A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)
Phase: PHASE2
Conditions: COVID-19
Sponsor: Kinevant Sciences GmbH

 
 
 
 
 
Study Number: KIN-1901-2001 
 
Study Title: A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to 
Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute 
Respiratory Distress Syndrome (ARDS) Secondary to Coronavirus Disease 2019 (COVID-19) 
 
 
 
Clinical Study Protocol 
 
Version 5.0 (Amendment 4): 17-Aug-2020 
NCT04351243 

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Protocol No. KIN-1901-2001 (Amendment 4) 
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CLINICAL STUDY PROTOCOL 
Study Title: 
A Multi-Center, Adaptive, Randomized, Double-blind, 
Placebo-controlled Study to Assess the Efficacy and Safety of 
Gimsilumab in Subjects With Lung Injury or Acute Respiratory 
Distress Syndrome (ARDS) Secondary to Coronavirus Disease 2019 
(COVID-19) 
Protocol Number: 
KIN-1901-2001 
Compound Name 
and/or Number: 
Gimsilumab (KIN-1901, formerly MORAb-022) 
Sponsor: 
Kinevant Sciences GmbH (“KSG”), a Swiss Limited Liability 
Company, is the sponsor of this study. Kinevant Sciences, Inc. 
(“KSI”), a Delaware corporation and an affiliate of KSG, has been 
engaged by KSG to manage the day-to-day operations of the study. 
All references to “Sponsor” contained herein shall refer to KSI, 
acting pursuant to a services agreement with KSG. 
Development Phase: 
2 
Indication: 
For the treatment of lung injury or ARDS secondary to COVID-19 
Current Version and 
Effective Date: 
Version 5.0 (Amendment 4): 17-Aug-2020 
Previous Version(s) 
and Effective Date(s): 
Version 1.0 (Original): 22-March-2020 
Version 2.0 (Amendment 1): 05-April-2020 
Version 3.0 (Amendment 2): 06-May-2020 
Version 4.0 (Amendment 3): 12-Jun-2020 
Study Director: 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property or under 
control of Sponsor, and is provided to you in confidence as an investigator, potential investigator or 
consultant, for review by you, your staff, and an applicable Institutional Review Board or Independent 
Ethics Committee. The information is only to be used by you in connection with authorized clinical 
studies of the investigational drug described in the protocol. You will not disclose any of the information 
to others without written authorization from Sponsor, except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered. 

DocuSign Envelope ID: CEEE68B0-D48A-4243-B942-66973BA5270B 
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SPONSOR SIGNATURE PAGE 
Study Title: A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled 
Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung 
Injury or Acute Respiratory Distress Syndrome (ARDS) Secondary to 
Coronavirus Disease 2019 (COVID-19) 
 
Protocol Number: KIN-1901-2001 
 
This protocol has been approved by a representative of Kinevant Sciences GmbH. The following 
signature documents this approval. 
 
 
 
 
 
8/17/2020 
 
Date 

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MEDICAL CONTACT/SPONSOR INFORMATION PAGE 
Sponsor Medical Contact/SAE Contact Information: 
 
Role 
Name 
 
Contact for Serious Adverse 
Events (SAEs) 
On discovery, all SAEs should be immediately reported (latest within 24 hours of 
knowledge of the event) to 
 
 
 
 
Study Sponsor 
Kinevant Sciences GmbH (“KSG”), a Swiss Limited Liability Company, is the sponsor of this 
study. Kinevant Sciences, Inc. (“KSI”), a Delaware corporation and an affiliate of KSG, has been 
engaged by KSG to manage the day-to-day operations of the study. All references to “Sponsor” 
contained herein shall refer to KSI, acting pursuant to a services agreement with KSG. 
 
Kinevant Sciences GmbH Registered Address: 
Viaduktstrasse 8 
4051 Basel 
Switzerland 
 
Kinevant Sciences, Inc. Address: 
151 West 42nd Street, 15th floor 
New York, NY, 10036 
USA 
Primary Medical Monitor 
(Europe) 
Primary Medical Monitor 
(US) 
Secondary Medical Monitor 

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INVESTIGATOR STATEMENT 
• I confirm agreement to conduct the study in compliance with the protocol. 
• I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study. 
• I agree to ensure that all associates, colleagues, and employees assisting in the conduct of 
the study understand their obligations and will comply with the study protocol. 
Mechanisms are in place to ensure that site staff receives the appropriate training and 
information throughout the study. 
 
 
 
 
 
 
 
Principal Investigator Name (Printed) 
Signature 
 
 
 
 
 
Date 
Site 
 
 
 
Study Site 
Name of Primary Investigator Site 
 
Address Line 1 
Address Line 2 
City, State, Country, Zip Code 

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TABLE OF CONTENTS 
Clinical Study Protocol ............................................................................................................... 1 
Sponsor Signature Page ............................................................................................................ 2 
Medical Contact/Sponsor Information Page ............................................................................ 3 
Investigator Statement ............................................................................................................... 4 
Table of Contents ........................................................................................................................ 5 
List of Tables ............................................................................................................................... 7 
List of Figures ............................................................................................................................. 8 
1. 
Protocol Summary for Study KIN-1901-2001 .................................................................... 9 
2. 
Introduction ....................................................................................................................... 20 
2.1. 
Study Rationale ........................................................................................................... 20 
2.1.1. 
COVID-19 Background, Clinical Course, and Immunopathogenesis .................. 20 
2.1.2. 
Rationale for Targeting GM-CSF in COVID-19 ................................................... 20 
2.2. 
Dose Rationale ............................................................................................................ 21 
2.3. 
Benefit/Risk Assessment ............................................................................................. 24 
3. 
Objectives and Endpoints ................................................................................................ 25 
4. 
Investigational Plan .......................................................................................................... 27 
4.1. 
Overall Study Design ................................................................................................... 27 
4.2. 
Scientific Rationale for Study Design .......................................................................... 28 
4.3. 
Treatment Arms and Duration ..................................................................................... 28 
5. 
Subject Population ........................................................................................................... 29 
5.1. 
Type and Number of Subjects ..................................................................................... 29 
5.2. 
Inclusion Criteria .......................................................................................................... 29 
5.3. 
Exclusion Criteria ........................................................................................................ 30 
5.4. 
Other Eligibility Criteria Considerations ....................................................................... 31 
5.5. 
Screening/Baseline ..................................................................................................... 31 
5.6. 
Lifestyle and/or Dietary Restrictions ............................................................................ 31 
5.6.1. 
Contraception ...................................................................................................... 31 
5.7. 
Withdrawal Criteria ...................................................................................................... 33 
5.7.1. 
Reasons for Withdrawal ...................................................................................... 33 
5.7.2. 
Subject Withdrawal Procedures .......................................................................... 33 
5.8. 
Toxicity Management Criteria ...................................................................................... 34 
5.8.1. 
Liver Chemistry Management Criteria ................................................................. 34 
5.8.2. 
Individual Stopping Criteria ................................................................................. 35 
5.8.3. 
Study Stopping Criteria ....................................................................................... 35 
5.8.4. 
Other Management Criteria ................................................................................. 35 
5.9. 
Subject and Study Completion .................................................................................... 35 
6. 
Study Treatment ................................................................................................................ 35 
6.1. 
Study Treatment .......................................................................................................... 35 
6.2. 
Administration of Study Treatments ............................................................................ 36 
6.3. 
Randomization / Study Treatment Assignment ........................................................... 36 
6.4. 
Blinding........................................................................................................................ 37 
6.5. 
Packaging and Labeling .............................................................................................. 38 
6.6. 
Preparation/Handling/Storage/Accountability .............................................................. 38 

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6.7. 
Compliance with Study Treatment Administration ....................................................... 39 
6.8. 
Treatment of Study Treatment Overdose .................................................................... 39 
6.9. 
Concomitant Medications and Non-Drug Therapies ................................................... 39 
6.9.1. 
Permitted Medications and Non-Drug Therapies ................................................ 39 
6.9.2. 
Prohibited Medications and Non-Drug Therapies ................................................ 40 
7. 
Study Assessments and Procedures .............................................................................. 40 
7.1. 
Schedule of Assessments (Treatment and Follow-up Periods) .................................. 42 
7.2. 
Informed Consent ........................................................................................................ 47 
7.3. 
Inclusion/Exclusion Criteria Eligibility Review ............................................................. 47 
7.4. 
Study Assessments and Procedures .......................................................................... 47 
7.4.1. 
Efficacy Assessments .......................................................................................... 47 
7.4.2. 
Safety and Other Assessments ........................................................................... 49 
8. 
Data Management ............................................................................................................. 53 
9. 
Statistical Considerations and Analyses ........................................................................ 54 
9.1. 
Sample Size Determination ......................................................................................... 54 
9.2. 
Randomization ............................................................................................................ 54 
9.3. 
Analysis Endpoints ...................................................................................................... 55 
9.3.1. 
Efficacy Endpoints ............................................................................................... 55 
9.3.2. 
Safety Endpoints ................................................................................................. 56 
9.3.3. 
Pharmacokinetic Endpoints ................................................................................. 56 
9.3.4. 
Biomarker Endpoints ........................................................................................... 56 
9.4. 
Analysis Populations ................................................................................................... 56 
9.5. 
Statistical Analyses/Methods ....................................................................................... 57 
9.5.1. 
Primary Efficacy Analyses ................................................................................... 57 
9.5.2. 
Sensitivity Analysis of the Primary Endpoint ....................................................... 57 
9.5.3. 
Analysis of the Key and Other Secondary Endpoints .......................................... 58 
9.5.4. 
Adjustment of Multiple Comparisons and Interim Analyses ................................. 58 
9.5.5. 
Handling of Missing Data ..................................................................................... 59 
9.5.6. 
Safety Analyses ................................................................................................... 59 
9.5.7. 
Sub-Group Analyses ........................................................................................... 59 
9.5.8. 
Timing of Analyses .............................................................................................. 60 
9.5.9. 
Pharmacokinetic, Biomarker, and Immunogenicity Analyses .............................. 60 
10. 
Adverse Events (AE) and Serious Adverse Events (SAEs) ....................................... 60 
10.1. Special Consideration for Assessment of Adverse Events ......................................... 60 
10.2. Definition of an Adverse Event .................................................................................... 61 
10.3. Definition of a Serious Adverse Event ......................................................................... 62 
10.4. Time Period and Frequency for Collecting AE and SAE Information .......................... 62 
10.5. Method of Detecting AEs and SAEs ............................................................................ 63 
10.6. Assessing Severity of AEs and SAEs ......................................................................... 63 
10.7. Assessing Causalities of AEs and SAEs ..................................................................... 64 
10.8. Follow-up of (non-serious) AEs and Serious AEs ....................................................... 64 
10.9. Regulatory Reporting Requirements for SAEs ............................................................ 64 
11. 
Pregnancy Reporting .................................................................................................... 65 
12. 
Responsibilities ............................................................................................................. 65 
12.1. Principal Investigator Responsibilities ......................................................................... 65 
12.1.1. 
Good Clinical Practice ......................................................................................... 65 
12.1.2. 
Institutional Review Board/Independent Ethics Committee Approval .................. 66 
12.1.3. 
Informed Consent ................................................................................................ 66 

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12.1.4. 
Confidentiality ...................................................................................................... 66 
12.1.5. 
Study Files and Retention of Records ................................................................. 66 
12.1.6. 
Electronic Case Report Forms (eCRF) ................................................................ 68 
12.1.7. 
Drug Accountability.............................................................................................. 68 
12.1.8. 
Inspections .......................................................................................................... 68 
12.1.9. 
Protocol Compliance ........................................................................................... 68 
12.2. Sponsor Responsibilities ............................................................................................. 68 
12.2.1. 
Protocol Modifications ......................................................................................... 68 
12.2.2. 
Study Report and Publications ............................................................................ 69 
12.3. Joint Investigator/Sponsor Responsibilities ................................................................. 69 
12.3.1. 
Access to Information for Monitoring ................................................................... 69 
12.3.2. 
Access to Information for Auditing or Inspections ................................................ 69 
12.3.3. 
Study Discontinuation .......................................................................................... 69 
13. 
References ..................................................................................................................... 70 
14. 
Appendices .................................................................................................................... 73 
14.1. Appendix 1: Abbreviations and Trademarks ............................................................... 73 
14.2. Appendix 2: Liver Safety Required Actions and Follow up Assessments ................... 77 
14.3. Appendix 3: Summary of Changes for Protocol Amendments .................................... 79 
 
 
LIST OF TABLES 
Table 2-1: Predicted Gimsilumab Exposure and Exposure Margins after Gimsilumab 
400 mg IV Compared to Highest IV Dose Studied in Study MORAb-022- 
001 in Humans and the NOEL IV Dose Studied in Cynomolgus Monkeys .......... 23 
Table 4-1: Treatment Arms for KIN-1901-2001 ........................................................................... 28 
Table 6-1: Treatment Descriptions for KIN-1901-2001 ............................................................... 36 
Table 6-2: Randomization Schema for KIN-1901-2001 .............................................................. 37 
Table 7-1: Estimated Sample Requirements Per Subject .......................................................... 40 
Table 7-2: Schedule of Assessments ......................................................................................... 42 
Table 7-3: List of Clinical Laboratory Analyses ........................................................................... 51 
Table 14-1: Summary of Changes: Amendment 1 ...................................................................... 79 
Table 14-2: Summary of Changes: Amendment 2 ...................................................................... 97 
Table 14-3: Summary of Changes: Amendment 3 .................................................................... 103 
Table 14-4: Summary of Changes: Amendment 4 .................................................................... 108 

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LIST OF FIGURES 
Figure 2-1: 
Simulated Serum Gimsilumab PK Profile After Gimsilumab 400 mg IV 
Day 1 and 200 mg IV Day 8a ............................................................................... 24 
 
Figure 4-1: 
Study Schematic ................................................................................................. 27 
 
Figure 7-1: 
National Early Warning Score ............................................................................. 49 

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1. 
PROTOCOL SUMMARY FOR STUDY KIN-1901-2001 
Synopsis 
 
Study Rationale 
In December 2019, the city of Wuhan, China experienced an outbreak of 
coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of 
March 2020, COVID-19 has become a global pandemic, and there are 
currently no approved agents available to treat coronaviruses [World 
Health Organization (WHO) COVID-19 Situation Report, 2020]. 
SARS-CoV-2 infection often induces an overactive immune response that 
causes significant lung damage, leading to acute respiratory distress 
syndrome (ARDS) and ultimately death. Granulocyte macrophage-colony 
stimulating factor (GM-CSF), a hematopoietic growth factor and 
immunomodulatory cytokine, is believed to be a key driver of cytokine 
storm and lung hyper-inflammation [Molfino, 2016; Sterner, 2019; Zhou, 
2020]. Targeting GM-CSF using an anti-GM-CSF antibody, gimsilumab 
(KIN-1901), represents a promising strategy to treat patients who have 
developed lung injury or ARDS secondary to COVID-19. 
Study Design 
Randomized, double-blind, placebo-controlled 
Study Objectives 
Primary Objective: 
• The primary objective is to evaluate the impact of intravenous (IV) 
treatment with gimsilumab on mortality in subjects with lung injury or 
ARDS secondary to COVID-19. 
Key Secondary Objectives: 
• To assess the effect of gimsilumab on ventilation requirements 
• To assess the effect of gimsilumab on overall duration of 
hospitalization 
Additional Secondary Objectives: 
• To assess the effect of gimsilumab on the need for Intensive Care Unit 
(ICU) level of care 
• To assess the effect of gimsilumab as measured by the National Early 
Warning Score (NEWS) 
• To assess the effect of gimsilumab as assessed by the Sequential 
Organ Failure Assessment (SOFA) score 
• To assess the effect of gimsilumab as measured by the 7-point ordinal 
scale 
• To assess the effect of gimsilumab on peripheral capillary oxygen 
saturation / fraction of inspired oxygen (SpO2/FiO2) 
• To assess the effect of gimsilumab on oxygenation requirements 
• To assess changes in on-treatment viral load 
• To assess the effect of gimsilumab on biomarkers of inflammation 
• To determine the pharmacokinetic (PK) properties of gimsilumab 
• To assess the immunogenicity of gimsilumab 
• To determine the safety and tolerability of gimsilumab 

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Exploratory Objectives: 
• To explore the effect of gimsilumab on serum cytokine concentrations 
and surfactant protein D (SP-D) 
• To explore the effect of gimsilumab on other measurements of lung 
injury that may be performed during standard care (e.g., Lung Injury 
Score [LIS], chest radiography, PaO2/FiO2 [P/F ratio], need for 
extracorporeal membrane oxygenation [ECMO]) 
• To explore the effect of gimsilumab on cardiac function (if measured) 
• To assess the effect of gimsilumab on renal function 
Study Population 
270 subjects (135 subjects per arm) who have a confirmed diagnosis of 
COVID-19 with clinical evidence of acute lung injury or ARDS 
Number of Planned 
Subjects 
270 total subjects are planned for this study. 
Arm 1 (Active drug): 135 subjects 
Arm 2 (Placebo): 135 subjects 
Study Treatments 
Gimsilumab 400 mg IV on Day 1 and 200 mg IV on Day 8, or matching 
placebo (saline solution) IV on Day 1 and on Day 8. The Day 8 dose will 
be omitted if the subject is discharged from the hospital or is no longer in 
need of supplemental oxygen or ventilatory support for >48 hours. 
Treatment and Study 
Duration 
This study will consist of a 2-week Treatment Period (last dose Day 8, if 
administered) and a 22-week Follow-up Period, for a total study duration 
of 24 weeks for each subject. 
Study Centers and 
Countries 
This study will be conducted at approximately 20 centers in the United 
States and potentially 6 centers in Mexico; other countries may be added, 
if needed. 

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Study Endpoint(s) 
Primary Endpoint: 
• 
Incidence of mortality by Day 43 
Key Secondary Endpoints: 
• 
Proportion of subjects who survived and were not requiring 
mechanical ventilation on Day 29 
• 
Mechanical ventilation-free days by Day 29 
• 
Time to hospital discharge by Day 43 
Additional Secondary Endpoints: 
• 
Incidence of mortality by Days 15, 22, 29, 85, and 169 
(End-of-Study [EoS]) 
• 
Proportion of subjects who survived and were not requiring 
mechanical ventilation on Days 15, 22, and 43. 
• 
Mechanical ventilation-free days for all subjects by Days 15, 22, 
and 43 
• 
ICU-free days for all subjects by Days 15, 22, 29, and 43. 
• 
Incidence of mechanical ventilation use for all subjects by Days 
15, 22, 29, and 43. 
• 
Incidence of ICU use for all subjects by Days 15, 22, 29, and 43 
• 
Time to death by Day 43 and Day 169 (EoS) 
• 
NEWS assessed daily while hospitalized 
• 
SOFA score, and each of the components, assessed daily while in 
the ICU 
• 
The percentage of subjects reporting each severity rating on the 
7-point ordinal scale, assessed daily while hospitalized and, if 
discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 169 
(assessed by phone) 
• 
Status on the 7-point ordinal scale, assessed daily while 
hospitalized and, if discharged from hospital, on Days 15, 22, 29, 
36, 43, 85, and 169 (assessed by phone) 
• 
Time to clinical improvement by 2 points on the 7-point ordinal 
scale 
• 
Change from Baseline in SpO2/FiO2, assessed daily while 
hospitalized 
• 
Incidence and duration of oxygen use during the study 
• 
Change from Baseline in viral load as measured by quantitative 
polymerase chain reaction (PCR) test on Days 2, 9, and day-of- 
discharge (DoD) 
• 
Change from Baseline in D-dimer, cardiac troponin I, lactate 
dehydrogenase (LDH), ferritin, and C-reactive protein (CRP) 
• 
Serum gimsilumab concentrations 
• 
Analysis of anti-gimsilumab antibodies (ADAs) 
Safety Endpoints: 
• 
Safety and tolerability, including assessment of clinical safety 
laboratory measurements, physical examinations, vital signs, 

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concomitant medications; cumulative incidence of adverse events 
(AEs), serious adverse events (SAEs), and severe AEs 
Exploratory Endpoints: 
• 
Change from Baseline in the cytokine panel and serum SP-D 
• 
Change from Baseline in LIS (if performed) 
• 
Change from Baseline in chest radiographic assessment (if 
performed) 
• 
Change from Baseline in P/F ratio, if performed 
• 
Incidence and duration of ECMO use 
• 
Change from Baseline in left ventricular ejection fraction (LVEF) 
(when measured) 
• Change from Baseline in estimated glomerular filtration rate 
(eGFR) [Modification of Diet in Renal Disease (MDRD) 
equation], assessed when central clinical safety laboratory 
measurements are collected during hospitalization 

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Inclusion Criteria 
An individual will be eligible for participation in this study only if all 
of the following inclusion criteria are met: 
1. Male or non-pregnant female age ≥18 years 
2. Subject (or legally authorized representative [LAR]) is able and 
willing to provide written or verbal informed consent, which includes 
compliance with study requirements and restrictions listed in the 
consent form. NOTE: If a subject or LAR must be consented verbally, 
the site must have a site policy for verbal consent and the consent must 
be clearly documented in the subject’s chart. 
3. Has documented laboratory-confirmed SARS-CoV-2 infection as 
determined by PCR or other approved clinical testing prior to 
randomization 
4. CRP ≥50 mg/L or serum ferritin ≥1,000 ng/mL. Results from CRP and 
ferritin tests performed within 8 days of randomization are acceptable 
for enrollment. 
5. Radiographic evidence of bilateral infiltrates. Acceptable imaging tests 
(chest X-ray, CT scans) done within 3 days of Day 1 can be used for 
inclusion. 
6. Subject has clinical evidence of lung injury [defined as (1) requiring 
supplemental oxygen ≥4L O2 to attempt to maintain ≥92% SpO2, or 
(2) P/F ratio ≤300 mmHg (can be imputed)], or meets clinical 
classification criteria for ARDS [ARDS Berlin Definition, 2012], 
secondary to COVID-19. 
7. Female subjects must agree to use an approved highly effective birth 
control (BC) method (<1% failure rate per year) throughout the study 
(until completion of the Day 85 Follow-up Visit), unless documented 
to have a reproductive status of non-childbearing potential or is 
postmenopausal: 
• 
Non-childbearing potential defined as pre-menopausal female with 
medical history of bilateral tubal ligation, bilateral oophorectomy 
(removal of the ovaries), or hysterectomy; hysteroscopic 
sterilization, 
• 
Postmenopausal defined as 12 months of spontaneous amenorrhea 
or with follicle stimulating hormone (FSH) confirmation. 
• 
Woman of childbearing potential (WCBP) who is already using an 
established method of highly effective contraception or agrees to 
use one of the allowed BC methods, for at least 28 days prior to 
the start of dosing (as determined by the Investigator Brochure or 
Investigator or designee) to sufficiently minimize the risk of 
pregnancy throughout study participation (until completion of the 
Day 85 Follow-up Visit). 
8. Males who are sexually active must agree to use one of the allowed 
BC methods. Male subjects must also agree to sufficiently minimize 
the risk of pregnancy throughout study participation (until completion 
of the Day 85 Follow-up Visit). 

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Exclusion Criteria 
1. Subject requires norepinephrine at a dose of >0.5 mcg/kg/min, or 
equivalent 
2. Subject has been intubated for >72 hours. Note: in the event of 
extubation and re-intubation, the calculation for the number of hours 
the subject has been intubated begins at the first intubation. 
3. Evidence of life-threatening dysrhythmia (e.g., ventricular tachycardia 
[VT], ventricular fibrillation [VF]), or cardiac arrest on presentation 
4. Evidence of new or preexisting decompensated heart failure. 
5. At the time of screening, subject is anticipated to require ECMO 
6. Absolute neutrophil count <1,000 per mm3 
7. Platelet count <50,000 per mm3 
8. History of known anti-GM-CSF autoantibodies (autoAb) or pulmonary 
alveolar proteinosis. Note: A negative anti-GM-CSF autoAb test result 
is not required at screening. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive 
pulmonary disease [COPD], pulmonary arterial hypertension [PAH], 
idiopathic pulmonary fibrosis [IPF], interstitial lung disease [ILD]) 
requiring supplemental oxygen therapy or mechanical ventilation 
pre-hospitalization (e.g., prior to COVID-19 diagnosis) 
10. Known or suspected active and untreated tuberculosis (TB), human 
immunodeficiency virus (HIV), hepatitis B or C infection 
• 
Results of TB, hepatitis B and C, and HIV tests are not required 
prior to enrollment if there is no suspicion of active infection, as 
per KIN-1901 Guidance on Active Infections Testing. 
11. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) 
>5 × upper limit of normal (ULN). 
12. eGFR <30 mL/min/1.73m2 (MDRD equation) or requiring 
hemofiltration or dialysis 
13. Use of any immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, 
anti-TNF, inhibitors of complement signaling), cell therapies (e.g., 
mesenchymal stem cells), or small molecule Janus kinase [JAK] 
inhibitors within the past 7 days or within five half-lives (whichever is 
longer), or planned use of any of these agents from Screening until 
Day 43 of the study, unless approved by the Medical Monitor. The 
following will be allowed/disallowed: 
• 
Immunomodulatory biologics for COVID-19 treatment are 
excluded and should not be used until Day 43 unless discussed 
with the Medical Monitor. Other non-biologic immunomodulators 
(non-JAK inhibitors), e.g., medicines for previous transplantation, 
or disease modifying anti-rheumatic drugs (DMARDS), and have 
had a stable dose for ≥8 weeks are permitted. 
• 
Subjects who have been treated with convalescent plasma (CP) 
prior to enrollment are eligible if the subject continues to meet all 
inclusion criteria at screening. Ongoing therapy with CP is 
allowable if clinically indicated in the view of the treating 
physician or the Investigator. 
• 
The use of investigational anti-viral treatment (e.g., remdesivir) is 
allowed if the subject continues to meet all inclusion criteria at 
screening. 

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14. Ongoing chronic (≥4 weeks) use of corticosteroids >10 mg/day of 
prednisone or equivalent at the time of randomization. A corticosteroid 
dose that has been tapered to 10 mg or less within 14 days of 
randomization is also prohibited. 
15. Pregnancy and/or breast feeding 
16. Unable to receive invasive or non-invasive ventilatory support 
17. Moribund condition in the opinion of the clinical team 
Database Locks 
The study database will be locked when all subjects complete the Day 43 
Visit, discontinue from the study early, or meet the primary mortality 
endpoint. The second lock will occur when the last subject completes the 
Day 169 EoS visit. 
In addition, there will be 2 database extracts (soft locks) for interim 
analyses, the first of which will be conducted when 60 subjects have been 
treated and have completed through Day 15; the DMC will review the data 
for safety and futility and provide their recommendations. The second 
interim analysis will be conducted when 100 subjects have completed at 
least the Day 29 Visit for non-mortality endpoints and have the data for 
the endpoint of mortality (by Day 43). 

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Statistical Analyses 
Sample Size and Power 
There will be 270 subjects with confirmed COVID-19 and clinical 
evidence of lung injury or ARDS (135 subjects per arm) with 1:1 
randomization. 
The comparisons between the treatment arms will have approximately 
80% power and alpha level 0.05 (two-sided) to demonstrate the significant 
reductions (15% versus 30%) of the primary endpoint between 
gimsilumab versus placebo. 
The study will enroll at least 40%, but no more than 60%, of total subjects 
in each of the two categories of clinical status : ([lung injury/mild ARDS] 
or [moderate/severe ARDS]) at Baseline, which will be used as the 
stratified factor in the randomization. 
Randomization 
The central stratified randomization will be used to assign subjects into 
one of the study treatment arms with an equal randomization ratio (1:1) 
with the stratification factors of subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) and country. 
Key Analysis Sets 
• The Intent-to-Treat (ITT) Population will include all randomized 
subjects who receive any amount of study drug. The ITT subjects will 
be analyzed according to randomized treatment, irrespective of 
whether or not they have prematurely discontinued. Subjects who 
withdraw from treatment and/or the study early will be followed for 
Day 43 all-cause mortality. All efficacy analyses will be performed 
using the ITT Population. 
• The Safety Population (SP) will include all randomized subjects who 
receive any amount of study drug. The SP will be analyzed according 
to the treatment received. This set will be used for the safety analyses. 
• The Per-Protocol (PP) Population will include all subjects in the ITT 
Population who complete the Day 43 Visit with no major protocol 
violations. The PP Population will be used for supportive analyses of 
the efficacy measurements. 

