A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of EQ001 in Subjects With Newly Diagnosed Acute Graft Versus Host Disease
Phase: PHASE1
Conditions: Acute-graft-versus-host Disease, aGVHD, GVHD, GVHD, Acute
Sponsor: Equillium

 
 
 
Study Title: 
A Phase 1B/2 Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, Pharmacodynamics, and Clinical 
Activity of EQ001 in Subjects with Newly Diagnosed 
Acute Graft Versus Host Disease 
Protocol Number: 
EQ001-aGVHD-001 
 
Investigational Product(s): 
EQ001 
 
Sponsor: 
Equillium, Inc. 
 
Development Phase: 
Phase 1b/2 
 
NCT Number: 
NCT03763318 
 
Document Version Date: 
 
24 February 2021 
 
 
 
 
CONFIDENTIAL 
 
Information contained in this protocol is proprietary and confidential in nature and may not be used, divulged, published, or 
otherwise disclosed to others except to the extent necessary to obtain approval of the Institutional Review Board/Independent 
Ethics Committee, or as required by law. Persons to whom this information is disclosed should be informed that this information 
is confidential and may not be further disclosed without the express permission of Equillium AUS Pty Ltd. 

Confidentiality Statement 
Information contained in this protocol is proprietary and confidential in nature and may not be used, 
divulged, published, or otherwise disclosed to others except to the extent necessary to obtain approval of the 
Institutional Review Board or as required by law. Persons to whom this information is disclosed should be 
informed that this information is confidential and may not be further disclosed without the express permission 
of Equillium, Inc. 
 
 
A PHASE 1B/2 STUDY TO EVALUATE THE SAFETY, TOLERABILITY, 
PHARMACOKINETICS, PHARMACODYNAMICS, AND CLINICAL ACTIVITY 
OF EQ001 IN SUBJECTS WITH NEWLY DIAGNOSED 
ACUTE GRAFT VERSUS HOST DISEASE 
CLINICAL STUDY PROTOCOL: EQ001-aGVHD-001 
IND Number: 
139877 
Indication: 
Acute Graft Versus Host Disease 
Sponsor: 
Equillium Inc. 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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SPONSOR SIGNATURE PAGE 
A PHASE 1b/2 STUDY TO EVALUATE THE SAFETY, TOLERABILITY, 
PHARMACOKINETICS, PHARMACODYNAMICS, AND CLINICAL ACTIVITY 
OF EQ001 IN SUBJECTS WITH NEWLY DIAGNOSED 
ACUTE GRAFT VERSUS HOST DISEASE 

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SYNOPSIS 
Name of Sponsor Company: Equillium, Inc. 
Name of Finished Product: EQ001 
Name of Active Ingredient: Itolizumab (Bmab 600)  
Title of Study: 
A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical 
Activity of EQ001 in Subjects with Newly Diagnosed Acute Graft Versus Host Disease 
Study Centers: 
Approximately 20 sites in North America. Additional sites and/or countries may be added, depending on subject 
accrual rates. 
Study Period: 
Approximately 12 months (2 months of treatment, 10 months 
follow-up, total of 12 months on study) for Part A and Part B 
Phase of Development: 
Phase 1b – Study Part A 
Phase 2 – Study Part B 
Objectives: 
The objectives of Part A of the study are to: 
Primary 
• Determine the safety and tolerability of intravenous (IV) dosing of EQ001 in subjects with newly 
diagnosed acute graft versus host disease (aGVHD) 
• Determine optimal IV dose level(s) of EQ001 in subjects with newly diagnosed aGVHD 
Secondary 
• To characterize the pharmacokinetics (PK) of EQ001 in subjects with newly diagnosed aGVHD 
• 
 
 
 
• To assess the clinical activity of EQ001 in subjects with newly diagnosed aGVHD 
The objectives of Part B of the study are to: 
Primary 
• To define the clinical activity of EQ001 in subjects with newly diagnosed aGVHD 
Secondary 
• To further characterize the safety, tolerability, 
 in subjects with newly diagnosed aGVHD 
Study Design: 
This is a multi-center study to evaluate the safety, tolerability, PK, 
, and clinical activity of EQ001 in subjects 
with an initial clinical presentation of aGVHD.  The study will enroll up to approximately 100 subjects in two (2) parts: 
• 
Part A – Open-label, cohort based, dose escalation component: 
Part A will enroll approximately 24 subjects in successive cohorts of 3 to 6 adult subjects each to determine 
the safety, tolerability, pharmacological, and biological activity of ascending IV doses of EQ001.  Once an 
optimal dose is determined in Part A of the study, up to approximately 15 additional subjects will be enrolled 
at the selected dose in order to collect more data. 
• 
Part B – Randomized, double-blind, placebo-controlled component: 
Part B will enroll approximately 60 additional subjects, randomized in a 2:1 ratio to either active treatment 
with an optimally defined dose of EQ001 (40) or placebo (20), to determine the safety, tolerability, and 
clinical activity of EQ001. 

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Informed consent for participation in the study will be obtained prior to any study-related procedures or 
assessments.  All subjects will be screened for potential participation, and those meeting eligibility criteria will be 
offered participation in the study.  The study will enroll subjects with an initial clinical diagnosis of aGVHD who 
require systemic immunosuppressive treatment.  All subjects will receive standard treatment for aGVHD with 
systemically administered corticosteroids, prednisone at approximately 1-2 mg/kg/day (or its equivalent) at the 
time of the first dose of study drug administration.  The first dose of study drug must be administered within 
72 hours (3 days) of receipt of the subject’s initial corticosteroid dose. 
Screening assessments will include: a medical history, physical exam, aGVHD organ stages and overall clinical 
grading
 aGVHD activity index [aGVHD-AI] 
, vital signs, an electrocardiogram 
(ECG), laboratory tests (clinical chemistries, hematology, coagulation panel, urinalysis, pregnancy test in females 
of childbearing potential only and viral serologies), study eligibility check, recording of prior and concomitant 
medications and treatments and collection of relevant biopsy data. 
During the study, subjects will undergo periodic evaluations including physical exams, aGVHD organ stages and 
overall clinical grading 
 aGVHD-AI
 vital signs, ECG, laboratory tests, PK (Part A 
only)/
 and anti-drug antibody (ADA) sampling, a skin biopsy (optional in Part B only), stool sample 
(optional in Part B only), recording of concomitant medication usage, adverse event (AE) monitoring, disease 
progression assessments and collection of relevant biopsy data. 
Part A of the study will utilize a standard 3 + 3 dose escalation design until a dose is selected.  Cohort enrollment 
will proceed in a sequential manner to evaluate escalating dose levels of EQ001: Cohort 1 – 0.4 mg/kg, Cohort 2 – 
0.8 mg/kg, Cohort 3 – 1.6 mg/kg, and Cohort 4 – 2.4 mg/kg.  Dose escalation will proceed if no predefined 
stopping criteria are met.  The dose-limiting toxicity (DLT) assessment period will be the first 29 days of 
treatment (i.e., Study Days 1 to 29) and will guide dose escalation decisions.  Subjects will be considered 
evaluable for DLT assessment if they have received at least two doses of study drug and completed study 
assessments through Study Day 29 or received at least one dose of study drug and had a DLT within the first 29 
days on study.  Enrollment of the next higher dose cohort will not commence until all safety data from all subjects 
from prior cohorts and all available safety data from the current cohort through Study Day 29 are reviewed by the 
Data and Safety Monitoring Committee (DSMC) and approval is granted for dose escalation.  
 
