A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Intravenous Infusion of CAP-1002 in Patients With COVID-19 (INSPIRE)
Phase: PHASE2
Conditions: Covid19
Sponsor: Capricor Inc.

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY 
EVALUATING THE SAFETY AND EFFICACY OF INTRAVENOUS INFUSION OF 
CAP-1002 IN PATIENTS WITH COVID-19 (INSPIRE) 
Protocol Number: 
CAP-1002-COVID-19-02 
NCT Number: 
NCT04623671 
Product Name: 
CAP-1002 Allogeneic Cardiosphere-
Derived Cells 
IND Number: 
 
Indication: 
Treatment of COVID-19 
Sponsor: 
Capricor, Inc. 
8840 Wilshire Boulevard, 2nd Floor 
Beverly Hills, CA 90211 
Sponsor Contact: 
 
VP of Clinical Development 
Capricor, Inc. 
Protocol Version: 
Amendment 2.5 
Original: 
Amendment 1: 
Amendment 2: 
Amendment 2.1: 
Amendment 2.2: 
Amendment 2.3: 
Amendment 2.4: 
Amendment 2.5: 
14 July 2020 
26 August 2020 
05 January 2021 
27 January 2021 
02 March 2021 
11 March 2021 
23 August 2021 
15 March 2022 
This document is confidential and proprietary to Capricor, Inc. and its affiliates. Acceptance of this document 
constitutes agreement by the recipient that no unpublished information contained herein will be reproduced, 
published, or otherwise disseminated or disclosed or used without the prior written approval of Capricor, Inc. and its 
affiliates, except that this document may be disclosed in any medium to appropriate clinical Investigators, 
Institutional Review Boards, and others directly involved in the clinical investigation that is the subject of this 
information under the condition that they keep the information strictly confidential. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 2 of 54 
Capricor, Inc. – Company Confidential 
INVESTIGATOR’S AGREEMENT 
Protocol Title: 
A Randomized, Double-Blind, Placebo-Controlled Study 
Evaluating the Safety and Efficacy of Intravenous Infusion of 
CAP-1002 in Patients with COVID-19 (INSPIRE) 
Short Title: 
CAP-1002 for Treatment of COVID-19  
Protocol Number: 
CAP-1002-COVID-19-2 
Amendment 2.5 Date:  
15 March 2022 
 
I have read this clinical protocol and agree to the conduct of the trial according to the investigative 
plan. I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol.  
 
 
Printed Name of Investigator 
 
 
Signature of Investigator   
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 3 of 54 
Capricor, Inc. – Company Confidential 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 4 of 54 
Capricor, Inc. – Company Confidential 
TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE .................................................................................................8 
1 
PROTOCOL SUMMARY ............................................................................................9 
1.1 
Synopsis ........................................................................................................................9 
1.2 
Schema ........................................................................................................................11 
1.3 
Schedule of Activities .................................................................................................12 
2 
INTRODUCTION ......................................................................................................15 
2.1 
Study Background and Rationale ...............................................................................15 
2.2 
Risk/Benefit Assessment ............................................................................................16 
2.2.1 
Known Potential Risks ...............................................................................................16 
2.2.2 
Known Potential Benefits ...........................................................................................16 
2.2.3 
Assessment of Potential Risks and Benefits ...............................................................17 
3 
OBJECTIVES AND ENDPOINTS ............................................................................17 
4 
STUDY DESIGN .......................................................................................................18 
4.1 
Overall Design ............................................................................................................18 
4.2 
Scientific Rationale for Study Design ........................................................................19 
4.3 
Justification for Dose ..................................................................................................19 
4.4 
End of Study Definition ..............................................................................................21 
5 
STUDY POPULATION .............................................................................................21 
5.1 
Inclusion Criteria ........................................................................................................21 
5.2 
Exclusion Criteria .......................................................................................................21 
5.3 
Lifestyle Considerations .............................................................................................22 
5.4 
Screen Failures ............................................................................................................22 
5.5 
Strategies for Recruitment and Retention ...................................................................22 
6 
STUDY INTERVENTION ........................................................................................22 
6.1 
Study Intervention(s) Administration .........................................................................22 
 
 
 
 
6.1.3 
Post-Infusion Monitoring ............................................................................................24 
6.1.4 
Safety Review .............................................................................................................25 
6.2 
Preparation/Handling/Storage/Accountability ............................................................25 
6.2.1 
Acquisition and Accountability ..................................................................................25 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 5 of 54 
Capricor, Inc. – Company Confidential 
 
 
 
 
 
 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................29 
6.3.1 
Randomization ............................................................................................................29 
6.3.2 
Blinding ......................................................................................................................29 
6.3.3 
Emergency Unblinding ...............................................................................................30 
6.4 
Study Intervention Compliance ..................................................................................30 
6.5 
Concomitant Therapy .................................................................................................30 
6.6 
Rescue Medicine .........................................................................................................30 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................31 
7.1 
Discontinuation of Study Intervention ........................................................................31 
7.1.1 
Early Stopping Rules ..................................................................................................31 
7.1.2 
Subject-Level Stopping Rules ....................................................................................31 
7.1.3 
Study-Level Stopping Rules .......................................................................................31 
7.2 
Participant Discontinuation/Withdrawal from the Study ...........................................32 
7.3 
Lost to Follow-Up .......................................................................................................32 
8 
STUDY ASSESSMENTS AND PROCEDURES ......................................................33 
8.1 
Assessments ................................................................................................................33 
8.1.1 
Ordinal Scale for Clinical Improvement .....................................................................33 
8.1.2 
Respiratory and Ventilator Status ...............................................................................34 
8.1.3 
Chest X-Ray ................................................................................................................34 
8.1.4 
SARS-CoV-2 Testing .................................................................................................34 
8.1.5 
Proteomic Assay .........................................................................................................34 
8.2 
Safety and Other Assessments ....................................................................................35 
8.2.1 
Vital Signs ..................................................................................................................35 
8.2.2 
Physical Examination .................................................................................................35 
8.2.3 
Electrocardiogram .......................................................................................................36 
8.2.4 
Clinical Laboratory Assessments ...............................................................................36 
8.2.5 
Demographics .............................................................................................................36 
8.2.6 
Medical History ..........................................................................................................36 
8.2.7 
Prior and Concomitant Therapies ...............................................................................37 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 6 of 54 
Capricor, Inc. – Company Confidential 
8.2.8 
Hospitalization ............................................................................................................37 
8.2.9 
Intensive Care Unit .....................................................................................................37 
8.3 
Adverse Events and Serious Adverse Events .............................................................37 
8.3.1 
Definition of Adverse Events .....................................................................................37 
8.3.2 
Definition of Serious Adverse Event ..........................................................................38 
8.3.3 
Classification of an Adverse Event .............................................................................38 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ...........................41 
8.3.5 
Adverse Event Reporting ............................................................................................41 
8.3.6 
Serious Adverse Event Reporting ...............................................................................41 
8.3.7 
Reporting Events to Participants ................................................................................42 
8.3.8 
Events of Special Interest ...........................................................................................42 
8.3.9 
Reporting of Pregnancy ..............................................................................................42 
9 
STATISTICAL CONSIDERATIONS .......................................................................43 
9.1 
Statistical Hypotheses .................................................................................................43 
9.2 
Sample Size Determination ........................................................................................43 
9.3 
Populations for Analyses ............................................................................................43 
9.4 
Statistical Analyses .....................................................................................................43 
9.4.1 
General Approach .......................................................................................................43 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................43 
9.4.3 
Analysis of the Secondary Endpoint(s) ......................................................................43 
9.4.4 
Safety Analyses ..........................................................................................................43 
9.4.5 
Baseline Descriptive Statistics ....................................................................................43 
9.4.6 
Planned Interim Analyses ...........................................................................................44 
9.4.7 
Sub-Group Analyses ...................................................................................................44 
9.4.8 
Tabulation of Individual Subject Data ........................................................................44 
9.4.9 
Exploratory Analyses ..................................................................................................44 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................44 
10.1 
Regulatory, Ethical, and Study Oversight Considerations .........................................44 
10.1.1 
Informed Consent Process ..........................................................................................44 
10.1.2 
Study Discontinuation and Closure ............................................................................45 
10.1.3 
Confidentiality and Privacy ........................................................................................45 
10.1.4 
Future Use of Stored Specimens and Data .................................................................45 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 7 of 54 
Capricor, Inc. – Company Confidential 
10.1.5 
Key Roles and Study Governance ..............................................................................45 
10.1.6 
Safety Oversight .........................................................................................................45 
10.1.7 
Clinical Monitoring ....................................................................................................46 
10.1.8 
Quality Assurance and Quality Control ......................................................................46 
10.1.9 
Data Handling and Record Keeping ...........................................................................47 
10.1.10 
Protocol Deviations ....................................................................................................47 
10.1.11 
Publication and Data Sharing Policy ..........................................................................47 
10.1.12 
Conflict of Interest Policy ...........................................................................................48 
10.2 
Additional Considerations ..........................................................................................48 
10.3 
Abbreviations ..............................................................................................................49 
10.4 
Protocol Amendment History .....................................................................................51 
11 
REFERENCES ...........................................................................................................53 
 