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Statistical Methods in General 
All statistical analyses will be conducted using SAS, Version 13.1 or later. 
Baseline characteristics will be summarized by treatment arm. For 
continuous measures the mean and standard deviation (SD) will be 
summarized. Categorical variables will be described by the proportion in 
each category. 
Efficacy Analyses 
The primary analysis of the efficacy endpoint (Mortality by Day 43) will 
be performed by using logistic regression [Ge, 2011] with treatment, 
country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] 
or [moderate/severe ARDS]) as covariates. The subjects who meet the 
criteria of endpoint will be summarized by the numbers and percentages of 
the incidence, with odds ratio and its 95% confidence interval (CI) 
presented for gimsilumab versus placebo, and p-value. 
The secondary analysis of the primary endpoint will be conducted by the 
Cox Proportional hazard model on the time to death. The median of the 
time to event from Kaplan-Meier curves will be presented for each 
treatment, and the hazard ratio of gimsilumab versus placebo will be 
presented with 95% CI, and p-value. 
Adjustment of Multiple Comparisons and Interim Analysis 
The interim analysis will be conducted when 60 subjects have been treated 
and have completed through Day 15; the DMC will review the data for 
safety and futility and provide their recommendations. 
The second interim analysis will be conducted when 100 subjects have 
completed at least the Day 29 Visit for non-mortality endpoints and have 
the data for the endpoint of mortality by Day 43. The objectives of the 
second interim analysis will be to stop the study by superiority, futility, or 
perform the sample size re-estimation. For controlling overall two-sided 
alpha of 0.05 overall for the final analysis on the primary endpoint of 
Mortality Day 43, 0.001 of the alpha will be used for the superiority 
comparison during the second interim analysis, and 0.049 will be used for 
the final analysis. The weighted average of two summary measures by 
Cui L, Hung HM, Wang [Cui, 1999] will be used, one based on the data 
collected in the interim analysis, and the other based on the data collected 
after the interim. 
Analyses in General 
All the continuous variables, including the changes from Baseline, will be 
summarized by the treatment with the means, SD, medians and the ranges. 
The Mixed Model with Repeated Measurements (MMRM) /Analysis of 
Covariance (ANCOVA) model with the treatment, country, subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]), and visit as the model term, and Baseline value as the covariate 
will be used to test for the significance of the treatment difference. The 
least square means, standard errors, 95% CIs and p-values will be 
presented. 

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All the categorical variables will be summarized by the treatment with the 
numbers and percentages of the subjects, and the treatment difference will 
be tested by using CMH test stratified by 1) country and 2) subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]). 
The time to event endpoints will be analyzed by using the Cox 
Proportional Hazard model with the treatment, country, and subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]) as the model term. The hazard ratio of gimsilumab versus 
placebo will be presented with 95% CI and p-value from the model. The 
Kaplan-Meier curves of the time to events will be presented for treatments 
on each endpoint. 
Handling of Missing Data 
Sensitivity analyses will be performed for the primary and key secondary 
endpoints by using multiple imputations for the missing data: 
• 
Tipping-point multiple imputation analysis 
Missing data will be imputed for Mortality by Day 43 with all possible 
combinations of Death or Survival in the two arms. The combination 
which alters the conclusion will be defined as the tipping point for 
evaluation on the robustness of the results. 
• 
Imputation differentiating the reasons of missing data from the 
early drop out 
The reasons of the lost to follow-up, SAEs/AEs, and the use of rescue 
medications will be identified, and the percentage of these subjects will be 
summarized by treatment. The data for informative censoring, such as the 
unfavorable or worst outcome, can be used to impute the missing data. 
More details will be pre-specified in the statistical analysis plan (SAP). 
Safety Analyses 
Safety will be assessed based on the SP for AEs, laboratory parameters, 
physical examination, vital signs, and clinical chemistries throughout the 
duration of the study. The safety analyses will include descriptive 
summaries by treatment arm of AEs. The number and percentage of 
participants reporting AEs and SAEs will be presented. Adverse events 
will be categorized by system organ class (SOC) and preferred term (PT) 
and summarized by the number of participants (and percentage) with at 
least 1 event, and the number of events. Adverse events will also be 
summarized by seriousness, grade, and study drug relationship for all 
participants. The continuous variables, including the changes from 
Baseline, will be summarized by descriptive statistics: mean, SD, and the 
range. The categorical variables, such as normal/abnormal will be 
summarized by the numbers and percentages at each visit, and the shift 
table from Baseline to each visit will be presented. 
Timing of Analyses with All Subjects 
The first unblinded analyses will be conducted when the last subject 
completes the Day 43 Visit, discontinues from the study early, or meets 

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the primary mortality endpoint (by Day 43). The second unblinded 
analyses will be conducted when the last subject completes the Day 169 
Follow-up Visit (EoS). 
The DMC will be responsible for closely reviewing the safety data from 
the unblinded interim analysis and for providing their recommendations. 
The detailed objectives and procedures of the interim analyses will be 
described in the DMC Charter. 
Pharmacokinetic, Biomarker, and Immunogenicity 
Data will be summarized by treatment arm. 
Statistical Analysis Plan (SAP) 
A detailed (revised) SAP will be signed and submitted to the agencies 
prior to the interim analysis of 100 subjects. 

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2. 
INTRODUCTION 
 
2.1. 
Study Rationale 
 
2.1.1. 
COVID-19 Background, Clinical Course, and Immunopathogenesis 
 
In December 2019, the city of Wuhan, China experienced an outbreak of coronavirus disease 
2019 (COVID-19), caused by a novel coronavirus, severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2). As of March 2020, COVID-19 has become a global pandemic 
[World Health Organization (WHO) COVID-19 Situation Report, 2020], and there are currently 
no approved agents available to treat coronaviruses. 
Although most infections are mild, approximately 20% of COVID-19 patients experience severe 
viral pneumonia that can progress to acute respiratory distress syndrome (ARDS) and death 
[Wu, 2019]. Clinical features of serious cases of COVID-19 resemble infections from severe 
acute respiratory syndrome coronavirus (SARS-CoV), which caused an epidemic in 2002-2003 
[Huang, 2020]. Immunopathological research into SARS-CoV defined three phases of disease: 
(1) fever, cough, and other systemic symptoms accompanied by an increase in viral load, (2) 
severe pneumonia that persists, despite a decline in viral load, due to a hyperactive immune 
response consisting of cytokine storm and significant macrophage/neutrophil lung infiltration, 
(3) pulmonary destruction and death [Lam, 2004; Channappanavar, 2017]. Emerging evidence 
suggests that cytokine storm and aberrant lung inflammation are similarly key features 
contributing to clinical worsening in COVID-19 [Huang, 2020; COVID-19 Investigation Team, 
2020; Kristas, 2020; Mehta, 2020]. Specifically, high concentrations of proinflammatory 
cytokines were found in COVID-19 patients, particularly those who were severely ill 
[Huang, 2020]. The observed cytokine signature was indicative of a T-helper-1 (Th1) cell 
inflammatory response [Huang, 2020], and activation of Th1 cells was found to increase as 
patients progressed to more severe disease [Zhou, 2020]. Analyses of bronchoalveolar lavage 
fluid revealed that severe COVID-19 patients also experienced overwhelming lung infiltration by 
highly inflammatory monocyte-derived macrophages [Liao, 2020]. 
 
2.1.2. 
Rationale for Targeting GM-CSF in COVID-19 
 
Granulocyte macrophage-colony-stimulating factor (GM-CSF), an important hematopoietic 
growth factor and immunomodulatory cytokine, is believed to be a key mediator of cytokine 
storm [Ishii 2016; Sterner, 2019; Turgues, 2018] and to contribute to SARS-CoV-induced ARDS 
[Channappanavar, 2016; Channappanavar, 2017]. GM-CSF was has been identified as a cytokine 
that is upregulated in the serum of COVID-19 patients [Huang, 2020]. Soon after, Zhou and 
colleagues reported that SARS-CoV-2 infection induced activation of immune cells that secreted 
large amounts of GM-CSF [Zhou, 2020]. The percentages of GM-CSF-expressing CD4+ T cells 
(Th1), CD8+ T cells, NK cells, and B cells were significantly higher in the blood of severe 
Intensive Care Unit (ICU)-admitted patients compared with healthy controls. This pan- 
lymphocyte observation was not seen when assessing IL-6 and TNF-α. Further, a 
GM-CSF+IFNγ+CD4+ T cell signature, which is associated with autoimmune encephalomyelitis 
[Stienne, 2020] and arthritis [Piper, 2014], was found in peripheral blood of ICU patients. These 
T cell responses were accompanied by significant upregulation of CD14+CD16+ inflammatory 

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monocytes, and a high percentage of monocytes secreted GM-CSF and IL-6, consistent with 
cytokine release syndrome (CRS) [Barrett, 2016]. The reported immunological changes appeared 
to be more pronounced in ICU-admitted patients versus non-ICU patients. Taken together, these 
results suggest that dysregulated GM-CSF expression from Th1 cells licenses pathogenic 
myeloid cell infiltration into the lung [Zhou, 2020]. These findings are consistent with the 
mechanisms of action of GM-CSF observed in other inflammatory lung conditions [Puljic, 2007; 
Willart, 2012; Shiomi, 2014; Molfino, 2016; Sheih, 2017; Kwon, 2018; Nobs, 2019] and in an 
animal model of SARS-CoV infection [Channappanavar, 2016]. Indeed, administration of 
recombinant GM-CSF (Leukine®) in a clinical setting can induce respiratory symptoms and even 
acute lung injury due to excessive myeloid cell mobilization [Kudlak, 2013]. 
This evidence suggests that GM-CSF stands as a key contributor to and regulator of the cytokine 
storm that characterizes progression to respiratory failure in COVID-19. Therefore, targeting 
GM-CSF represents a promising strategy for curbing immunopathological lung damage while 
buying time for viral clearance. This immunomodulatory strategy is supported by current 
guidelines from the China National Health Commission stating that glucocorticoids, intravenous 
immunoglobulin, and the anti-IL-6R antibody tocilizumab, which is U.S. Food and Drug 
Administration (FDA)-approved for CAR-T-related CRS, may be used to treat severely ill 
COVID-19 patients [Novel Coronavirus Pneumonia Diagnosis and Treatment Plan, 2020]. 
GM-CSF is thought to act upstream and stimulate the expression of IL-6 and other pro- 
inflammatory cytokines during CRS, making a GM-CSF-targeting strategy potentially more 
advantageous for dampening overactive immune responses than other cytokine-targeting 
approaches [Ishii, 2016; Barrett, 2016]. Based on significant preclinical evidence in animal 
models [Sterner, 2019; Tugues, 2018] a Phase 1/2 clinical trial is ongoing to assess the benefit of 
an anti-GM-CSF antibody (lenzilumab) in CAR-T-related CRS, and a Phase 2/3 trial of 
lenzilumab is planned for the treatment of CRS in graft versus host disease [Humanigen, Inc., 
2020]. Interestingly, a randomized, placebo-controlled phase 2 trial demonstrated statistically 
significant efficacy of lenzilumab on pulmonary function in eosinophilic asthmatics, consistent 
with the overall hypothesis that GM-CSF is a critical mediator of lung hyper-inflammation 
[Molfino, 2016]. 
Ultimately, GM-CSF’s master regulatory effect on cytokine storm and lung inflammation 
warrants the clinical investigation of an anti-GM-CSF antibody, gimsilumab (KIN-1901), in 
patients with lung injury or ARDS secondary to COVID-19. Gimsilumab administered 
intravenously or subcutaneously was shown to be well-tolerated in phase 1 clinical trials in 
healthy volunteers and rheumatoid arthritis patients (Studies MORAb-022-001 and 
KIN-1901-1001). Over 1,000 patients have been administered anti-GM-CSF(R) antibodies in 
clinical trials, with acceptable safety profiles seen to date [Hamilton, 2020]. 
 
2.2. 
Dose Rationale 
Gimsilumab will be administered intravenously (IV) on 2 occasions, 400 mg on Day 1 and 
200 mg on Day 8. 
A Phase 1 first-in-man study (MORAB-022-001) was conducted to assess safety, tolerability, 
pharmacokinetics (PK), and pharmacodynamics (PD) of single-dose IV gimsilumab in healthy 
subjects and subjects with rheumatoid arthritis (RA) [Gimsilumab Investigator Brochure, current 
edition]. Doses ranged from 0.0085 to 10 mg/kg in that study, with the highest doses (0.36 mg/kg 

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to 10 mg/kg) administered to subjects with RA. Study MORAB-022-001 showed the PK were 
dose-proportional over the entire dose range, with no differences noted between healthy subjects 
and subjects with RA. Although AEs (headache, nasopharyngitis, flu-like symptoms) were 
encountered more frequently in the gimsilumab group, they were graded mild to moderate and 
were not dose-related. 
Subcutaneous administration of gimsilumab was evaluated in ongoing study KIN-1901-1001. 
Single- and repeat-dose (once weekly for 4 doses) gimsilumab was administered to healthy 
volunteers to evaluate safety and pharmacokinetics. Based on a blinded safety data review on 
26 Feb 2020, gimsilumab was well-tolerated with no serious adverse events (SAEs), the majority 
AEs (67%) were injection site reactions (erythema, tenderness, bruising) [Gimsilumab 
Investigator Brochure, current edition]. 
GM-CSF stimulates increased levels of CD11b on neutrophils, thus inhibition of GM-CSF 
signaling can be measured through suppression of CD11b stimulation index [Sakagami, 2010; 
Nadicksbernd, 2013]. PD measurements with ex vivo stimulation of CD11b from study MORAb- 
022-001 suggested IV doses as low as 0.7 mg/kg caused suppression of CD11b expression, 
demonstrating pharmacologic activity. Observed serum concentrations from the gimsilumab 
first-in-human study suggested serum concentrations of ~20 µg/mL were associated with an 
ACR20 response in subjects with RA and the IC90 determined from the CD11b stimulation 
assay was 25 µg/mL [Gimsilumab Investigator Brochure, current edition]. As there is no 
nonclinical data at this time that can further inform the expected efficacious dose range for 
gimsilumab in the treatment of ARDS, a target trough serum concentration of 20 µg/mL was 
selected for this study. The intent is to maintain a trough concentration above ~20 µg/mL in the 
majority of subjects for the entire 2-week dosing period to maximize the potential to bind 
excessive levels of GM-CSF during ARDS. 
A population PK model of IV gimsilumab was developed from the IV first-in-human study. 
Based on this model, simulations were conducted to a select an appropriate dose regimen. While 
the prior study using IV gimsilumab utilized mg/kg dosing, a ‘flat dose’ regimen (not body 
weight adjusted) was selected for this study to simplify administration in this setting. Simulations 
accounted for a range in subject body weight to select an appropriate flat dose. Using this model, 
a dose of 400 mg on Day 1 results in a median trough serum concentration of 29 µg/mL on Day 
8. Based on the expected variability in exposure and range in subject body weight, the serum 
trough concentration at the lower bound of the 80% prediction interval (i.e., the 10th percentile) 
is expected to be ~20 µg/mL (Figure 2-1), i.e., 90% of subjects are expected to achieve serum 
concentrations above the target. A second dose of gimsilumab 200 mg on Day 8 maintains the 
trough concentration at these levels for an additional week. Based on the duration of ICU time in 
both survivors and non-survivors from a Chinese cohort of ~7 days [Zhou, 2020], two doses, i.e., 
a 14-day treatment period, was considered appropriate for this study. If subjects are discharged 
from the hospital or are no longer in need of supplemental oxygen or ventilatory support for 
>48 hours, the planned Day 8 dose will be omitted. 
The predicted exposure after gimsilumab 400 mg IV on Day 1 (the highest exposure expected 
during the study) is approximately half that observed at 10 mg/kg IV in subjects with RA (Table 
2-1). The expected Cmax at the 90th percentile is also expected to be less than the geometric mean 
Cmax observed previously at 10 mg/kg IV. In addition, the predicted exposure margins after 
400 mg IV compared to the monkey 26-week IV toxicology study is presented in Table 2-1. The 
no-observed-effect level (NOEL) in the monkey was 200 mg/kg IV once weekly; the NOEL was 

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the highest dose tested. The exposures observed in monkeys were at least 40× greater than those 
expected in the current study. Thus, given the observed safety profile and the pharmacologic 
activity at the expected exposures in the current study, gimsilumab 400 mg Day 1 and 200 mg 
Day 8 was selected for the present study. 
Gimsilumab vials are to be diluted in 0.9% saline, the resultant concentration 
is 
similar or less than those demonstrated to be safe in monkey IV toxicology studies. Gimsilumab 
is to be infused over a 
resulting in a rate no higher than 
This rate is similar to the highest rate previously administered to subjects with RA, that was well 
tolerated. 
 
Table 2-1: Predicted Gimsilumab Exposure and Exposure Margins after Gimsilumab 
400 mg IV Compared to Highest IV Dose Studied in Study MORAb-022-001 in 
Humans and the NOEL IV Dose Studied in Cynomolgus Monkeys 
 
Gimsilumab 
Dose 
Median Predicted 
Gimsilumab Exposure 
Predicted Exposure Margin 
(X-fold) Compared to RA 
Patients Gimsilumab 10 
mg/kg IVa 
Predicted Exposure Margin 
(X-fold) Compared to 
Cynomolgus Monkey 200 
mg/kg/week, IVb 
Cmax 
AUC 
Cmax 
AUC 
Cmax 
AUC 
400 mg IV 
128 
µg/mL 
17,860 
µg/mL 
2.1 
2.0 
92 
41 
a. 
Median predicted exposure after planned dose divided by observed geometric mean at 10 mg/kg IV in RA patients 
(Cmax = 267 µg/mL; AUC0-∞ = 35,100 µg.h/mL) 
b. 
Median predicted exposure after planned dose divided by observed mean at 200 mg/kg IV in male and female monkeys at 
Day 176 (gender averaged Cmax = 11,800 µg/mL; AUC0-∞ = 731,000 µg.h/mL) 

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Figure 2-1:
Simulated Serum Gimsilumab PK Profile After Gimsilumab 400 mg IV Day 1
and 200 mg IV Day 8a
a.
Median (line) and 10th and 90th percentiles (shaded area); 20 µg/mL target concentration (dashed)
2.3.
Benefit/Risk Assessment
Summaries of findings from both non-clinical and clinical studies conducted to date can be found 
in the Gimsilumab Investigator Brochure, current edition.
Gimsilumab is a new molecular entity. There are limited data on the therapeutic effect of
gimsilumab in humans, signals of clinical benefit and pharmacodynamic effects were observed 
in subjects with RA treated with single doses of IV gimsilumab ≥0.7 mg/kg and provide a
gimsilumab dose range that has the potential to show clinical benefit in subjects with lung injury 
and ARDS secondary to COVID-19. In healthy subjects, the most frequently reported AE was 
headache. Other reported AEs included nasopharyngitis and flu-like symptoms in subjects 
receiving gimsilumab. For subjects with RA, no AE was reported by more than 1 subject. One 
subject with RA who received gimsilumab 3 mg/kg experienced a SAE of follicular neoplasia of
thyroid/thyroid neoplasm which was considered by the investigator to be mild in severity and not 
related to test article.

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3. 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
Primary 
• The primary objective is to evaluate the impact of 
intravenous (IV) treatment with gimsilumab on 
mortality in subjects with lung injury or ARDS 
secondary to COVID-19. 
• Incidence of mortality by Day 43 
Secondary 
Key secondary objectives include the following: 
• 
To assess the effect of gimsilumab on ventilation 
requirements 
• 
To assess the effect of gimsilumab on overall 
duration of hospitalization 
Additional secondary objectives include the following: 
• 
To assess the effect of gimsilumab on the need for 
Intensive Care Unit (ICU) level of care 
• 
To assess the effect of gimsilumab as measured by 
the National Early Warning Score (NEWS) 
• 
To assess the effect of gimsilumab as assessed by 
the Sequential Organ Failure Assessment (SOFA) 
score 
• 
To assess the effect of gimsilumab as measured by 
the 7-point ordinal scale 
• 
To assess the effect of gimsilumab on peripheral 
capillary oxygen saturation / fraction of inspired 
oxygen (SpO2/FiO2) 
• 
To assess the effect of gimsilumab on oxygenation 
requirements 
• 
To assess changes in on-treatment viral load 
• 
To assess the effect of gimsilumab on biomarkers of 
inflammation 
• 
To determine the pharmacokinetic (PK) properties of 
gimsilumab 
• 
To assess the immunogenicity of gimsilumab 
• 
To determine the safety and tolerability of gimsilumab 
Key secondary endpoints include the following: 
• 
Proportion of subjects who survived and were not 
requiring mechanical ventilation on Day 29 
• 
Mechanical ventilation-free days by Day 29 
• 
Time to hospital discharge by Day 43 
Additional secondary endpoints include the following: 
• 
Incidence of mortality by Days 15, 22, 29, 85, and 
169 (End-of-Study [EoS]) 
• 
Proportion of subjects who survived and were not 
requiring mechanical ventilation on Days 15, 22, 
and 43 
• 
Mechanical ventilation-free days for all subjects by 
Days 15, 22, and 43 
• 
ICU-free days for all subjects by Days 15, 22, 29, and 
43 
• 
Incidence of mechanical ventilation use for all 
subjects by Days 15, 22, 29, and 43 
• 
Incidence of ICU use for all subjects by Days 15, 22, 
29, and 43 
• 
Time to death by Day 43 and Day 169 (EoS) 
• 
NEWS assessed daily while hospitalized 
• 
SOFA score, and each of the components, assessed 
daily while in the ICU 
• 
The percentage of subjects reporting each severity 
rating on the 7-point ordinal scale, assessed daily 
while hospitalized and, if discharged from hospital, on 
Days 15, 22, 29, 36, 43, 85, and 169 (assessed by 
phone) 
• 
Status on the 7-point ordinal scale, assessed daily 
while hospitalized and, if discharged from hospital, on 
Days 15, 22, 29, 36, 43, 85, and 169 (assessed by 
phone) 
• 
Time to clinical improvement by 2 points on the 
7-point ordinal scale 
• 
Change from Baseline in SpO2/FiO2, assessed daily 
while hospitalized 
• 
Incidence and duration of oxygen use during the 
study 

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OBJECTIVES 
ENDPOINTS 
• 
Change from Baseline in viral load as measured by 
quantitative polymerase chain reaction (PCR) test on 
Days 2, 9, and day-of-discharge (DoD) 
• 
Change from Baseline in D-dimer, cardiac troponin I, 
lactate dehydrogenase (LDH), ferritin, and C-reactive 
protein (CRP) 
• 
Serum gimsilumab concentrations 
• 
Analysis of anti-gimsilumab antibodies (ADAs) 
Safety endpoints: 
• 
Safety and tolerability, including assessment of 
clinical safety laboratory measurements, physical 
examinations, vital signs, concomitant medications; 
cumulative incidence of adverse events (AEs), 
serious adverse events (SAEs), and severe AEs 
Exploratory 
Exploratory objectives include the following: 
• 
To explore the effect of gimsilumab on serum 
cytokine concentrations and surfactant protein D 
(SP-D) 
• 
To explore the effect of gimsilumab on other 
measurements of lung injury that may be performed 
during standard care (e.g., Lung Injury Score [LIS], 
chest radiography, PaO2/FiO2 [P/F ratio], need for 
extracorporeal membrane oxygenation [ECMO]) 
• 
To explore the effect of gimsilumab on cardiac 
function (if measured) 
• 
To assess the effect of gimsilumab on renal function 
Exploratory endpoints include the following: 
• 
Change from Baseline in the cytokine panel and 
serum SP-D 
• 
Change from Baseline in LIS (if performed) 
• 
Change from Baseline in chest radiographic 
assessment (if performed) 
• 
Change from Baseline in P/F ratio, if performed 
• 
Incidence and duration of ECMO use 
• 
Change from Baseline in left ventricular ejection 
fraction (LVEF) (when measured) 
• 
Change from Baseline in eGFR [Modification of Diet 
in Renal Disease (MDRD) equation], assessed when 
central clinical safety laboratory measurements are 
collected during hospitalization 

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4. 
INVESTIGATIONAL PLAN 
 
4.1. 
Overall Study Design 
This is a randomized, adaptive, double-blind, placebo-controlled study in male and/or female 
subjects who are at risk of developing, or have developed, ARDS consequent to moderate to 
severe COVID-19. 
This study will include subjects with moderate-to-severe disease. There will be 2 treatment arms, 
one receiving blinded gimsilumab, and one receiving blinded placebo. 
Efficacy, safety, tolerability, PK, and PD of gimsilumab will be assessed in hospitalized adult 
subjects diagnosed with COVID-19. 
Randomization will be stratified by country and subject’s clinical status at Baseline: 
• Lung injury/mild ARDS 
• Moderate/severe ARDS 
Clinical classification criteria are defined in Section 9.1. 
 
A schematic of the study design is presented in Figure 4-1. Subjects will be assessed daily while 
hospitalized. Follow-up assessments are planned through Week 24, for a total study duration 
post-randomization of approximately 169 days (24 weeks). Follow-up visits at Days 15, 22, 29, 
36, 43, 85, and 169 will be performed by phone if the subject has been discharged from the 
hospital. All subjects will undergo a series of efficacy, safety, and laboratory assessments as 
detailed in the Schedule of Assessments, Table 7-2. 
 
Figure 4-1: 
Study Schematic 
 
ARDS = acute respiratory distress syndrome; CRP = C-reactive protein; EoS = End of Study; IV = intravenous; ICU = 
Intensive Care Unit; NEWS = National Early Warning Score; SOFA = Sequential Organ Failure Assessment 

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4.2. 
Scientific Rationale for Study Design 
COVID-19 is a newly emerging disease with a clinical spectrum that ranges from asymptomatic 
to severe and potentially lethal. The variability between clinical courses of different individuals 
may make uncontrolled data highly unreliable. Further, the immunopathogenesis of COVID-19 
is currently not well understood, and thus the risk-benefit of immunomodulatory agents in 
COVID-19 has not been established. It is difficult to predict whether altering the immune 
response during an acute infection will have a harmful effect via prevention of viral clearance or 
a beneficial effect via dampening of overactive inflammation. For these reasons, this study will 
be prospective, randomized, double-blinded, and placebo-controlled to minimize bias. 
Preliminary evidence suggests that major deterioration, including progression to lung injury or 
ARDS, occurs within the first 1 to 2 weeks of hospitalization, warranting the 2-week treatment 
period chosen for this study [Huang, 2020; Zhou, 2020]. 
 
The target patient population, patients with lung injury or ARDS secondary to COVID-19, was 
selected based on the putative mechanism of action of the anti-GM-CSF approach in this disease. 
Severely ill COVID-19 patients have significant inflammatory macrophage infiltration into the 
damaged lung as well as cytokine storm syndrome [Liao, 2020; Mehta, 2020]. In inflammatory 
pulmonary conditions, GM-CSF acts to mobilize bone marrow progenitor cells to the lung and 
differentiate them into inflammatory myeloid cells [Kudlak, 2013; Molfino, 2016]. During 
cytokine storm, GM-CSF is thought to induce and perpetuate a “positive feedback” loop with 
other pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, thereby contributing to 
immunopathological consequences [Tugues, 2018; Sterner, 2019; Hamilton, 2020]. Taken 
together, targeting GM-CSF presents an opportunity to both block the damaging macrophage 
lung infiltration and quell the hyper-inflammation characteristic of this particular stage of 
COVID-19. 
 