 
 
 
Part B of the study will be randomized, double blinded, and placebo controlled, and will commence following the 
completion of Part A and approval by the DSMC.  In Part B, up to 60 subjects will be enrolled to better define the 
safety, tolerability,
, and immunogenicity of EQ001, and to explore the clinical activity of EQ001 
in subjects with newly diagnosed aGVHD. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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experiences a DLT, then 3 additional subjects will be enrolled at the same dose level for a total of up to 
6 evaluable subjects.  If 1 out of the 6 subjects experience a DLT, then escalation may proceed to the next higher 
dose level.  If two (2) or more subjects experience a DLT, no additional subjects will be enrolled in the cohort, and 
the next lower dose level will enroll additional subjects for a total of 6 evaluable subjects. 
AEs will be graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) 
v5.0.  Further, the relationship of each AE to the study drug will be assessed by the investigator as related, 
probably related, possibly related, unlikely related, or not related.  
 
 
 
 
 
 
 
Subject Stopping Criteria: 
Dosing of EQ001 will be permanently discontinued in a subject if any of the following occurs: 
During Part A: 
• Any DLT 
 
 
 
  
During Part B: 
• Study drug related toxicity that cannot be controlled with supportive care despite 1 dose reduction and/or delay 
of treatment for up to 1 week 
 
 
 
  
During any part of the study: 
• Withdrawn consent 
• Investigator or Sponsor considers that the subject will not benefit from further investigational product  
• Pregnancy 
• Subject is not able to comply with the study requirements 
• Sponsor terminates the study 
• A regulatory authority mandates study dosing cessation 
Number of Subjects Planned: 
Up to approximately 100 subjects with newly diagnosed aGVHD are planned to be enrolled in the study. 
Diagnosis and Main Criteria for Inclusion:  
Inclusion Criteria: 
Subjects must meet all the following inclusion criteria to be eligible for study participation: 
1. Male or female subject at least 18 years of age for Part A, and at least 12 years of age for Part B. 
2. Recipients of first allogeneic hematopoietic stem cell transplantation (alloHSCT) using myeloablative or 
non-myeloablative conditioning regimens. 
 
 
 
 

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7. Deemed by the investigator to be likely to comply with the protocol for the duration of subject’s enrollment. 
Exclusion Criteria: 
Subjects meeting any of the following exclusion criteria are not eligible for study participation: 
1. Presence of morphologic relapsed primary malignancy, treatment for relapse after alloHSCT was performed, 
or requirement for rapid immunosuppressive treatment withdrawal for early malignancy relapse. 
2. Evidence of graft failure based on cytopenia(s), as determined by the investigator. 
3. Evidence of post-transplant lymphoproliferative disease. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Safety evaluations may also include changes in the subject’s physical examination findings, vital signs, and ECG 
findings. 
 
 
A detailed description of data analysis and statistical methods to be used will be outlined separately in a Statistical 
Analysis Plan (SAP). 
 
 

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TABLE OF CONTENTS 
 
 
Synopsis ...........................................................................................................................................4 
 
 
 
 
1. 
INTRODUCTION ................................................................................................................21 
1.1. 
Background ...............................................................................................................21 
1.2. 
Itolizumab .................................................................................................................21 
 
 
 
 
 
 
 
 
 
 
 
 
1.6. 
Rationale for Evaluating EQ001 for the Treatment of aGVHD ...............................25 
1.7. 
Rationale for Selection of Starting Dose ..................................................................26 
2. 
STUDY OBJECTIVES ........................................................................................................27 
2.1. 
Study Part A ..............................................................................................................27 
2.1.1. 
Primary Objectives ......................................................................................27 
2.1.2. 
Secondary Objectives ..................................................................................27 
2.2. 
Study Part B ..............................................................................................................27 
2.2.1. 
Primary Objective........................................................................................27 
2.2.2. 
Secondary Objective....................................................................................27 
3. 
INVESTIGATIONAL PLAN ..............................................................................................28 
3.1. 
Overall Study Design and Plan .................................................................................28 
3.2. 
Data and Safety Monitoring Committee (DSMC), Dose-Limiting Toxicity, 
and Stopping Criteria ................................................................................................30 
3.2.1. 
Dose-Limiting Toxicities ............................................................................31 
3.2.2. 
Subject Stopping Criteria ............................................................................31 

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3.2.3. 
Study Stopping Criteria ...............................................................................32 
3.3. 
Rationale for Study Design .......................................................................................32 
3.4. 
Study Duration and Number of Centers ...................................................................33 
4. 
STUDY POPULATION SELECTION ................................................................................34 
4.1. 
Study Population .......................................................................................................34 
 
 
4.3. 
Inclusion Criteria ......................................................................................................34 
4.4. 
Exclusion Criteria .....................................................................................................35 
5. 
STUDY TREATMENT(S) ..................................................................................................37 
 
 
5.2. 
Study Drug ................................................................................................................37 
5.3. 
Treatment(s) Administered .......................................................................................38 
5.3.1. 
Part A ...........................................................................................................38 
5.3.2. 
Part B ...........................................................................................................38 
 
 
 
 
5.4. 
Prior and Concomitant Medication ...........................................................................40 
5.4.1. 
Permitted Therapies .....................................................................................40 
5.4.2. 
Prohibited Therapies....................................................................................41 
5.5. 
Treatment Compliance ..............................................................................................41 
 