 
 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 8 of 54 
Capricor, Inc. – Company Confidential 
 
 
 
STATEMENT OF COMPLIANCE 
The protocol will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with International Council on Harmonization and Good 
Clinical Practice (ICH-GCP), and applicable regulatory requirements.  
In accordance with Food and Drug Administration (FDA) regulatory requirements, 21 CFR 54.4, 
the Investigator will be required to complete a financial disclosure form provided by Capricor prior 
to participation in the protocol. Each Investigator shall provide Capricor sufficient accurate 
financial information to allow Capricor to submit complete and accurate certification or disclosure 
statements (FDA Forms 3454 and/or 3455) as required by the FDA regulations. Investigators shall 
promptly update this information if any relevant changes occur in the course of the trial or for 1 
year following completion of the trial. 
The clinical site is required to follow their institutional guidelines for obtaining initial approval by 
the Institutional Review Board (IRB) and for submitting continuing reviews to the IRB. Subject 
enrollment at a clinical site will not commence until initial IRB approval documentation has been 
received and reviewed by Capricor. The composition and conduct of this committee must conform 
to the United States Code of Federal Regulations (CFR) and ICH E6.  
The informed consent must be reapproved in accordance with the clinical site’s IRB policies or at 
least annually.  
Capricor will provide the clinical site with serious adverse drug reactions and any other applicable 
correspondences during the trial. The clinical site is to follow their institutional policies for 
reporting these correspondences and documents to their IRB.  
All IRB approvals and all materials approved/acknowledged by the IRB for this protocol, 
including the subject consent form or safety event notifications, must be maintained by the 
Investigator, and made available for inspection. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 9 of 54 
Capricor, Inc. – Company Confidential 
1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Title: 
A Randomized, Double-Blind, Placebo-Controlled, Pilot, Phase 2 Exploratory Study 
Evaluating the Safety and Efficacy of Intravenous Infusion of CAP-1002 in Patients 
with COVID-19 (INSPIRE) 
Study Description: 
This is a randomized, double-blind, placebo-controlled, Pilot, Phase 2 Exploratory 
study that will enroll subjects with a clinical diagnosis of COVID-19 confirmed by 
laboratory testing and who are in severe or critical condition as indicated by life-
support measures.  
Objectives: 
 
The primary objectives of the study are to determine the safety and effectiveness of 
intravenously infused CAP-1002 in improving clinical outcomes in severely or 
critically ill patients with COVID-19. 
Endpoints: 
Several exploratory safety and efficacy endpoints will be measured to evaluate the 
effects of CAP-1002 treatment on the morbidity and mortality of severely or 
critically ill patients with COVID-19. The endpoints are as follows: 
• All-cause mortality. 
• Ordinal Scale of Clinical Improvement, absolute values, and changes from 
start of treatment to Days 2, 3, 7, 15, and 30. 
• Time to a 1-point decrease on the Ordinal Scale of Clinical Improvement 
from start of treatment. 
• Area under the severity versus time curve, where severity is defined by the 
Ordinal Scale of Clinical Improvement and time is measured from start of 
treatment to Days 2, 3, 7, 15, and 30. 
• Days of supplemental oxygen or mechanical ventilation start of treatment (up 
to 90 days). 
• First Intensive Care Unit (ICU) discharge. 
• Days in ICU from start of treatment (up to 90 days). 
• Discharge from hospital. 
• Days hospitalized from start of treatment (up to 90 days). 
• Severity of ARDS as defined by the Berlin criteria, absolute values, and 
changes from start of treatment to Days 2, 3, 7, 15, and 30. 
• Cytokine and biomarker results, absolute values, and changes from start of 
treatment to Days 2, 3, 7, 15, and 30. 
 
• Adverse events (AEs) and serious adverse events (SAEs) within 90 days from 
start of treatment. 
Study Population: 
Inclusion criteria will be assessed during Screening: 
• Male or female subjects at least 18 years of age at time of consent. 
• Diagnosis of SARS-CoV-2 infection confirmed by real-time reverse 
transcription polymerase chain reaction (RT-PCR) assay. In the absence of 
the availability of an RT-PCR test, patients who have previously tested 
positive for COVID-19 (PCR or non-PCR based methods) and/or in the 
opinion of the Principal Investigator meet the clinical diagnostic criteria for 
study inclusion will be eligible for participation in this study. 
• Compromised respiratory status as defined by arterial oxygen saturation < 
94% (oxygen saturation measured by pulse oximetry) OR cardiomyopathy 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 10 of 54 
Capricor, Inc. – Company Confidential 
due to COVID-19 (defined as a new drop in ejection fraction to ≤ 50% during 
COVID-19 with no evidence of obstructive coronary artery disease based on 
medical records review). 
• Elevation of at least 1 inflammatory marker (IL-1, IL-6, IL-10, TNF-α, 
ferritin, CRP) defined as ≥ 2× upper limit of laboratory normal reference 
value. 
• Written informed consent provided by subject or legal representative. 
 
Exclusion criteria will be assessed during Screening: 
• Currently receiving extracorporeal membrane oxygenation (ECMO) or high 
frequency oscillatory ventilation (HFOV). 
• Patients who have been intubated. 
• Patients with established positive bacterial blood cultures prior to enrollment 
or suspicion of superimposed bacterial pneumonia. 
• Patients with untreated human immunodeficiency virus (HIV) infection. 
• Creatinine clearance less than 30 mL/minute. 
• Liver function tests > 5 upper limit of normal.  
• Current or history (within the previous 5 years) of systemic autoimmune or 
connective tissue disease. 
• Known allergy or hypersensitivity to any of the IP constituents such as 
dimethyl sulfoxide (DMSO) or bovine proteins. 
• Treatment with a cell therapy product within 12 months prior to 
randomization. 
• Participation in an ongoing protocol studying an experimental drug or device. 
• Pregnant or breastfeeding female subjects, and sexually active female subjects 
of childbearing potential not willing to use contraceptive methods. 
Phase: 
2 
Description of 
Sites/Facilities Enrolling 
Participants: 
This is a multi-center protocol with multiple Principal Investigators in the United 
States. 
Description of Study 
Intervention: 
Eligible subjects will be randomized to either the CAP-1002 or placebo group (1:1 
ratio) and undergo baseline safety and efficacy assessments approximately 1 to 5 
days prior to the administration of investigational product (IP). Treatment 
administration consists of 1 peripheral IV infusion of IP   
 for a total of 150M 
CDCs or matching placebo) administered at the clinical site. Subjects will receive 1 
administration of IP on study Day 1. Background standard of care treatment and 
practices will be maintained for all patients enrolled in the study. 
Study Duration: 
6 months 
Participant Duration: 
All subject participation will be a maximum of 13 weeks from Screening. 
 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 11 of 54 
Capricor, Inc. – Company Confidential 
1.2 
Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 14 of 54 
Capricor, Inc. – Company Confidential 
15 IP will be ordered approximately 1 to 5 days prior to the infusion (Day 1) in Treatment Phase to allow for enough time for IP delivery. Please see the IP Manual 
for ordering instructions and timelines. 
16 Subjects will be observed for at least 2 hours post-infusion, including vital signs assessments every 15 minutes. The clinical site will observe local institutional 
policies related to parenteral infusions and post-infusion monitoring. A site Investigator will assess the subject for AEs. 
17 Monitoring for infiltration or extravasation at the site of peripheral venous access every 15 minutes from pre-infusion through 2 hours post-infusion.  
18 As noted in footnote 3, adverse events will be monitored on a daily basis while the subject is hospitalized on study. For any allergic reaction, a tryptase blood 
sample will be collected and analyzed locally per protocol.  
19 Outcome data includes information related to clinical status and survival including, but not limited to ARDS diagnosis by Berlin criteria, ICU information, 
hospitalization, disposition, and mortality.  
 