4.3. 
Treatment Arms and Duration 
Each subject will participate for approximately 24 weeks, with a 2-week Treatment Period (last 
dose on Day 8) and a 22-week Follow-up Period. A summary of the treatment arms is presented 
in Table 4-1. 
 
Table 4-1: Treatment Arms for KIN-1901-2001 
 
Arm 
Randomized Treatment and Population 
N 
Arm 1 
Gimsilumab (400 mg) as a single IV infusion on Day 1 followed by a single 200 mg IV 
infusion on Day 8 
135 
Arm 2 
Placebo (0.9% saline solution) IV infusion on Day 1 and Day 8a 
135 
a. 
The Day 8 dose will be omitted if the subject is discharged from the hospital or is no longer in need of supplemental 
oxygen or ventilatory support for >48 hours. 

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5. 
SUBJECT POPULATION 
 
5.1. 
Type and Number of Subjects 
A sufficient number of subjects will be enrolled to achieve approximately 270 evaluable subjects 
total, with 135 subjects per treatment arm. 
In order to manage the total study enrollment, the Sponsor may suspend screening and/or 
enrolment at any site or study-wide at any time. 
Deviations from inclusion and exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability, or subject safety; 
therefore, adherence to the criteria as specified in the protocol is essential. 
 
5.2. 
Inclusion Criteria 
An individual will be eligible for inclusion in this study only if all the following criteria are met. 
1. Male or non-pregnant female age ≥18 years 
2. Subject (or legally authorized representative [LAR]) is able and willing to provide written 
or verbal informed consent, which includes compliance with study requirements and 
restrictions listed in the consent form. NOTE: If a subject or LAR must be consented 
verbally, the site must have a site policy for verbal consent and the consent must be 
clearly documented in the subject’s chart. 
3. Has documented laboratory-confirmed SARS-CoV-2 infection as determined by PCR or 
other approved clinical testing prior to randomization 
4. C-reactive protein ≥50 mg/L or serum ferritin ≥1000 ng/mL. Results from CRP and 
ferritin tests performed within 8 days of randomization are acceptable for enrollment. 
5. Radiographic evidence of bilateral infiltrates. Acceptable imaging tests (chest X-ray, CT 
scans) done within 3 days of Day 1 can be used for inclusion. 
6. Subject has clinical evidence of lung injury [defined as (1) requiring supplemental 
oxygen ≥4L O2 to attempt to maintain ≥92% SpO2, or (2) PaO2/FiO2 ≤300 mmHg (can be 
imputed)] or meets clinical classification criteria for ARDS [ARDS Berlin Definition, 
2012], secondary to COVID-19 
7. Female subjects must agree to use an approved highly effective birth control (BC) 
method (<1% failure rate per year) throughout the study (until completion of the Day 85 
Follow-up Visit), unless documented to have a reproductive status of non-childbearing 
potential or is postmenopausal: 
• Non-childbearing potential defined as pre-menopausal female with medical 
history of bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries), 
or hysterectomy; hysteroscopic sterilization, 
• Postmenopausal defined as 12 months of spontaneous amenorrhea or with follicle 
stimulating hormone (FSH) confirmation. 
• Woman of childbearing potential (WCBP) who is already using an established 
method of highly effective contraception or agrees to use one of the allowed BC 

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methods listed in Section 5.6.1, for at least 28 days prior to the start of dosing (as 
determined by the Investigator Brochure or Investigator or designee) to 
sufficiently minimize the risk of pregnancy throughout study participation (until 
completion of the Day 85 Follow-up Visit). 
8. Males who are sexually active must agree to use one of the allowed BC methods listed in 
Section 5.6.1. Male subjects must also agree to sufficiently minimize the risk of 
pregnancy throughout study participation (until completion of the Day 85 Follow-up 
Visit). 
 
5.3. 
Exclusion Criteria 
An individual will NOT be eligible for inclusion in this study if any of the following criteria 
apply. 
1. Subject requires norepinephrine at a dose of >0.5 mcg/kg/min, or equivalent 
2. Subject has been intubated for >72 hours. Note: in the event of extubation and 
re-intubation, the calculation for the number of hours the subject has been intubated 
begins at the first intubation. 
3. Evidence of life-threatening dysrhythmia (e.g., ventricular tachycardia [VT], ventricular 
fibrillation [VF]) or cardiac arrest on presentation 
4. Evidence of new or preexisting decompensated heart failure 
5. At the time of screening, subject is anticipated to require ECMO 
6. Absolute neutrophil count <1,000 per mm3 
7. Platelet count <50,000 per mm3 
8. History of known anti-GM-CSF autoAb or pulmonary alveolar proteinosis. Note: A 
negative anti-GM-CSF autoAb test result is not required at screening. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive pulmonary disease 
[COPD], pulmonary arterial hypertension [PAH], idiopathic pulmonary fibrosis [IPF], 
interstitial lung disease [ILD]) requiring supplemental oxygen therapy or mechanical 
ventilation pre-hospitalization (e.g., prior to COVID-19 diagnosis) 
10. Known or suspected active and untreated tuberculosis (TB), human immunodeficiency 
virus (HIV), hepatitis B or C infection. 
• Results of TB, hepatitis B and C, and HIV tests are not required prior to enrollment if 
there is no suspicion of active infection, as per KIN-1901 Guidance on Active 
Infections Testing. 
11. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >5 × upper limit 
of normal (ULN) 
12. eGFR <30 mL/min/1.73m2 (MDRD equation) or requiring hemofiltration or dialysis 
13. Use of any immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, anti-TNF, inhibitors 
of complement signaling), cell therapies (e.g., mesenchymal stem cells), or small 
molecule JAK inhibitors within the past 7 days or within five half-lives (whichever is 
longer), or planned use of any of these agents from Screening until Day 43 of the study, 
unless approved by the Medical Monitor. The following will be allowed/disallowed: 

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• Immunomodulatory biologics for COVID-19 treatment are excluded and should not 
be used until Day 43 unless discussed with the Medical Monitor. Other non-biologic 
immunomodulators (non-JAK inhibitors), e.g., medicines for previous 
transplantation, or disease modifying anti-rheumatic drugs (DMARDS), and have had 
a stable dose for ≥8 weeks are permitted. 
• Subjects who have been treated with convalescent plasma (CP) prior to enrollment 
are eligible if the subject continues to meet all inclusion criteria at screening. Ongoing 
therapy with CP is allowable if clinically indicated in the view of the treating 
physician or the Investigator. 
• The use of investigational anti-viral treatment (e.g., remdesivir) is allowed if the 
subject continues to meet all inclusion criteria at screening. 
14. Ongoing chronic (≥4 weeks) use of corticosteroids >10 mg/day of prednisone or 
equivalent at the time of randomization. A corticosteroid dose that has been tapered to 
10 mg or less within 14 days of randomization is also prohibited. 
15. Pregnancy and/or breast feeding 
16. Unable to receive invasive or non-invasive ventilatory support 
17. Moribund condition in the opinion of the clinical team 
 
5.4. 
Other Eligibility Criteria Considerations 
Individuals who marginally fail to meet eligibility requirements may be rescreened (once), on a 
case-by-case basis, as determined by the Medical Monitor. 
To assess any potential impact on subject eligibility with regard to safety, the Investigator must 
refer to the following document(s) for detailed information regarding warnings, precautions, 
contraindications, AEs, and other significant data pertaining to the investigational product being 
used in this study: 
• Gimsilumab Investigator Brochure, current edition 
 
5.5. 
Screening/Baseline 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
never subsequently randomized. A minimal set of screen failure information is required 
including demography, screen failure details, eligibility criteria, and any SAEs. Screen failure 
data will not be recorded within the Case Report Form (CRF). 
 
5.6. 
Lifestyle and/or Dietary Restrictions 
 
5.6.1. 
Contraception 
 
The potential effects of gimsilumab on embryofetal or postnatal development have not been 
assessed in animals or humans. ICH M2 (R2) defines “highly effective methods of birth control” 
as those, alone or in combination, that result in a low failure rate (<1 pregnancy per 100 women 
in a year). 

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All female and male study subjects must use a highly effective birth control method (<1% failure 
rate per year) until completion of the Day 85 Follow-up Visit, unless they have a reproductive 
status of, sterile, non-childbearing, or postmenopausal (confirmed by FSH). Additionally, female 
partners of eligible male study subjects must use, in parallel, an allowed method of contraception 
Non-childbearing potential is defined as pre-menopausal female with documented bilateral tubal 
ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy; hysteroscopic 
sterilization. 
Postmenopausal female is defined as 12 consecutive months of spontaneous amenorrhea and 
with FSH confirmation. 
Woman of Childbearing potential (WCBP) are required to use a highly effective BC method 
(<1% failure rate per year): [Hatcher, 2007] 
• Subdermal implant that meets high effectiveness criteria (<1% rate of failure per 
year), stated in the product label 
• Intrauterine device (IUD) or intrauterine system (IUS) that meets high effectiveness 
criteria (<1% rate of failure per year), stated in the product label 
• Oral or injected contraceptives having established use (for at least 30 days); of either 
combined (estrogen- and progestogen) or progestogen alone 
• Male partner with vasectomy and documentation of azoospermia 
• “Double barrier” method, male partner(s) mutual agreement of male condom use in 
combination with: 
o female diaphragm/cervical cap plus spermicide (cream, gel, film, or 
suppository) 
o contraceptive vaginal ring 
o percutaneous contraceptive patches 
Sexually active male subjects must agree to use highly effective birth control (BC) methods. As 
applicable, in parallel to his study participation, his female partner(s) must also use an effective 
method of contraception (listed above). Males allowed to enroll in this study are responsible for 
minimizing the risk of pregnancy (until completion of the Day 85 Follow-up Visit). 
• Vasectomy and documentation of azoospermia 
• Male condom plus female partner use of one of the highly effective contraceptive 
methods listed immediately above, based on the female partner’s childbearing 
potential 
These allowed methods of contraception are only effective when used consistently, correctly and 
in accordance with the Investigator Brochure. The Investigator is responsible for ensuring that all 
study subjects fully understand the importance of this requirement and how to properly use these 
methods of contraception. 

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5.7. 
Withdrawal Criteria 
 
5.7.1. 
Reasons for Withdrawal 
 
An Investigator may discontinue/withdraw a study subject’s participation in the study if any of 
the following criteria apply: 
• Any clinical AE, laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest 
of the subject 
 
• Pregnancy of female subject 
 
• Major protocol violation 
 
• Behavioral and/or administrative reason 
 
• Subject request to discontinue/withdraw consent for any reason. It is important to 
document whether the withdrawal of consent is primarily due to an AE, lack of 
efficacy, or other reason. 
 
• Discontinuation of the study at the request of the Sponsor, regulatory agency, or an 
Institutional Review Board / Independent Ethics Committee 
 
• Liver toxicity where criteria as specified in Section 5.8.1 are met and no compelling 
alternate cause is identified 
 
If a subject meets a withdrawal criterion during treatment, an Early Termination Visit will be 
required. Subjects withdrawn for any reason will not be replaced. 
 
5.7.2. 
Subject Withdrawal Procedures 
 
If a subject is prematurely discontinued from investigational product(s), the Investigator must 
make every effort to perform an Early Termination (ET) Visit per the Schedule of Assessments 
(Table 7-2), and document the primary reason for withdrawal. 
In cases where the subject cannot be reached for phone follow-up visits, the site should attempt 
to contact the subject as soon as possible. The site should also counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain whether the subject wishes 
to and/or should continue in the study based on previous non-compliance. In cases where the 
subject cannot be reached, the site should make every effort to regain contact with the subject 
(3 documented telephone calls and if necessary a certified letter to the subject’s last known 
mailing address) so that they can appropriately be withdrawn from the study with a primary 
reason of “Lost to Follow-up”. 
Subjects who withdraw from treatment and/or the study early, for any reason, will be followed 
for Day 43 all-cause mortality, whenever possible. 

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5.8. 
Toxicity Management Criteria 
 
5.8.1. 
Liver Chemistry Management Criteria 
 
Liver chemistry criteria have been designed to assure subject safety and evaluate liver event 
etiology (in alignment with the FDA premarketing clinical Drug-induced Liver Injury guidance). 
Timely results of local labs should be used to make the decision to proceed to the second dose. 
Guidance on LFT abnormalities based upon results of LOCAL lab testing: 
1) If a subject has ALT in the normal range prior to study drug administration and develops 
significant elevation >5× ULN after study drug administration, in the absence of a clear 
alternative reason for the change (e.g., hypotension, vasopressor support), this should be 
considered related to study drug and reported as a SAE; procedures described in 
Appendix 2: Liver Safety Required Actions and Follow up Assessments should be 
followed, and the Medical Monitor should be informed. 
2) For subjects with elevated transaminase levels prior to study drug administration who do 
not meet exclusion criterion #11 (alanine aminotransferase [ALT] or aspartate 
aminotransferase [AST] >5× upper limit of normal [ULN]), if after administration of 
study drug the LFTs continue to worsen and no alternate explanation for elevation is 
provided, the following will apply: 
a. If ALT >8× ULN, then this should be reported as a SAE; procedures described in 
Appendix 2: Liver Safety Required Actions and Follow up Assessments will 
be followed, and the Medical Monitor should be informed. If the Investigator is 
considering withholding the second dose of study drug, then a discussion with the 
Medical Monitor is mandatory. Note that subjects with ALT or AST 
abnormalities secondary to multi-organ impairment due to COVID-19 may still 
benefit from the second dose of gimsilumab. 
b. If LFTs are elevated but are not >8× ULN, then daily LFTs (including AST, 
ALT, alkaline phosphatase, and total bilirubin with fractionation) should be 
followed. 
i.  If during follow up ALT or AST increases to >8× ULN, then this should 
be reported as a SAE and then discussed with the Medical Monitor 
concerning the need to withhold the second dose. 
ii. If a subject has AST or ALT 3 to 8× ULN in conjugation with total 
bilirubin >2× ULN or INR >1.5, then this should be reported as a SAE; 
procedures described in Appendix 2: Liver Safety Required Actions 
and Follow up Assessments should be followed. Subjects meeting these 
criteria should not receive a second dose of study drug. 
iii. If during follow up the above stopping criteria are not met and the 
Investigator believes that the subject is suitable to receive a second dose of 
study drug and all eligibility criteria are met for the second dose, then the 
second dose (Day 8) of study drug may be administered. 
3) Any worsening of LFTs that is greater than would be expected due to COVID-19 alone 
that do not rise to the level of an SAE should be reported as an AE. 

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4) A discussion with the Medical Monitor is mandatory prior to withholding the second 
dose of study drug. 
 
5.8.2. 
Individual Stopping Criteria 
 
Infusion of study treatment in an individual subject may be interrupted (and the Day 8 dose held, 
if appropriate) if the subject experiences a treatment-related Grade ≥3 AE or at the discretion of 
the investigator. Under these circumstances, the Medical Monitor must be notified. 
 
5.8.3. 
Study Stopping Criteria 
 
It is understood the safety profile of gimsilumab in the critical care setting of patients with 
impending or established ARDS is not yet understood. Reassuringly the anti-GM-CSF class of 
molecules has been studied in many subjects in multiple Phase 2 trials and to date no specific 
safety signal of concern has been noted to date. In principal, concerns for targeting GM-CSF 
include respiratory tract infection and pulmonary alveolar proteinosis. Hence while the rationale 
for targeting GM-CSF in the setting of severe viral pneumonia with or without ARDS is strong, 
there is concern over AEs and patient safety. 
To ensure subject safety, the sponsor plans a number of measures. An independent Data 
Monitoring Committee (DMC) will be appointed to review unblinded safety and efficacy data on 
an ongoing basis. The Chair of the DMC will issue a Charter outlining the specific plan for 
safety review including both early stopping rules for adverse safety events and also early 
stopping rules for futility, and early stopping rules for efficacy. 
 
5.8.4. 
Other Management Criteria 
 
For an individual study participant, Medical Monitor notification criteria include, but are not 
limited to: 
• 
Relevant severe signs or symptoms, or significant changes in any of the safety 
assessments, that put the safety of the individual at risk (e.g. laboratory tests or vital 
signs, etc.) as judged by the Investigator. 
 
5.9. 
Subject and Study Completion 
A completed subject is 1 who has completed the Treatment Period and the Follow-up Period 
(through the Day 169 End-of-Study [EoS] Follow-up Visit). 
 
6. 
STUDY TREATMENT 
 
6.1. 
Study Treatment 
The term ‘study treatment’ is used throughout the protocol to describe any dose of gimsilumab or 
placebo; study treatments are presented in Table 6-1. 

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Table 6-1: Treatment Descriptions for KIN-1901-2001 
 
Study Treatment 
Product name: 
Gimsilumab 
Placebo 
Formulation description: 
 
0.9% sodium chloride 
Dosage form: 
Vial 
NA 
Unit dose 
strength(s)/Dosage level(s): 
 
 
Route of 
Administration/Duration 
Intravenous infusion on Day 1 and Day 
8 
Intravenous infusion on Day 1 and Day 
8 
Dosing instructions: 
Infuse the entire contents of the IV bag 
via the intravenous route over a 1-hour 
period. Flush the line with 0.9% saline 
to ensure the entire contents is 
administered. 
Infuse the entire contents of the IV bag 
via the intravenous route over a 1-hour 
period ±20 minutes. Flush the line with 
0.9% saline to ensure the entire 
contents is administered. 
Procurement 
Gimsilumab: manufactured for 
Kinevant Sciences GmbH 
Saline: Procured by clinical site 
Saline: Procured by clinical site 
 
6.2. 
Administration of Study Treatments 
Study treatment will be infused intravenously over a period of 
. The start and 
stop time of the infusion will be recorded, including if the infusion had to be stopped or rate 
reduced. Further details are available in the Study Pharmacy Manual. 
Administration of study treatment will be performed by qualified personnel as specified in the 
Schedule of Assessments (Table 7-2). 
 
6.3. 
Randomization / Study Treatment Assignment 
Randomization will occur centrally using an interactive voice or web response system using 
central stratified randomization. Subjects determined to be eligible for enrollment based upon 
screening evaluations will be randomized to receive study treatments according to one of the 
treatments listed in Table 6-2. 
The study will enroll at least 40%, but no more than 60%, of total subjects in each of the two 
categories of clinical status: ([lung injury/mild ARDS] or [moderate/severe ARDS]) at Baseline, 
which will be used as the stratified factor in the randomization. 

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Table 6-2: Randomization Schema for KIN-1901-2001 
 
Arm 
Group 
Ratio 
Treatment Description 
1 
Active Study Drug 
1 
Gimsilumab 400 mg single IV infusion on Day 1 
Gimsilumab 200 mg single IV infusion on Day 8 
2 
Placebo 
1 
Normal saline single IV infusion on Day 1 
Normal saline single IV infusion on Day 8 
 
6.4. 
Blinding 
The study is double-blind. The study pharmacist (and/or qualified pharmacy staff member), and 
the bioanalytical laboratory analysts will be unblinded to study treatment. 
Study treatment will be administered to each subject by blinded qualified personnel at the study 
site. Once diluted in 100 mL 0.9% saline, active gimsilumab and placebo infusion bags are 
indistinguishable. 
The following will apply regarding the unblinding of study treatment: 
• 
The Investigator or treating physician may unblind a subject’s treatment assignment only in 
the case of an emergency OR in the event of a serious medical condition when knowledge 
of the study treatment is essential for the appropriate clinical management or welfare of the 
subject as judged by the Investigator. 
 
• 
Investigators have direct access to the subject’s individual study treatment. 
• 
The Investigator should make every effort to first contact the Medical Monitor or 
appropriate study personnel to discuss options before unblinding the subject’s treatment 
assignment. 
• 
If the Sponsor personnel are not contacted before the unblinding, the Investigator must 
notify the Sponsor as soon as possible after unblinding. 
• 
The date and reason for the unblinding must be fully documented in the CRF. 
• 
The Sponsor or their designee may unblind the treatment assignment for any subject with an 
SAE. If the SAE requires that an expedited regulatory report be sent to one or more 
regulatory agencies, a copy of the report, identifying the subject’s treatment assignment, will 
be sent to Investigators in accordance with local regulations. 
A subject will be withdrawn if the subject’s treatment code is unblinded by the Investigator or 
treating physician. The primary reason for discontinuation (the event or condition which led to 
the unblinding) will be recorded in the CRF. 

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Investigational study treatment clinical supplies will be provided in 
6.5. 
Packaging and Labeling 
 
IV doses of gimsilumab or placebo will be prepared by the site pharmacy, dispensed, and 
administered to subjects by clinic staff at the study site in a container having a label that includes 
at a minimum the study number, subject number, and study treatment name (“gimsilumab or 
placebo”). 
All labels for gimsilumab vials to be distributed will meet all applicable requirements of 
Annex 13 of Good Manufacturing Practices: Manufacture of Investigational Medicinal Products 
(July 2010) and/or other local regulations as applicable. 
 
6.6. 
Preparation/Handling/Storage/Accountability 
Gimsilumab study treatment will be diluted in 100 mL 0.9% saline prior to infusion using aseptic 
technique by qualified personnel per the clinical site standard operating procedures. 
Placebo study treatment will utilize 100 mL 0.9% saline solution with the addition of 4 mL 
(Day 1) or 2 mL (Day 8) sterile 0.9% saline solution using aseptic technique by qualified 
personnel per the clinical site standard operating procedures. 
Refer to the Study Pharmacy Manual for additional details. 
Gimsilumab vials are to be stored at 
and require temperature monitoring. Temperature 
excursions are to be reported to the Sponsor. 
• 
Only subjects enrolled in the study may receive study treatment and only authorized site 
staff may supply or administer study treatment. All study treatments must be stored in a 
secure environmentally controlled and monitored (manual or automated) area in 
accordance with the labelled storage conditions with access limited to authorized site 
staff. 
• 
The Investigator or delegated personnel is responsible for study treatment 
accountability, reconciliation, and record maintenance (i.e. receipt, reconciliation and 
final disposition records). 
• 
Further guidance and information for final disposition of unused study treatment are 
provided in the Study Pharmacy Manual. 
• 
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or the Sponsor Study 
Contact. 
• 
A Material Safety Data Sheet (MSDS) describing occupational hazards and 
recommended handling precautions either will be provided to the Investigator, where 
this is required by local laws, or is available upon request from the Sponsor. 

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6.7. 
Compliance with Study Treatment Administration 
Subjects are dosed in the hospital. They will receive study treatment directly from the 
Investigator or designee, under medical supervision. The date and time of each dose 
administered in the hospital will be recorded in the source documents. The dose of study 
treatment and study subject identification will be confirmed at the time of dosing by a member of 
the study site staff other than the person administering the study treatment. 
 
6.8. 
Treatment of Study Treatment Overdose 
For this study, any single administration of gimsilumab >400 mg will be considered an overdose. 
The Sponsor does not recommend specific treatment for an overdose. There have been no 
previous reports of overdose (accidental or deliberate) with gimsilumab. 
In the event of an overdose the Investigator or treating physician should: 
• contact the Medical Monitor immediately; 
 
• closely monitor the subject for AEs/SAEs and laboratory abnormalities; 
 
• obtain a plasma sample for PK analysis if requested by the Medical Monitor (determined 
on a case-by-case basis); 
 
• document the quantity of the excess dose as well as the duration of the overdosing in the 
CRF. 
 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the subject. 
 
6.9. 
Concomitant Medications and Non-Drug Therapies 
Best possible medication history for the 30 days prior to enrollment will be collected, and 
include, at a minimum, the drug name (generic or tradename) and start date and stop date (or 
ongoing). 
It would be expected that gimsilumab would reduce the effectiveness of GM-CSFs, such as 
Luekine® (sargramostim), Leucomax® (molgramostim) and Regramostim. No other drug 
interactions are known or expected. 
 
6.9.1. 
Permitted Medications and Non-Drug Therapies 
 
Treatment with convalescent plasma or investigational anti-viral therapies (e.g., remdesivir) will 
be allowed. 
Use of any concomitant medication (including investigational agents) should be recorded in the 
study source records, including the doses administered, dates and times of administration and the 
reason for administration. 

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6.9.2. 
Prohibited Medications and Non-Drug Therapies 
 
Use of tocilizumab or any other immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, anti- 
TNF), cell therapies (e.g., mesenchymal stem cells), or small molecules (e.g., JAK inhibitors) is 
prohibited from Screening until Day 43 of the study unless approved by the Medical Monitor. 
 
7. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are not allowed with the exception of immediate safety concerns. 
Therefore, adherence to the study design requirements, including those specified in the Schedule 
of Assessments (Table 7-2), are essential and required for study conduct. 
This section lists the procedures and parameters of each planned study assessment. The exact 
timing of each assessment is listed in the Schedule of Assessments, (Table 7-2). 
Note: All subjects who are discharged from the hospital will undergo all Day-of-Discharge 
(DoD) Visit assessments. All subjects who discontinue from the study prematurely will undergo 
all Early Termination (ET) Visit assessments, whenever possible. 
Once a subject is discharged from the hospital every effort MUST be made to ensure visit 
timepoints listed on the Schedule of Assessments (Table 7-2) are completed via phone or 
telemed. All visits are required to be completed for every subject unless the subject dies or 
withdraws consent. If a subject is deemed lost to follow-up every effort should be made to check 
vital status records at each visit time point to obtain survival status. Proper follow-up and 
documentation should be completed per GCP/ICH guidelines before deeming a subject lost to 
follow-up. 
The following points must be noted, if assessments are scheduled for the same nominal time, 
THEN the assessments should occur in the following order: 
1. vital signs 
2. blood draws 
Note: The timing of the assessments should allow the blood draw to occur at the exact nominal 
time. 
The Institutional Review Board (IRB)/Independent Ethics Committee (IEC) will be informed of 
any safety issues that require alteration of the safety monitoring scheme or amendment of the 
Informed Consent Form. 
If the subject completes all in hospital assessments, approximately 250 mL of blood will be 
collected over the duration of the study (Table 7-1). 
 