 
5.7. 
Enrollment or Randomization and Blinding .............................................................41 
5.7.1. 
Part A ...........................................................................................................41 
5.7.2. 
Part B ...........................................................................................................42 
 
 
6. 
STUDY PROCEDURES ......................................................................................................44 
6.1. 
Screening and Informed Consent ..............................................................................44 
6.2. 
Demographics and Medical History .........................................................................44 
6.3. 
Physical Exam...........................................................................................................45 
6.4. 
Vital Signs.................................................................................................................45 
6.5. 
Disease Progression Assessment ..............................................................................45 

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6.6. 
aGVHD Organ Stages, Overall aGVHD Clinical Grades, aGVHD Activity 
Index Scoring Algorithm, and Ann Arbor Risk Score..............................................46 
6.7. 
Biopsy Review ..........................................................................................................46 
6.8. 
Minimal Residual Disease (MRD) ...........................................................................46 
6.9. 
Chronic GVHD (cGVHD) ........................................................................................46 
6.10. 12-Lead Electrocardiography ...................................................................................46 
6.11. Clinical Laboratory Tests..........................................................................................47 
6.11.1. Local Laboratory Parameters ......................................................................47 
6.11.2. Central Laboratory Parameters ....................................................................48 
6.11.2.1. Pharmacokinetic (Part A only) ..................................................48 
6.11.2.2. Anti-Drug Antibody (ADA) and Neutralizing ADA (NAB) ....48 
 
 
 
 
 
 
6.11.3. Priority for Laboratory Sample Collection ..................................................51 
6.11.4. Research Use of Stored Human Samples, Specimens, or Data ...................51 
6.12. Removal of Subjects from the Study ........................................................................51 
7. 
ADVERSE EVENTS ...........................................................................................................52 
7.1. 
Severity .....................................................................................................................52 
7.2. 
Relationship ..............................................................................................................53 
7.3. 
Clinical Laboratory Adverse Events .........................................................................53 
7.4. 
Serious Adverse Events ............................................................................................54 
7.5. 
Reporting Adverse Events ........................................................................................54 
7.5.1. 
Reporting Procedures for Non-Serious Adverse Events .............................54 
7.5.2. 
Reporting Procedures Serious Adverse Events ...........................................55 
 
 
7.7. 
Expected Clinical Adverse Events in Subjects with aGVHD...................................56 
 
 
 
 
 
 
 
 
 
 

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9. 
PLANNED STATISTICAL METHODS .............................................................................66 
9.1. 
General Considerations .............................................................................................66 
 
 
9.3. 
Analysis Populations.................................................................................................66 
9.3.1. 
Safety Population ........................................................................................66 
9.3.2. 
Pharmacokinetic Analysis Population (Part A) ...........................................66 
 
 
9.3.4. 
Efficacy Population (Part B) .......................................................................67 
9.4. 
Subject Disposition ...................................................................................................67 
9.5. 
Demographics and Baseline Characteristics .............................................................67 
9.6. 
Statistical Analysis of Pharmacokinetic Variables ...................................................67 
9.7. 
Safety Analysis .........................................................................................................67 
 
 
9.9. 
Efficacy Analyses .....................................................................................................68 
9.10. Interim Analysis ........................................................................................................68 
10. 
ADMINISTRATIVE CONSIDERATIONS ........................................................................69 
10.1. Investigator Responsibilities .....................................................................................69 
10.2. Institutional Review Board (IRB) Approval .............................................................69 
10.3. Ethical Conduct of the Study ....................................................................................70 
10.4. Subject Information and Consent .............................................................................70 

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10.5. Confidentiality ..........................................................................................................71 
10.6. Study Initiation .........................................................................................................72 
10.7. Case Report Forms and Study Records ....................................................................72 
10.8. Study Monitoring ......................................................................................................73 
10.9. Access to Source Documentation .............................................................................73 
10.10. Study or Study Site Termination ..............................................................................73 
 
 
10.13. Quality Assurance .....................................................................................................74 
10.14. Retention of Data ......................................................................................................75 
10.15. Study Report and Publications ..................................................................................75 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse events of special interest 
aGVHD 
acute graft versus host disease 
aGVHD-AI 
acute Graft Versus Host Disease Activity Index 
ALC 
absolute lymphocyte count 
ALCAM 
activated leukocyte cell adhesion molecule  
alloHSCT 
allogeneic hematopoietic stem cell transplantation  
ALT 
alanine aminotransferase (SGPT) 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase (SGOT) 
AUC 
area under the time-concentration curve 
BUN 
blood urea nitrogen 
CFR 
Code of Federal Regulations 
cGVHD 
chronic graft versus host disease 
Cl 
Clearance 
Cmax 
maximum serum drug concentration 
Cmin 
minimum serum drug concentration 
CMV 
Cytomegalovirus 
CRF 
case report form 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLI 
donor lymphocyte infusion 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DSMC 
Data and Safety Monitoring Committee 
EBV 
Epstein Barr virus 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EOI 
end of infusion 
ET 
early termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
GI 
Gastrointestinal 
GVHD 
graft versus host disease 
HBV 
hepatitis B virus 
Hct 
Hematocrit 
HCV 
hepatitis C virus 
Hgb 
Hemoglobin 
HHV-6 
human herpes virus 6 
HIPAA 
Health Information Portability and Accountability Act 

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HSCT 
hematopoietic stem cell transplantation  
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonisation  
IgG1 
immunoglobulin G1  
IND 
Investigational New Drug  
INR 
International Normalized Ratio 
 
 
IRB 
Institutional Review Board 
IV 
Intravenous 
IWRS 
interactive web response system 
LDH 
lactic dehydrogenase 
LYO 
Lyophilization 
mAb 
monoclonal antibody 
MAGIC 
Mount Sinai Acute GVHD International Consortium 
MedDRA 
Medical Dictionary for Regulatory Activities 
NAB 
neutralizing ADA 
NYHA 
New York Heart Association 
PBMC 
peripheral blood mononuclear cell 
 
 
Ph.Eur. 
European Pharmacopoeia 
PK 
Pharmacokinetics 
PT 
preferred term 
RBC 
red blood cells 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
Sc 
scavenger receptor cysteine-rich 
SCID 
severe combined immune deficiency 
SGOT 
serum glutamic oxaloacetic transaminase (AST) 
SGPT 
serum glutamic pyruvic transaminase (ALT) 
SOC 
system organ class 
t½ 
half-life 
TCR 
T cell receptor 
TEAEs 
treatment-emergent adverse events 
TESAEs 
treatment-emergent serious adverse events 
Th17 
T helper 17  
Tmax 
time to maximum serum concentration 
ULN 
upper limit of normal 
USP 
United States Pharmacopeia 
US 
United States 
Vd 
volume of distribution 
WBC 
white blood cell (count) 

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1.6. 
Rationale for Evaluating EQ001 for the Treatment of aGVHD 
As the number of HSCTs continues to increase each year, the importance and need for effective 
therapies to prevent the occurrence of GVHD and treat both aGVHD and cGVHD and thereby 
improve outcomes for this potentially curative therapy cannot be over-emphasized.  
 