 
 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
2 
INTRODUCTION 
2.1 
Study Background and Rationale 
Coronavirus disease 2019 (COVID-19) is an emerging outbreak caused by the severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization 
(WHO), COVID-19 has reached pandemic status with over 23 million confirmed cases worldwide 
as of August 26, 2020. Infected patients experience mild to severe flu-like symptoms, which 
require weeks of quarantine and/or hospitalization to recover and prevent spread of the virus. When 
severe, COVID-19 is characterized by hyper-inflammation, cytokine storm, and elevations of 
cardiac-injury biomarkers. Indeed, cardiac injury appears to be a prominent feature of the disease 
occurring in 20% to 30% of hospitalized patients and contributing to 40% of deaths.1 
Compared with severe acute respiratory syndrome (SARS) of 2002-2003, COVID-19 appears to 
have a lower case-fatality rate. The symptomatic case-fatality risk is 1.4% but increases 
substantially when the patient is greater than 60 years of age. Despite the relatively low case-
fatality risk, however, the basic reproductive number (R0) is around 2.0 to 2.5 suggesting that it 
spreads more easily.2 
Immune cells, particularly T lymphocytes, monocytes, and macrophages have been implicated in 
the underlying pathology of SARS,3 and COVID-19 appears to have the same pathophysiology. 
Critically ill COVID-19 patients suffer from a cytokine storm, a form of immune over-reaction 
characterized by increased plasma concentrations of several pro-inflammatory mediators.4 
Cytokine storm is a hallmark of severe disease. Such patients generally develop acute respiratory 
distress syndrome (ARDS) and are characterized by multiple organ failure and elevation of key 
inflammatory markers, including interleukin (IL)-6, IL-2, IL-7, tumor necrosis factor (TNF)-α, 
and C-reactive protein (CRP). 
Several pathological mechanisms of COVID-19 can be targeted by cardiosphere-derived cells, 
CDCs, such as CAP-1002. CDCs are progenitor/stromal cells isolated from human heart tissue 
with immunomodulatory, anti-fibrotic, and pro-regenerative properties. They work by secreting 
nanoparticles (exosomes), which transfer genetic material to target cells inducing profound 
phenotypic changes.5 
CDCs have previously been tested in clinical trials for myocardial infarction, heart failure with 
reduced and preserved ejection fraction, Duchenne muscular dystrophy (DMD), and pulmonary 
hypertension as well as hypoplastic left ventricle. The reported outcomes from these trials have 
shown the disease-modifying bioactivity of CDCs.6 
Within the framework of SARS-CoV-2 pathogenesis, multiple pathways known to be CDC 
sensitive may serve as therapeutic targets. These targets include pro-inflammatory pathways 
(TNF-α, interferon [IFN]-γ, IL-1, and IL-6) and anti-inflammatory pathways (regulatory T cells 
and IL-10) that have been explored in animal models of myocardial ischemia, myocarditis, 
muscular dystrophy, heart failure with preserved ejection fraction, non-ischemic dilated 
cardiomyopathy, and pulmonary hypertension. Given that CDCs polarize macrophages to an anti-
inflammatory (healing) immunomodulatory phenotype, CDCs may subsequently attenuate 
cytokine storm. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 17 of 54 
Capricor, Inc. – Company Confidential 
damage are commonly observed in these patients, which may become permanent if left untreated. 
To that end, CDC-exosomes have been shown to improve function, blunt inflammation, decrease 
fibrosis, and promote heart repair in several nonclinical models of cardiomyopathy.7,8,9 The data 
from these studies suggest that CDCs and CDC-exosomes, which have shown to recapitulate the 
effects of the cells (CDCs),6,7 may resolve key pathological mechanisms driving organ damage 
and disability in patients surviving COVID-19 infection. No current therapeutic agent effectively 
targets cytokine storm and subsequent long-term organ damage. CDCs, such as CAP-1002, 
represent a logical therapeutic candidate to improve survival and decrease lung and heart damage 
in critically ill COVID-19 patients. 
2.2.3 
Assessment of Potential Risks and Benefits 
Based on data collected from the DMD clinical studies, the benefit-risk balance for CAP-1002 is 
considered favorable and warrants additional clinical investigation in indications characterized by 
cytokine-induced inflammation. 
3 
OBJECTIVES AND ENDPOINTS 
The primary objectives of the study are to determine the safety and effectiveness of intravenously 
infused CAP-1002 in improving clinical outcomes in severely or critically ill patients with 
COVID-19. 
Several exploratory safety and efficacy endpoints will be measured to evaluate the effects of CAP-
1002 treatment on the morbidity and mortality of severely or critically ill patients with COVID-
19. The endpoints are as follows: 
• All-cause mortality. 
• Ordinal Scale of Clinical Improvement, absolute values, and changes from start of 
treatment to Days 2, 3, 7, 15, and 30. 
• Time to a 1-point decrease on the Ordinal Scale of Clinical Improvement from start of 
treatment. 
• Area under the severity versus time curve, where severity is defined by the Ordinal Scale 
of Clinical Improvement and time is measured from start of treatment to Days 2, 3, 7, 15, 
and 30. 
• Days of supplemental oxygen or mechanical ventilation from start of treatment (up to 90 
days). 
• First Intensive Care Unit (ICU) discharge 
• Days in ICU from start of treatment (up to 90 days). 
• Discharge from hospital. 
• Days hospitalized from start of treatment (up to 90 days). 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 18 of 54 
Capricor, Inc. – Company Confidential 
• Severity of ARDS as defined by the Berlin criteria, absolute values, and changes from 
start of treatment to Days 2, 3, 7, 15, and 30. 
• Cytokine and biomarker results, absolute values, and changes from start of treatment to 
Days 2, 3, 7, 15, and 30. 
• Adverse events (AEs) and serious adverse events (SAEs) within 90 days from start of 
treatment. 
4 
STUDY DESIGN 
4.1 
Overall Design 
This is a randomized, double-blind, placebo-controlled study that will enroll subjects with a 
clinical diagnosis of COVID-19 confirmed by laboratory testing and who are in severe or critical 
condition as indicated by life-support measures. Prior to protocol procedures, informed consent 
will be obtained from the subject or a legally authorized representative. Subjects will undergo a 
screening evaluation to determine eligibility based on the protocol inclusion and exclusion criteria. 
Up to 60 subjects will be enrolled and treated in the study. Replacement of non-treated subjects 
will be allowed with sponsor agreement. 
Eligible subjects will be randomized to either the CAP-1002 or placebo group (1:1 ratio) and 
undergo baseline safety and efficacy assessments approximately 1 to 5 days prior to the 
administration of investigational product (IP). Treatment administration consists of 1 peripheral 
IV infusion of IP (   
 for a total of 150M CDCs or matching placebo) administered at the 
clinical site. Subjects will receive 1 administration of IP on study Day 1. Background standard of 
care treatment and practices will be maintained for all patients enrolled in the study. 
There is no planned dose adjustment. Should an acute toxicity arise during the infusion (e.g., 
hypersensitivity reaction or pulmonary decompensation), the infusion should be terminated 
immediately, and the actual total dose administered recorded. Any decision about re-challenging 
should be made after discussions with the Investigator, Medical Monitor, and other medical experts 
who may be required to make an informed decision. 
A schematic of the protocol design is provided in Section 1.2 and a summary of all activities is 
provided in Section 1.3. 
Subjects will be randomized in a 1:1 allocation to either the CAP-1002 (150M CDCs) or placebo 
group. See Section 6.3.1 for additional details related to randomization.  
Subjects will complete Screening followed by a Treatment and Follow-up phase. A detailed 
medical history will be collected, including the presence of any co-morbidities and risk factors 
believed to be associated with COVID-19 outcomes (e.g., age, gender, diabetes, chronic 
obstructive pulmonary disease [COPD] or respiratory conditions, body mass index, cardiovascular 
or renal disease) or emergent factors since the time of infection. Screening and randomization will 
be conducted approximately 1 to 5 days prior to IP administration to allow enough time for IP 
delivery to the clinical site. Eligibility must be reviewed and confirmed on Day 1 prior to the 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 21 of 54 
Capricor, Inc. – Company Confidential 
150M CDCs was selected as a dose
 