Table 7-1: Estimated Sample Requirements Per Subject 
 
Approximate sample 
volume per collection 
(mL) 
Number of collection 
time points 
Approximate total 
volume collected (mL) 
Clinical laboratory tests 
16.5 
9 
148.5 
Viral screen / Quantiferon® 
11 
1 
11 
Anti-GM-CSF autoAb 
4 
1 
4 
PK blood sampling 
4 
3 
12 
Anti-gimsilumab antibodies 
4 
4 
16 

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Cytokine panel 
8.5 
5 
42.5 
SP-D 
3.5 
4 
14 
FSH (if necessary) 
3.5 
1 
3.5 
Total: 
251.5 

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7.1. 
Schedule of Assessments (Treatment and Follow-up Periods) 
Table 7-2: Schedule of Assessments 
 
Schedule of Assessments: Screening and Treatment Period 
Screen 
Baselinea 
On-Treatment 
Assessments 
(only done if in hospital) 
DoDo / 
ET 
Study Day (± Window) 
-7 to 1 
1 
Days 2 – 14, inclusive 
(All ± 1 day) 
-1 
Week 
0 
0 
1 to 2 
— 
Informed consent and randomization 
X 
Inclusion/Exclusion criteria 
X 
Xb 
Demographic information, medical history, prior medicationsc 
X 
Local QuantiFERON® testd 
X 
Local Viral Screen (HBsAG, HCV RNA/Ag, HIV)d 
X 
Height and Weighte 
X 
Local Urine pregnancy test β-hCG and follicle-stimulating hormone (FSH, women only)f 
X 
Central sample for anti-GM-CSF autoAbd (result not required for determination of eligibility) 
X 
Chest X-ray or chest CT scan (within 3 days of Day 1) 
X 
Local qualitative sample (e.g., nasopharyngeal swab) for PCR SARS-CoV-2 (if not already documented) 
X 
Central quantitative sample (e.g., nasopharyngeal swab) for PCR SARS-CoV-2g 
X 
Days 2 and 9 
X 
Physical examinationh and vital signs (blood pressure, heart rate, respiration rate, and body temperature)i 
X 
X 
Daily, only while hospitalized 
X 
Central clinical laboratory measurements (hematology, blood chemistry [including CRP, ferritin, LDH, 
procalcitonin, troponin I], coagulation [including D-dimer], and urinalysis)j 
X 
X 
Days 4 and 8 
X 
Administration of IV study drugk 
X 
Day 8 
Central PK samples for quantification of gimsilumab serum concentration 
Predose 
Predose on Day 8 
X 
Central samples for cytokine panel 
X 
Days 4 and 8 
X 

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Schedule of Assessments: Screening and Treatment Period 
Screen 
Baselinea 
On-Treatment 
Assessments 
(only done if in hospital) 
DoDo / 
ET 
Study Day (± Window) 
-7 to 1 
1 
Days 2 – 14, inclusive 
(All ± 1 day) 
-1 
Week 
0 
0 
1 to 2 
— 
Central samples for SP-D measurement 
X 
Day 8 
X 
Central sample for immunogenicity (antibodies to gimsilumab) 
X 
X 
7-point Ordinal Scale 
X 
Daily, only while hospitalized 
X 
National Early Warning Score (NEWS) 
X 
Daily, only while hospitalized 
X 
SOFA score 
X 
Daily, only while in ICU 
X 
SpO2/FiO2, and if performed, PaO2/FiO2 (can be imputed) 
X 
X 
Daily, only while hospitalized 
X 
Oxygenation requirements 
X 
X 
Daily, only while hospitalized 
X 
Ventilation requirementsl 
X 
X 
Daily, only while hospitalized 
X 
ECMO requirements 
X 
Daily, only while hospitalized 
X 
Concomitant medications/concurrent proceduresm 
X 
Daily, only while hospitalized 
X 
Adverse event monitoringn 
X 
Daily, only while hospitalized 
X 
β-hCG = beta human chorionic gonadotropin; anti-GM-CSF autoAb = anti-granulocyte macrophage colony- stimulating factor auto-antibody; DoD = Day of Discharge from hospital; ECMO = 
extracorporeal membrane oxygenation; EoS = End-of-Study; ET = early termination; FiO2 = fraction of inspired oxygen; FSH = follicle stimulation hormone; HBsAg = hepatitis B surface 
antigen; HCVAb = hepatitis C virus antibodies; HIV = human immunodeficiency virus; ICU = Intensive Care Unit; IGRA = interferon gamma release assay; IV = intravenous; PCR = polymerase 
chain reaction; PK = pharmacokinetics; PPD = purified protein derivative; PPE = personal protective equipment; SOFA = sequential organ failure assessment; SP-D = serum surfactant protein D; 
SpO2 = peripheral capillary oxygen saturation; TB = tuberculosis 
a. Baseline assessments should be performed prior to study drug administration. Assessments performed within 48 hours of Baseline do not need to be repeated at Baseline. 
b. Verification that no changes affecting eligibility have occurred since Screening will be performed at the Baseline/Day 1 Visit. 
c. Collect medication history from the 30 days leading up to, and including, the time of the Screening Visit, including date of onset of COVID-19 symptoms, prescription medications, over-the- 
counter medications, and herbal supplements/vitamins. 
d. Sample will be collected, but enrollment can continue without receiving results first. HCV testing can be RNA or Ag, only to confirm suspected infection. If a subject is diagnosed with latent TB 
(positive QuantiFERON Gold or PPD), hepatitis B or C, or HIV during the study, the Investigator must discuss this with the medical monitor and a decision will then be made concerning the 
second dose of gimsilumab, if applicable. In the event the QuantiFERON Gold assay is not available, and the site performs a different IGRA such as T Spot, then the alternative IGRA will be 
acceptable for patient screening and enrollment. Enrollment should not be delayed to obtain the QuantiFERON Gold assay in lieu of the IGRA available at the site. If no IGRA test is available, 
PPD can be used. If TB testing and viral serology is missed during screening it must be completed and results received prior to the second dose of study drug. If not completed or unable to 
obtain results further discussion with the medical monitor is required. 

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Schedule of Assessments: Screening and Treatment Period 
Screen 
Baselinea 
On-Treatment 
Assessments 
(only done if in hospital) 
DoDo / 
ET 
Study Day (± Window) 
-7 to 1 
1 
Days 2 – 14, inclusive 
(All ± 1 day) 
-1 
Week 
0 
0 
1 to 2 
— 
e. Height will be assessed only once (at Screening). Estimated height and weight are acceptable if unable to be measured due to patient clinical condition. 
f. The Screening sample can be assessed using local laboratory services for Screening/Eligibility purposes. The local laboratory values must also be documented in the eCRF. 
Note: FSH will be performed to confirm postmenopausal status only in women who have not had 12 months of spontaneous amenorrhea. 
g. When at all possible, if only 1 nostril is swabbed for viral assessments, the same nostril should be used for all subsequent samples. 
h. An abbreviated, targeted physical examination will be performed based on the subject’s clinical status and what the clinic staff feel is appropriate. Note: If a physical examination is performed 
as standard of care by appropriate personnel the same day that consent is signed or the same day of any scheduled study visit, results from that examination may be used if PPE is not 
available or if study site staff consider additional examinations are unwarranted due to already having been performed as standard of care.. 
i. Vital signs will be assessed at all timepoints specified above. On study drug administration days, vital signs will be assessed pre-dose (within 15 minutes) and ± 30 minutes post end of 
infusion. Note: If vital signs measurements are performed as standard of care by appropriate personnel the same day that consent is signed or the same day of any scheduled study visit, 
results from that assessment may be used if PPE is not available or if study site staff consider additional measurements are unwarranted due to already having been performed as standard of 
care.. 
j. ALT, AST, CRP, and Ferritin can be assessed using local laboratory services for Screening The local laboratory values must be documented in the eCRF. 
k. Subjects will receive a single IV infusion of blinded study treatment on Day 1 and Day 8. The Day 8 dose will be omitted if the subject is discharged or is no longer in need of supplemental 
oxygen or ventilatory support for >48 hours. 
l. If subject is receiving mechanical ventilation, the following parameters will be recorded: type of ventilation (CPAP, BiPAP, or intubation), FiO2, SpO2, ventilation rate, pulse, tidal volume, 
positive end-expiratory pressure (PEEP), and airway pressure. 
m. Collect information on concomitant medications and concurrent procedures from the time of informed consent through the EoS Visit (or ET Visit if subject discontinues early), including 
prescription medications, over-the-counter medications, and herbal supplements/vitamins. 
n. Adverse event monitoring will include assessment of treatment-emergent AEs (TEAEs), serious adverse events (SAEs), and severe AEs (Grade 3 or 4 events). 
o. DoD assessments can be performed one day prior to discharge if the subject has been labelled as “ready for discharge.” 
Note: SCREENING LABORATORY ASSESSMENTS: For all screening laboratory assessments, if more than one result is available during the screening period, the most recent value will be 
used as the screening value and for determination of eligibility. 
Note: All subjects who are discharged from the hospital will undergo all Day-of-Discharge (DoD) Visit assessments; daily in-hospital assessments will only need to be performed once on DoD. 
All subjects who discontinue from the study prematurely will undergo all Early Termination (ET) Visit assessments, whenever possible. All subjects who discontinue treatment and/or the study 
early will be followed for Day 43 all-cause mortality. 

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Schedule of Assessments: Follow-up Period 
(Visits will be in-hospital or by phone, if subject has been discharged) 
Study Day (± Window) 
15 
(± 2) 
22 
(± 2) 
29 
(± 2) 
36 
(± 2) 
43a 
(± 2) 
85 
(± 2) 
EoS 
169 
(± 2) 
DoD / 
ET 
Week 
2 
3 
4 
5 
6 
12 
24 
— 
Procedures/Assessments 
SOFA Score 
Daily, only if in ICU, through Day 43 
X 
National Early Warning Score (NEWS) 
Daily, only while hospitalized, through Day 43 
X 
Central samples for cytokine panel 
Hosp 
Hosp 
Central samples for SP-D measurement 
Hosp 
Hosp 
Central sample for immunogenicity (antibodies to gimsilumab) 
Hosp 
Hosp 
Hosp 
Central clinical laboratory measurements (hematology, blood chemistry 
[including CRP, ferritin, LDH, procalcitonin, troponin I], coagulation 
[including D-dimer], and urinalysis)b 
Hosp 
Hosp 
Hosp 
Hosp 
Hosp 
X 
SpO2/FiO2, and if performed, PaO2/FiO2 (can be imputed) 
Daily, only while hospitalized, through Day 43 
X 
Oxygenation requirements 
Daily, only while hospitalized, through Day 43c 
X 
Ventilation requirements 
Daily, only while hospitalized, through Day 43 
X 
ECMO requirements 
Daily, only while hospitalized, through Day 43 
X 
Concomitant medications/concurrent procedures 
Daily, only while hospitalizedd 
X 
X 
X 
Physical examination and vital signs (blood pressure, heart rate, 
respiration rate, and body temperature) 
Hosp 
Hosp 
Hosp 
Hosp 
Hosp 
X 
7-point Ordinal Scale 
Daily, only while hospitalized, through Day 43d 
X 
X 
X 
Adverse event monitoringe 
Daily, only while hospitalizedd 
X 
X 
X 
ECMO = extracorporeal membrane oxygenation; EoS = End-of-Study; FiO2 = fraction of inspired oxygen; Hosp = Assessment to be performed only if subject has not been discharged; ICU = 
Intensive Care Unit; SOFA = sequential organ failure assessment; SP-D = serum surfactant protein D; SpO2 = peripheral capillary oxygen saturation 
a. 
Day 43 will be used for the primary all-cause mortality endpoint. 
b. 
For all on-study laboratory assessments, if central laboratory assessments cannot be collected for any reason, best efforts will be made to record local laboratory data. 
c. 
IF DISCHARGED, will be measured via phone follow-up on Day 15, 22, 29, 36, and 43. 
d. 
IF DISCHARGED, will be measured via phone follow-up on Day 15, 22, 29, 36, 43, 85, and 169. 

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Schedule of Assessments: Follow-up Period 
(Visits will be in-hospital or by phone, if subject has been discharged) 
Study Day (± Window) 
15 
(± 2) 
22 
(± 2) 
29 
(± 2) 
36 
(± 2) 
43a 
(± 2) 
85 
(± 2) 
EoS 
169 
(± 2) 
DoD / 
ET 
Week 
2 
3 
4 
5 
6 
12 
24 
— 
Procedures/Assessments 
e. 
Adverse event monitoring will include assessment of treatment-emergent AEs (TEAEs), serious adverse events (SAEs), and severe AEs (Grade 3 or 4 events) 
Note: Assessments at time points indicated with “Hosp” will only be conducted if the subject has not yet been discharged from the hospital. Assessments indicated with an ‘X’ will be performed 
in-hospital if the subject has not been discharged or via phone if subject has been discharged from the hospital. 
Note: All subjects who are discharged from the hospital will undergo all Day-of-Discharge (DoD) Visit assessments; daily in-hospital assessments will only need to be performed once on DoD. 
All subjects who discontinue from the study prematurely will undergo all Early Termination (ET) Visit assessments, whenever possible. 
All subjects who discontinue treatment and/or the study early will be followed for Day 43 all-cause mortality. 

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7.2. 
Informed Consent 
Documented consent (including regulatory compliant electronic methods) must be obtained from 
each potential subject prior to participating in all study procedures. Consent must be documented 
by the subject’s dated signature or by the subject’s legally acceptable representative’s dated 
signature on a consent form along with the dated signature of the person conducting the consent 
discussion. 
A copy of the signed and dated consent form should be given to the subject before participation 
in the study. 
The initial informed consent form, any subsequent revised written informed consent form and 
any written information provided to the subject must receive the IRB/ERC’s approval/favorable 
opinion in advance of use. The subject or his/her legally acceptable representative should be 
informed in a timely manner if new information becomes available that may be relevant to the 
subject’s willingness to continue participation in the study. The communication of this 
information will be provided and documented via a revised consent form or addendum to the 
original consent form that captures the subject’s dated signature or by the subject’s legally 
acceptable representative’s dated signature. 
Specifics about the study and the study population will be added to the consent form template at 
the protocol level. 
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations and 
Sponsor requirements. 
 
7.3. 
Inclusion/Exclusion Criteria Eligibility Review 
All inclusion and exclusion criteria will be reviewed by the Investigator or qualified designee at 
the Screening Visit to ensure that the subject qualifies for the study. 
All inclusion criteria must be met and none of the exclusion criteria may apply. No eligibility 
waivers will be granted. 
Subjects found ineligible during review of inclusion/exclusion will not proceed through the 
remaining screening process. 
 
7.4. 
Study Assessments and Procedures 
 
7.4.1. 
Efficacy Assessments 
 
7.4.1.1. 
Measures of clinical support 
 
At each assessment day, the following measure of clinical support should be assessed: 
• Hospitalization 
• Oxygen requirement (via nasal cannula, mask, or high-flow nasal cannula) 
• Non-invasive mechanical ventilation (i.e., CPAP or BiPAP) 

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• Mechanical ventilator requirement (via endotracheal tube or tracheostomy tube) 
• ECMO requirement 
 
7.4.1.2. 
7-Point Ordinal Scale 
 
The ordinal scale is an assessment of the clinical status at the first assessment of a given study 
day [WHO COVID-19 Master Protocol, 2020]. Each day, the worse score for the previous day 
will be recorded (i.e., on Study Day 3, the worse Day 2 score is obtained and recorded as the 
score for Day 2). 
The scale is as follows: 
1. Not hospitalized, no limitations on activities; 
2. Not hospitalized, limitation on activities; 
3. Hospitalized, not requiring supplemental oxygen; 
4. Hospitalized, requiring supplemental oxygen; 
5. Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 
6. Hospitalized, on invasive mechanical ventilation or ECMO; 
7. Death. 
 
7.4.1.3. 
Sequential Organ Failure Assessment (SOFA) 
 
The SOFA score will be assessed daily for subjects while in the ICU. 
 
7.4.1.4. 
National Early Warning Score (NEWS) 
 
The NEW Score has demonstrated an ability to discriminate patients at risk of poor outcomes 
[WHO Master Protocol, 2020]. This score is based on 7 clinical parameters (Figure 7-1). The 
NEW Score is used as an efficacy measure. 
These parameters can be obtained from the hospital chart using the last measurement prior to the 
time of assessment. This is recorded for the day obtained (i.e., on Study Day 3, the Day 3 score is 
obtained and recorded as Day 3). Each parameter and the final score will be recorded. 
This should be evaluated at the first assessment of a given study day. 

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Figure 7-1: 
National Early Warning Score 
 
Level of consciousness = alert (A), and arousable only to voice (V) or pain (P), and unresponsive (U) 
 
7.4.2. 
Safety and Other Assessments 
 
7.4.2.1. 
Physical Examinations 
 
Abbreviated, targeted physical examinations (i.e., assessments of the skin, respiratory, 
cardiovascular system, and abdomen [liver and spleen]), will be performed at time points 
specified in the Schedule of Assessments (Table 7-2) and will be based on the subject’s clinical 
status and what the clinic staff feel is appropriate. 
Height and weight will be measured and recorded at Screening only, if possible. 
Note: If a physical examination is performed as standard of care by appropriate personnel the 
same day that consent is signed or the same day of any scheduled study visit, results from that 
examination may be used if personal protective equipment (PPE) is not available or if study site 
staff consider additional examinations are unwarranted due to already having been performed as 
standard of care. 
 
7.4.2.2. 
Vital Signs 
 
Vital signs including blood pressure, heart rate, respiration rate, and temperature (oral, tympanic, 
or axillary) will be obtained at time points specified in the Schedule of Assessments (Table 7-2). 
The same method for assessing temperature should be used at all visits for each individual 
subject, if possible. 

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Note: If vital signs measurements are performed as standard of care by appropriate personnel the 
same day that consent is signed or the same day of any scheduled study visit, results from that 
examination may be used if PPE is not available or if study site staff consider additional 
measurements are unwarranted due to already having been performed as standard of care. 
 
7.4.2.3. 
Cardiovascular Assessments 
 
7.4.2.3.1. Echocardiograms 
 
Echocardiograms may be performed as standard of care, at the discretion of the Investigator. If 
an echocardiogram is performed, LVEF will be recorded, if assessed. 
 
7.4.2.4. 
Follicle Stimulating Hormone (FSH), Viral Serology, and Tuberculosis 
Assessments 
 
Follicle stimulating hormone (FSH) will be performed at screening, for women only, to confirm 
postmenopausal status in women who have not had 12 months of spontaneous amenorrhea. 
A blood sample will be collected at Screening as specified in the Schedule of Assessments 
(Table 7-2), for viral serology and TB testing, but enrollment can continue without receiving the 
results first. HCV testing can be RNA or Ag, only to confirm suspected infection. If a subject is 
diagnosed with latent TB (positive QuantiFERON Gold or purified protein derivative [PPD]), 
hepatitis B or C, or HIV during the study, the Investigator must discuss this with the medical 
monitor and a decision will then be made concerning the second dose of gimsilumab, if 
applicable. In the event the QuantiFERON Gold assay is not available, and the site performs a 
different IGRA such as T Spot, then the alternative IGRA will be acceptable for patient 
screening and enrollment. Enrollment should not be delayed to obtain the QuantiFERON Gold 
assay in lieu of the IGRA available at the site. If no IGRA test is available, PPD can be used. If 
TB testing and viral serology is missed during screening it must be completed and results 
received prior to the second dose of study drug. If not completed or unable to obtain results 
further discussions with the medical monitor will be required. 
 
7.4.2.5. 
Clinical Safety Laboratory Assessments 
 
All protocol required laboratory assessments must be conducted in accordance with the 
Laboratory Manual, and the Schedule of Assessments (Table 7-2). Laboratory requisition forms 
must be completed, and samples must be clearly labelled with the subject number, protocol 
number, site/center number, and visit date. Details for the preparation and shipment of samples 
will be provided by the laboratory and are detailed in the Laboratory Manual. Reference ranges 
for all safety parameters will be provided to the site by the laboratory responsible for the 
assessments. 
For all on-study laboratory assessments, if central laboratory assessments cannot be collected for 
any reason, best efforts will be made to record local laboratory data. 
If additional non-protocol specified laboratory assessments are performed at the institution’s 
local laboratory and result in a change in subject management or are considered clinically 

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significant by the Investigator (e.g., SAE or AE or dose modification) the results must be 
recorded. 
Hematology, clinical chemistry, coagulation, urinalysis and additional parameters to be tested are 
listed in (Table 7-3). 
 
Table 7-3: List of Clinical Laboratory Analyses 
 
Hematology 
Coagulation 
Platelet Count 
MCV 
Eosinophils 
Prothrombin Time (PT) 
RBC Count 
MCH 
Basophils 
D-dimer 
WBC Count (absolute) 
MCHC 
Activated partial thromboplastin time 
(aPTT) 
Reticulocyte Count 
Neutrophils 
Fibrinogen 
Hemoglobin 
Lymphocytes 
Cardiac Enzymes 
Hematocrit 
Monocytes 
Troponin I 
 
Clinical Chemistry 
BUN 
Total CO2 
AST (SGOT) 
Creatine Kinase 
Creatinine 
Calcium 
ALT (SGPT) 
NT-proBNP 
Glucose 
Ferritin 
Albumin 
FSH (blood) 
(only at screening for 
postmenopausal confirmation) 
Sodium 
C-reactive 
Protein (CRP) 
Alkaline phosphatase 
Potassium 
Lactate 
dehydrogenase 
(LDH) 
Total bilirubin 
Chloride 
Procalcitonin 
Total Protein 
 
Urinalysis 
Glucose 
pH 
Clarity 
Protein 
Blood 
Color 
Ketones 
Nitrite 
Urobilinogen 
Specific gravity 
Leukocytes 
Bilirubin 

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7.4.2.6. 
SARS-CoV-2 Viral Assessments 
 
A local qualitative sample (e.g., nasopharyngeal swab) for PCR SARS-CoV-2 will be collected 
at Screening for determination of eligibility (if not already documented); all other on-study 
samples will be central quantitative samples. 
When at all possible, if only 1 nostril is swabbed for viral assessments, the same nostril should 
be used for all subsequent samples. 
 
7.4.2.7. 
Respiratory Assessments 
 
Safety assessment includes FiO2 and SpO2. If indicated, additional follow up tests may be 
performed at Investigator discretion after consultation with the Medical Monitor. 
If subject is receiving mechanical ventilation, the following parameters will be recorded: type of 
ventilation (high-flow nasal cannula, non-rebreather mask, CPAP, BiPAP, or intubation), FiO2, 
SpO2, ventilation rate, pulse, tidal volume, positive end-expiratory pressure (PEEP), and airway 
pressure. 
Respiratory assessments, when available, will be used to determine the Lung Injury Score (LIS) 
as an exploratory endpoint. The LIS is a composite scoring system including P/F ratio, the level 
of PEEP, the extent of infiltrates on chest X-ray or computerized tomography (CT) scan and 
respiratory static compliance. 
 
7.4.2.8. 
Pharmacokinetic Assessments 
 
Blood samples for PK analysis of serum gimsilumab will be collected at the time points 
indicated in the Schedule of Assessments (Table 7-2). The actual date and time of each blood 
sample collection will be recorded. The time of gimsilumab/placebo dosing on Day 1 will be t=0 
for relative timing of PK samples. 
Processing, storage, and shipping procedures are provided in the Laboratory Manual. 
Serum PK analysis will be performed under the oversight and control of the Sponsor, the details 
of which will be included in the Laboratory Manual. Concentrations of gimsilumab will be 
determined in serum samples using the currently approved bioanalytical methodology. 
 
7.4.2.9. 
Biomarker Assessments 
 
Blood samples for determination of serum cytokines and a safety biomarker SP-D will be 
collected at the time points indicated in the Schedule of Assessments (Table 7-2). The actual date 
and time of each blood sample collection will be recorded. The time of gimsilumab/placebo 
dosing on Day 1 will be t=0 for relative timing of PD samples. 
The cytokine/chemokine panel may include: GM-CSF, G-CSF, IL-1β, IL-2, IL-6, IL-7, IL-8, 
IL-10, IL-15, IL-17A, IL-17A/F, IL-23p19, IFN-γ, TNF-α, IP10 (CXCL10), MCP1 (CCL2), 
MIP1A (CCL3), and CCL17. 
A subset of these cytokines/chemokines will be tested initially, further testing may be performed 
based on results of other study endpoints and emerging scientific information. 

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Concentrations of biomarkers will be determined using qualified or validated assays. 
 
7.4.2.10. 
Immunogenicity Assessments 
 
A single blood sample for the assessment of anti-GM-CSF autoAb will be collected at Screening 
(this result is not required to determine eligibility). 
Blood samples for serum ADA analysis will be collected at the time points indicated in the 
Schedule of Assessments (Table 7-2). The actual date and time of each blood sample collection 
will be recorded. The time of gimsilumab/placebo dosing on Day 1will be t=0 for relative timing 
of ADA samples. 
Processing, storage, and shipping procedures are provided in the Laboratory Manual. 
Serum analysis will be performed under the oversight and control of the Sponsor, the details of 
which will be included in the Laboratory Manual. ADAs will be determined in serum samples 
using the currently approved bioanalytical methodology. 
 
7.4.2.11. 
Safety Monitoring 
 
It is understood the safety profile of gimsilumab in the critical care setting of patients with 
impending or established ARDS is not yet understood. Reassuringly the anti-GM-CSF class of 
molecules has been studied in many subjects in multiple Phase 2 trials [Hamilton, 2020] and to 
date no specific safety signal of concern has been noted to date. In principal concerns for 
targeting GM-CSF include respiratory tract infection and pulmonary alveolar proteinosis. Hence 
while the rationale for targeting GM-CSF in the setting of severe viral pneumonia with or 
without ARDS is strong, there is concern over AEs and patient safety. 
To ensure subject safety, the sponsor will appoint an independent DMC to review unblinded 
safety and efficacy data on an ongoing basis. The Chair of the DMC will issue a Charter 
outlining the specific plan for safety review including both early stopping rules for adverse safety 
events and also early stopping rules for futility, and early stopping rules for efficacy. 
 
8. 
DATA MANAGEMENT 
For this study, subject data will be entered into Sponsor-approved electronic database and 
combined with data provided from other sources in validated datasets then transmitted 
electronically to the Sponsor or designee. 
Management of clinical data will be performed in accordance with applicable Sponsor approved 
standards and data cleaning procedures to ensure the integrity of the data, e.g., re resolving errors 
data queries, and inconsistencies in the data, and datasets in CDISC SDTM/AdaM formats. 
AEs and concomitant medication terms will be coded using the most current versions of the 
Medical Dictionary for Regulatory Activities (MedDRA) and the World Health Organization 
Drug Dictionary Enhanced (WHO-DDE), respectively. 
The Principal Investigator will retain original source documents and the Sponsor will receive 
CRF-required data as electronic datasets. Subject initials will not be collected or transmitted to 
the Sponsor. 

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The detailed Data Management Plan (DMP) will be generated and approved prior to the study 
database lock when all subjects complete the Day 43 Visit, discontinue from the study early, or 
meet the primary endpoint of mortality (by Day 43). 
The study database will be locked when all subjects complete the Day 43 Visit, discontinue from 
the study early, or meet the primary mortality endpoint. The second lock will occur when the last 
subject completes the Day 169 EoS visit. 
In addition, there will be 2 database extracts (soft locks) for interim analyses, the first of which 
will be conducted when 60 subjects have been treated and have completed through Day 15; the 
DMC will review the data for safety and futility and provide their recommendations. The second 
interim analysis will be conducted when 100 subjects have completed at least the Day 29 Visit 
for non-mortality endpoints and have the data for the endpoint of mortality (by Day 43). 
 
9. 
STATISTICAL CONSIDERATIONS AND ANALYSES 
 
9.1. 
Sample Size Determination 
There will be 270 subjects (135 subjects per treatment arm) with 1:1 randomization. 
The comparisons between the treatment arms will have approximately 80% power and two-sided 
alpha level 0.05 to demonstrate the significant reduction of the incidences (15% versus 30%) in 
the primary endpoint between gimsilumab versus placebo. 
The study will enroll at least 40%, but no more than 60%, of total subjects in each of the 
2 categories of clinical status : ([lung injury/mild ARDS] or [moderate/severe ARDS]) at 
Baseline, which will be used as the stratified factor in the randomization. 
Lung injury is defined as (1) requiring supplemental oxygen >4L O2 to maintain >92% SpO2, or 
(2) PaO2/FiO2 ≤300 mmHg (can be imputed). 
ARDS [ARDS Berlin Definition, 2012] is defined as: 
• Bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules; 
• Respiratory failure not fully explained by cardiac failure or fluid overload; 
• Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no 
risk factor present. 
• ARDS severity categories are defined as: 
o Mild: 200 mmHg, < PaO2/FiO2, ≤300 mmHg with PEEP or CPAP ≥5 cm H2O. 
o Moderate: 100 mmHg, < PaO2/FiO2, ≤200 mmHg with PEEP ≥5 cm H2O. 
o Severe: PaO2/FiO2 ≤100 mmHg with PEEP ≥5 cm H2O. 
 
9.2. 
Randomization 
The central stratified randomization will be used to assign subjects into 1 of the 2 study treatment 
arms with an equal randomization ratio (1:1) with the stratification factors of subject’s clinical 
status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) and country. 

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Hypotheses 
This is a double-blind, placebo-controlled, randomized trial testing a superiority hypothesis of 
significant reduction of the gimsilumab versus placebo in the percentage of the primary endpoint. 
 