 
 
 
 
 
  
 
 
  
 
 
 
 
Thus, there is an urgent unmet medical need for development of targeted, safe, and effective 
treatment strategies for both aGVHD and cGVHD to improve long-term post-transplant 
outcomes and quality of life for HSCT recipients. 

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1.7. 
Rationale for Selection of Starting Dose 
A robust body of clinical data exists to inform the selection of a starting dose, and dose regimen, 
for EQ001 in this study. 
 
 
 
 
 
 
 

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2. 
STUDY OBJECTIVES 
2.1. 
Study Part A 
2.1.1. 
Primary Objectives 
The primary objectives of Part A of this study are: 
• 
Determine the safety and tolerability of intravenous (IV) dosing of EQ001 in subjects with 
newly diagnosed acute graft versus host disease (aGVHD) 
• 
Determine optimal IV dose level(s) of EQ001 in subjects with newly diagnosed aGVHD 
2.1.2. 
Secondary Objectives 
The secondary objectives of Part A of this study are as follows: 
• 
To characterize the pharmacokinetics (PK) of EQ001 in subjects with newly diagnosed 
aGVHD 
 
 
 
 
 
• 
To assess the clinical activity of EQ001 in subjects with newly diagnosed aGVHD 
2.2. 
Study Part B 
2.2.1. 
Primary Objective 
The primary objective of Part B of this study is to define the clinical activity of EQ001 in 
subjects with newly diagnosed aGVHD. 
2.2.2. 
Secondary Objective 
The secondary objective of Part B of this study is to further characterize the safety, tolerability, 
 of EQ001 in subjects with newly diagnosed aGVHD. 

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3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This is a multi-center study to evaluate the safety, tolerability, PK, 
and clinical activity of 
EQ001 in subjects with an initial clinical presentation of aGVHD.  The study will enroll up to 
approximately 100 subjects in two (2) parts 
 
• 
Part A – Open-label, cohort based, dose escalation component: 
Part A will enroll approximately 24 subjects in successive cohorts of 3 to 6 adult subjects 
each to determine the safety, tolerability, pharmacological, and biological activity of 
ascending IV doses of EQ001.  Once an optimal dose is determined in Part A of the study, up 
to approximately 15 additional subjects will be enrolled at the selected dose in order to 
collect more data. 
• 
Part B – Randomized, double-blind, placebo-controlled component: 
Part B will enroll approximately 60 additional subjects, randomized in a 2:1 ratio to either 
active treatment with an optimally defined dose of EQ001 (40) or placebo (20), to determine 
the safety, tolerability, and clinical activity of EQ001.  
Part A of the study will utilize a standard 3 + 3 dose escalation design until a dose is selected.  
Cohort enrollment will proceed in a sequential manner to evaluate the escalating dose levels of 
EQ001 (Section 5.3.1).  Dose escalation will proceed as long as no predefined stopping criteria 
are met.  The dose-limiting toxicity (DLT) assessment period will be the first 29 days of 
treatment (i.e., Study Days 1 to 29) and will guide dose escalation decisions.  Subjects will be 
considered evaluable for DLT assessment if they have received at least two doses of study drug 
and completed through Study Day 29 or received at least one dose of study drug and had a DLT 
within the first 29 days on study.  Enrollment of the next higher dose cohort will not commence 
until all safety data from all subjects from prior cohorts and all available safety data from the 
current cohort through Study Day 29 are reviewed by the Data and Safety Monitoring Committee 
(DSMC) and approval is granted for dose escalation.  An optimal dose of EQ001 will be 
determined based on all available data, including safety, tolerability, 
. 
Once a dose is selected, up to approximately 15 additional subjects will be enrolled at the 
selected dose in order to collect more data. 
Part B of the study will be randomized, double blinded, and placebo controlled, and will commence 
following the completion of Part A and approval by the DSMC.  In Part B, approximately 
60 subjects will be enrolled to better define the safety, tolerability,
, 
and to explore the clinical activity of EQ001 in subjects with newly 
 
 aGVHD. 
After informed consent has been obtained, all subjects will be screened for potential 
participation, and those meeting eligibility criteria will be offered participation in the study.  The 
study will enroll subjects with an initial clinical diagnosis of aGVHD requiring systemic 
immunosuppressive treatment.  All subjects must receive their first dose of study drug within 
72 hours (3 days) of the subject’s initial systemically administered corticosteroid dose. 

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The systemically administered corticosteroid treatment will be prednisone, at approximately 1-
2 mg/kg/day (or its equivalent) at the time of first dose of study drug administration; however, the 
investigator can adjust dosing as clinically indicated during the study according to the 
recommended treatment and tapering schedule 
 
Subjects in Parts A and B will have the same study assessments except as noted.  All subjects 
will have two (2) months of dosing comprising five (5) doses of study drug, administered IV 
every fourteen (14) days, and ten (10) months of follow up for a total of twelve (12) months in 
the study. The follow-up period will consist of a 2-month Safety Follow-Up period (through Day 
169) and then an 8-month Long-Term Follow-Up period (through Day 337). 
 
 overview of the study timeline for Part A and Part B, respectively. During the 
Long-Term Follow-Up period, the site will phone subjects on Study Days 253 and 337 to collect 
information on disease status (disease relapse or cGVHD), long-term survival, and safety (eg, 
recent hospitalization or SAEs). 