. 
4.4 
End of Study Definition 
The end of the study is defined as completion of the last visit or procedure for the last enrolled 
participant (as shown in the Schedule of Activities, Section 1.3) in the trial globally. 
A participant is considered to have completed the study if he or she has completed all phases of 
the study including the last visit or the last scheduled procedure shown in the Schedule of 
Activities, Section 1.3. In addition, participants will be considered to have ended the study as 
follows: 
• Death on study 
• Withdrawal of informed consent or early termination; all data collected prior to this will 
remain in the database (refer to Section 7.2). 
5 
STUDY POPULATION 
5.1 
Inclusion Criteria 
Inclusion criteria will be assessed during Screening: 
1. Male or female subjects at least 18 years of age at time of consent. 
2. Diagnosis of SARS-CoV-2 infection confirmed by real-time reverse transcription 
polymerase chain reaction (RT-PCR) assay. In the absence of the availability of an RT-
PCR test, patients who have previously tested positive for COVID-19 (PCR or non-PCR 
based methods) and/or in the opinion of the Principal Investigator meet the clinical 
diagnostic criteria for study inclusion will be eligible for participation in this study. 
3. Compromised respiratory status as defined by arterial oxygen saturation < 94% (oxygen 
saturation measured by pulse oximetry) OR cardiomyopathy due to COVID-19 (defined as 
a new drop in ejection fraction to ≤ 50% during COVID-19 with no evidence of obstructive 
coronary artery disease based on medical records review). 
4. Elevation of at least 1 inflammatory marker (IL-1, IL-6, IL-10, TNF-α, ferritin, CRP) 
defined as ≥ 2× upper limit of laboratory normal reference value. 
5. Written informed consent provided by subject or legal representative. 
5.2 
Exclusion Criteria 
Exclusion criteria will be assessed during Screening: 
1. Currently receiving extracorporeal membrane oxygenation (ECMO) or high frequency 
oscillatory ventilation (HFOV). 
2. Patients who have been intubated. 
3. Patients with established positive bacterial blood cultures prior to enrollment or suspicion 
of superimposed bacterial pneumonia. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 30 of 54 
Capricor, Inc. – Company Confidential 
Site personnel and subjects, staff members at clinical research organizations (CROs), and Capricor 
personnel will remain blinded to treatment assignment throughout trial conduct. An unblinded 
DSMB, unblinded statistician, and the DSMB administrator will remain firewalled from any 
blinded individual involved in trial conduct, services, and/or oversight.  
Please refer to Section 6.3.3 for more information related to emergency unblinding of the IP. 
6.3.3 
Emergency Unblinding 
To maintain the overall scientific integrity of the clinical trial, unblinding or code breaks should 
occur only in exceptional circumstances when knowledge of the actual treatment is absolutely 
essential for further management and treatment of the subject. Subject safety must always be the 
first consideration in making such a determination. Investigators are encouraged to discuss this 
with the Medical Monitor prior to unblinding. In case of an emergency, the Investigator has the 
sole responsibility for determining if unblinding of a subject’s treatment assignment is warranted. 
If unblinding is deemed to be necessary, the Investigator should use the mechanism for emergency 
unblinding outlined in the Manual of Procedures. If a subject’s treatment assignment is unblinded, 
Capricor must be notified within 24 hours after breaking the blind. The date and reason that the 
blind was broken must be recorded in the source documentation. The Investigator is encouraged 
to maintain the blind as much as possible. Knowledge of the actual allocation can generally be 
limited and not disclosed to the subject and/or other trial personnel including personnel at other 
investigative sites, monitors, Capricor, or other personnel involved in the trial; there should be no 
written or verbal disclosure of the code in any corresponding subject documents. Unblinding 
should not necessarily be a reason for termination from the trial. 
6.4 
Study Intervention Compliance 
Investigational product will be administered in an inpatient setting per clinical site standards and 
by appropriately trained medical personnel who will document the actual volume administered at 
each infusion. 
Investigational product administration occurs on study Day 1 after the subject has been deemed 
eligible and randomized. Should a subject’s treatment schedule need to be altered, the Medical 
Monitor should be contacted to discuss the subject-specific case and out-of-window administration 
of IP.  
6.5 
Concomitant Therapy 
Use of any concomitant therapies to treat COVID-19 will be documented. 
Investigative sites will be requested to provide consistent background standard of care to all 
enrolled subjects.  
6.6 
Rescue Medicine 
Since all patients with COVID-19 will be managed in an ICU, IV or intramuscular epinephrine 
and other treatments to manage a severe allergic reaction will be readily available for all patients 
receiving CAP-1002 in the event of an allergic reaction. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 31 of 54 
Capricor, Inc. – Company Confidential 
7 
STUDY INTERVENTION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
7.1.1 
Early Stopping Rules 
Since a primary concern is not to add risk to subjects who are already considered to be in severe 
or critical condition from the effects of COVID-19, safety of each enrolled subject will be 
monitored. Stopping rules on the subject level and study level have been defined to ensure subjects 
are not exposed to significant risk.  
Should a subject-level stopping criterion be met the subject will discontinue the infusion but 
continue in the trial without receiving any further administration of IP.  
Should a study-level stopping event criterion be met enrollment will be halted until a decision to 
continue, suspend, or terminate enrollment and treatment is made by the DSMB. 
The DSMB Charter discusses unblinding of subject treatment assignments to assess stopping rules. 
7.1.2 
Subject-Level Stopping Rules 
The following stopping rules apply for an individual subject: 
• Anaphylactic reaction assessed as related to the administration of IP during the infusion 
requiring immediate termination of the infusion.  
• Hemodynamic compromise, as categorized by new sustained hypotension, assessed as 
related to the administration of IP during the infusion requiring immediate termination of 
the infusion.  
• Grade 4 AEs during the infusion assessed as related to IP by the clinical care team. 
If an individual subject should experience a stopping criterion during the infusion including an 
anaphylactic reaction, hemodynamic compromise, or Grade 4 AE, as defined by the 3 criteria 
above, the infusion will be terminated immediately and not restarted. 
7.1.3 
Study-Level Stopping Rules 
Enrollment and treatment in the trial will be paused in the event any of the following criterion is 
met: 
• Death of a subject within 24 hours of IP administration until the death is adjudicated by the 
CEC as being unlikely related to CAP-1002. 
• Death of a subject occurring at any time after 24 hours of IP administration during the study 
with cause of death being initially assessed by the Investigator as related to IP and 
confirmed to be related to CAP-1002 by the DSMB.  
• Anaphylactic reaction in a subject during administration of IP or within 24 hours after the 
infusion initially assessed by the Investigator as related to IP and confirmed to be related 
to CAP-1002 by the DSMB. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 32 of 54 
Capricor, Inc. – Company Confidential 
• Two Grade 3 or Grade 4 SAEs initially assessed by the Investigator as related to IP or 
administration procedure and confirmed to be related to CAP-1002 or administration 
procedure by the DSMB. 
During the enrollment and treatment pause, the CEC will review the observed SAE(s) and 
adjudicate the event(s) as outlined in the CEC Charter. The DSMB will review the results of the 
CEC adjudication and determine whether enrollment and treatment should be continued, 
suspended, or terminated if one of the protocol’s study-level stopping criteria is met.  
Should any of the events outlined above be reported without assessment of the Investigator or the 
relationship identified by the Investigator is not related to IP, the trial will continue while the event 
is adjudicated by the CEC. The CEC will provide the results of the event adjudication to the DSMB 
for their review and study-stopping rule evaluation. No more than 1 additional subject will be 
treated within a 24-hour interval after the event has been submitted to the CEC for adjudication 
and until a study continuation decision has been made by the DSMB.  
The recommendation of the DSMB will be one of the following in accordance with the DSMB 
Charter: 
• Continue enrollment per protocol or with modifications 
• Temporarily suspend enrollment and/or treatment to obtain additional data or resolve an 
issue 
• Terminate trial due to unfavorable safety signal; significant and unfavorable change in the 