9.3. 
Analysis Endpoints 
 
9.3.1. 
Efficacy Endpoints 
 
Primary endpoint: 
• Incidence of mortality by Day 43 
Key Secondary Endpoints: 
• 
Proportion of subjects who survived and were not requiring mechanical ventilation on 
Day 29 
• 
Mechanical ventilation-free days by Day 29 
• 
Time to hospital discharge by Day 43 
Additional Secondary Endpoints: 
• 
Incidence of mortality by Days 15, 22, 29, 85, and 169 (End-of-Study [EoS]). 
• 
Proportion of subjects who survived and were not requiring mechanical ventilation on Days 
15, 22, and 43. 
• 
Mechanical ventilation-free days for all subjects by Days 15, 22, and 43 
• 
ICU-free days for all subjects by Days 15, 22, 29, and 43. 
• 
Incidence of mechanical ventilation use for all subjects by Days 15, 22, 29, and 43. 
• 
Incidence of ICU use for all subjects by Days 15, 22, 29, and 43 
• 
Time to death by Day 43 and Day 169 (EoS) 
• 
NEWS assessed daily while hospitalized 
• 
SOFA score, and each of the components, assessed daily while in the ICU 
• 
The percentage of subjects reporting each severity rating on the 7-point ordinal scale, 
assessed daily while hospitalized and, if discharged from hospital, on Days 15, 22, 29, 36, 
43, 85, and 169 (assessed by phone) 
• 
Status on the 7-point ordinal scale, assessed daily while hospitalized and, if discharged from 
hospital, on Days 15, 22, 29, 36, 43, 85, and 169 (assessed by phone) 
• 
Time to clinical improvement by 2 points on the 7-point ordinary scale 
• 
Change from Baseline in SpO2/FiO2, assessed daily while hospitalized 
• 
Incidence and duration of oxygen use during the study 
• 
Change from Baseline in viral load as measured by quantitative PCR test on Days 2, 9, and 
DoD 
• 
Change from Baseline in D-dimer, cardiac troponin I, LDH, ferritin, and CRP 
• 
Serum gimsilumab concentrations 

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• 
Analysis of anti-gimsilumab antibodies (ADAs) 
Exploratory Endpoints: 
• 
Change from Baseline in the cytokine panel and SP-D 
• 
Change from Baseline in LIS (if performed) 
• 
Change from Baseline in chest radiographic assessment (if performed) 
• 
Change from Baseline in P/F ratio, if performed 
• 
Incidence and duration of ECMO use 
• 
Change from Baseline in LVEF (when measured) 
• 
Change from Baseline in eGFR (MDRD equation), assessed when central clinical safety 
laboratory measurements are collected during hospitalization 
 
9.3.2. 
Safety Endpoints 
 
Safety and tolerability, including assessment of clinical safety laboratory measurements, physical 
examinations, vital signs, concomitant medications; cumulative incidence of AEs, SAEs, and 
severe AEs. 
 
9.3.3. 
Pharmacokinetic Endpoints 
 
Serum gimsilumab concentration at time points as specified in the Schedule of Assessments 
(Table 7-2). 
 
9.3.4. 
Biomarker Endpoints 
 
Change from Baseline in the cytokine panel and serum SP-D will be measured at time points as 
specified in the Schedule of Assessments (Table 7-2). 
 
9.4. 
Analysis Populations 
Key Analysis Sets 
• The Intent-to-treat (ITT) Population will include all randomized subjects who receive any 
amount of study drug. The ITT subjects will be analyzed according to randomized treatment, 
irrespective of whether or not they have prematurely discontinued. Subjects who withdraw 
from treatment and/or the study will be followed for Day 43 all-cause mortality. All efficacy 
analyses will be performed using the ITT Population. 
• The Safety Population (SP) will include all randomized subjects who receive any amount of 
study drug. The SP will be analyzed according to the treatment received. This set will be used 
for the safety analyses. 
• The per-protocol (PP) Population will include all subjects in the ITT Population who 
complete the Day 43 Visit with no protocol major violations. The PP Population will be used 
for supportive analyses of the efficacy measurements. 

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9.5. 
Statistical Analyses/Methods 
All statistical analyses will be conducted on SAS Version 13.1 or later. 
In general, all the continuous variables, including the changes from Baseline, will be summarized 
by the treatment with the mean, standard deviation (SD), median and the range. The Mixed 
Model with Repeated Measurements (MMRM) /Analysis of Covariance (ANCOVA) model with 
the treatment, country, subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]), and visits as the model term will be used to test for the significance of 
the treatment difference. The least square means, standard errors, 95% CIs and p-values will be 
presented. 
All the categorical variables will be summarized by the treatment with the numbers and 
percentages of the subjects, and the treatment difference, the odds ratio and 95% CI will be 
tested by using logistical model (Ge, 2011) with the Treatment, country, and subject’s clinical 
status at baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) for binary outcome. 
The CMH test will be used for other categorical outcomes. 
The time to event endpoints will be analyzed by using the Cox Proportional Hazard model with 
the treatment, country , and subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]) as the model term. The hazard ratio of gimsilumab versus placebo will 
be presented with 95% CI and p-value from the model. The Kaplan-Meier curves of the time to 
events will be presented for treatments on each endpoint. 
The sites, which enrolled small number of subjects, will be combined in the statistical models. A 
blinded data review will be conducted for pooling the sites. 
An SAP will be prepared and sent to agencies prior to the interim analysis. 
 
9.5.1. 
Primary Efficacy Analyses 
 
The primary analysis of the primary endpoint will be performed by using the logistical regression 
with the Treatment, country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] 
or [moderate/severe ARDS]). The subjects who died by Day 43 (by Day 169) will be 
summarized by the numbers and percentages, difference of the percentages, the odds ratio and its 
95% CI presented for gimsilumab versus placebo, and p-value. 
The secondary analysis of the primary endpoint will be conducted by using the Cox Proportional 
Hazard model with treatment, country and subject’s clinical status at Baseline ([lung injury/mild 
ARDS] or [moderate/severe ARDS] on the time to death. The median of the time to event from 
Kaplan-Meier curves will be presented for each treatment, and the hazard ratio of the 
gimsilumab dose level versus placebo will be presented with 95% CI, and p-values. 
 
9.5.2. 
Sensitivity Analysis of the Primary Endpoint 
 
Sensitivity analyses will be performed using all randomized subjects and using a multiple 
imputation method, such as the tipping point method, to handle missing data, as described in 
Section 9.5.5. 

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The Per-Protocol (PP) Population will be used for the primary and secondary analysis of the 
primary endpoint as additional supportive analyses. 
 
9.5.3. 
Analysis of the Key and Other Secondary Endpoints 
 
Secondary endpoints will be analyzed as follows: 
• Incidence data (e.g., incidence of new or increased oxygen use) will be summarized as a 
percent with 95% CIs. The logistic regression model with treatment, country, and 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]) will be used for the odds ratio of gimsilumab versus placebo, 95% CIs and p- 
values. 
• Change in ordinal scale at specific time points will be summarized by proportions 
(e.g., proportion who have a 1-, 2-, 3-, or 4-point improvement or 1-, 2-, 3-, 4-point 
worsening). The CMH test on combined subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) will be used for treatment difference. 
The odds ratio of gimsilumab versus placebo, 95% CIs and p-values will be provided. 
• Duration of event free (e.g., mechanical ventilation free days) will be summarized 
according to median days with quartiles. The Wilcoxon rank test will be used for the 
treatment difference. 
• The continuous variables, including the changes from baseline, will be summarized by 
the treatment with the mean, standard deviation (SD), median, and the range. PK 
summaries will include geometric mean and geometric coefficient of variation. The 
Mixed Model with Repeated Measurements (MMRP)/Analysis of Covariance 
(ANCOVA) with the treatment, country, subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]), and visit as the model term, and 
baseline value as the covariate will be used for the treatment difference. The least square 
means, standard errors, 95% CIs and p-values will be presented. 
• The time-to-event endpoints will be summarized with Kaplan Meier curves and 95% 
confidence bounds by the treatment. The Cox Proportional Hazard model with treatment, 
country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]) as model terms will be used. The hazard ratio of gimsilumab 
versus placebo will be presented with 95% CI and p-values. 
 
9.5.4. 
Adjustment of Multiple Comparisons and Interim Analyses 
 
The interim analysis will be conducted when 60 subjects have been treated and have completed 
through Day 15; the DMC will review the data for safety and futility and provide their 
recommendations. 
The second interim analysis will be conducted when 100 subjects have completed at least the 
Day 29 Visit for non-mortality endpoints and have the data for the endpoint of mortality (by 
Day 43). 
The objectives of the second interim analysis will be to stop the study by superiority, futility, or 
perform the sample size re-estimation. For controlling overall two-sided alpha of 0.05 overall for 
the final analysis on the primary endpoint of Mortality Day 43, 0.001 of the alpha will be used 

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for the superiority comparison during the second interim analysis, and 0.049 will be used for the 
final analysis for Day 43. The weighted average of two summary measures by Cui L, Hung HM, 
Wang [Cui, 1999] will be used, one based on the data collected in the interim analysis, and the 
other based on the data collected after the interim. 
 
9.5.5. 
Handling of Missing Data 
 
Sensitivity analyses will be performed for the primary and key secondary endpoints using 
multiple imputations for the missing data: 
• Tipping-point multiple imputation analysis 
Missing data will be imputed for mortality by Day 43 with all possible combinations of death or 
survival in the two arms. The combination which alters the conclusion will be defined as the 
tipping point for evaluation on the robustness of the results. 
• Imputation differentiating the reasons of missing data from the early drop out 
The reasons of the lost to follow-up, SAEs/AEs, and the use of rescue medications will be 
identified, and the percentage of these subjects will be summarized by treatment. The data for 
informative censoring, such as the unfavorable or worst outcome, can be used to impute the 
missing data. 
 
9.5.6. 
Safety Analyses 
 
Safety will be assessed based on the SP for AEs, laboratory parameters, physical examination, 
vital signs, and clinical chemistries throughout the duration of the study. The safety analyses will 
include descriptive summaries by treatment arm of AEs. The number and percentage of 
participants reporting AEs and SAEs will be presented. Adverse events will be categorized by 
system organ class (SOC) and preferred term (PT) and summarized by the number of participants 
(and percentage) with at least 1 event, and the number of events. Adverse events will also be 
summarized by seriousness, grade, and study drug relationship for all participants. The 
continuous variables, including the changes from Baseline, will be summarized by descriptive 
statistics: mean, SD, and the range. The categorical variables, such as normal/abnormal will be 
summarized by the numbers and percentages at each visit, and the shift table from Baseline to 
each visit will be presented. 
 
9.5.7. 
Sub-Group Analyses 
 
Subgroup analyses for the primary outcomes will evaluate the treatment effect across the 
following subgroups: country, subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]), country, age, and sex. A forest plot will display confidence intervals 
across subgroups. Interaction tests will be conducted to determine whether the effect of treatment 
varies by subgroup. 

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9.5.8. 
Timing of Analyses 
 
The first unblinded analysis will be conducted when the last subject completes the Day 43 Visit, 
discontinues the study early, or meets the primary endpoint of mortality (by Day 43). The final 
analysis will be conducted when the last subject completes the Day 169 (EoS) Visit. The first 
interim analysis will be conducted when 60 subjects have been treated and have completed 
through Day 15; the DMC will review the data for safety and futility and provide their 
recommendations. 
The second interim analysis will be conducted when 100 subjects have completed at least the 
Day 29 Visit for non-mortality endpoints and have the data for the endpoint of mortality (by Day 
43). The objectives of the second interim analysis will include the claim of superiority or futility 
to stop the study, or the reassessment of sample size, and/or modifications of the populations. 
The DMC will be responsible for closely reviewing the safety data from the unblinded interim 
analysis and for providing their recommendations. The detailed objectives and procedures, 
including close monitoring of the safety data and the boundaries of futility will be described in 
the SAP and the DMC Charter. 
 
9.5.9. 
Pharmacokinetic, Biomarker, and Immunogenicity Analyses 
 
Serum gimsilumab concentrations will be summarized using descriptive statistics. 
Biomarker analyses will be based on the Safety Population and biomarker (SP-D, 
cytokine/chemokine, anti-GM-CSF autoAb) concentrations will be summarized by treatment 
using descriptive statistics. 
Immunogenicity analysis will be based on the Safety Population and anti-drug antibody data will 
be reported in the format provided by the bioanalytical laboratory. 
Further details will be provided in the SAP. 
 
10. 
ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS 
(SAES) 
The Investigator or site staff is responsible for detecting, documenting and reporting events that 
meet the definition of an AE or SAE. 
The Investigator is not obligated to actively seek AEs or SAEs in former study participants. 
However, if the Investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably related to the 
investigational product or study participation, the Investigator should promptly notify the 
Sponsor. 
 
10.1. 
Special Consideration for Assessment of Adverse Events 
It is recognized that the patient population in the ICU will experience a number of common 
aberrations in laboratory values, signs and symptoms due to the severity of their underlying 
disease and the impact of standard therapies. These will not necessarily constitute an AE unless 

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they require significant intervention, lead to discontinuation of blinded study drug, or are 
considered to be of concern in the investigator’s clinical judgement. 
Death should be recorded both as a SAE and as the outcome of ONE event, i.e. one event should 
be determined to be the primary cause of death. The 'clinical' AE that resulted in death is the AE 
and the death information supports the clinical AE. 'Death' is not entered as an AE unless the 
cause of death is unknown. In such case the AE term is 'Unspecified fatal event' until the cause 
of the death is known. 
 
10.2. 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject, 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. 
Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of a medicinal product. 
Events meeting the definition of an AE include but are not limited to: 
• 
Any clinically significant, new or worsening, abnormal laboratory test results 
(hematology, clinical chemistry, or urinalysis) or findings from other safety assessments 
(e.g., ECGs, radiological scans, vital signs measurements. Clinical significance is 
determined by the medical and scientific judgement of the Investigator. 
• 
Worsening of a chronic or intermittent pre-existing condition including an increase in 
frequency, intensity and/or duration of a condition. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction (e.g., with 
medications or food). 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational product or a concomitant medication (overdose without the presence of 
an AE are to be reported as a protocol violation). 
• 
New infections occurring on-study, regardless of infection type (i.e., viral, bacterial, 
fungal, etc.) will be reported as AEs. 
Events that do not meet the definition of an AE include: 
• 
Anticipated day-to-day fluctuations of a pre-existing condition(s), (including the 
disease under study), that do not represent a clinically significant exacerbation or 
worsening. 
• 
Abnormal or worsening laboratory, (including imaging) findings or other safety 
findings that are not clinically significant. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy). However, the 
condition that leads to the procedure is to be considered a reportable AE. 

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• 
If applicable, the disease/disorder being studied, or expected progression, signs, or 
symptoms of the disease/disorder being studied, unless more severe than expected for 
the subject’s condition. 
• 
Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
10.3. 
Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence that, at any dose: 
• Results in death 
• Is life-threatening 
NOTE: The term 'life-threatening' in the definition of 'serious' refers to an event in which 
the subject was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
• Requires hospitalization or prolongation of existing hospitalization 
NOTE: “Hospitalization” includes admission to the hospital of any duration. 
Complications that occur during hospitalization are AE sand are SAEs if they prolong a 
hospitalization or meets any other serious criteria. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
Baseline is not considered an AE. 
• Results in disability/incapacity 
NOTE: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences of 
relatively minor medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may interfere or 
prevent everyday life functions but do not constitute a substantial disruption. 
• Is a congenital anomaly/birth defect 
• Is an important medical event that may jeopardize the participant or may require medical 
or surgical intervention to prevent one of the outcomes listed above. Examples of such 
events are invasive or malignant cancers, allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse. 
 
10.4. 
Time Period and Frequency for Collecting AE and SAE 
Information 
 
• 
AEs will be collected from the start of Study Treatment until the follow-up contact, at 
the timepoints specified in the Schedule of Assessments (Table 7-2). 

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• 
SAEs related to study procedures or investigational product will be collected from the 
time of subject informed consent until the follow-up contact is completed. 
• 
Medical occurrences that begin prior to the start of study treatment but after obtaining 
informed consent may be recorded on the Medical History/Current Medical Conditions 
section of the CRF. 
• 
All SAEs will be recorded and reported to the Sponsor within 24 hours of awareness. 
 
10.5. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non- 
leading verbal questioning of the subject is the preferred method to inquire about AE occurrence. 
Appropriate questions include: 
• 
“How are you feeling?” 
• 
“Have you had any (other) medical problems since your last visit/contact?” 
• 
“Have you taken any new medicines, other than those provided in this study, since your 
last visit/contact? 
 
10.6. 
Assessing Severity of AEs and SAEs 
Severity describes the intensity of a specific event (as in mild, moderate, or severe myocardial 
infarction); the event itself, however, may be of relatively minor medical significance, such as a 
severe headache. This is not the same as “serious,” which is based on participant/event outcome 
or action taken. The Investigator must determine the severity of each AE according to the 
following criteria. 
 
Criteria for Determining the Grade/Severity of Adverse Event Terms 
 
Grade 
Criteria 
1/Mild 
Asymptomatic or mild symptoms, clinical or diagnostic 
observations only; intervention not indicated 
2/Moderate 
Minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
3/Severe or medically significanta 
Not immediately life threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living. 
4/Life-threateninga 
Life threatening consequences; urgent intervention 
indicated 
5/Death 
Death related adverse events 
a    Severe AEs include both Grade 3 and Grade 4 AEs. 

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10.7. 
Assessing Causalities of AEs and SAEs 
Regulatory authorities require that both investigator and sponsor assess whether there is a 
reasonable possibility that the study treatment caused each AE. This assessment requires careful 
medical consideration of each event in relationship to the timing of drug administration, the 
presence of other factors which may have caused the event (underlying illness, concomitant 
medication, complications, exposure to other toxins or allergens, environmental factors, etc.), 
and the effects of stopping and/or restarting the study treatment. 
The investigator will assess the causality of each reported AE as follows: 
• 
Probably related: an AE occurring at a reasonable time following administration of a 
drug, where other causes are unlikely, there is evidence to suggest that the drug caused 
the event, and/or where the event recurs after reintroduction of the drug (without other 
explanation for the recurrence). 
• 
Possibly related: an AE occurring at a reasonable time following administration of a 
drug and for which there is a reasonable possibility that the drug caused the event, e.g., 
there is some evidence to suggest a causal relationship. 
• 
Not related: an AE with poor or no relationship to the timing of drug administration, or 
where another cause such as underlying disease, complications, or other medications 
reasonably explains the event, or where the event does not recur after continued 
administration or reintroduction of the drug for an adequate period. 
 
10.8. 
Follow-up of (non-serious) AEs and Serious AEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs, and non-serious AEs, will be followed until resolution, 
until the condition stabilizes, until the event is otherwise explained, or until the subject is lost to 
follow-up. Ongoing AEs may be closed after consultation between the Sponsor and Medical 
Monitor. 
 
10.9. 
Regulatory Reporting Requirements for SAEs 
On discovery, all SAEs should be immediately reported (latest within 24 hours of knowledge of 
 
See Section 6.4 for emergency unblinding service contact information. 
Prompt notification by the Investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a product 
under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and any other 
regulatory agencies about the safety of a product under clinical investigation. The Sponsor will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC and Investigator. 
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Investigator safety reports are prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and are forwarded to Investigators as necessary. 
 
11. 
PREGNANCY REPORTING 
• 
All female subjects will be tested for pregnancy prior to dosing. Subjects testing 
positive for pregnancy will be ineligible for study participation. 
• 
Any pregnancy reported between the time of informed consent and completion of the 
Day 85 Follow-up Visit or an Early Termination Visit must be reported to the Sponsor 
within 2 weeks of learning of the pregnancy. 
• 
Female subjects who become pregnant will also be followed to determine the outcome 
of the pregnancy. Information on the status of the mother and child will be provided to 
the Sponsor. Generally, follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any premature termination of the pregnancy will be reported. 
 
12. 
RESPONSIBILITIES 
 
12.1. 
Principal Investigator Responsibilities 
12.1.1. 
Good Clinical Practice 
 
The Principal Investigator will ensure that this study is conducted in accordance with the 
principles of the “Declaration of Helsinki” (as amended in Edinburgh, Tokyo, Venice, Hong 
Kong, and South Africa), International Conference on Harmonisation (ICH) guidelines, or with 
the laws and regulations of the country in which the research is conducted, whichever affords the 
greater protection to the study subject. For studies conducted under a United States IND, the 
Investigator will ensure that the basic principles of “Good Clinical Practice,” as outlined in 
21 Code of Federal Regulations (CFR 312), subpart D, “Responsibilities of Sponsors and 
Investigators,” 21 CFR, part 50, 1998, and 21 CFR, part 56, 1998, are adhered to. These 
standards are consistent with the requirements of the European Community Directive 
2001/20/EC. 
Since this is a “covered” clinical trial, the Principal Investigator will ensure that 21 CFR, Part 54, 
1998, is adhered to; a “covered” clinical trial is any “study of a drug or device in humans 
submitted in a marketing application or reclassification petition subject to this part that the 
applicant or FDA relies on to establish that the product is effective (including studies that show 
equivalence to an effective product) or that make a significant contribution to the demonstration 
of safety.” This requires that Principal Investigators and all sub-investigators must provide 
documentation of their financial interest or arrangements with the Sponsor, or proprietary 
interests in the drug being studied. This documentation must be provided before participation of 
the Investigator and any sub-investigator. The Principal Investigator and sub-investigator agree 
to notify the Sponsor of any change reportable interests during the study and for one year 
following completion of the study. Study completion is defined as the date that the last subject 
has completed the protocol defined activities. 

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12.1.2. 
Institutional Review Board/Independent Ethics Committee Approval 
 
This protocol and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) will be submitted by the Investigator to an IRB or IEC. Approval from the IRB or IEC 
must be obtained before starting the study and should be documented in a letter to the 
Investigator specifying the protocol number, protocol version, protocol date, documents 
reviewed, and date on which the committee met and granted the approval. 
Any modifications made to the protocol after receipt of IRB or IEC approval must also be 
submitted to the IRB or IEC for approval before implementation. 
 
12.1.3. 
Informed Consent 
 
The Principal Investigator or designee is responsible for obtaining written informed consent from 
each individual participating in this study after adequate explanation of the aims, methods, 
objectives, and potential hazards of the study and before undertaking any study-related 
procedures. The Investigator must utilize an IRB or IEC-approved consent form for documenting 
written informed consent. Each informed consent will be appropriately signed and dated by the 
subject or the subject’s legally authorized representative and the person obtaining consent. 
 
12.1.4. 
Confidentiality 
 
The Principal Investigator must assure that subjects’ anonymity will be strictly maintained and 
that their identities are protected from unauthorized parties. Only subject number, date of birth, 
and an identification code (i.e., not names) should be recorded on any form or biological sample 
submitted to the Sponsor, IRB or IEC, or laboratory. The Principal Investigator must keep a 
screening log showing codes, names, and addresses for all subjects screened and for all subjects 
enrolled in the trial. 
The Principal Investigator agrees that all information received from the Sponsor, including but 
not limited to the Investigator Brochure, this protocol, CRFs, the investigational new drug, and 
any other study information, remain the sole and exclusive property of the Sponsor during the 
conduct of the study and thereafter. This information is not to be disclosed to any third party 
(except employees or agents directly involved in the conduct of the study or as required by law) 
without prior written consent from the Sponsor. The Investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain. 
 
12.1.5. 
Study Files and Retention of Records 
 
The Principal Investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented and the study data to be subsequently verified. These 
documents should be classified into at least the following two categories: (1) Investigator’s study 
file, and (2) subject clinical source documents. 

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The Investigator’s study file will contain the protocol/amendments, CRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence. 
The required source data should include the following for each subject: 
• 
subject identification (name, date of birth, gender); 
• 
documentation that subject meets eligibility criteria, i.e., history, physical examination, 
and confirmation of diagnosis (to support inclusion and exclusion criteria); 
• 
participation in trial (including trial number); 
• 
trial discussed and date of informed consent; 
• 
dates of all visits; 
• 
documentation that protocol specific procedures were performed; 
• 
results of efficacy parameters, as required by the protocol; 
• 
start and end date (including dose regimen) of trial medication (preferably drug 
dispensing and return should be documented as well); 
• 
record of all AEs and other safety parameters (start and end date, and preferably 
including causality and intensity); 
• 
concomitant medication (including start and end date, dose if relevant; dose changes 
should be motivated); 
• 
date of trial completion and reason for early discontinuation, if applicable. 
All clinical study documents must be retained by the Principal Investigator until at least 2 years 
after the last approval of a marketing application in an ICH region (i.e., United States, Europe, or 
Japan) and until there are no pending or contemplated marketing applications in an ICH region; 
or, if no application is filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and regulatory authorities have been notified. The 
Principal Investigator may be required to retain documents longer if required by applicable 
regulatory requirements, by local regulations, or by an agreement with the Sponsor. The 
Investigator must notify the Sponsor before destroying any clinical study records. 
Should the Principal Investigator wish to assign the study records to another party or move them 
to another location, the Sponsor must be notified in advance. 
If the Investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the Principal Investigator and the 
Sponsor to store these in sealed containers outside of the site so that they can be returned sealed 
to the Investigator in case of a regulatory audit. When source documents are required for the 
continued care of the subject, appropriate copies should be made for storage outside of the site. 
Unused biological samples remaining at the conclusion of this study may be retained in an 
appropriate storage facility by the Sponsor for a period up to 10 years for purposes of this study. 

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12.1.6. 
Electronic Case Report Forms (eCRF) 
 
For each subject enrolled, an eCRF must be completed and signed by the Principal Investigator 
or sub-investigator (as appropriate) within a reasonable time period after data collection. This 
also applies to records for those subjects who fail to complete the study (even during a pre- 
randomization screening period if an eCRF was initiated). If a subject withdraws from the study, 
the reason must be noted on the eCRF. If a subject is withdrawn from the study because of a 
treatment-limiting AE, thorough efforts should be made to clearly document the outcome. 
12.1.7. 
Drug Accountability 
 
The Investigator or designee (i.e., pharmacist) is responsible for ensuring adequate accountability 
of all used and unused investigational medicinal product, placebos, and comparators. This 
includes acknowledgment of receipt of each shipment of study product (quantity and condition), 
subject dispensing records, and returned or destroyed study product. Dispensing records will 
document quantities received from the Sponsor and quantities dispensed to subjects, including 
lot number, date dispensed, subject identifier number, and the initials of the person dispensing 
the medication. 
At study initiation, the monitor will evaluate the site’s standard operating procedure for 
investigational medicinal product disposal/destruction in order to ensure that it complies with the 
Sponsor requirements. Drug may be returned or destroyed on an ongoing basis during the study 
if appropriate. At the end of the study, following final drug inventory reconciliation by the 
monitor, the study site will ship all unused investigational medicinal product supplies to the 
designated depot, according to these procedures. If the site cannot meet the Sponsor’s 
requirements for disposal, arrangements will be made between the site and the Sponsor or its 
representative for destruction or return of unused investigational medicinal product supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study. 
 
12.1.8. 
Inspections 
 
The Principal Investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from the Sponsor or its representatives, to IRBs or 
IECs, or to regulatory authority or health authority inspectors. 
12.1.9. 
Protocol Compliance 
 
The Principal Investigator is responsible for ensuring the study is conducted in accordance with 
the procedures and evaluations described in this protocol. 
12.2. 
Sponsor Responsibilities 
12.2.1. 
Protocol Modifications 
 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by the Sponsor. All protocol modifications must be submitted to the IRB or IEC in 

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accordance with local requirements. Approval must be obtained before changes can be 
implemented. 
12.2.2. 
Study Report and Publications 
 
A clinical study report will be prepared and provided to the regulatory agency(ies). The Sponsor 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases. 
12.3. 
Joint Investigator/Sponsor Responsibilities 
12.3.1. 
Access to Information for Monitoring 
 
In accordance with ICH Good Clinical Practice guidelines, the study monitor must have direct 
access to the Principal Investigator’s source documentation in order to verify the data recorded in 
the CRFs for consistency. 
The monitor is responsible for routine review of the CRFs at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the CRFs. The Investigator agrees to cooperate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved. 
12.3.2. 
Access to Information for Auditing or Inspections 
 
Representatives of regulatory authorities or of the Sponsor may conduct inspections or audits of 
the clinical study. If the Principal Investigator is notified of an inspection by a regulatory 
authority the Principal Investigator or designee agrees to notify the Medical Monitor 
immediately. The Principal Investigator agrees to provide to representatives of a regulatory 
agency or the Sponsor access to records, facilities, and personnel for the effective conduct of any 
inspection or audit. 
12.3.3. 
Study Discontinuation 
 
The Sponsor reserves the right to terminate the study at any time. Should this be necessary, the 
Sponsor will arrange discontinuation procedures and notify the appropriate regulatory 
authority(ies), IRBs, and IECs. In terminating the study, the Sponsor and the Principal 
Investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests. 