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3.2. 
Data and Safety Monitoring Committee (DSMC), Dose-Limiting Toxicity, and 
Stopping Criteria 
The purpose of the DSMC is to provide an unbiased review of the safety data generated by the 
clinical trial.  An independent DSMC will be established to review clinical trial data prior to dose 
escalation and during Part B on an as-needed basis.  A statistician, serving as a non-voting 
member to the DSMC, will provide data preparation support to the DSMC.  A sponsor representative 
will also serve as a non-voting member of the DSMC to facilitate sponsor internal planning. 
The Chair of the DSMC will be informed by the Protocol Chair or the Sponsor of the potential 
need for ad hoc meetings and will coordinate such meetings.  A formal DSMC Charter will be 
prepared and finalized prior to study enrollment. 
The DSMC will review all available clinical and laboratory safety data at defined intervals 
during the conduct of each cohort in Part A and periodically during Part B of the study.  Based 
on a review of available data, the DSMC will make recommendations regarding the continuation, 
discontinuation or modification of the study, cohort advancement (during Part A), and 
progression to Part B of the study. 
During Part A of the study, the DSMC will apply the following dose-escalation rules per cohort. 
• 
For each cohort, if 0 of the 3 initial evaluable subjects experiences a DLT (see 
Section 3.2.1 for DLT definition), then escalation may occur to the next higher dose level. 
• 
If 1 of the 3 initial subjects experiences a DLT, then 3 additional subjects will be enrolled at 
the same dose level for a total of up to 6 evaluable subjects. 
• 
If 1 out of the 6 subjects experience a DLT, then escalation may proceed to the next higher 
dose level. 
• 
If two (2) or more subjects experience a DLT, no additional subjects will be enrolled in the 
cohort, and the next lower dose level will enroll additional subjects for a total of 6 evaluable 
subjects. 

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The Sponsor will apply the following criteria to the determination of optimal dose in Part A of 
the study: 
• 
Adequate safety without DLT 
and 
 
 
If more than one dose meets these criteria, then additional safety, tolerability, PK,
 and 
efficacy data will be taken into consideration to select a dose. 
DSMC decisions regarding advancement to the next higher cohort will be governed by the 
principle that the study is not intended to define a maximally tolerated dose (MTD).  As such, no 
further dose escalations will occur once the second of two administered dose levels meet the 
criteria for an optimal dose, even if the observed safety and tolerability profile of the second 
(higher) dose level supports further dose escalation. 
Additional subjects may be enrolled in cohorts if approved by the DSMC to further characterize 
drug safety, tolerability, or efficacy.  Also, the DSMC may recommend modification of the doses 
to be evaluated, to not initiate specific dose cohorts, to initiation additional dose cohorts, or to 
terminate the study if it is deemed necessary.  Appropriate regulatory approvals will be obtained 
prior to initiation of any recommended changes by the DSMC, as required. 
3.2.1. 
Dose-Limiting Toxicities 
During the 3+3 dose-escalation of Part A, any of the following events that are considered by the 
investigator to be at least possibly related to the study drug are considered DLTs during the DLT 
window Study Days 1–29: 
 
  
 
  
3.2.2. 
Subject Stopping Criteria 
Dosing of EQ001 will be permanently discontinued in a subject if any of the following occur: 
During Part A: 
• 
Any DLT 
 
 
 
  
During Part B: 
• 
Study drug related toxicity that cannot be controlled with supportive care, despite 1 dose 
reduction and/or delay of treatment for up to 1 week 

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During any part of the study: 
• 
Withdrawn consent 
• 
Investigator or Sponsor considers that the subject will not benefit from further investigational 
product  
• 
Pregnancy 
• 
Subject is not able to comply with the study requirements 
• 
Sponsor terminates the study 
• 
A regulatory authority mandates study dosing cessation 
The investigator will classify AEs that are observed in a subject as either expected to occur based 
on the underlying disease (Section 7.7) and/or are consistent with the AE profile in the current 
EQ001 Investigator’s Brochure, or unexpected based on their prior clinical experience and 
management of aGVHD patients. 
3.2.3. 
Study Stopping Criteria 
The DSMC can recommend stopping the study at any time based on emerging safety data.  
 
 
 
 
 
 
 
If the recommendation of the DSMC is to halt study dosing for all subjects or pause enrollment, 
it can be resumed based on the recommendation of the DSMC after further review of all 
available safety data and notifications of/submission to appropriate regulatory agencies and 
institutional review committees, in line with country-specific regulations. 
3.3. 
Rationale for Study Design 
The design of this study includes both an open-label (Part A) as well as a double-blinded and 
placebo-controlled (Part B) component.  A two-part study utilizing different designs was chosen 
to support the attainment of the objectives that are specific to each part of the study. 
Part A has been designed to explore the safety and tolerability of ascending dose levels of the IV 
administration of multiple doses of EQ001.  An open-label design is supported by the availability 
of extensive safety and tolerability data on itolizumab for which to compare the open-label safety 
data generated in this study.  A cohort-based dose escalation design was chosen to rigorously 
evaluate, and conservatively escalate, IV doses of EQ001. Once a dose is selected in Part A, up 
to 15 additional subjects will be enrolled at that dose level for additional data. 

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Part B has been designed to explore the clinical activity of the IV administration of multiple 
doses of EQ001.  A blinded, placebo-controlled design was chosen to provide the most 
rigorously assessments of efficacy possible in aGVHD. 
3.4. 
Study Duration and Number of Centers 
Each subject will have 2 months of treatment and 10 months of follow-up (2 months of safety 
follow-up and 8 months of long-term follow-up), for a total of 12 months on study.  
This study will be conducted at approximately 20 clinical sites in North America.  Additional 
sites and/or countries may be added, depending on subject accrual rates. 

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7. Deemed by the investigator to be likely to comply with the planned procedure as required 
by the protocol for the duration of the study. 
4.4. 
Exclusion Criteria 
Subjects meeting any of the following exclusion criteria are not eligible for study participation: 
1. Presence of morphologic relapsed primary malignancy, treatment for relapse after 
alloHSCT was performed, or requirement for rapid immunosuppressive treatment 
withdrawal for early malignancy relapse. 
2. Evidence of graft failure based on cytopenia(s), and as determined by the investigator. 
3. Evidence of post-transplant lymphoproliferative disease 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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14. As determined by the investigator, any medical, psychiatric, or other condition or 
circumstance that is likely to negatively affect: the subject’s participation in this clinical 
study, the subject’s safety, or the reliability of the study data. 