risk/benefit ratio which could harm or be toxic to participants; scientific value of the trial 
is insufficient. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
Every effort will be made to have each randomized subject complete all elements of the protocol. 
If a subject has been randomized and withdraws prior to being discharged from the hospital, all 
attempts must be made to perform assessments indicated for the Day 7 visit (i.e., final in-person 
comprehensive visit). For any subject that withdraws prior to Day 90 all attempts must be made to 
complete the Day 90 assessments for early termination. 
Criteria for withdrawal from trial participation include the following reasons: 
• A subject may withdraw his or her consent at any time without prejudice to their care. 
• At the discretion of the Investigator, the subject may be withdrawn from the trial for lack 
of adherence to the investigational plan.  
7.3 
Lost to Follow-Up 
A subject will be considered lost to follow-up if the subject fails to appear (either in-patient, by 
telephone, email, or other electronic means) for the final 90-day follow-up assessment. In general, 
3 separate documented contact attempts (e.g., via telephone calls and e-mail) will be made to locate 
or recall the subject, or at least to determine the subject’s health status. These efforts will be 
documented in the subject’s study file. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 33 of 54 
Capricor, Inc. – Company Confidential 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Assessments 
Trial assessments will be performed as outlined in Schedule of Activities (Section 1.3). 
The Investigator is responsible for ensuring that the informed consent process is conducted and 
documented appropriately by trained clinical staff. A signed informed consent form, which has 
been approved by the Sponsor and clinical site IRB, is required. The Principal Investigator, or a 
designed and qualified individual, will provide a thorough explanation of the objectives, patient 
responsibilities, risks, and benefits of the protocol and will fully address all concerns raised by the 
patient and/or legal representative. After all issues have been adequately resolved, and the 
Investigator has confirmed that the patient has been fully consented, the patient or legal 
representative, will be asked to sign the informed consent. The consent process must be fully 
documented in the medical chart, and a signed copy of the consent must be given to the patient or 
legal representative.  
For the purposes of this protocol, randomized subjects are considered enrolled in the protocol. 
Subjects will complete Screening followed by a Treatment and Follow-up phase (Section 1.2). 
Screening and randomization will be conducted approximately 1 to 5 days prior to IP 
administration to allow enough time for IP delivery to the clinical site. Standard of care laboratory 
and imaging assessments conducted during the index hospitalization within 7 days prior to protocol 
consent may be used for screening visit assessments and eligibility determination.  
The Investigator must review all screening assessments and verify that the subject meets all 
eligibility requirements for this protocol. A subject cannot be randomized until attestation of 
eligibility is recorded in the medical record by the Investigator. In addition, confirmation of 
continued eligibility must be recorded in the source documentation prior to the infusion (Day 1) 
of Treatment Phase. 
The Treatment Phase comprises 1 administration of IP. Treatment occurs on Day 1 and protocol 
assessments are performed on Days 2, 3, 7 (± 1 day), 15 (± 1 day), 30 (± 3 days), 60 (± 3 days), 
and 90 (± 7 days). Baseline safety and efficacy assessments will be conducted prior to the 
treatment. Follow-up will either be conducted in the inpatient setting or as a phone follow-up 
should the subject be discharged. 
Assessments to evaluate efficacy will be performed at trial visits as indicated in Schedule of 
Activities (Section 1.3). 
8.1.1 
Ordinal Scale for Clinical Improvement 
The Ordinal Scale for Clinical Improvement was developed by a special WHO committee to help 
measure clinical improvement and/or survival in the COVID-19 patient population. The 
Investigator must review the scale and record the clinical status of the subject using the 0-8 scale 
(Table 2). 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 35 of 54 
Capricor, Inc. – Company Confidential 
inflammatory and T cell response, angiogenesis, and vascular injury (including CRP, IL-1, IL-6, 
TNF-α, IL-10, IFN-γ, GM-CSF, MCP1, MCP4, MIP1a, MIP1b, and MIP3a). 
The discovery proteomic platform relies on data-independent acquisition mass spectrometry (DIA-
MS, also known as SWATH) and enables the simultaneous quantitative analysis of hundreds of 
plasma proteins in support of disease and therapeutic studies. The DIA-MS pipeline routinely 
quantifies >1,500 proteins in disease plasma including potential COVID-19 mechanistic proteins 
such as ACE, ACE2, angiotensinogen, ferritin, serum amyloid, S100b, and TGF-α. The quantified 
plasma proteins are broadly involved in various aspects of acute phase response, inflammation, 
immune response, redox signaling, endothelial dysfunction, vascular reactivity, heart disease, lipid 
metabolism, kidney function, and brain and pulmonary damage. It is anticipated that these assays, 
applied to COVID-19 samples, will provide a critical path towards discovering novel circulating 
biomarkers of disease severity and therapeutic responsiveness to CAP-1002 in critically ill 
COVID-19 patients. 
Please see the laboratory manual for further information on the proteomic assay, collection of the 
blood sample and shipping procedures.  
8.2 
Safety and Other Assessments 
Assessments to evaluate safety will be performed at trial visits as indicated in Schedule of 
Activities (Section 1.3). 
8.2.1 
Vital Signs  
Heart rate, systolic and diastolic blood pressure, respiratory rate, body temperature, and blood 
oxygen saturation (SpO2) will be measured and documented. SpO2 will be measured at room air 
and on device, if applicable.  
Vital signs will be performed using equipment provided by the clinical sites that have been 
properly calibrated per institutional guidelines.  
On Day 1, vital signs will be captured every 15 minutes from pre-infusion through 2 hours post-
infusion.  
8.2.2 
Physical Examination  
The physical examination will be a review of the major organ systems, including general 
appearance, anthropometrics (height and weight), HEENT (head, eye, ear, nose, and throat), 
lymphatic, respiratory, cardiovascular, chest, abdomen, gastrointestinal, and musculoskeletal.  
Clinically significant findings prior to the start of IP administration are to be captured as medical 
history.  
Clinically significant findings after the start of IP administration are captured and reported as AEs 
if they meet the definitions of an AE per Section 8.3.1. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 36 of 54 
Capricor, Inc. – Company Confidential 
8.2.3 
Electrocardiogram  
A 12-lead ECG will be performed using equipment provided by the clinical site that has been 
maintained per institutional guidelines. The Investigator or other designee must provide his/her 
date signature on the original paper tracing attesting to the authenticity of the ECG machine 
interpretation or their over-read and reinterpretation. The presence or absence of abnormalities will 
be recorded.  
On Day 1 of the treatment a 12-lead ECG will be performed within 4 hours pre-infusion and within 
1 hour post-infusion.  
8.2.4 
Clinical Laboratory Assessments 
All laboratory assessments are to be collected following the standard institutional procedures for 
blood collection and submitted to the local institution laboratory for analysis with exception of the 
cytokine assay, which will be submitted to a central laboratory for analysis. If the central laboratory 
is unable to perform the assay, then the local institution laboratory will be utilized for analysis.  
The following laboratory assessments will be collected per the Schedule of Activities (Section 
1.3):  
• Urine or serum beta human chorionic gonadotropin (IU/L) for women of child-bearing 
potential  
• Complete blood count with differentials 
• Comprehensive metabolic panel, including liver function tests 
• Troponin I 
• Myoglobin (serum) 
• Procalcitonin 
• C-reactive protein 
• Ferritin 
• Cytokine assay (IL-1, IL-6, TNF-α, INF-γ, IL-10) 
Standard of care laboratory assessments done during the index hospitalization within 7 days prior 
to protocol consent may be used for screening visit assessments and eligibility determination.  
8.2.5 
Demographics 
For all subjects screened, date of birth, ethnicity, race, and sex will be captured.  
8.2.6 
Medical History 
Relevant and significant medical and surgical history will be confirmed at screening. This will 
include any comorbidities and risk factors believed to be associated with COVID-19 outcomes 
(diabetes, COPD or respiratory conditions, cardiovascular and renal disease). 
Oxygen requirements prior to CAP-1002 administration will be captured as part of medical history.  