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13. 
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Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: The Berlin 
Definition. JAMA. 2012;307(23):2526-33. 
Barrett DM, Singh N, Hofmann T, et al. Interleukin 6 Is Not Made By Chimeric Antigen 
Receptor T Cells and Does Not Impact Their Function. Blood. 2016;128(22):654. 
doi:10.1182/blood.V128.22.654.654. 
Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated type I interferon and inflammatory 
monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host 
Microbe. 2016;19(2):181-193. doi:10.1016/j.chom.2016.01.007. 
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and 
consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529- 
539. doi:10.1007/s00281-017-0629-x. 
Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization 
(http://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/) 
Coronavirus disease 2019 (COVID-19) situation reports. World Health Organization. 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports Accessed 
March 17, 2020. 
Cui L, Hung HM, Wang SJ. Modification of sample size in group sequential clinical trials. 
Biometrics. 1999;55:853–7. 
Gimsilumab Investigator’s Brochure, Current Edition. 
Ge M, Durham LK, and Meyer DR. Covariate-adjusted difference in proportions from clinical 
trials using logistic regression and weighted risk differences. Drug Information Journal 
2011;45:4 
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. Contraceptive 
Technology. 19th edition. New York: Ardent Media, 2007(a): 24. Table 3-2. 
Hamilton JA. GM-CSF in inflammation. J Exp Med. 2020;217(1)pii:e20190945. 
doi:10.1084/jem.20190945. 
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus 
in Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/s0140-6736(20)30183-5. 
Ishii K, Shalabi H, Yates B, et al. Tocilizumab-Refractory Cytokine Release Syndrome (CRS) 
Triggered By Chimeric Antigen Receptor (CAR)-Transduced T Cells May Have Distinct 
Cytokine Profiles Compared to Typical CRS. Blood. 2016;128(22):3358. 
doi:10.1182/blood.V128.22.3358.3358. 

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Kristas SK, Ronconi G, Caraffa A, et al. Mast cells contribute to coronavirus-induced 
inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020;34(1). doi: 
10.23812/20-Editorial-Kritas. 
Kwon OC, Lee E, Chang E, et al. IL-17A+GM-CSF+ Neutrophils Are the Major Infiltrating Cells 
in Interstitial Lung Disease in an Autoimmune Arthritis Model. Front Immunol. 2018;9:1544. 
doi:10.3389/fimmu.2018.01544. 
Kudlak K, DeMuro JP, Hanna AF, et al. Acute lung injury following the use of granulocyte- 
macrophage colony-stimulating factor. Int J Crit Illn Inj Sci. 2013;3(4):279-281. 
doi:10.4103/2229-5151.124168. 
Lam CWK, Chan MHM, Wong CK. Severe Acute Respiratory Syndrome: Clinical and 
Laboratory Manifestations. Clin Biochem Rev. 2004;25(2):121-132. 
Liao M, Liu Y, Yuan J, et al. The landscape of lung bronchoalveolar immune cells in COVID-19 
revealed by single-cell RNA sequencing. Pre-Print. 2020. 
https://doi.org/10.1101/2020.02.23.20026690. 
Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and 
immunosuppression. Lancet. 2020. doi:10.1016/S0140-6736(20)30628-0. 
Molfino NA, Kuna P, Leff JA, et al. Phase 2, randomised placebo-controlled trial to evaluate the 
efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately 
controlled asthma. BMJ Open. 2016;6(1):e007709. doi:10.1136/bmjopen-2015-007709. 
Nobs SP, Kayhan M, Kopf M. GM-CSF intrinsically controls eosinophil accumulation in the 
setting of allergic airway inflammation. J Allergy Clin Immunol. 2019;143(4):1513-1524.e2. 
doi:10.1016/j.jaci.2018.08.044. 
Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 7th Edition). China 
Law Translate. https://www.chinalawtranslate.com/en/coronavirus-treatment-plan-7/. Published 
March 10, 2020. Accessed March 15, 2020. 
Pipeline: Humanigen. Humanigen, Inc. https://www.humanigen.com/pipeline. Accessed March 
14, 2020. 
Piper C, Pesenacker AM, Bending D, et al. T Cell Expression of Granulocyte–Macrophage 
Colony-Stimulating Factor in Juvenile Arthritis Is Contingent Upon Th17 Plasticity. Arthritis 
Rheumatol. 2014;66(7):1955-1960. doi:10.1002/art.38647. 
Nadicksbernd J. CD11b expression on granulocytes after induction by granulocyte-macrophase 
colony stimulating factor in EDT whole blood by flow cytometry. PPD Primary Validation 
Summary. 2013. 
Puljic R, Benediktus E, Plater-Zyberk C, et al. Lipopolysaccharide-induced lung inflammation is 
inhibited by neutralization of GM-CSF. Eur J Pharmacol. 2007;557(2-3):230-235. 
doi:10.1016/j.ejphar.2006.11.023. 

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Sakagami T, Suzuki T, Carey B, Chalk C, Trapnell B. A Novel Assay To Measure GM-CSF 
Signaling In Clinical Blood Specimens. Am J Respir Crit Care Med. 2010; 181:A2987. 
Sheih A, Parks WC, Ziegler SF. GM-CSF produced by the airway epithelium is required for 
sensitization to cockroach allergen. Mucosal Immunol. 2017;10(3):705-715. 
doi:10.1038/mi.2016.90. 
Shiomi A, Usui T, Ishikawa Y, et al. GM-CSF but Not IL-17 Is Critical for the Development of 
Severe Interstitial Lung Disease in SKG Mice. J Immunol. 2014;193(2):849-859. 
doi:10.4049/jimmunol.1303255. 
Sterner RM, Sakemura R, Cox MF, et al. GM-CSF inhibition reduces cytokine release syndrome 
and neuroinflammation but enhances CAR-T cell function in xenografts. Blood. 
2019;133(7):697-709. doi:10.1182/blood-2018-10-881722. 
Stienne C, Michieletto MF, Benamar M, et al. Foxo3 Transcription Factor Drives Pathogenic T 
Helper 1 Differentiation by Inducing the Expression of Eomes. Immunity. 2016;45(4):774-787. 
doi:10.1016/j.immuni.2016.09.010. 
The COVID-19 Investigation Team. First 12 patients with coronavirus disease 2019 (COVID- 
19) in the United States. Pre-Print. 2020. https://doi.org/10.1101/2020.03.09.20032896. 
Tugues S, Anorim A, Spath S, et al. Graft-versus-host disease, but not graft-versus-leukemia 
immunity, is mediated by GM-CSF-licensed myeloid cells. Sci Transl Med. 2018;10(469). 
doi:10.1126/scitranslmed.aat8410. 
Willart MAM, Deswarte K, Pouliot P, et al. Interleukin-1α controls allergic sensitization to 
inhaled house dust mite via the epithelial release of GM-CSF and IL-33. J Exp Med. 
2012;209(8):1505-17. doi:10.1084/jem.20112691. 
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 
2019 (COVID-19) Outbreak in China. JAMA. 2020. doi:10.1001/jama.2020.2648. 
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with 
COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020; 395 (10229): 1054- 
1062. https://doi.org/10.1016/S0140-6736(20)30566-3. 
Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory 
CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. 
Pre-Print. 2020. https://doi.org/10.1101/2020.02.12.945576. 

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14. 
APPENDICES 
 
14.1. 
Appendix 1: Abbreviations and Trademarks 
 
Antibody 
Ab 
ADA(s) 
Anti-drug antibodies 
AE(s) 
Adverse event(s) 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
ARDS 
Acute Respiratory Distress Syndrome 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
BC 
Birth control 
CI 
Confidence interval 
CKD 
Chronic kidney disease 
Cmax 
Maximum concentration 
CMO 
Cochran-Mantel-Haenszel 
CO2 
Carbon dioxide 
COPD 
Chronic obstructive pulmonary disease 
COVID-19 
Coronavirus Disease 2019 
CPAP 
Continuous positive airway pressure 
CPK 
Serum creatine phosphokinase 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CRS 
Cytokine release syndrome 
CT 
Computerized tomography 
DMC 
Data Monitoring Committee 
DMP 
Data Management Plan 
DoD 
Day-of-Discharge (from hospital) 
ECG(s) 
Electrocardiogram(s) 
ECMO 
Extracorporeal membrane oxygenation 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EoS 
End-of-Study 

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ET 
Early Termination 
FDA 
U.S. food and drug administration 
FiO2 
fraction of inspired oxygen 
FSH 
Follicle stimulating hormone 
G-CSF 
Granulocytecolony stimulating factor 
GFR 
Glomerular filtration rate 
GM-CSF 
Granulocyte macrophage-colony stimulating factor 
HBsAg 
Hepatitis B 
HCVAb 
Hepatitis C 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
ICH 
International Conference on Harmonisation 
ICU 
Intensive Care Unit 
IEC 
Independent ethics committee 
IGRA 
Interferon gamma release assay 
ILD 
Interstitial lung disease 
IPF 
Idiopathic pulmonary fibrosis 
IRB 
Institutional review board 
ITT 
Intent-to-Treat 
IUD 
Intrauterine device 
IUS 
Intrauterine system 
IV 
Intravenous(ly) 
KSG 
Kinevant Sciences GmbH 
KSI 
Kinevant Sciences, Inc. 
LDH 
Lactate dehydrogenase 
LIS 
Lung Injury Score 
LVEF 
Left ventricular ejection fraction 
mAb 
Monoclonal antibody 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical dictionary for regulatory activities 

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MMRM 
Mixed model with repeated measures 
MSDS 
Material safety data sheet 
NEWS 
National Early Warning Score 
NOEL 
No-observed-effect level 
PAH 
Pulmonary arterial hypertension 
PaO2 
Partial pressure of oxygen 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PEEP 
Positive end-expiratory pressure 
P/F 
PaO2/FiO2 ratio 
PK 
Pharmacokinetic 
PP 
Per-Protocol 
PT 
Preferred term 
RA 
Rheumatoid arthritis 
RBC 
Red blood cell 
RR 
Respiration Rate 
SAE(s) 
Serious adverse event(s) 
SAP 
Statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SD 
Standard deviation 
SOC 
System organ class 
SOFA 
Sequential Organ Failure Assessment 
SP 
Safety Population 
SP-D 
Surfactant protein D 
SpO2 
peripheral capillary oxygen saturation 
t1/2 
Elimination half-life 
TB 
Tuberculosis 
Th1 
T-helper-1 
TNF-α 
Tumor Necrosis Factor- alpha 
ULN 
Upper limit or normal 
VF 
Ventricular fibrillation 
VT 
Ventricular tachycardia 
WBC 
White blood cell count 

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WCBP 
Woman of childbearing potential 
WHO 
World Health Organization 
WHO-DDE 
World health organization drug dictionary enhanced 

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14.2. 
Appendix 2: Liver Safety Required Actions and Follow up 
Assessments 
Phase I Liver chemistry stopping criteria have been designed to assure subject safety and to 
evaluate liver event etiology (in alignment with the FDA Drug-induced Liver Injury: 
Premarketing Clinical Evaluation). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U 
CM174090.pdf 
 
Liver Safety Process 
The procedures listed below are to be followed if a subject has ALT, bilirubin and/or INR 
elevations that meet the definition of an SAE (defined in Section 10.3): 
• 
Notify the Medical Monitor within 24 hours of learning of the abnormality to confirm 
follow-up. 
• 
Complete the liver event case report forms. 
• 
Upon completion of the safety follow-up withdraw the subject from the study unless further 
safety follow-up is required. 
• 
Make every reasonable attempt to have subjects return to the clinic within 24 hours for 
repeat liver chemistries, additional testing, and close monitoring (with specialist or 
hepatology consultation recommended). 
• 
Monitor subjects twice weekly until liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) resolve, stabilize or return to within Baseline values. 
• Obtain viral hepatitis serology including: 
• 
Hepatitis A IgM antibody. 
• 
Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM). 
• 
Hepatitis C ribonucleic acid (RNA). 
• 
Cytomegalovirus IgM antibody. 
• 
Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile 
antibody or monospot testing). 
• 
Hepatitis E IgM antibody. 
• Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH). 
• Assess eosinophilia 
• Record the appearance or worsening of clinical symptoms of hepatitis (fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash or eosinophilia) on the AE 
CRF. 
• Record use of concomitant medications, acetaminophen, herbal remedies, other over the 
counter medications, or putative hepatotoxins on the Concomitant Medications CRF. 

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• Record alcohol use on the Liver Events CRF. 
• Anti-nuclear antibody, anti-smooth muscle antibody, Type 1 anti-liver kidney microsomal 
antibodies and quantitative total immunoglobulin G (IgG or gamma globulins). 
• Serum acetaminophen adduct HPLC assay (quantifies potential acetaminophen contribution 
to liver injury in subjects with definite or likely acetaminophen use in the preceding week 
[James, 2009]. 
The Liver Imaging and/or Liver Biopsy CRFs are also to be completed if these tests are 
performed. 
 
References 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. 
Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen Overdose and 
Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784. 

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14.3. 
Appendix 3: Summary of Changes for Protocol Amendments 
The original Protocol (Version 1.0) was approved on 22-March-2020, and has been amended 
4 times; Protocol Amendment 1 (Version 2.0) was approved on 05-April-2020, Protocol 
Amendment 2 (Version 3.0) was approved on 06-May-2020, Protocol Amendment 3 
(Version 4.0) was approved on 12-June-2020, and Protocol Amendment 4 (Version 5.0) was 
approved on 17-August-2020. 
Summaries of changes are presented in Table 14-1 for Amendment 1, Table 14-2 for 
Amendment 2, Table 14-3 for Amendment 3, and Table 14-4 for Amendment 4. 
 
Table 14-1: Summary of Changes: Amendment 1 
 
Section(s) Changed 
Description of Changes 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Justification of Changes 
The protocol was amended, prior to implementation, based on feedback 
from the FDA. These changes are summarized below. 
Global change: Version and date 
were updated throughout the entire 
protocol. 
Version 1: 22-March-2020 
Version 2: 05-April-2020 
Contact information for serious 
adverse events was added to the 
administrative information at the 
beginning of the document. 
Monitors listed above (may be contacted during daytime or after-hours). 
On discovery, all SAEs should be immediately reported (latest within 24 
hours of knowledge of the event) to 
Synopsis and Section 3 
Study objectives were revised to identify key secondary objectives and 
clarify secondary and exploratory objectives. 
Primary Objective: 
• 
The primary objective is to evaluate the impact on mortality of 
the intravenous (IV) treatment ofwith gimsilumab on mortality in 
subjects with lung injury or ARDS secondary to COVID-19. 
Key Secondary Objectives: 
• To assess the effect of gimsilumab on ventilation requirements 
• To assess the effect of gimsilumab on the need for Intensive Care 
Unit (ICU) level of care 
• To assess the effect of gimsilumab on overall duration of 
hospitalization 
Additional Secondary efficacy Objectives: 
o Time to an improvement of 1 category from admission on the 
7-point ordinal scale; 
o Subject clinical status on the 7-point ordinal scale; 

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Table 14-1: Summary of Changes: Amendment 1 
 
Section(s) Changed 
Description of Changes 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
o Mean change from Baseline in ranking on the 7-point ordinal 
scale; 
• Time to hospital discharge (DoD) or to a To assess the effect of 
gimsilumab as measured by the National Early Warning Score 
(NEWS)of ≤4 and maintained for 24 hours, whichever occurs first; 
o Change from Baseline in NEWS (only if hospitalized). 
• To assess the effect of gimsilumab as assessed by the Sequential 
Organ Failure Assessment (SOFA) score 
• To assess the effect of gimsilumab as measured by the 7-point 
ordinal scale 
• To assess the effect of gimsilumab on peripheral capillary oxygen 
saturation / fraction of inspired oxygen (SpO2/FiO2) 
• To assess the effect of gimsilumab on oxygenation requirements 
• To assess changes in on-treatment viral load over time 
• To assess the effect of gimsilumab on biomarkers of inflammation 
• To determine the pharmacokinetic (PK) properties of gimsilumab 
• To assess the immunogenicity of gimsilumab 
• To determine the safety and tolerability of IV gimsilumab 
• To assess immunogenicity in subjects receiving IV gimsilumab. 
• To assess the effects of IV gimsilumab on renal function over time. 
• To assess the pharmacodynamic (PD) effects of IV gimsilumab on 
the following: 
o Duration of need of supplemental oxygenation; 
o Need for mechanical ventilatory support; 
Duration of hospitalization. 
Exploratory Objectives: 
• To explore the laboratory parameterseffect of sepsis during therapy 
including sequential organ failure assessment (SOFA) score ≥2 for 
any organ parameter, white blood cell count (WBC) >12,000 or 
<4,000 per mm3, heart rate (HR) >100 beats/minute, respiration rate 
(RR) >20 breaths/minute. 
• Serum anti GM-CSF autoantibodies, C-reactive protein,gimsilumab 
on serum cytokine concentrations,including GM-CSF, and surfactant 
protein D (SP-D). 
• PercentTo explore the effect of subjects with SARS-CoV-2 detectable 
in oropharyngeal (OP) sample at Days 8, 15, and 29 (if hospitalized), 
and at DoD. 
• To assess the effects of IV gimsilumab on cardiac function over time. 
• Incidence of gimsilumab on other measurements of lung injury that 
may be performed during standard care (e.g., Lung Injury Score 
[LIS], chest radiography, PaO2/FiO2 [P/F ratio], need for 
extracorporeal membrane oxygenation ([ECMO) procedures (if 
applicable).]) 

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• To explore the pharmacokineticseffect of gimsilumab on cardiac 
function (if measured) 
To assess the effect of IVgimsilumab on renal function 
Synopsis and Section 4.3 
Study duration was revised to allow for a longer follow-up period. 
This study will consist of a 2-week Treatment Period (last dose Day 8, if 
administered) and a 422-week Follow-up Period, for a total study duration 
of 624 weeks for each subject. 
Synopsis, Section 3, and Section 
9.3.1 
Endpoints were revised to correspond with the revised objectives. 
Primary Endpoint: 
• Incidence of mortality by Day 43 (End-of-Study [EoS]) 
Key Secondary Endpoints: 
• Incidence and duration of mechanical ventilation use during the study 
• Number of days in the ICU 
• Number of days of inpatient hospitalization 
Additional Secondary Endpoints: 
• Incidence of mortality by Day 15, Day 29, Day 85, and Day29 169 
(End-of-Study [EoS]) 
• NEWS assessed daily while hospitalized 
• SOFA score assessed daily while in the ICU 
• The percentage of subjects reporting each severity rating on the 
7-point ordinal scale (time frame: study duration). The ordinal scale is 
an assessment of the clinical status at the first assessment of a given 
study day. The scale is as follows:, assessed daily while hospitalized 
and, if discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 
169 (assessed by phone) 
1. Not hospitalized, no limitations on activities; 
2. Not hospitalized, limitation on activities; 
3. Hospitalized, not requiring supplemental oxygen; 
4. Hospitalized, requiring supplemental oxygen; 
5. Hospitalized, on non-invasive ventilation or high-flow oxygen 
devices; 
6. Hospitalized, on invasive mechanical ventilation or ECMO; 
7. Death. 
• Status on the 7-point ordinal scale, assessed daily while hospitalized 
and, if discharged from hospital, on the day of discharge (DoD), and 
on Days 15, 22, 29, 36, 43, 85, and 43 (169 (assessed by phoneif 

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discharged from the hospital).)NEWS assessed daily while 
hospitalized 
• SafetyChange from Baseline in SpO2/FiO2, assessed daily while 
hospitalized 
• Incidence and tolerability, including assessmentduration of 
changesoxygen use during the study 
• Change from Baseline in viral load (as measured by quantitative 
polymerase chain reaction [(PCR]) test), physical examinations, vital 
signs, electrocardiograms (ECGs), clinical safety laboratory 
measurements, local injection site tolerability; concomitant 
medications; cumulative incidence of adverse events (AE)s, serious 
adverse events (SAEs),on Days 2, 9, and severe AEs.day-of- 
discharge (DoD) 
• Change from Baseline in D-dimer, cardiac troponin I, lactate 
dehydrogenase (LDH), ferritin, and C-reactive protein (CRP) 
• Serum gimsilumab concentrations 
• Analysis of anti-gimsilumab antibodies (ADAs) 
• Assessment of change from Baseline to Day 15 (if hospitalized) and 
at DoD in the following parameters: 
o Peripheral capillary oxygen saturation/fraction of inspired oxygen 
(SpO2/FiO2) ratio by day 
o Glomerular filtration rate (GFR), calculated 
• Oxygenation-free days in the first 28 days (to Day 29). 
• Incidence and duration of new or increased oxygen use during the 
study. 
• Ventilator free days in the first 28 days (to Day 29).Incidence and 
duration of new mechanical ventilation use during the study. 
Safety Endpoints: 
• Safety and tolerability, including assessment of clinical safety 
laboratory measurements, physical examinations, vital signs, 
electrocardiograms (ECGs), local injection site tolerability, 
concomitant medications; cumulative incidence of adverse events 
(AEs), serious adverse events (SAEs), and severe AEs 
Exploratory Endpoints: 
• ChangesChange from Baseline in the following biomarkers:cytokine 
panel and serum SP-D, and C-reactive protein (CRP). 
• Serum anti GM-CSF autoantibodiesChange from Baseline in Lung 
Injury Score (LIS) (if performed). 
• Change from Baseline in chest radiographic assessment (if 
performed). 

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• Change from Baseline in P/F ratio, if performed 
• Incidence and duration of ECMO use 
• Serum gimsilumab concentrations. 
• If bronchoalveolar lavage (BAL) is performed as standard of care: 
Change in BAL biomarkers of fibroproliferation (procollagen and 
cytokine panel) and cell count differential (BAL sample will be 
collected and stored for possible future analysis).Change from 
Baseline in left ventricular ejection fraction (LVEF) (when measured). 
• Change from Baseline partial pressure of oxygen (PaO2)/FiO2 
(P/F ratio), if performed 
• Number and percentage of subjects on ECMO. 
• Number of days on ECMO. 
• Number and percentage of subjects successfully removed from 
ECMO.Change from Baseline in estimated glomerular filtration rate 
(eGFR) [Modification of Diet in Renal Disease (MDRD) equation], 
assessed when central clinical safety laboratory measurements are 
collected during hospitalization 
Synopsis and Section 5.2 
Inclusion criteria were revised to reflect feedback from the FDA, including 
a longer Follow-up Period. 
An individual will be eligible for participation in this study only if all 
of the following inclusion criteria are met: 
1. Male or non-pregnant female age 18 to 79 years, inclusive 
2. Subject (or legally authorized representative) is able and willing to 
provide written informed consent, which includes compliance with study 
requirements and restrictions listed in the consent form. 
3. Has laboratory-confirmed SARS-CoV-2 infection as determined by 
PCR or other approved clinical testing <72 hours prior to randomization 
4. SubjectCRP ≥50 mg/L or serum ferritin ≥1,000 ng/mL 
5. Radiographic evidence of bilateral infiltrates 
6. Subject has clinical evidence of lung injury [defined as (1) requiring 
supplemental oxygen >4L O2 to maintain >92% SpO2, or (2) P/F ratio 
≤300 mmHg (can be imputed)], or meets clinical classification criteria for 
ARDS [ARDS Berlin Definition, 2012] or has clinical evidence of lung 
injury,], secondary to COVID-19. 
• 
Lung injury is defined as PaO2/FiO2 ≤300 mmHg, without 
invasive or non-invasive ventilation (or with positive end- 
expiratory pressure [PEEP] or continuous positive airway 
pressure [CPAP] <5 cm H2O). 
• 
ARDS is defined as: 

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o 
Bilateral opacities — not fully explained by effusions, 
lobar/lung collapse, or nodules; 
o 
Respiratory failure not fully explained by cardiac 
failure or fluid overload; 
o 
Need objective assessment (e.g., echocardiography) 
to exclude hydrostatic edema if no risk factor 
present. 
o 
Mild: 200 mm Hg, < PaO2/FiO2, ≤300 mm Hg with 
PEEP or CPAP ≥5 cm H2O. 
o 
Moderate: 100 mm Hg, < PaO2/FiO2, ≤200 mm Hg 
with PEEP ≥5 cm H2O. 
7. Severe: PaO2/FiO2 ≤100 mm Hg with PEEP ≥5 cm H2O.Female 
subjects must agree to use an approved highly effective birth control (BC) 
method (<1% failure rate per year) throughout the study (until completion 
of their EoSthe Day 85 Follow-up Visit), unless documented to have a 
reproductive status of non-childbearing potential or is postmenopausal: 
• 
Non-childbearing potential defined as pre-menopausal female 
with medical history of bilateral tubal ligation, bilateral 
oophorectomy (removal of the ovaries), or hysterectomy; 
hysteroscopic sterilization, 
• 
Postmenopausal defined as 12 months of spontaneous 
amenorrhea; with follicle stimulating hormone (FSH) 
confirmation. 
• 
Woman of childbearing potential (WCBP) who is already using 
an established method of highly effective contraception or 
agrees to use one of the allowed BC methods, for at least 28 
days prior to the start of dosing (as determined by the 
Investigator Brochure or Investigator or designee) to sufficiently 
minimize the risk of pregnancy throughout study participation 
(until completion of their EoSthe Day 85 Follow-up Visit). 
8. Males who are sexually active must agree to use one of the allowed 
BC methods. Male subjects must also agree to sufficiently minimize the 
risk of pregnancy throughout study participation (until completion of their 
EoSthe Day 85 Follow-up Visit). 
Synopsis and Section 5.3 
Exclusion criteria were revised to reflect feedback from the FDA. 
1. Clinical evidence of pneumonia due to bacterial infection or viral (not 
SARS-CoV-2) infection.Clinical Subject requires norepinephrine at a dose 
of >0.5 mcg/kg/min, or equivalent 
2. Subject has been intubated for >72 hours 
3. Evidence of multi-organlife-threatening dysrhythmia (e.g., ventricular 
tachycardia [VT], ventricular fibrillation [VF]), or cardiac arrest on 
presentation 

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4. Evidence of new or preexisting decompensated heart failure. 
5. At the time of screening, subject is anticipated to require ECMO 
6. Absolute neutrophil count <2000 mm3 
7. Platelet count <50,000 mm3 
8. History of known anti-GM-CSF antibodiesautoantibodies (autoAb) or 
pulmonary alveolar proteinosis. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive 
pulmonary disease [COPD], pulmonary arterial hypertension [PAH], 
idiopathic pulmonary fibrosis [IPF], interstitial lung disease [ILD]) requiring 
long-termbaseline oxygen therapy or mechanical ventilation. 
pre-hospitalization 
10. Positive QuantiFERON® test at Screening. 
10. Positive serology forSuspected or confirmed untreated, active 
hepatitis B (HBsAG), hepatitis C (HCVAb), or tuberculosis (TB), human 
immunodeficiency virus (HIV) at Screening), hepatitis B or C infection 
11. Subject meets inclusion criteria but is not expected to be able to be 
managed by the institution personnel with invasive or non-invasive 
ventilatory support.Alanine aminotransferase (ALT) /or Aspartate 
aminotransferase (AST) >5 × upper limit of normal (ULN) 
12. Stage 4 severe chronic kidney disease (CKD, eGFR 
<30 mL/min/1.73m2 (MDRD equation) or requiring hemofiltration or 
dialysis. 
13. Use within the past 60 days, or planned use,Use of any 
investigational drug or any immunomodulatory biologic (e.g., anti-IL-1, 
anti-IL-6R, anti-TNF) within the past 60 days, or planned use of any of 
these agents during the study 
14. Chronic (≥4 weeks) use of corticosteroids >10 mg/day of prednisone 
or equivalent 
15. Pregnancy and/or breast feeding 
16. Anticipated transfer to another hospital which is not a study site 
within 72 hours.Unable to receive invasive or non-invasive ventilatory 
support 
17. Moribund condition as determined byin the opinion of the clinical 
team investigator. 
18. Allergy to any study medication. 
Synopsis and Section 8, Section 
9.5.4, and Section 9.5.8 
Database lock information was update throughout the document to reflect 
longer study duration and database lock timeframes. 
The study database will be locked when all subjects complete the Day 43 
(EoS) Visit, discontinue from the study early, or meet the primary mortality 