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5. 
STUDY TREATMENT(S) 
 
 
 
 
5.2. 
Study Drug 
In Part A, all subjects will receive their cohort assigned dose of EQ001.  In Part B, subjects will 
be randomized in a blinded fashion to either EQ001 or placebo using a 2:1 allocation. 
The study drugs are: 
• 
EQ001, containing the active ingredient itolizumab (Bmab 600), a humanized recombinant 
IgG1 mAb that selectively targets the extracellular Sc membrane-distal domain 1 of human 
CD6
 
• 
Placebo is a sterile, clear, colorless, preservative-free solution with the same formulation 
(minus the drug) as EQ001
 

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5.4.2. 
Prohibited Therapies 
 
 
 
 
 
 
 
 
 
 
  
If a determination is made to treat a subject with any these therapies or medications during the 
study, the Medical Monitor should be informed.  Subjects will be asked to remain in the study 
and complete the remaining visits, but no additional study drug will be administered. 
5.5. 
Treatment Compliance 
The study drug will be administered open-label in Part A and in a blinded fashion in Part B at the 
clinic/facility by a qualified staff member.  The date and start and stop times of the infusion will 
be recorded.  
 
 
 
 
 
 
 
 
5.7. 
Enrollment or Randomization and Blinding 
It is the responsibility of the investigator to ensure that subjects are eligible to participate in the 
study prior to enrollment and continue to remain eligible throughout the study.  An interactive 
web response system (IWRS) will be used for the study to ensure study drug inventory, 
accountability and appropriate cohort allocation and blinded treatment assignment.  The site’s 
unblinded Pharmacist or designee will have access to the IWRS  and all treatment assignments. 
5.7.1. 
Part A 
Part A of the study is open-label.  Once informed consent has been obtained, all screening 
procedures have been assessed, and study eligibility has been confirmed, subjects will be 
enrolled to receive EQ001 on Study Day 1.  The study Pharmacist or designee will access the 

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IWRS to enroll the subject into the study, receive cohort assignment, dose level, record drug 
accountability, and request resupply. 
5.7.2. 
Part B 
Part B of the study will be randomized, double blinded, and placebo controlled.  Subjects will be 
randomized in a 2:1 ratio to an optimal dose of EQ001 (as determined in Part A) or placebo. 
Once informed consent has been obtained, all screening procedures have been assessed, and 
study eligibility has been confirmed, subjects will be randomized to receive either EQ001 or 
placebo on Study Day 1.  The unblinded study Pharmacist or designee will access the IWRS to 
randomize the subject into the study, receive the blinded treatment assignment, dose level, record 
drug accountability, and request resupply. 
Investigators, site staff, subjects, and the Sponsor and/or designee will be blinded to treatment 
assignment.  The unblinded pharmacist or designee will be instructed not to divulge the 
treatment administered of any subject with the blinded site personnel, study subject, caregiver, 
and/or Sponsor or designee. 
The blind should be broken only if knowledge of the subject’s treatment allocation would 
facilitate specific emergency treatment.  Unblinding procedures are provided in the Pharmacy 
Manual.  The investigator must contact the Sponsor and/or designee prior to unblinding a 
subject’s treatment assignment.  In the event of an emergency when unblinding is necessary and 
the Sponsor and/or designee could not be contacted, the investigator should contact the Sponsor 
and/or designee as soon as possible after the unblinding. 
 
 
 
 
 
 
 
Upon completion or termination of the study, all unused and partially used (if allowed by 
site/institutional procedure to be retained) investigational product must be returned to the 
Sponsor (or designated agent) unless the Sponsor authorizes the study site to destroy 
investigational product. 
If the Sponsor authorizes the study site to destroy investigational product, the investigator is 
responsible to ensure that arrangements are made for proper disposal.  Written authorization 
should be issued by the Sponsor; procedures for proper disposal should be established according 
to applicable regulations, guidelines, and procedures; and appropriate records of the disposal 
should be documented and forwarded to the Sponsor. 

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If the study site is unable to destroy the investigational product, the unblinded study monitor will 
facilitate the return of unused and/or partially used investigational product. 

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6. 
STUDY PROCEDURES 
Subjects in Parts A and B will have the same study assessments except as noted.  The following 
assessments will be conducted during screening and at selected time points specified in the 
Schedules of Events 
 and in Protocol Section 8.  Additional 
procedures deemed necessary as part of standard of care may be performed at the discretion of 
the investigator.  All missed visits and any performed procedures that are not protocol-specified 
activities must be documented in the subject’s medical record and the appropriate electronic case 
report form (eCRF). 
6.1. 
Screening and Informed Consent 
Before subjects commence any study-specific activities or procedures, the Sponsor requires a 
copy of the study site’s written Institutional Review Board (IRB) approval of the protocol, 
informed consent form (ICF), and all other subject information and/or recruitment material, if 
applicable.  Each subject (or legally acceptable representative) must sign and date the ICF before 
participating in study-specific activities. 
After the ICF is signed, the subject enters screening.  Each subject will be assigned a unique 
subject number at the time of screening.  Subject numbers will be sequential within each study 
site.  If more than one (1) assessment is performed during screening, the initial assessment 
closest to the enrollment date and time will be used for eligibility.  Subjects must have their first 
dose of study drug within 72 hours (3 days) of their first corticosteroid dose, therefore, sites 
should consent and start screening subjects as soon as aGVHD is suspected. 
This subject number, assigned at the time of screening, will be used to identify the subject 
throughout the study and must be used on all study documentation related to that subject.  The 
subject identification number will remain constant throughout the entire study; it must not be 
changed after initial assignment.  Each study site will maintain a list identifying all subjects by 
subject identification number and initials. 
After completing the screening period, the subject will be evaluated by the investigator to 
confirm eligibility.  A subject is considered enrolled when the investigator decides that all of the 
eligibility criteria are met.  The investigator will document this decision and date and time in the 
subject’s medical record and the eCRF.  Screen failure subjects will be entered into the eCRF.  
Investigators will maintain a screening log of all potential study candidates that includes limited 
information about each candidate, dates, and outcome of screening process (e.g., enrolled into 
study, reason for ineligibility, or withdrawal of consent). 
6.2. 
Demographics and Medical History 
Demographic data including sex, age, race, and ethnicity will be collected. 
The investigator or designee will collect medical and surgical history that started prior to 
enrollment, including information on the subject’s concurrent medical conditions.  All findings 
will be recorded on the medical history eCRF. 