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 37 of 54 
Capricor, Inc. – Company Confidential 
8.2.7 
Prior and Concomitant Therapies 
All therapies the subject receives will be recorded from Screening through study completion on 
the Concomitant Therapies Log. Modifications to the therapy regimen will be confirmed at a 
minimum at each timed protocol visit.  
IP and the protocol-defined components should not be recorded on the Concomitant Therapy Log. 
However, these administrations are to be captured in the source documentation to ensure 
appropriate administration of IP. In addition, saline flushes do not need to be captured.  
8.2.8 
Hospitalization 
Information pertaining to the index hospitalization and any subsequent hospital admission will be 
collected including date of hospitalization, date of hospital discharge, reason for hospitalization, 
and disposition at time of discharge. 
8.2.9 
Intensive Care Unit  
Information pertaining to the ICU admission and life-saving measures taken will be collected 
including date(s) and reason(s) for ICU admission, date(s) of ICU discharge, and disposition at 
time of discharge. 
8.3 
Adverse Events and Serious Adverse Events 
8.3.1 
Definition of Adverse Events 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related. It may be indicated by physical sign, symptom, clinically significant 
laboratory abnormalities, and/or disease temporally associated with a medical (investigational) 
treatment, procedure, or product, whether or not related to the medical (investigational treatment, 
procedure, or product. This definition includes intercurrent illnesses or injuries, exacerbation of 
pre-existing conditions, or events occurring due to abuse or overdose.  
Any condition that was pre-existing is not an adverse event unless there is a change in the nature, 
severity, or degree of the condition.  
Clinical laboratory abnormalities are considered AEs when deemed clinically significant by the 
Investigator and/or lead to a change in the subject’s functional status.  
An AE does not include:  
• Medical or surgical procedures (e.g., colonoscopy, biopsy). The medical condition that 
leads to the procedure is an AE. 
• Social or convenience hospital admissions where an untoward medical occurrence did not 
occur. 
• Day-to-day fluctuations of pre-existing disease or conditions present or detected at the start 
of the trial that do not worsen. 
• 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. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 38 of 54 
Capricor, Inc. – Company Confidential 
All Investigators conducting investigative studies supported by Capricor must report both expected 
and unexpected SAEs to Capricor, or designee, and their individual IRB in compliance with their 
institutional policies. Please see Section 8.3.5 or further details on AE reporting. 
8.3.2 
Definition of Serious Adverse Event 
An AE is considered “serious” if, in the view of either the Investigator or Capricor, it results in 
any of the following outcomes:  
• Death 
• Life-threatening adverse event 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
• Congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based upon appropriate medical judgment, they may jeopardize 
the subject and may require medical or surgical intervention to prevent one of the outcomes listed 
in this definition.  
Examples of such medical events include bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias, or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.  
Complications that occur during a hospitalization are AEs. When the hospitalization is prolonged 
due to the complication or the complication fulfills any other serious criteria, the event is reported 
as an SAE. Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an SAE. Please see Section 8.3.6 or further details on SAE 
reporting. 
8.3.3 
Classification of an Adverse Event 
8.3.3.1 
Severity of Adverse Event 
Investigators will monitor all subjects for AEs during the protocol and establish a diagnosis for an 
event based on signs, symptoms, and/or other clinical information. It is important to distinguish 
that individual signs and symptoms of the event are not AEs and should not be reported.  
For each AE, the Investigator will evaluate the causality and severity, report the action taken, and 
event outcome and disclose whether or not it caused the subject to discontinue trial participation. 
The following severity scale will be used as a guideline to differentiate the severity of adverse 
events:  
• Mild (Grade 1): Asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
• Moderate (Grade 2): Moderate; minimal, local, or noninvasive intervention indicated; 
limited age-appropriate instrumental ADL*. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 39 of 54 
Capricor, Inc. – Company Confidential 
• Severe (Grade 3): Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**. 
• Life-Threatening or Disabling (Grade 4): Life-threatening consequences; urgent 
intervention indicated. 
• Fatal (Grade 5): Death related to AE 
An AE that is assessed as severe should not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event. An event is described as serious when it meets one of 
the pre-defined outcomes noted in Section 8.3.2. Both an AE and SAE can be assessed as severe. 
However, an AE of severe intensity may not meet SAE definition requirements. 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
**Self-care ADL refer to bathing, dressing, and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
8.3.3.2 
Causality of Adverse Event 
The Investigator will assess the relationship (causality) of an AE to the IP and administration 
procedure.  
Causality will be defined as follows:  
• Probable: adverse events that, after careful medical evaluation, are considered with a high 
degree of certainty to be related to the IP or administration procedure. The following 
characteristics will apply: 
o A reasonable temporal relationship exists between the event and the IP or 
administration procedure, and 
o The event is a known reaction to the IP or administration procedure, which cannot 
be explained by an alternative etiology commonly occurring in the 
population/individual.  
• Possible: adverse events that, after careful medical evaluation, do not meet the criteria for 
a probable relationship to the IP or administration procedure, but for which a connection 
has reasonable certainty. The following characteristics apply: 
o The event occurs after exposure to the IP or administration procedure, and  
o The event is not a known reaction to the IP or administration procedure, but cannot 
be explained by a commonly occurring alternative etiology, or 
o In the absence of a temporal relationship, the event cannot reasonably be explained 
by an alternative etiology.  
• Unlikely: adverse events that, after careful medical evaluation, do not meet the criteria for 
possible or probable relationship to IP or administration procedure and for which a 
connection is unlikely. The following characteristics will apply: 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 41 of 54 
Capricor, Inc. – Company Confidential 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up 
All AEs will be reported from the signing of the ICF and are followed by the clinical site until an 
outcome is known or the subject’s participation in the protocol concludes at either the Day 90 or 
early termination, whichever occurs first.  
The clinical site is expected to review all ongoing AEs at each visit. AEs are followed until 
resolution or until no further changes in the event are expected (i.e., the point at which a subject 
experiencing an AE is treated successfully and stabilized even though he or she may continue to 
experience lingering sequelae that may never resolve), or it is agreed that further follow-up of the 
event is not warranted (e.g., non-serious, IP unrelated, ongoing at final visit). See Section 8.3.5 for 
reporting ongoing AEs at the end of protocol participation.  
For SAEs that were incomplete or ongoing at the time of initial submission, the clinical site is 
required to submit follow-up SAE Report Forms when event information is available to the 
research site personnel and/or an outcome is known.  
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must promptly 
notify the sponsor. 
8.3.5 
Adverse Event Reporting 
All AEs occurring after the initiation of the initial dose of IP will be considered treatment 
emergent. Any ongoing AE that has not been resolved at the time of protocol completion or early 
termination for a subject will be marked as ongoing on the Adverse Event Log.  
All AEs will be entered in the electronic data capture system (EDC) on to the Adverse Event Log 
by trained site personnel at the investigative site. 
8.3.6 
Serious Adverse Event Reporting 
Expected and unexpected SAEs must be reported to the Sponsor and entered into EDC within 24 
hours of discovery of the event. For events that do not have complete information available at the 
time of initial report, the investigative site will submit all available information at the time of the 
submission. All SAE Report Forms must be signed by an Investigator and submitted with available 
source documentation. All source documentation must be de-identified prior to submission.  
Should access to the EDC system be unavailable, SAEs and subsequent follow-up information 
must be reported to Capricor, or designee, via the following:  
• Email: 
 