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endpoint. The second lock will occur when the last subject completes the 
Day 169 EoS visit. 
In addition, there will be 12 database extractextracts (soft locklocks) for 
interim analysis, analyses, the first of which is towill be performed when 
~40% of plannedconducted when 60 subjects have been treated and 
have completed 7 days of follow-up; the DMC will review the data for 
safety and futility and provide their recommendations. The second interim 
analysis will be conducted when 50% of total subjects are discharged 
from the hospital, complete the Day 43 (EoS) Visit, discontinue the study 
early, or meet the primaryendpoint of mortality endpoint.(by Day 43). 
Synopsis and throughout 
Statistical analysis information regarding analysis sets (Section 9.4), 
adjustments for multiple comparisons (Section 9.5.4), and timing of the 
analyses (Section 9.5.8) was updated to reflect the longer study duration 
and additional interim database lock. 
Key Analysis Sets 
• The Intent-to-Treat (ITT) Population will include all randomized 
subjects who receive any amount of study drug, have a Baseline 
assessment of efficacy endpoint, and at least 1 post-treatment 
assessment of efficacy endpoint. The ITT subjects will be analyzed 
according to randomized treatment, irrespective of whether or not 
they have prematurely discontinued. Subjects who withdraw from 
treatment and/or the study early will be followed for Day 43 all-cause 
mortality. All efficacy analyses will be performed using the ITT 
Population. 
• The Safety Population (SP) will include all randomized subjects who 
receive any amount of study drug. The SP will be analyzed 
according to the treatment received. This set will be used for the 
safety analyses. 
• The Per-Protocol (PP) Population will include all subjects in the ITT 
Population who complete the Day 43 Visit with no major protocol 
violations. The PP Population will be used for supportive analyses of 
the efficacy measurements. 
Adjustment of Multiple Comparisons: There is no need to adjust the 
significance level 0.05 (two-sided) in the analysis since there is only one 
1 primary endpoint and one1 gimsilumab dose level versus placebo. 
However, The interim analysis will be conducted when ~40% of 
planned60 subjects are discharged from the hospital, complete the Day 
43 (EoS) Visit, discontinue the study early, or meet the primary mortality 
endpoint. Therehave been treated and have completed 7 days of follow- 
up; the DMC will bereview the split of alpha 0.05 to be 0.001data for the 

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interim analysis and 0.049 for the final analysis of the primary 
endpointsafety and futility and provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 Visit, discontinue 
the study early, or meet the endpoint of mortality (by Day 43). 
There will be the split of alpha 0.05 to be 0.001 for the 2nd interim analysis 
and 0.049 for the final analysis of the primary endpoint, as the 2nd interim 
analysis may claim for the superior efficacy for the stop of the study early. 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Timing of Analyses 
The final first unblinded analyses will be conducted when the last subject 
completes the Day 43 (EoS) Visit, discontinues from the study early, or 
meets the primary mortality endpoint (by Day 43). The second unblinded 
analyses will be conducted when the last subject completes the Day 169 
Follow-up Visit (EoS). 
The first interim analysis can be conducted when ~40%will be when 60 
subjects have been treated and have completed 7 days of plannedfollow- 
up; the DMC will review the data for safety and futility and provide their 
recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43(EoS) Visit, 
discontinue the study early, or meet the primaryendpoint of mortality 
endpoint. The Data Monitoring Committee (DMC)(by Day 43). The 
objectives of the second interim analysis will include the claim of superior 
efficacy or futility to stop the study, the reassessment of sample size, 
and/or modifications of the populations. 
The DMC will be responsible for this closely reviewing the safety data 
from the unblinded interim analysis and for informing the sponsor about 
the results and the recommendation for the study. providing their 
recommendations. The detailed objectives and procedures of the interim 
analyses will be described in the study protocol,DMC Charter; these can 
be the claim of early stop of the study for superiority, futility, re- 
assessment of the final sample size, and/or the study population. In 
addition, the DMC will review the safety data when 10%, 25%, 50%, and 
75% of planned subjects complete the Day 43 (EoS) Visit. A SAP and 
DMC Charter will be generated with detailed information, including the 
boundaries of the superiority and futility for the interim analysis. 

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Section 4.1 Overall Study Design 
The text and study schematic were revised to reflect the longer Follow-up 
Period. 
Subjects will be assessed daily while hospitalized. Follow-up 
isassessments are planned through Week 6,24, for a total study duration 
post-randomization of approximately 43169 days.Subjects will be asked 
to participate in(24 weeks). Follow-up visits at Days 15, 22, 29, 36, 43, 85 
and 43; these follow-up visits169 will be performed by phone if the subject 
has been discharged from the hospital. 
Section 4.3 Treatment Arms and 
Duration 
The text was revised to reflect longer overall study duration. 
Each subject will participate for approximately 624 weeks, with a 2-week 
Treatment Period (last dose on Day 8) and a 422-week Follow-up Period. 
Synopsis and Section 5.6.1 
Contraception 
The text was revised to update the contraception duration requirements. 
All female and male study subjects must use a highly effective birth 
control method (<1% failure rate per year) throughoutuntil completion of 
the studyDay 85 Follow-up Visit, unless they have a reproductive status 
of, sterile, non-childbearing, or postmenopausal (confirmed by FSH). 
Males allowed to enroll in this study are responsible for minimizing the 
risk of pregnancy (until completion of studythe Day 85 Follow-up Visit). 
Section 5.7.1 Reasons for Withdrawal 
Text was added to specify that withdrawn subjects will not be replaced. 
If a subject meets a withdrawal criterion during treatment, an Early 
Termination Visit will be required. Subjects withdrawn for any reason will 
not be replaced. 
Section 5.7.2 Subject Withdrawal 
Procedures 
Text regarding subject withdrawal procedures was revised. 
Should a In cases where the subject fail to attend the cliniccannot be 
reached for a required study visitphone follow-up visits, the site should 
attempt to contact the subjectand re-schedule the missed visit as soon as 
possible. The site should also counsel the subject on the importance of 
maintaining the assigned visit schedule and ascertain whether the subject 
wishes to and/or should continue in the study based on previous non- 
compliance. In cases where the subject does not return for the 
rescheduled visit or cannot be reachedto reschedule the missed visit, the 
site should make every effort to regain contact with the subject 
(3 documented telephone calls and if necessary a certified letter to the 
subject’s last known mailing address) so that they can appropriately be 
withdrawn from the study with a primary reason of “Lost to Follow-up”. 

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Subjects who withdraw from treatment and/or the study early, for any 
reason, will be followed for Day 43 all-cause mortality, whenever possible. 
Section 5.9 Subject and Study 
Completion 
Text regarding study completion was revised to reflect the longer Follow- 
up Period. 
A completed subject is one1 who has completed the Treatment Period, 
includingand the scheduled Phone Follow-up Assessments (Period 
(through the Day 43;169 End-of-Study [EoS]).] Follow-up Visit). 
Section 6.4 Blinding 
Text regarding study blinding and treatment administration was revised 
for clarification and to add the emergency contact information. 
The study is double-blind. The study pharmacist (and/or qualified 
pharmacy staff member), study treatment administration personnel, and 
the bioanalytical laboratory analysts will be unblinded to study treatment. 
Study treatment will be administered to each subject by blinded qualified 
personnel at the study site. The presentation of the study treatment 
(solution color) will be obscured from the study subject and other study 
personnel using a colored covering or sleeve for the IV bag containing 
study treatment and opaque IV line. Further details will be provided in the 
Study Reference Manual.Once diluted in 100 mL 0.9% saline, active 
gimsilumab and placebo infusion bags are indistinguishable. 
For this study you may contact: 
Section 7 Study Assessments and 
Procedures 
The text and Table 7-1 regarding 
blood sample amount were revised to 
account for the longer study duration. 
The study assessments and procedures were revised to specify the 
follow-up for subjects who are discharged from the hospital and/or 
discontinue from the study early. 
Note: All subjects who are discharged from the hospital will undergo all 
Day-of-Discharge (DoD) Visit assessments. All subjects who discontinue 
from the study prematurely will undergo all Early Termination (ET) Visit 
assessments, whenever possible. 
It is expected that no more than 150If the subject completes all in hospital 
assessments, approximately 250 mL of blood will be collected over the 
duration of the study, including any extra assessments that may be 
required (Table 7-1). 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments (Table 7-2) was revised to include 
additional assessments, remove assessments that will not be performed, 
and to accommodate the longer study duration. 

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Table 7-2 now has been split into 2 parts, one for the Treatment Period 
and one for the Follow-up Period. 
Laboratory assessments were clarified for local vs central labs; related 
conduct that is done at the same timepoints was combined (i.e., 
demographic information, medical history, and prior medication); viral 
sample swabs were corrected from oropharyngeal samples to 
nasopharyngeal samples; SOFA score was added; laboratory 
assessments were clarified; footnotes were revised for clarification. 
Section 7.4.1.3 Sequential Organ 
Failure Assessment (SOFA) 
Section was added to include Sequential Organ Failure Assessment 
(SOFA). 
The SOFA score will be assessed daily for patients while in the ICU. 
Section 7.4.2.1 Physical 
Examinations 
Text regarding physical examinations was revised to be more conducive 
to the in-patient hospital conditions. 
An abbreviatedAbbreviated, targeted physical examination will include, at 
a minimum,examinations (i.e., assessments of the skin, respiratory, 
cardiovascular system, and abdomen ([liver and spleen]), will be 
performed at time points specified in the Schedule of Assessments (Table 
7-2) and will be based on the subject’s clinical status and what the clinic 
staff feel is appropriate. 
Height and weight will also be measured and recorded at Screening only, 
if possible. 
Section 7.4.2.2 Vital Signs 
Text regarding vital signs was revised to remove position requirements. 
Vital signs including blood pressure, heart rate, respiration rate, and 
temperature (oral, tympanic, or axillary) will be obtained at time points 
specified in the Schedule of Assessments (Table 7-2after the subject has 
rested quietly in a supine position for 10 minutes.). 
The same method for assessing temperature should be used at all visits 
for each individual subject, if possible. 
Section 7.4.2.3.1 Electrocardiograms 
Section for 12-lead electrocardiograms was removed. 
ECGs will be measured in supine position after at least 5 minutes rest. 
Standard, 12-lead electrocardiograms (ECGs) will be obtained during the 
study using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTcF intervals. 
Section 7.4.2.4 Clinical Safety 
Laboratory Assessments 
Text was added to clarify sample collection information. 
Table 7-3 was revised to include additional laboratory samples. 

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For all on-study laboratory assessments, if central laboratory 
assessments cannot be collected for any reason, best efforts will be 
made to record local laboratory data. 
NT-proBNP, ferritin, C-reactive protein, lactate dehydrogenase, and 
procalcitonin were added to Table 7-3. 
Section 7.4.2.5: SARS-CoV-2 Viral 
Assessments 
SARS-CoV-2 Viral Assessments section was added to the protocol. 
A local qualitative sample (e.g., nasopharyngeal swab) for PCR 
SARS-CoV-2 will be collected at Screening for determination of eligibility 
(if not already documented); all other on-study samples will be central 
quantitative samples. 
When at all possible, if only 1 nostril is swabbed for viral assessments, 
the same nostril should be used for all subsequent samples. 
Section 7.4.2.6 Respiratory 
Assessments 
Additional examples of ventilation type were added. 
If subject is receiving mechanical ventilation, the following parameters will 
be recorded: type of ventilation (high-flow nasal cannula, non-rebreather 
mask, CPAP, BiPAP, or intubation), FiO2, SpO2, ventilation rate, pulse, 
tidal volume, positive end-expiratory pressure (PEEP), and airway 
pressure. 
Section 7.4.2.8 Biomarker 
Assessments 
Text was revised to include “chemokine” and to remove text regarding 
bronchoalveolar lavage and CRP markers. 
The cytokine/chemokine panel may include: GM-CSF, G-CSF, IL-1β, IL-2, 
IL-6, IL-7 IL-10, IL-15, IL-17A, IL-17A/F, IL-23p19, IFN-γ, TNF-α, IP10 
(CXCL10), MCP1 (CCL2), MIP1A (CCL3), and CCL17. 
A subset of these cytokines/chemokines will be tested initially, further 
testing may be performed based on results of other study endpoints and 
emerging scientific information. 
Concentrations of biomarkers will be determined using qualified or 
validated assays. 
CRP markers are to be determined by the local laboratory (Section ). 
If a bronchoalveolar lavage (BAL) is performed as standard of care, a 
sample will be collected for potential future analysis of select cytokines 
and procollagen. The actual date and time of the sample will be recorded. 
Section 8 Data Management 
The text was revised to reflect the longer study duration and additional 
interim analysis. 
The detailed Data Management Plan (DMP) will be generated and 
approved prior to the start study database lock when all subjects 

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complete the Day 43 Visit, discontinue from the study early, or meet with 
the primary endpoint of enrolling subjects.mortality (by Day 43). 
The study database will be locked when all subjects complete the Visit of 
Day 43 (Day 43 Visit, discontinue from the study early, or meet the 
primary mortality endpoint. The second lock will occur when the last 
subject completes the Day 169 EoS), reach the primary endpoint early, or 
discontinue from the study. visit. 
In addition, there will be 12 database extractextracts (soft locklocks) for 
interim analyses, the first of which will be conducted when 60 subjects 
have been treated and have completed 7 days of follow-up; the DMC will 
review the data for safety and futility and provide their recommendations. 
The second interim analysis, which is towill be performedconducted when 
~4050% of plannedtotal subjects are discharged from the hospital, 
complete the Day 43 (EoS) Visit, discontinue the study early, or meet the 
primaryendpoint of mortality endpoint.(by Day 43). 
Section 9.1 Sample Size 
Determination 
Sample size was updated to include the definitions of lung injury and 
ARDS. 
Lung injury is defined as (1) requiring supplemental oxygen >4L O2 to 
maintain >92% SpO2, or (2) PaO2/FiO2 ≤300 mmHg (can be imputed). 
ARDS [ARDS Berlin Definition, 2012] is defined as: 
• 
Bilateral opacities — not fully explained by effusions, lobar/lung 
collapse, or nodules; 
• 
Respiratory failure not fully explained by cardiac failure or fluid 
overload; 
• 
Need objective assessment (e.g., echocardiography) to exclude 
hydrostatic edema if no risk factor present. 
• 
ARDS severity categories are defined as: 
o Mild: 200 mmHg, < PaO2/FiO2, ≤300 mmHg with PEEP or 
CPAP ≥5 cm H2O. 
o Moderate: 100 mmHg, < PaO2/FiO2, ≤200 mmHg with 
PEEP ≥5 cm H2O. 
o Severe: PaO2/FiO2 ≤100 mmHg with PEEP ≥5 cm H2O. 
Section 9.3.2 Safety Endpoints 
Text regarding safety endpoints was revised to remove viral load, ECGs, 
and local injection site tolerability. 
Safety and tolerability, including assessment of changes from Baseline in 
viral load (PCR test),clinical safety laboratory measurements, physical 
examinations, vital signs,ECGs, clinical safety laboratory measurements, 
local injection site tolerability; concomitant medications; cumulative 
incidence of AEs, SAEs, and severe AEs. 

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Section(s) Changed 
Description of Changes 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Section 9.3.3Pharmacokinetic 
Endpoints 
Text was revised to remove specific timepoints and refer to the Schedule 
of Assessments. 
Serum gimsilumab concentration at time points as specified in the 
Schedule of Assessments (Table 7-2). pre-dose on Day 1 and Day 8. 
Section 9.3.4 Biomarker Endpoints 
“Pharmacodynamic” was replaced with “Biomarker” and serum CRP was 
removed. 
Pharmacodynamic Biomarker Endpoints 
ChangesChange from Baseline in serum CRP,the cytokine, panel and 
serum SP-D concentrations will be measured at time points as specified 
in the Schedule of Assessments (Table 7-2). 
Section 9.5.3 Analysis of the 
Secondary Endpoints 
Section was revised to update the information regarding the continuous 
variables. 
The continuous variables, including the changes from baseline, will be 
summarized by the treatment with the meansmean, standard deviations, 
mediansdeviation (SD), median, and the rangesrange. PK summaries will 
include geometric mean and geometric coefficient of variation. 
Section 9.5.4 Adjustment of Multiple 
Comparisons 
Section was revised to reflect the increased study duration, additional 
interim database lock, and methods for the key secondary endpoints. 
There is no need to adjust the significance level 0.05 (two2-sided) in the 
analysis since there is only one 1 primary endpoint and one 1 gimsilumab 
dose level versus placebo. However, The interim analysis will be 
conducted when ~40%60 subjects have been treated and have 
completed 7 days of plannedfollow-up; the DMC will review the data for 
safety and futility and provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 (EoS) Visit, 
discontinue the study early, or meet the primaryendpoint of mortality 
endpoint.(by Day 43). 
There will be the split of alpha 0.05 to be 0.001 for the 2nd interim analysis 
and 0.049 for the final analysis of the primary endpoint, as the 2nd interim 
analysis may claim for the superior efficacy for the stop of the study early. 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Section 9.5.8 Timing of Analyses 
Text regarding timing of analyses was revised to reflect the longer study 
duration and the additional interim analysis. 
The final analysesfirst unblinded analysis will be conducted when the last 
subject completes the study at Day 43 (EoS) Visit, meetdiscontinues the 

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study early, or meets the primary endpoint early, or early discontinued 
from the study. of mortality (by Day 43). The final analysis will be 
conducted when the last subject completes the Day 169 (EoS) Visit. 
The first interim analysis can be conducted when ~40% of plannedwill be 
conducted when 60 subjects have been treated and have completed 
7 days of follow-up; the DMC will review the data for safety and futility and 
provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 (EoS) Visit, 
discontinue the study early, or meet the primary mortality endpoint. of 
mortality (by Day 43). The objectives of the second interim analysis will 
include the claim of superior efficacy or futility to stop the study, the 
reassessment of sample size, and/or modifications of the populations. 
The DMC will be responsible for this unblinded analysis and inform the 
sponsor about the results and the recommendation of conducting the 
study, which can be the early stop of the study for the superiority, futility, 
the re-assessment of the sample size, and/or closely reviewing the 
modification of the study population.safety data from the unblinded interim 
analysis and for providing their recommendations. The detailed objectives 
and procedures, including close monitoring of the safety data and the 
boundaries of the interim analysessuperiority or futility will be described in 
the SAP and the DMC Charter.In addition, the DMC will review the safety 
data when 10%, 25%, 50%, and 75% of planned subjects complete the 
Day 43 (EoS) Visit. A DMC Charter will be generated with detailed 
information 
Section 9.5.9 Pharmacokinetic, 
Biomarker, and Immunogenicity 
Analyses 
“Pharmacokinetic, Biomarker, and Immunogenicity Analyses” section was 
added. 
Serum gimsilumab concentrations will be summarized using descriptive 
statistics. 
Biomarker analyses will be based on the Safety Population and biomarker 
(SP-D, cytokine/chemokine, anti-GM-CSF autoAb) concentrations will be 
summarized by treatment using descriptive statistics. 
Immunogenicity analysis will be based on the Safety Population and anti- 
drug antibody data will be reported in the format provided by the 
bioanalytical laboratory. 
Further details will be provided in the SAP. 
Section 10.1 Special Consideration 
for Assessment of Adverse Events 
“Special Consideration for Assessment of Adverse Events” section was 
added. 

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as underlined. 
It is recognized that the patient population in the ICU will experience a 
number of common aberrations in laboratory values, signs and symptoms 
due to the severity of their underlying disease and the impact of standard 
therapies. These will not necessarily constitute an AE unless they require 
significant intervention, lead to discontinuation of blinded study drug, or 
are considered to be of concern in the investigator’s clinical judgement. 
Death should not be recorded as an event but should be recorded as the 
outcome of ONE event, i.e. one event should be determined to be the 
primary cause of death. The 'clinical' AE that resulted in death is the 
adverse event and the death information supports the clinical AE. 'Death' 
is not entered as an adverse event unless the cause of death is unknown. 
In such case the AE term is 'Unspecified fatal event' until the cause of the 
death is known. 
Section 10.2 Definition of Adverse 
Events 
Text regarding infections was added for clarification. 
New infections occurring on-study, regardless of infection type (i.e., viral, 
bacterial, fungal, etc.) will be reported as AEs. 
Section 10.9 Regulatory Reporting 
Requirements for SAEs 
Text was added regarding SAE reporting. 
On discovery, all SAEs should be immediately reported (latest within 24 
hours of knowledge of the event) to 
See Section 6.4 for emergency unblinding service contact information. 
Section 11 Pregnancy Reporting 
The text was revised to clarify the follow-up period for pregnancy 
reporting. 
Any pregnancy reported between the time of informed consent and 
completion of the End-of-Study Day 85 Follow-up Visit or an Early 
Termination Visit must be reported to the Sponsor within 2 weeks of 
learning of the pregnancy. 
Section 12.1.7 Drug Accountability 
Text regarding disposal of study drug was revised. 
At the end of the study, following final drug inventory reconciliation by the 
monitor, the study site will dispose of and/or destroy ship all unused 
investigational medicinal product supplies, including empty containers to 
the designated depot, according to these procedures. 
Section 13 References 
References were added. 

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as underlined. 
Nadicksbernd J. CD11b expression on granulocytes after induction by 
granulocyte-macrophase colony stimulating factor in EDT whole blood by 
flow cytometry.  PPD Primary Validation Summary. 2013. 
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of 
adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort 
study. The Lancet. 2020; 395 (10229): 1054-1062. 
https://doi.org/10.1016/S0140-6736(20)30566-3. 
Section 14.1: Abbreviations were added to the list of abbreviations, and unused abbreviations were removed from 
the list of abbreviations. 

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Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Global change: Synopsis and 
throughout 
Version and date were updated throughout the entire protocol. 
Version 2: 05-April-2020 
Version 3: 06-May-2020 
Global change: Synopsis and 
throughout 
Minor edits, including changing “patient(s)” to “subject(s)” where 
applicable and minor spacing and spelling corrections. 
Medical Contact/Sponsor Information 
Page 
Text referring to Medical Monitoring Plan was deleted because the 
Medical Monitoring Plan is not relevant to the protocol (only relevant to 
Sponsor and CRO). 
See the Medical Monitoring Plan for more details. 
Synopsis, Section 3 Objectives and 
Endpoints, and Section 9.3.1 Efficacy 
Endpoints 
Key secondary endpoints were revised to clarify actual intent of the study, 
as follows: 
• Incidence and duration of subjects who survived and were not on 
mechanical ventilation use on Day 15, Day 22, Day 29, and Day 43 
• Incidence of mechanical ventilation use, and ventilation-free days 
during the study 
• NumberIncidence of ICU use, and ICU-free days induring the 
ICUstudy 
• Number of days of inpatient hospitalization 
Synopsis and Section 5.2 Inclusion 
Criteria 
The following inclusion criteria were revised: 
1. Male or non-pregnant female age ≥18 to 79 years, inclusive 
Justification: to be less restrictive, as sites were having to exclude 
patients who otherwise met all entry criteria. 
3. Has documented laboratory-confirmed SARS-CoV-2 infection as 
determined by PCR or other approved clinical testing prior to 
randomization 
Justification: to clarify the requirement for documentation of disease 
status 
4. CRP ≥50 mg/L or serum ferritin ≥1,000 ng/mL. Results from CRP and 
ferritin tests performed within 8 days of randomization are acceptable for 
enrollment. 
Justification: to clarify the timing window for CRP and ferritin results used 
for entry criteria 
5. Radiographic evidence of bilateral infiltrates. Acceptable imaging tests 
(chest X-ray, CT scans) done within 3 days of Day 1 can be used for 
inclusion. 

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Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Justification: to clarify the timing window for imaging results used for entry 
criteria 
6. Subject has clinical evidence of lung injury [defined as (1) requiring 
supplemental oxygen >≥4L O2 to attempt to maintain >≥92% SpO2, or (2) 
P/F ratio ≤300 mmHg (can be imputed)], or meets clinical classification 
criteria for ARDS [ARDS Berlin Definition, 2012], secondary to COVID-19. 
Justification: to clarify the intent of the requirements. 
Synopsis and Section 5.3 Exclusion 
Criteria 
The following exclusion criteria were revised: 
6. Absolute neutrophil count <20001000 per mm3 
Justification: limit was corrected to reflect the original intent of the protocol 
7. Platelet count <50,000 per mm3 
Justification: clerical fix 
8. History of known anti-GM-CSF autoantibodies (autoAb) or pulmonary 
alveolar proteinosis. Note: A negative anti-GM-CSF autoAb test result is 
not required at screening. 
Justification: to clarify that the site does not need to wait for the result 
before enrolling the subject into the study. 
9. Severe chronic respiratory disease (e.g., known chronic obstructive 
pulmonary disease [COPD], pulmonary arterial hypertension [PAH], 
idiopathic pulmonary fibrosis [IPF], interstitial lung disease [ILD]) requiring 
baselinesupplemental oxygen therapy or mechanical ventilation 
pre-hospitalization (e.g., prior to COVID-19 diagnosis) 
Justification: “baseline” was removed to avoid confusion with Study 
baseline. 
10. SuspectedKnown or confirmed suspected active and untreated,active 
tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B or C 
infection 
• 
Results of TB, hepatitis B and C, and HIV tests are not required 
prior to enrollment if there is no suspicion of active infection, as 
per KIN-1901 Guidance on Active Infections Testing. 
Justification: to clarify that the site does not need to wait for the result 
before enrolling the subject into the study as long as there is no suspicion 
or knowledge of active infection. 
18. 13. Use ofinvestigational drug or any immunomodulatory biologic 
(e.g., anti-IL-1, anti-IL-6R, anti-TNF), cell therapies (e.g., 
mesenchymal stem cells), or small molecules (e.g., Janus kinase 
[JAK] inhibitors) within the past 607 days or within five half-lives 
(whichever is longer), or planned use of any of these agents from 

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Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Screening until Day 43 of the study, unless approved by the Medical 
Monitorduring the study. The following will be allowed: 
• 
Subjects who have been treated with convalescent plasma (CP) 
prior to enrollment are eligible if the subject continues to meet all 
inclusion criteria at screening. 
• 
The use of investigational anti-viral treatment (e.g., remdesivir) is 
allowed if the subject continues to meet all inclusion criteria at 
screening. 
Justification: to further clarify what is allowed and disallowed based on 
emerging standards of care. 
Synopsis and Section 9.5.1 Primary 
Efficacy Analyses 
The following statistical analysis information was revised to clarify which 
statistical models are being used, and to remove hierarchical testing: 
Efficacy Analyses: 
The secondary analysis of the primary endpoint will be conducted by 
using log rank test and/or the Cox Proportional model on the time to event 
of the primary endpoint. The median of the time to event from Kaplan- 
Meier curves will be presented for each treatment, and the hazard ratio of 
gimsilumab versus placebo will be presented with 95% CI, and p-value. 
Adjustment of Multiple Comparisons: 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Section 5.8 Toxicity Management 
Criteria 
Additional text was added for management of abnormalities in liver 
function tests (LFTs) to specify how the sites should address LFT 
abnormalities to maintain consistency across sites. 
Guidance on LFT abnormalities based upon results of LOCAL lab 
testing: 
1) If a subject has ALT in the normal range prior to study drug 
administration and develops significant elevation >5× ULN after 
study drug administration, in the absence of a clear alternative 
reason for the change (e.g., hypotension, vasopressor support), 
this should be considered related to study drug and reported as 
a SAE; procedures described in Appendix 2: Liver Safety 
Required Actions and Follow up Assessments should be 
followed, and the Medical Monitor should be informed. 
2) For subjects with elevated transaminase levels prior to study 
drug administration who do not meet exclusion criterion #11 
(alanine aminotransferase [ALT] or aspartate 
aminotransferase [AST] >5× upper limit of normal [ULN]), if 
after administration of study drug the LFTs continue to worsen 

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as underlined. 
and no alternate explanation for elevation is provided, the 
following will apply: 
a. If ALT >8× ULN, then this should be reported as a 
SAE; procedures described in Appendix 2: Liver 
Safety Required Actions and Follow up 
Assessments will be followed, and the Medical Monitor 
should be informed. If the Investigator is considering 
withholding the second dose of study drug, then a 
discussion with the Medical Monitor is mandatory. Note 
that subjects with ALT or AST abnormalities secondary 
to multi-organ impairment due to COVID-19 may still 
benefit from the second dose of gimsilumab. 
b. If LFTs are elevated but are not >8× ULN, then daily 
LFTs (including AST, ALT, alkaline phosphatase, and 
total bilirubin with fractionation) should be followed. 
i.  If during follow up ALT or AST increases to 
>8× ULN, then this should be reported as a 
SAE and then discussed with the Medical 
Monitor concerning the need to withhold the 
second dose. 
If a subject has AST or ALT 3 to 8× ULN in conjugation with total 
bilirubin >2× ULN or INR >1.5, then this should be reported as a SAE; 
procedures described in Appendix 2The Medical Monitor must be 
notified if a subject meets the following liver chemistry criteria: 
ALT ³5 × the ULN 
ii. : Liver Safety Required Actions and Follow 
up Assessments should be followed. 
Subjects meeting these criteria should not 
receive a second dose of study drug. 
iii. If during follow up the above stopping criteria 
are not met and the Investigator believes that 
the subject is suitable to receive a second 
dose of study drug and all eligibility criteria are 
met for the second dose, then the second 
dose (Day 8) of study drug may be 
administered. 
3) Any worsening of LFTs that is greater than would be expected 
due to COVID-19 alone that do not rise to the level of an SAE 
should be reported as an AE. 
4) A discussion with the Medical Monitor is mandatory prior to 
withholding the second dose of study drug. 