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6.3. 
Physical Exam 
The investigator or designee will conduct a complete physical exam during screening and a 
targeted physical exam at selected time points thereafter.  Physical exam finding prior to the first 
dose of study drug will be recorded on the medical history eCRF page and clinically significant 
findings after the first dose of study drug will be recorded as AEs. 
At a minimum, the complete physical exam should include assessments of the head and neck, skin, 
nervous system, lungs, cardiovascular system, abdomen, thyroid, lymph nodes, and extremities. 
A targeted physical exam will include assessment of any new subject complaints or changes 
from baseline, including clinical grade of aGVHD at diagnosis and organ involvement at 
diagnosis, infusion-related reactions, and examinations for potential hypersensitivity reactions. 
6.4. 
Vital Signs 
The following vital sign measurements will be performed: systolic and diastolic blood pressure, 
pulse, respiration rate, and temperature.  On dosing days, vital signs will be monitored pre-dose 
and every 30 minutes (± 5 minutes) 
 
The subject must be in seated or in a semi-recumbent position in a rested and 
calm state for at least 10 minutes before vital signs are collected.  The position selected for a 
subject should be the same throughout the study and documented on the vital signs eCRF. 
Height will be measured without shoes at screening. 
Weight without shoes will be obtained at screening.  On dosing days, weight will be collected 
pre-dose.  The weight at screening will be used to calculate all study drug doses unless there has 
been a change in weight by 20% or greater. An additional subsequent change in dosing will not 
occur unless there is a change in weight of 20% or more from the new weight that required the 
dosing change to be made (no longer referencing back to the Screening weight at subsequent 
doses). 
 
 
 
 
 
 
 

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6.7. 
Biopsy Review 
Any relevant tissue biopsy (eg, gastrointestinal, liver, bone marrow, or skin), performed per 
standard of care to support the clinical diagnosis and/or management of a subject’s aGVHD at 
any time prior to and during the subject’s enrolment, should be collected and the clinical data 
derived from the biopsy entered into the eCRF. Biopsies that were performed prior to and during 
screening to confirm the diagnosis of aGVHD should be recorded. 
6.8. 
Minimal Residual Disease (MRD) 
Assessments of MRD should be captured if they were done anytime from the time of the HSCT 
through baseline (Day 1). 
6.9. 
Chronic GVHD (cGVHD) 
An assessment of cGVHD will be performed during the long-term follow-up visits. 
6.10. 12-Lead Electrocardiography 
The subject must be in a seated, semi-recumbent, or supine position in a rested and calm state for 
at least 10 minutes before ECG assessment is conducted.  Each 12-lead ECG should be 
performed prior to blood draws, dosing (if applicable, except for Baseline post-dose ECG), or 
other invasive procedures. 
In Part A, a single ECG will be recorded using the site’s standard ECG equipment.  The 
investigator or designated study site physician will review, sign, and date all ECGs.  The original 
ECGs will be retained with the subject’s source documents.  At the request of the Sponsor, a 
copy of the original ECG will be made available to the Sponsor.  Each ECG should capture QRS, 
QT, QTc, RR, and PR intervals and be documented on the ECG eCRF. 
In Part B, ECGs in triplicate taken over 5 minutes will be recorded using the ECG equipment 
provided and transmitted to a central ECG reader.  The ECG results will be assessed by blinded, 
independent, central review to evaluate changes in ECG intervals and morphology as compared 

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with pretreatment ECGs.  An ECG manual will be provided. The investigator or designated study 
site physician will also review, sign, and date all ECGs.  The original ECGs will be retained with 
the subject’s source documents. 
Any clinically significant abnormal ECG findings will be recorded as AEs. 
6.11. Clinical Laboratory Tests 
6.11.1. 
Local Laboratory Parameters 
Blood samples will be collected 
 
, Protocol Section 8 and below.  All safety laboratory test will be conducted at the 
local clinic/facility.  Samples will be collected pre-dose on study dosing days.  Repeat laboratory 
testing is not required if a test was already performed within the specified time window for 
collection.  Samples may be analyzed for the tests outlined in this protocol and for any additional 
tests necessary to ensure subject safety.  These may include, but are not limited to, investigation 
of unexpected results.  Subjects will be in a seated, semi-recumbent, or supine position during 
blood collection.  
 

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6.11.2. 
Central Laboratory Parameters 
Blood, skin biopsy, and stool samples will be collected 
 
 Protocol Section 8 and below from screening through the follow-
up visits and submitted to the central laboratories for analysis.  
 
 
 
6.11.2.1. 
Pharmacokinetic 
 
In Part A only, serum will be assayed for EQ001 concentrations using a validated assay.  PK 
samples will be collected at time points specified below.  Based on emerging PK data, the actual 
collection times may change after discussion between the investigator and Sponsor.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.11.2.2. 
Anti-Drug Antibody (ADA) and Neutralizing ADA (NAB) 
Serum samples will be obtained for detection of ADA against EQ001 as outlined below and if 
required a neutralizing ADA assay will be run on the same sample.  Samples will be batched and 
run at the end of Part A and at the end of Part B.  
 
 
 
 
 
 
 
 
 
 
 

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6.11.4. 
Research Use of Stored Human Samples, Specimens, or Data 
De-identified data obtained from this study may be shared with other academic institutions after 
completion of the study.  Furthermore, any remaining plasma, blood, and tissue samples may be 
stored for future analysis to help understand the markers for disease state, progression, and 
response to treatment as new discoveries emerge.  
 
 
 
 
6.12. Removal of Subjects from the Study 
At any time, the investigator can remove a subject from the study or stop study drug dosing if 
deemed necessary for subject safety.  The Sponsor also reserves the right to terminate the study 
at any time.  All data normally collected at completion of the study must be collected at the time 
of the subject’s early termination or termination of the study (see Section 8.12 or Section 8.15, as 
appropriate). If consent has not been withdrawn, AEs will continue to be collected as described 
in Section 7. 
A termination case report form (CRF) page will be completed for every subject enrolled, whether 
or not the subject completed the study.  The reason for any early discontinuation from the study 
should be indicated on this form.  Separate CRF entries will document whether each subject 
completed all doses of study drug, or if not, the reason a subject terminated study drug early. 
The investigator will discuss with the subject/subject’s parent(s) or legally acceptable 
representative(s) the most appropriate way to withdraw to ensure the subject’s health.  Should a 
subject (or a legally acceptable representative) request or decide to withdraw consent, all efforts 
will be made to complete and report the observations as thoroughly as possible up to the date of 
withdrawal. 

