Subjects in this population were analyzed according to the treatment group to which they were randomized. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. Those participants who had Baseline and post-baseline data on Days 7 and 28 were included in the analyses.

Analysis of the Number and Percent of Participants who Experienced All-Cause Mortality at Day 7 and Day 28 in the Full Analysis Set

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included subjects who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. The participants who had post-baseline data on Days 7 and 28 were included in the all-cause mortality analyses.

Analysis of number of participants who improve by >= 2 categories on the NIAID 8-point scale from baseline to Day 7 and Day 28 in the full analysis set.% = 100 x n/N', where N' = number of participants with non-missing values at baseline and the specified post-baseline visit. Participants who died prior to the Day 7 or Day 28 were imputed as 1.

Full Analysis (FA) Population: The FA Population was a subset of the ITT Population and included participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy evaluation. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the FA Population. Those participants who had post-baseline data on Day 7 and 28 were included in analyses.

Summary of Time to Return to Prehospitalization Oxygen Requirement in the Intent-to-Treat Population

Intent-to-Treat (ITT) Population: The ITT Population was defined as all participants randomized. Participants in this population were analyzed according to the treatment group to which they were assigned at randomization.

A summary of plasma razuprotafib concentrations for samples collected on Day 1 and 6 in the pharmacokinetic population. All results were summarized descriptively by treatment group.

Pharmacokinetic (PK) Population: The PK Population was defined as all randomized subjects who received at least 1 dose of study drug and had least 1 PK sample with plasma concentration.