A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF

INTERVENTION: Product Name: n/a Product Code: RO7021610/F01 (Active) Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: n/a Current Sponsor code: RO7021610 Other descriptive name: UTTR1147A, IL22‐Fc, IL‐22Fc Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use Product Name: Astegolimab Product Code: RO7187807/F01 Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: Astegolimab Current Sponsor code: RO7187807 Other descriptive name: MSTT1041A, anti‐ ST2 (IgG2) human monoclonal antibody Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 70‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use CONDITION: Severe coronavirus disease 2019 (COVID‐19) pneumonia ; MedDRA version: 23.0 Level: LLT Classification code 10084383 Term: Novel COVID‐19‐infected pneumonia System Organ Class: 100000004862 ; MedDRA version: 23.0 Level: LLT Classification code 10084270 Term: SARS‐CoV‐2 acute respiratory disease System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: • To evaluate the efficacy of MSTT1041A compared with placebo and of UTTR1147A compared with placebo in combination with standard of care (SOC) on the basis of clinical status assessed using a 7‐category ordinal scale at Day 28 Primary end point(s): 1. Clinical status assessed using a 7‐category ordinal scale at Day 28 Secondary Objective: • To evaluate the efficacy of MSTT1041A compared with placebo and of UTTR1147A compared with placebo in combination with SOC on the basis of time to clinical improvement, time to improvement of at least 2 categories relative to baseline on a 7‐category ordinal scale of clinical status, incidence of mechanical ventilation, ventilator‐free days to Day 28, incidence and duration of intensive care unit (ICU) stay, time to clinical failure, mortality rate, time to hospital discharge or “ready for discharge”, duration of supplemental oxygen, duration of hypoxemia, and proportion of patients alive and free of respiratory failure; • To evaluate the safety of MSTT1041A compared with placebo and of UTTR1147A compared with placebo in combination with SOC for the treatment of severe COVID‐19 pneumonia; • To characterize the pharmacokinetic profile of MSTT1041A and UTTR1147A ; • To evaluate the immune response to UTTR1147A and MSTT1041A Timepoint(s) of evaluation of this end point: 1. At Day 28 INCLUSION CRITERIA: • Age >=18 years • Hospitalized with COVID‐19 pneumonia confirmed per WHO criteria and evidenced by chest X‐ray or CT scan • Peripheral capillary oxygen saturation (SpO2) <= 93% or partial pressure of oxygen/fraction of inspired oxygen <= 300 mmHg or requiring supplemental oxygen to maintain SpO2 > 93% Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 195 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 105 SECONDARY OUTCOME: Secondary end point(s): 1. Time to clinical improvement, defined as a National Early Warning Score 2 (NEWS2) of <= 2 maintained for 24 hours; 2. Time to improvement of at least 2 categories relative to baseline on a 7‐category ordinal scale of clinical status; 3. Incidence of mechanical ventilation; 4. Ventilator‐free days to Day 28; 5. Incidence of ICU stay ; 6. Duration of ICU stay; 7. Time to clinical failure; 8. Mortality rate at Days 7, 14, 21, 28, and 60; 9. Time to hospital discharge or “ready for discharge”; 10. Duration of supplemental oxygen; 11. Duration of hypoxemia (<= 93% on room air); 12. Proportion of patients alive and free of respiratory failure at Day 28; 13. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0; 14. Change from baseline in targeted vital signs, targeted clinical laboratory test results, and targeted ECG parameters; 15. Serum concentration of MSTT1041A at specified timepoints; 16. Serum concentration of UTTR1147A at specified timepoints; 17. Prevalence of anti‐drug antibodies (ADAs) at baseline and incidence of ADAs during the study Timepoint(s) of evaluation of this end point: 1‐3 Up to Day 60; 4. Up to Day 28; 5‐7. Up to Day 60; 8. At Days 7, 14, 21, 28, and 60; 9‐11. Up to Day 60; 12. At Day 28; 13. Up to Day 60; 14. From baseline to Day 60; 15‐16. Day 1‐3, 7, 15, 21, 28, 60 or at early discontinuation visit; 17. Day 1, 15, 28, 60 or at early discontinuation visit