• Fax: 
 
Capricor will promptly upon discovery, report serious and unexpected AEs for which there is a 
reasonable possibility that the investigative therapy (i.e., administration product and/or 
investigative product) caused the events to the FDA in accordance with 21 CFR 312.32 regulations 
and ICH E2A guidelines.  

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 42 of 54 
Capricor, Inc. – Company Confidential 
For protocols conducted under an Investigational New Drug Application (IND), FDA regulations 
require reporting of any serious suspected adverse reaction that is unexpected according to the 
current IB. A serious adverse reaction is defined as any adverse event for which there is a 
reasonable possibility that the drug/biologic caused the AE. For the purposes of IND safety 
reporting, “reasonable possibility” means there is evidence to suggest a causal relationship 
between the drug/biologic and the adverse event. 
Suspected unexpected serious adverse reactions (SUSARs) are SAEs that are unexpected and are 
possibly or probably related to participation in the research. Expedited reporting is required for all 
SUSARs. Capricor will send an IND Safety Report to the FDA within 7 calendar days of receipt 
for fatal or life-threatening events, and within 15 calendar days of receipt for non-fatal or non-life-
threatening events that qualify for expedited reporting. 
All SAEs must be reported to the respective IRB in accordance with the clinical site’s policies. 
Copies of the submission will be collected by Capricor.  
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) the Sponsor will review and notify the IRB, 
if appropriate, according to local requirements. 
All SAEs will be reported to the DSMB per the milestones outlined in the DSMB Charter or more 
frequently at the discretion of the Medical Monitor. All SAEs will be reviewed by the Medical 
Monitor and CEC. 
8.3.7 
Reporting Events to Participants 
Not applicable. 
8.3.8 
Events of Special Interest 
Other adverse events (OAEs) will be identified by the Medical Monitor during the evaluation of 
safety data for the Clinical Study Report. Significant AEs of particular clinical importance, other 
than SAEs and those AEs leading to discontinuation of the subject from the trial, will be classified 
as OAEs.  
8.3.9 
Reporting of Pregnancy 
Should a female subject be impregnated, or a female be impregnated by a male subject during the 
time of AE reporting, the clinical site is required to notify Sponsor within 24 hours of learning 
about the pregnancy. The clinical site will receive the Pregnancy Reporting Form to complete and 
submit to the Sponsor.  
All pregnancies will be followed until the pregnancy outcome is known. In addition, pregnancies 
that are ongoing at the time of protocol completion will be followed until the outcome is known. 
The clinical site is responsible for outcome reporting via the Pregnancy Reporting Form, including 
spontaneous or voluntary termination, details of birth, and the presence or absence of any birth 
defects, congenital abnormalities, or maternal and newborn complications. 
The pregnancy is not an AE for the male subject unless there is a suspicion that the IP interfered 
with the effectiveness of a contraceptive medication. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 43 of 54 
Capricor, Inc. – Company Confidential 
9 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
This is a limited interventional study with a primary objective of determining whether CAP-1002 
can be safely and effectively used in subjects who are severely or critically ill due to COVID-19. 
9.2 
Sample Size Determination 
Up to a total of 60 subjects (approximately 30 in each group, CAP-1002 and placebo) will be 
enrolled, randomized, and treated in this study. Adequate information is not currently available for 
formal sample size calculations for this study. The proposed study size reflects a reasonable 
estimate of subject numbers to support descriptive and correlative assessments involving clinical 
safety and efficacy information to support further clinical studies. 
9.3 
Populations for Analyses 
All analyses will be based on the modified intention-to-treat (mITT) population of enrolled 
subjects. 
9.4 
Statistical Analyses 
9.4.1 
General Approach 
The SAP will be finalized prior to un-blinding, and it will include a more technical and detailed 
description of the statistical analyses described in this section. Unless otherwise noted in the SAP, 
continuous variables will be summarized using the following descriptive statistics: n (non-missing 
sample size), mean, standard deviation, median, maximum, and minimum. The frequency and 
percentages (based on the non-missing sample size) of observed levels will be reported for all 
categorical measures. 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) 
See Section 9.4.9. 
9.4.3 
Analysis of the Secondary Endpoint(s) 
See Section 9.4.9. 
9.4.4 
Safety Analyses 
See Section 9.4.9. 
9.4.5 
Baseline Descriptive Statistics 
Summaries of demographic variables such as age, sex, ethnicity, and race will be presented by 
cohort and overall. Summaries of baseline clinical laboratory values will be presented by cohort 
and overall. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 44 of 54 
Capricor, Inc. – Company Confidential 
9.4.6 
Planned Interim Analyses 
Early analyses of the clinical data may occur and will include safety and efficacy. 
9.4.7 
Sub-Group Analyses 
Not applicable. 
9.4.8 
Tabulation of Individual Subject Data 
In general, all data will be listed, sorted by cohort and subject, and when appropriate by visit 
number within subject. 
9.4.9 
Exploratory Analyses 
Safety will be evaluated by examining the rates of any SAEs, including Grade 3 or 4 AEs or death 
that are found to be related or potentially related to CAP-1002 during hospitalization or out 60 
days after last treatment. The event rates, their associated 95% confidence intervals, and Kaplan-
Meier curves of the times to events will be estimated. 
Inferential and descriptive statistics will be used to summarize status measures such as mortality, 
ICU and hospitalization times, life support measures, and changes in cytokines and biomarkers. 
Clinical improvement using the median changes from baseline together with shift tables of changes 
in severity of ARDS and Ordinal Scale of Clinical Improvement will be examined. Multivariable 
analyses may be performed to estimate the contributions of baseline demographic and risk factors 
to both safety and efficacy outcomes. Additional inferential statistics may be used for efficacy 
testing, as appropriate. A detailed description for the statistical methods will be included in the 
Statistical Analysis Plan for the study.  
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Informed Consent Process 
The Investigator will ensure that the subject and legal representative (applicable only if the subject 
is medically unable to provide consent) are given full and adequate oral and written information 
about the nature, purpose, possible risk, and benefit of the protocol. Subjects and legal 
representatives must also be notified that they are free to discontinue from the protocol at any time. 
The subject and legal representative should be given the opportunity to ask questions and allowed 
time to consider the information provided. 
The subject must sign and date the informed consent form prior to performing any protocol 
procedures. Specific requirements and guidelines for providing consent by a legal representative 
will be determined by the clinical site’s IRB.  

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 45 of 54 
Capricor, Inc. – Company Confidential 
10.1.2 
Study Discontinuation and Closure 
The protocol may be terminated at any time and for any reason, including but not limited to a 
decision by the DSMB, action by the FDA, or decision by Capricor. 
10.1.3 
Confidentiality and Privacy 
Confidentiality of all subject records will be maintained according to Health Insurance Portability 
and Accountability Act (HIPAA) guidelines. Investigators, clinical site IRBs, Capricor, and the 
FDA may review source documentation for enrolled subjects as necessary, but all unique patient 
and hospital identifiers will be removed prior to review. If the results of this protocol are published, 
the data will be presented in aggregate with all subject identifiers removed.  
10.1.4 
Future Use of Stored Specimens and Data 
Data collected for this study will be analyzed and stored. After the study is completed, the de-
identified, archived data will be transmitted to and stored for use by other researchers including 
those outside of the study. Permission to transmit data will be included in the informed consent.  
With the subject’s approval and as approved by local IRBs, de-identified biological samples will 
be stored with the same goal as that of sharing of data. These samples could be used to research 
COVID-19 complications and to improve treatment. 
During the conduct of the study, an individual subject can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent with regard to 
biosample storage may not be possible after the study is completed.  
10.1.5 
Key Roles and Study Governance 
The study is sponsored and monitored by Capricor, Inc. 
10.1.6 
Safety Oversight 
10.1.6.1 
Clinical Events Committee 
The purpose of the Clinical Events Committee is to provide consistent and unbiased adjudication 
of clinical outcomes and specified events through independent review of source documentation. 
The charge of the CEC is to review source documents and to adjudicate the classification of all 
potential primary safety endpoint events. Site will be provided instructions in the Manual of 
Procedures on how to collect and submit event information required for CEC review. The 
individuals that serve on the committee will be appointed by the Sponsor, are independent from 
all other trial activities, and are not affiliated in any way to the investigative site. The CEC will 
consist of physicians with expertise in critical care, infectious disease, pulmonology and/or 
cardiology. The frequency of the CEC meetings is detailed in the CEC Charter.  
The CEC will adjudicate all potential early stopping events for relatedness to CAP-1002 and 
severity as outlined in the CEC Charter. Adjudication of potential early stopping events will be 
shared with the Sponsor, Medical Monitor, and DSMB to help guide DSMB’s decisions for trial 
termination and recommendations for continuation or suspension of the trial. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 46 of 54 
Capricor, Inc. – Company Confidential 
10.1.6.2 
Data Safety Monitoring Board 
To meet the protocol’s ethical responsibility to its subjects, an independent Data Safety Monitoring 
Board will monitor results of this study. The board consists of physicians and biostatistician(s) 
appointed by the Sponsor who have no formal involvement or conflict of interest with the 
Investigators, investigative sites, subjects, or Capricor. The DSMB will act in a senior advisory 
capacity regarding data and safety matters throughout the duration of the study. The board will 
meet on a periodic basis according to the DSMB Charter to monitor the available information 
regarding safety, efficacy, and quality of trial conduct. The DSMB will communicate their 
recommendations directly to the Sponsor. The investigative sites will have no contact with 
members of the DSMB and no voting member of the committee may participate in the trial as an 
Investigator.  
The DSMB, in cooperation with the Medical Monitor, will review all CEC adjudicated events to 
determine whether a potential early stopping event was met and make a decision whether study 
enrollment should be terminated or provide a recommendation to continue or suspend the trial. 
Additional information on evaluating early stopping events is located in the Safety Monitoring 
Plan, DSMB Charter, and CEC Charter.  
10.1.7 
Clinical Monitoring 
The Sponsor will employ a risk-based approach to monitoring for this study. This will be 
accomplished via remote monitoring of data with a focus on safety, outcome measures, data 
completion and data outliers. The Sponsor will also centrally monitor study logs including the 
Informed Consent Log and Adverse Event Log periodically to ensure that the clinical site is 
adhering to protocol and procedures.  
The frequency of monitoring visits will be outlined in a separate clinical monitoring plan. 
The primary objectives of the Sponsor are to educate, support, identify and resolve issues related 
to protocol activities. The Clinical Research Associate (CRA) will discuss the protocol in detail 
and clarify any areas of uncertainty. At the initiation of the study, the CRA will conduct a tutorial 
on the protocol, data collection, adverse event reporting, and IP ordering.  
10.1.8 
Quality Assurance and Quality Control 
10.1.8.1 
Qualifications and Trainings 
Capricor will implement and maintain quality control and quality assurance procedures to ensure 
compliance with the protocol, GCP, and all applicable regulatory requirements, and may conduct 
a quality assurance audit(s). 
Clinical Investigators will be physicians with expertise in the clinical care of COVID-19 patients.  
All Investigators and coordinators will be trained by Capricor, or designee, in the specifics of the 
protocol, IP, and administration procedure during the site initiation visit in advance of the first 
subject enrollment.  