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Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Section 6.1 Study Treatment 
Unit dose strength/dosage level information was revised for placebo in 
Table 6-1 and in the text; information for placebo was not previously 
included, so it was added for completeness. 
NA / 
of sterile 0.9% sodium chloride added to 100 mL 0.9% 
salinesodium chloride. 
Section 6.6 Preparation/ Handling/ 
Storage/ Accountability 
Placebo mixing information was revised to reflect placebo preparation. 
Placebo study treatment will utilize 100 mL 0.9% saline solution with no 
admixturethe addition of 
(Day 8) sterile 0.9% saline 
solution using aseptic technique by qualified personnel per the clinical site 
standard operating procedures. 
Section 6.9 Concomitant Medications 
and Non-Drug Therapies 
Spelling correction: 
It would be expected that gimsilumab would reduce the effectiveness of 
GM-CSFs, such as Luekine® (sargranostimsargramostim), Leucomax® 
(molgramostim) and Regramostim. No other drug interactions are known 
or expected. 
Section 6.9.1 Permitted Medications 
and Non-Drug Therapies 
Text regarding permitted medications was revised to include prior or 
concomitant use of convalescent plasma and/or anti-viral therapies to 
reflect emerging standards of care. 
Treatment with convalescent plasma or investigational anti-viral therapies 
(e.g., remdesivir) will be allowed. 
Use of any concomitant medication (including investigational agents) 
should be recorded in the study source records, including the doses 
administered, dates and times of administration and the reason for 
administration. 
Section 6.9.2 Prohibited Medications 
and Non-Drug Therapies 
Section was updated to further clarify what is allowed and disallowed 
based on emerging standards of care. 
Use of any investigational drug (i.e., the subject is using the drug as part 
of a clinical trial), tocilizumab or any other immunomodulatory biologic 
(e.g., anti-IL-1, anti-IL-6R, anti-TNF), cell therapies (e.g., mesenchymal 
stem cells), or small molecules (e.g., JAK inhibitors) is prohibited during 
the study, from Screening until Day 43 of the study unless approved by 
the Medical Monitor. 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments was revised to clarify study days and 
weeks. Timepoints were clarified for the Follow-up Period. 
Clarifications were added regarding screening laboratory assessments to 
be consistent with revisions to entry criteria as follows: 

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Central sample for anti-GM-CSF autoAbd (result not required for 
determination of eligibility) 
Footnote d: Sample will be collected, but enrollment can continue without 
receiving results first. HCV testing can be RNA or Ag, only to confirm 
suspected infection. If a subject is diagnosed with latent TB (positive 
QuantiFERON Gold or purified protein derivative [PPD]), hepatitis B or C, 
or HIV during the study, the Investigator must discuss this with the 
medical monitor and a decision will then be made concerning the second 
dose of gimsilumab, if applicable. 
Note: SCREENING LABORATORY ASSESSMENTS: For all screening 
laboratory assessments, if more than one result is available during the 
screening period, the most recent value will be used as the screening 
value and for determination of eligibility. 
Section 7.4.2.8 Biomarker 
Assessments 
IL-8 was added to the list of the cytokine/chemokine panel for 
completeness. 
The cytokine/chemokine panel may include: GM-CSF, G-CSF, IL-1β, IL-2, 
IL-6, IL-7, IL-8, IL-10, IL-15, IL-17A, IL-17A/F, IL-23p19, IFN-γ, TNF-α, 
IP10 (CXCL10), MCP1 (CCL2), MIP1A (CCL3), and CCL17. 
Section 9.5.3 Analysis of the 
Secondary Endpoints 
Text regarding time to event endpoints was moved, and other revisions 
were made as follows: 
• The time-to-event endpoints will be summarized with Kaplan Meier 
curves and 95% confidence bounds by the treatment. the Cox 
Hazard Proportional model with treatment, country, and subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]) as model terms will be used. The hazard 
ratio of gimsilumab versus placebo will be presented with 95% CI and 
p-values. 
Justification: The time to event endpoints are now at the end of the 
secondary endpoints, so the statistical methods for the analysis is 
also moved to the end. 
• Change in ordinal scale at specific time points will be summarized by 
proportions (e.g., proportion who have a 1-, 2-, 3-, or 4-point 
improvement or 1-, 2-, 3-, 4-point worsening). The CMH test 
controlled by country and subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) will be used for 
treatment difference. The odds ratio of gimsilumab versus placebo, 
9095% CIs and p-values will be provided. 
Justification: 90% was in error, corrected to 95% 
• Duration of event free (e.g., duration of mechanical ventilation free 
days) will be summarized according to median days with quartiles. 

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Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
The Wilcoxon rank test will be used for the treatment difference. 
Justification: to remove the bias introduced by death 
• Incidence data (e.g., incidence of new or increased oxygen use) will 
be summarized as a percent with 95% confidence intervals. The 
CMH test controlled by country and subject’s clinical status at 
Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) will be 
used for treatment difference. The odds ratio of gimsilumab versus 
placebo, 905% CIs and p-values will be provided. 
Justification: 90% was in error, corrected to 95% 
• The time-to-event endpoints will be summarized with Kaplan Meier 
curves and 95% confidence bounds by the treatment. The log rank 
test and/or the Cox Hazard Proportional model with treatment, 
country, and subject’s clinical status at Baseline ([lung injury/mild 
ARDS] or [moderate/severe ARDS]) as model terms will be used. 
The hazard ratio of gimsilumab versus placebo will be presented with 
95% CI and p-values. 
9.5.4 Adjustment of Multiple 
Comparisons 
Text regarding hierarchical endpoint analyses was deleted as hierarchical 
testing was removed from the study. 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Section 10.1 Special Consideration 
for Assessment of Adverse Events 
Language was revised to clarify that Death should be considered both an 
SAE and an outcome. 
Death should not be recorded both as an event but should be recordeda 
SAE and as the outcome of ONE event, i.e. one event should be 
determined to be the primary cause of death. 
 
 
Table 14-3: Summary of Changes: Amendment 3 
 
Section(s) Changed 
Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Global change: Synopsis and 
throughout 
Version and date were updated throughout the entire protocol. 
Version 3: 06-May-2020 
Version 4: 12 June 2020 

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Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Global change: Synopsis and 
throughout 
Minor edits, including formatting, spelling, and grammar corrections. 
Synopsis and Section 3 Objectives 
and Endpoints 
One of the key secondary objectives was moved to additional secondary 
objectives due to changing criteria for ICU level of care during the 
evolution of the current pandemic: 
• To assess the effect of gimsilumab on the need for Intensive Care 
Unit (ICU) level of care 
Synopsis, Section 3 Objectives and 
Endpoints, and Section 9.3.1 Efficacy 
Endpoints 
Key secondary and additional secondary endpoints were revised to clarify 
actual intent of the study, as follows: 
Key secondary endpoints (only those changes are shown): 
• Incidence Proportion of subjects who survived and not on requiring 
mechanical ventilation on Day 15, Day 22, Day 29, and Day 43 
• Mechanical ventilation-free days by Day 29 
• Time to hospital discharge by Day 43 
• 
Incidence of mechanical ventilation use, and ventilation-free days during 
the study 
• 
Incidence of ICU use, and ICU-free days during the study 
• Number of days of inpatient hospitalization 
Additional secondary endpoints (only those changed are shown): 
• Incidence of mortality by Day 15 Day 29, and Day 85, and Day 169 
(End-of-Study [EoS]) 
• 
Proportion of subjects who survived and were not requiring mechanical 
ventilation on Day 15, 22, and 43 
• 
Mechanical ventilation-free days for all subjects by Day 15, 22, and 43 
• 
ICU-free days for all subjects by Day 15, 22, 29, and 43 
• 
Incidence of mechanical ventilation use for all subjects by Day 15, 22, 
29, and 43 
• 
Incidence of ICU use for all subjects by Day 15, 22, 29, and 43 
• Time to death by Day 43 and Day 169 (EoS) 
• 
SOFA score, and each of the components, assessed daily while in the 
ICU 
• 
Time to clinical improvement by 2 points on the 7-point ordinal scale 
Synopsis and Section 9.5.1 Primary 
Efficacy Analyses 
The following statistical analysis information was revised to clarify which 
statistical models are being used, and to remove hierarchical testing: 
Efficacy Analyses: 
The secondary analysis of the primary endpoint will be conducted by 
using log rank test and/or the Cox Proportional model on the time to event 
of the primary endpoint. The median of the time to event from Kaplan- 

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Meier curves will be presented for each treatment, and the hazard ratio of 
gimsilumab versus placebo will be presented with 95% CI, and p-value. 
Adjustment of Multiple Comparisons: 
The 3 key secondary endpoints will be analyzed by hierarchical testing 
procedure following the order of the list of endpoints, and each endpoint 
will be analyzed at 0.05 alpha level. 
Synopsis, Section 8 (Data 
Management), and Section 9 
(Statistical Considerations and 
Analyses section) 
Revisions were made due to FDA feedback and Sponsor decision 
regarding timing of interim analyses, and to reflect that the study is 
currently being conducted in 1 country only. 
Efficacy Analyses: 
The primary analysis of the efficacy endpoint (Mortality by Day 43) will be 
performed by using logistic regression [Ge, 2011] with treatment, site, and 
Cochran-Mantel-Haenszel (CMH) test, controlled by subject’s clinical 
status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]). 
Adjustment of Multiple Comparisons and Interim Analysis: 
The second interim analysis will be conducted when 50% of total 100 
subjects are discharged from the hospital, have completed the Day 2943 
Visit, discontinue the study early, or meet the endpoint of mortality (by 
Day 2943). The objectives of the second interim analysis will be to stop 
the study by futility, or perform the sample size re-estimation. 
There will be the split of alpha 0.05 to be 0.001 for the 2nd interim analysis 
and 0.049 for the final analysis of the primary endpoint, as the 2nd interim 
analysis may claim for the superior efficacy for the stop of the study early. 
For controlling overall two-sided alpha of 0.05 for the final analysis on the 
primary endpoint of Mortality Day 43, the weighted average of two 
summary measures by Cui L, Hung HM, Wang [Cui, 1999] will be used, 
one based on the data collected in the interim analysis, and the other 
based on the data collected after the interim. 
Analyses in General: 
All the categorical variables will be summarized by the treatment with the 
numbers and percentages of the subjects, and the treatment difference 
will be tested by using CMH test stratified by 1) countrysite and 2) 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]). 
The time to event endpoints will be analyzed by using the Cox 
Proportional Hazard model with the treatment, subject’s clinical status at 
Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]), and 
countrysite as the model term. 
Handling of Missing Data 
For the efficacy analyses, the multiple imputation method, including the 
tipping point method, will be used to handle the missing data as the 

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sensitivity analyses. No imputation will be used for any missing data in 
safety analysis. 
Separate analyses will be performed for the primary and key secondary 
endpoints by using multiple imputations for the missing data: 
• 
Tipping-point multiple imputation analysis 
Missing data will be imputed for Mortality by Day 43 with all possible 
combinations of Death or Survival in the two arms. The combination 
which alters the conclusion will be defined as the tipping point for 
evaluation on the robustness of the results. 
• 
Imputation differentiating the reasons of missing data from the 
early drop out 
The reasons of the lost to follow-up, SAEs/AEs, and the use of rescue 
medications will be identified, and the percentage of these subjects will be 
summarized by treatment. The data for informative censoring, such as the 
unfavorable or worst outcome, can be used to impute the missing data. 
More details will be pre-specified in the statistical analysis plan (SAP). 
Timing of Analyses with All Subjects: 
The first unblinded analyses will be conducted when the last subject 
completes the Day 43 Visit, discontinues from the study early, or meets 
the primary mortality endpoint (by Day 43). The second unblinded 
analyses will be conducted when the last subject completes the Day 169 
Follow-up Visit (EoS). 
In addition, there will be 2 database extracts (soft locks) for interim 
analyses, the first of which will be conducted when 60 subjects have been 
treated and have completed through Day 15; the DMC will review the 
data for safety and futility and provide their recommendations. The 
second interim analysis will be conducted when 50% of total 100 subjects 
who have completed the Day 4329 Visit, discontinue the study early, or 
have met the endpoint of mortality (by Day 4329). 
The first interim analysis will be when 60 subjects have been treated and 
have completed 7 days of follow-up; the DMC will review the data for 
safety and futility and provide their recommendations. 
The second interim analysis will be conducted when 50% of total subjects 
are discharged from the hospital, complete the Day 43 Visit, discontinue 
the study early, or meet the endpoint of mortality (by Day 43). The 
objectives of the second interim analysis will include the claim of superior 
efficacy or futility to stop the study, the reassessment of sample size, 
and/or modifications of the populations. 
The DMC will be responsible for closely reviewing the safety data from 
the unblinded interim analysis and for providing their recommendations. 
The detailed objectives and procedures of the interim analyses will be 

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described in the DMC Charter. ; these can be the claim of early stop of 
the study for superiority, futility, re-assessment of the final sample size, 
and/or the study population. A SAP and DMC Charter will be generated 
with detailed information, including the boundaries of the superiority and 
futility for the interim analysis. 
Statistical Analysis Plan (SAP): 
A detailed (revised) SAP will be signed and submitted to the agencies 
prior to the interim analysis of 100 subjects. 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments was revised to clarify the EoS/Early Term 
assessments. 
Abbreviations were revised, as needed. 
Language was added to footnote d to clarify acceptable testing for TB. 
the event the QuantiFERON Gold assay is not available, and the site 
performs a different IGRA such as T Spot, then the alternative IGRA will 
be acceptable for patient screening and enrollment. Enrollment should not 
be delayed to obtain the QuantiFERON Gold assay in lieu of the IGRA 
available at the site. If no IGRA test is available, PPD can be used. 
Section 7 Study Assessments and 
Procedures 
Language was added to clarify the follow-up conduct for the study. 
Once a subject is discharged from the hospital every effort MUST be 
made to ensure visit timepoints listed on the Schedule of Assessments 
(Table 7-2) are completed via phone or telemed. All visits are required to 
be completed for every subject unless the subject dies or withdraws 
consent. If a subject is deemed lost to follow-up every effort should be 
made to check vital status records at each visit time point to obtain 
survival status. Proper follow-up and documentation should be completed 
per GCP/ICH guidelines before deeming a subject lost to follow-up. 
Section 13 (References) 
New references were added based on text that was added to the 
protocol. 
Appendix 3: Summary of Changes for 
Protocol Amendments (Section 14.3) 
Table 14-3 was added to explain changes made in Protocol 
Amendment 3. 

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Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
Global change: Synopsis and 
throughout 
Version and date were updated throughout the entire protocol. 
Version 4: 12 June 2020 
Version 5: 17-August-2020 
Global change: Synopsis and 
throughout 
Minor edits, including formatting, spelling, and grammar corrections; 
headers updated throughout. 
Medical Contact/Sponsor Information 
Page 
Secondary Medical Monitor name and contact information was updated to 
reflect staffing change. 
Synopsis, Study Centers and 
Countries 
The synopsis was updated to reflect the addition of another country and to 
revise the planned number of sites in the US and potential number of sites in 
Mexico and to clarify that other countries may be added later. 
The number of study centers and locations where this study will be 
conducted are to be determinedThis study will be conducted at approximately 
20 centers in the United States and potentially 6 centers in Mexico; other 
countries may be added, if needed. 
Synopsis and Section 5.2 Inclusion 
Criteria 
Inclusion criterion #2 was revised to allow for verbal consent to participate 
in the study. Inclusion criterion #7 was revised to clarify that FSH only 
needs to be done to confirm postmenopausal status in women who have 
not had spontaneous amenorrhea for 12 consecutive months. 
2. Subject (or legally authorized representative [LAR]) is able and willing 
to provide written or verbal informed consent, which includes compliance 
with study requirements and restrictions listed in the consent form. NOTE: 
If a subject or LAR must be consented verbally, the site must have a site 
policy for verbal consent and the consent must be clearly documented in 
the subject’s chart. 
7. Postmenopausal defined as 12 months of spontaneous amenorrhea or 
with follicle stimulating hormone (FSH) confirmation. 
Synopsis and Section 5.3 Exclusion 
Criteria 
Exclusion criterion #2 was revised to clarify time of intubation. Exclusion 
criteria #13 and #14 were revised to match the clarification memos that 
were sent to sites prior to this amendment. 
2. Subject has been intubated for >72 hours. Note: in the event of 
extubation and re-intubation, the calculation for the number of hours the 
subject has been intubated begins at the first intubation. 
13. Use of any immunomodulatory biologic (e.g., anti-IL-1, anti-IL-6R, 
anti-TNF, inhibitors of complement signaling), cell therapies (e.g., 
mesenchymal stem cells), or small molecules (e.g., Janus kinase [JAK] 

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inhibitors) within the past 7 days or within five half-lives (whichever is 
longer), or planned use of any of these agents from Screening until 
Day 43 of the study, unless approved by the Medical Monitor. The 
following will be allowed/disallowed: 
• 
Immunomodulatory biologics for COVID-19 treatment are 
excluded and should not be used until Day 43 unless discussed 
with the Medical Monitor. Other non-biologic immunomodulators 
(non-JAK inhibitors), e.g., medicines for previous transplantation, 
or disease modifying anti-rheumatic drugs (DMARDS) and have 
had a stable dose for ≥8 weeks are permitted. 
• 
Subjects who have been treated with convalescent plasma (CP) 
prior to enrollment are eligible if the subject continues to meet all 
inclusion criteria at screening. Ongoing therapy with CP is 
allowable if clinically indicated in the view of the treating 
physician or the Investigator. 
• 
The use of investigational anti-viral treatment (e.g., remdesivir) is 
allowed if the subject continues to meet all inclusion criteria at 
screening. 
14. Ongoing cChronic (≥4 weeks) use of corticosteroids >10 mg/day of 
prednisone or equivalent at the time of randomization. A corticosteroid 
dose that has been tapered to 10 mg or less within 14 days of 
randomization is also prohibited. 
Synopsis, Section 8 (Data 
Management), and Section 9 
(Statistical Considerations and 
Analyses section) 
Revisions were made to reflect that the interim analysis was changed to 
include stop for superiority as well as mortality at day 43 and to add 
country instead of site as a stratification factor since another country was 
added. 
Database Locks: 
The second interim analysis will be conducted when 100 subjects have 
completed at least the Day 29 Visit for non-mortality endpoints, or and 
have met the data for the endpoint of mortality (by Day 2943). 
Efficacy Analyses: 
The primary analysis of the efficacy endpoint (Mortality by Day 43) will be 
performed by using logistic regression [Ge, 2011] with treatment, 
sitecountry, and subject’s clinical status at Baseline ([lung injury/mild 
ARDS] or [moderate/severe ARDS]). 
Adjustment of Multiple Comparisons and Interim Analysis: 
There is no need to adjust the significance level 0.05 (two-sided) in the 
analysis since there is only 1 primary endpoint and 1 gimsilumab dose 
level versus placebo. The interim analysis will be conducted when 60 
subjects have been treated and have completed through Day 15; the 
DMC will review the data for safety and futility and provide their 
recommendations. 

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Description of Changes and Justification 
Deleted text is indicated as strikethrough, new or moved text is indicated 
as underlined. 
The second interim analysis will be conducted when 100 subjects have 
completed at least the Day 29 Visit for non-mortality endpoints, or and 
have met the data for the endpoint of mortality (by Day 2943). The 
objectives of the second interim analysis will be to stop the study by 
superiority, futility, or perform the sample size re-estimation. 
For controlling overall two-sided alpha of 0.05 overall for the final 
analysis on the primary endpoint of Mortality Day 43, 0.001 of the alpha 
will be used for the superiority comparison during the second interim 
analysis, and 0.049 will be used for the final analysis. And tThe weighted 
average of two summary measures by Cui L, Hung HM, Wang [Cui, 1999] 
will be used, one based on the data collected in the interim analysis, and 
the other based on the data collected after the interim. 
Analyses in General: 
All of the continuous variables, including the changes from Baseline, will 
be summarized by the treatment with the means, SD, medians and the 
ranges. The Mixed Model with Repeated Measurements (MMRM) 
/Analysis of Covariance (ANCOVA) model with the treatment, sitecountry, 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]), and visit as the model term, and Baseline 
value as the covariate will be used to test for the significance of the 
treatment difference. The least square means, standard errors, 95% CIs 
and p-values will be presented. 
All the categorical variables will be summarized by the treatment with the 
numbers and percentages of the subjects, and the treatment difference 
will be tested by using CMH test stratified by 1) sitecountry and 2) 
subject’s clinical status at Baseline ([lung injury/mild ARDS] or 
[moderate/severe ARDS]). 
The time to event endpoints will be analyzed by using the Cox 
Proportional Hazard model with the treatment, sitecountry, and subject’s 
clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe 
ARDS]) as the model term. The hazard ratio of gimsilumab versus 
placebo will be presented with 95% CI and p-value from the model. The 
Kaplan-Meier curves of the time to events will be presented for treatments 
on each endpoint. 
Section 4.1 Overall Design 
Text was revised to reflect the addition of another country: 
Randomization will be stratified by sitecountry and subject’s clinical status 
at Baseline 
Sections 2.2 Dose Rationale, 6.1 
Study Treatment, and 6.2 
Administration of Study Treatments 
Table 6-1 was revised to allow a window for the timing of the infusion 
given the clinical care setting. 

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Deleted text is indicated as strikethrough, new or moved text is indicated 
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Infuse the entire contents of the IV bag via the intravenous route over a 
Flush the line with 0.9% saline to ensure the 
entire contents is administered. 
 
Section 7.1 Schedule of 
Assessments 
The Schedule of Assessments footnotes were revised to clarify the 
following: screening serology and TB test results do not need to be 
received prior to enrollment, physical examinations and vital signs 
measurements performed as standard of care may not need to be 
repeated, local laboratory values must be documented in the eCRF, and 
DoD assessments can be performed one day prior to discharge if the 
subject has been labelled as “ready for discharge.”. 
Abbreviations were revised, as needed. 
Section 7.4.2.1 Physical 
Examinations 
Language was added to clarify that physical examinations performed as 
standard of care may not need to be repeated. 
Note: If a physical examination is performed as standard of care by 
appropriate personnel the same day that consent is signed or the same 
day of any scheduled study visit, results from that examination may be 
used if personal protective equipment (PPE) is not available or if study 
site staff consider additional examinations are unwarranted due to already 
having been performed as standard of care. 
Section 7.4.2.2 Vital Signs 
Language was added to clarify that vital signs measurements performed 
as standard of care may not need to be repeated. 
Note: If vital signs measurements are performed as standard of care by 
appropriate personnel the same day that consent is signed or the same 
day of any scheduled study visit, results from that examination may be 
used if PPE is not available or if study site staff consider additional 
measurements are unwarranted due to already having been performed as 
standard of care. 
Section 7.4.2.4 Follicle Stimulating 
Hormone (FSH), Viral Serology, and 
Tuberculosis Assessments 
This section was added to allow for clarifying text to be included in the 
main body of the protocol. 
Follicle stimulating hormone (FSH) will be performed at screening, for 
women only, to confirm postmenopausal status in women who have not 
had 12 months of spontaneous amenorrhea. 
A blood sample will be collected at Screening as specified in the 
Schedule of Assessments (Table 7-2), for viral serology and TB testing, 
but enrollment can continue without receiving the results first. HCV testing 
can be RNA or Ag, only to confirm suspected infection. If a subject is 
diagnosed with latent TB (positive QuantiFERON Gold or purified protein 
derivative [PPD]), hepatitis B or C, or HIV during the study, the 

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Investigator must discuss this with the medical monitor and a decision will 
then be made concerning the second dose of gimsilumab, if applicable. In 
the event the QuantiFERON Gold assay is not available, and the site 
performs a different IGRA such as T Spot, then the alternative IGRA will 
be acceptable for patient screening and enrollment. Enrollment should not 
be delayed to obtain the QuantiFERON Gold assay in lieu of the IGRA 
available at the site. If no IGRA test is available, PPD can be used. If TB 
testing and viral serology is missed during screening it must be completed 
and results received prior to the second dose of study drug. If not 
completed or unable to obtain results further discussions with the medical 
monitor will be required. 
Section 9.2 Randomization 
Text added to reflect the addition of another country. 
The central stratified randomization will be used to assign subjects into 1 
of the 2 study treatment arms with an equal randomization ratio (1:1) with 
the stratification factors of subject’s clinical status at Baseline ([lung 
injury/mild ARDS] or [moderate/severe ARDS]) and country. 
Appendix 3: Summary of Changes for 
Protocol Amendments (Section 14.3) 
Text was revised to reflect the new Amendment. 
The original Protocol (Version 1.0) was approved on 22-March-2020, and 
has been amended 34 times; Protocol Amendment 1 (Version 2.0) was 
approved on 05-April-2020, Protocol Amendment 2 (Version 3.0) was 
approved on 06-May-2020, and Protocol Amendment 3 (Version 4.0) was 
approved on 12-June-2020, and Protocol Amendment 4 (Version 5) was 
approved on 17-August-2020. 
Summaries of changes are presented in Table 14-1 for Amendment 1, 
Table 14-2 for Amendment 2, and Table 14-3 for Amendment 3, and 
Table 14-4 for Amendment 4. 
Table 14-4 was added to explain changes made in Protocol 
Amendment 4.