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 47 of 54 
Capricor, Inc. – Company Confidential 
10.1.8.2 
Good Clinical Practice  
All Investigators, coordinators and other site personnel involved in care of trial subjects, and/or 
research data collection must have documentation that they have successfully completed their 
institutionally required GCP or other Human Subject Protection courses. 
10.1.8.3 
HIPAA or Other Privacy Training 
All Investigators and coordinators must have documentation that they have successfully completed 
the institutional requirements to ensure subject rights, privacy, and security under HIPAA. 
10.1.8.4 
Site Initiation 
IRB approval and the clinical trial agreement between the clinical site and Capricor must be signed 
and executed prior to the site initiation. Additionally, the completed Form FDA 1572, applicable 
CVs and other regulatory documents must be on file with Capricor prior to site initiation. A 
representative from Capricor, or designee, will conduct a site initiation prior to enrollment of the 
first subject. Investigators, study coordinator(s), investigational pharmacist(s), and infusion 
personnel/nurse educator will participate on the site initiation webinar.  
10.1.9 
Data Handling and Record Keeping 
In order to capture the highest quality data for this protocol, data will be recorded on case report 
forms with ongoing review of the data collection by the Sponsor. Access to clinical study 
information will be based on individuals’ role and responsibilities. Data capture is designed to be 
in full compliance with ICH-GCP.  
Full information on data management is outlined in the Data Management Plan for this protocol.  
10.1.10 
Protocol Deviations 
Efforts to maximize adherence to the protocol will be made through careful and comprehensive 
training, review of trial data collected, and routine communication with all site Investigators. 
All protocol deviations and violations are to be documented and captured on the Protocol 
Deviation Log. The clinical site is responsible for reporting deviations and violations to the IRB 
per the IRB’s reporting guidelines. Capricor will ensure reporting to the proper local and federal 
regulatory authorities in accordance with all applicable federal and local regulations.  
Capricor will determine the course of action based on the severity of the deviation or violation. 
These may include but are not limited to withdrawal of the subject, additional training at the site, 
additional site monitoring, and/or other appropriate courses of action. In addition, the Medical 
Monitor and biostatistician will review the circumstances of each deviation and violation to 
determine whether data can reasonably be included in any trial analyses. 
10.1.11 
Publication and Data Sharing Policy 
Recognizing the importance of communicating clinical trial results to the public and the medical 
and scientific communities in an accurate and complete manner, the first manuscript of the trial to 
include results for publication in a peer-reviewed scientific journal will be authored by the 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 48 of 54 
Capricor, Inc. – Company Confidential 
Principal Investigator and/or other designees assigned by Capricor. All participating Investigators, 
key site personnel, committees, and committee members will be listed in an appendix as part of 
the main manuscript.  
An individual Investigator has the right to publish his/her data after the initial publication unless 
no such publication is published before the first anniversary of the finalization of the protocol 
database, in which case, the Investigator may publish or submit for publication a manuscript 
without further delay according to the terms and conditions in the Clinical Trial Agreement. 
Additional manuscripts targeting data not included in the first publication are anticipated and 
encouraged. In such cases, the Investigator(s) should submit ideas for these additional manuscripts 
to Capricor to ensure that activity between the Investigator and Sponsor in analyzing the data is 
coordinated, prioritize data analyses, and help determine authorship. 
10.1.12 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 
of this trial. Capricor has established policies and procedures for all study team members to 
disclose all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest. 
10.2 
Additional Considerations 
Not applicable. 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 49 of 54 
Capricor, Inc. – Company Confidential 
10.3 
Abbreviations 
Abbreviation 
Definition 
AE 
adverse event 
ARDS 
acute respiratory distress syndrome 
CBC 
complete blood count 
CDCs 
cardiosphere-derived cells 
CEC 
Clinical Event Committee 
CFR 
Code of Federal Regulations 
CMP 
comprehensive metabolic panel 
COPD 
Chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
DMD 
Duchenne muscular dystrophy 
DMSO 
dimethyl sulfoxide 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
ECMO 
extracorporeal membrane oxygenation 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FiO2 
fraction of inspired oxygen 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HED 
human equivalent dose 
HEENT 
head, eye, ear, nose, and throat 
HFOV 
high frequency oscillatory ventilation 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
 
 
IB 
Investigator’s Brochure 
ICH 
International Council on Harmonization 
ICU 
Intensive Care Unit 
IFN 
interferon 
IL 
interleukin 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 50 of 54 
Capricor, Inc. – Company Confidential 
IND 
Investigational New Drug Application 
IP 
investigational product (CAP-1002 or Placebo) 
IRB 
Institutional Review Board 
ITT 
intention to treat 
IV 
intravenous 
MCB 
Master Cell Bank 
MSC 
mesenchymal stem cells 
OAE 
other adverse events 
R0 
reproductive number 
RT-PCR 
reverse transcriptase-polymerase chain reaction 
SAE 
serious adverse event 
SARS 
severe acute respiratory syndrome 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SpO2 
blood oxygen saturation 
SUSAR 
suspected unexpected serious adverse reactions 
TNF 
tumor necrosis factor 
T-regs 
regulatory T lymphocytes 
WHO 
World Health Organization 
 

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 53 of 54 
Capricor, Inc. – Company Confidential 
11 
REFERENCES 
1.
Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients
with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;e201017.
2.
Callaway E, Cyranoski D, Mallapaty S, Stoye E, Tollefson J. The coronavirus pandemic
in five powerful charts. Nature. 2020;579(7800):482-483.
3.
Gu J, Gong E, Zhang B, et al. Multiple organ infection and the pathogenesis of SARS. J
Exp Med. 2005;202(3):415‐424.
4.
Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-
nCoV: host-directed therapies should be an option. Lancet. 2020;395(10224):e35‐e36.
5.
Marbán E. The secret life of exosomes: What bees can teach us about next-generation
therapeutics. J Am Coll Cardiol. 2018;71(2):193-200.
6.
Marbán E. A mechanistic roadmap for the clinical application of cardiac cell therapies. Nat
Biomed Eng. 2018;2(6):353‐361.
7.
Ibrahim AG, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration
triggered by cell therapy. Stem Cell Reports. 2014;2(5):606‐619. Published 2014 May 8.
8.
de Couto G, Gallet R, Cambier L, et al. Exosomal microRNA transfer into macrophages
mediates cellular postconditioning. Circulation. 2017;136(2):200‐214.
9.
Gallet R, Dawkins J, Valle J, et al. Exosomes secreted by cardiosphere-derived cells reduce
scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine
myocardial infarction. Eur Heart J. 2017;38(3):201‐211.
10.
Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes
and immunosuppression. Lancet. 2020;395(10229):1033‐1034.
11.
Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev
Cardiol. 2020;17(5):259‐260.
12.
Yu ZX, Ji MS, Yan J, et al. The ratio of Th17/Treg cells as a risk indicator in early acute
respiratory distress syndrome. Crit Care. 2015;19(1):82. Published 2015 Mar 11.
13.
Bonios M, Terrovitis J, Chang CY, et al. Myocardial substrate and route of administration
determine acute cardiac retention and lung bio-distribution of cardiosphere-derived cells.
J Nucl Cardiol. 2011;18(3):443-450.
14.
Hong SJ, Hou D, Brinton TJ, et al. Intracoronary and retrograde coronary venous
myocardial delivery of adipose-derived stem cells in swine infarction lead to transient
myocardial trapping with predominant pulmonary redistribution. Catheter Cardiovasc
Interv. 2014;83(1):E17-E25.
15.
Malliaras K, Smith RR, Kanazawa H, et al. Validation of contrast-enhanced magnetic
resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model
of convalescent myocardial infarction. Circulation. 2013;128(25):2764-2775.
16.
Malliaras K, Li TS, Luthringer D, et al. Safety and efficacy of allogeneic cell therapy in
infarcted rats transplanted with mismatched cardiosphere-derived cells. Circulation.
2012;125(1):100-112.

CAP-1002 for Treatment of COVID-19 
Protocol No. CAP-1002-COVID-19-2 
Amendment 2.5; 15 March 2022 
Page 54 of 54 
Capricor, Inc. – Company Confidential 
17.
Chambers DC, Enever D, Lawrence S, et al. Mesenchymal stromal cell therapy for chronic
lung allograft dysfunction: results of a first-in-man study. Stem Cells Transl Med.
2017;6(4):1152-1157.
18.
Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-
controlled, randomized trial of mesenchymal stem cells in COPD. Chest.
2013;143(6):1590-1598.
19.
Wilson JG, Liu KD, Zhuo H, et al. Mesenchymal stem (stromal) cells for treatment of
ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015;3(1):24-32.