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7. 
ADVERSE EVENTS 
An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease or any worsening of a pre-existing condition temporally associated with the 
use of a study drug, whether or not related to the study drug.  AEs that occur after the first dose 
of EQ001 or during the study treatment and safety follow-up periods will be documented on the 
AE eCRF.  The investigator will assess the AE severity and relationship of the AE to study drug.  
The investigator will treat the subject as medically required. 
Laboratory values that are outside the laboratory reference range should be reported as AEs only 
if considered clinically significant by the investigator. 
From the time of obtaining informed consent through the first administration of study drug, all 
SAEs and nonserious AEs related to protocol mandated procedures will be recorded on the 
SAE/AE eCRF.  All other untoward medical occurrences observed during screening, including 
exacerbation or changes in medical history, will be captured on the medical history eCRF.  
Details on recording and reporting AEs are provided below.  
AEs will be collected through Study Day 169 for subjects who complete study drug through 
Day 57. AEs will be collected through Study Day 85 for subjects who discontinue study drug 
early. Recent hospitalizations and SAEs, if applicable, will be recorded at the Day 253 and 337 
visits. 
The investigator’s clinical judgment should be used to determine whether a subject is to be 
withdrawn due to an AE.  In the event the subject requests to withdraw from study-related 
treatment, the subject should be asked to return for all remaining study visits through Study Day 
169.  In the event a subject is withdrawn from study, an early-termination visit should be 
completed. 
All subjects experiencing AEs while on study drug, including clinically significant abnormal 
laboratory values, whether or not associated with use of the study drug, must be monitored until 
the condition returns to normal, returns to the subject’s baseline, until the investigator determines 
the AE has reached a stable outcome and is no longer clinically significant, or the subject is 
considered lost to follow up. 
If consent has not been withdrawn, all deaths should be reported through Study Day 337, even if 
study drug has been discontinued. 
7.1. 
Severity 
All AEs, both serious and non-serious, will be assessed for severity using the Common 
Terminology Criteria for Adverse Events (CTCAE) v5.0.  The CTCAE scale includes unique 
clinical descriptions of AEs that are categorized by anatomy and/or pathophysiology.  Reference 
the following website: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf 
The CTCAE scale displays Grades 1 through 5 with unique clinical descriptions of severity for 
each AE (including abnormal laboratory values) based on this general guideline provided in the 
CTCAE scale.  For any AEs not covered by CTCAE the conventional definition of severity will 
be used. 

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• 
Grade 1 (Mild) AE: minor; no specific medical intervention; marginal clinical relevance 
• 
Grade 2 (Moderate) AE: minimal intervention; local intervention; noninvasive intervention 
• 
Grade 3 (Severe) AE: significant symptoms requiring hospitalization or invasive intervention 
• 
Grade 4 (Life-threatening or disabling) AE: Complicated by acute, life-threatening 
complications; need for intensive care or emergent invasive procedure 
• 
Grade 5 Fatal AE 
7.2. 
Relationship 
The investigator or qualified sub-investigator is responsible for assessing the relationship to 
study drug using clinical judgment and the following considerations: 
• 
Related: The AE is definitely related to study medication administration. 
• 
Probably Related: There is a high degree of certainty that the AE is related to study 
medication administration. 
• 
Possibly Related: The AE could be related either to study medication administration or to 
concurrent disease/medication. 
• 
Unlikely Related: There is a high degree of certainty that the AE is NOT related to study 
medication administration. 
• 
Not Related: The AE is clearly due to other causes (e.g., concurrent medication, underlying 
disease, etc.)  
The relationship to study-related procedures (e.g., invasive procedures such as venipuncture) 
should be assessed using the following considerations: 
• 
Related: The AE is definitely related to study-related procedures. 
• 
Probably Related: There is a high degree of certainty that the AE is related study-related 
procedures. 
• 
Possibly Related: The AE could be related either to study-related procedures or to concurrent 
disease/medication. 
• 
Unlikely Related: There is a high degree of certainty that the AE is NOT related to study-
related procedures. 
• 
Not Related: The AE is clearly due to other causes (e.g., concurrent medication, underlying 
disease, etc.).In making a causality assessment of an AE, consideration should be made as to 
whether or not the event is expected to occur due to the underlying disease based on the 
investigator’s prior clinical experience in the management of aGVHD (see Section 7.5.1). 
7.3. 
Clinical Laboratory Adverse Events 
The investigator is responsible for reviewing the results of all laboratory tests as they become 
available and determining whether an abnormal value in an individual study subject represents a 
clinically significant change from the subject’s baseline value(s).  The investigator may repeat 
the laboratory test or request additional tests to verify the results of the original laboratory tests. 
In general, abnormal laboratory findings without clinical significance (based on the investigator's 
judgment) are not to be recorded as AEs.  However, laboratory value changes that require 

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treatment or adjustment in current therapy are considered AEs.  Where applicable, clinical 
sequelae (not the laboratory abnormality) are to be recorded as the AE. 
7.4. 
Serious Adverse Events 
An SAE is defined by federal regulation as any AE occurring at any dose that results in any of 
the following outcomes: 
• 
death, 
• 
life-threatening AE (Note: A life-threatening AE is one that, in the view of the investigator, 
places the subject at immediate risk of death from the reaction as it occurred), 
• 
hospitalization or prolongation of existing hospitalization, 
• 
a persistent or significant disability/incapacity, or 
• 
a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life threatening, or require hospitalization 
may be considered an SAE 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 allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in subject hospitalization, or the development of drug dependency or drug abuse. 
An unexpected AE is any event for which the specificity or severity is not consistent with the AE 
profile in the current EQ001 Investigator’s Brochure. 
All SAEs, regardless of cause(s) or relationship to study drug, must be reported within 24 hours 
to the study Sponsor and/or designee. 
7.5. 
Reporting Adverse Events 
7.5.1. 
Reporting Procedures for Non-Serious Adverse Events 
The investigator is responsible for ensuring that all AEs observed by the investigator or designee 
or reported by the subject are reported using the AE eCRF. 
The investigator will assign the following AE attributes: 
• 
AE diagnosis or syndrome(s), if known (if not known, signs or symptoms) 
• 
Dates of onset and resolution (if resolved) 
• 
Severity 
• 
Relatedness to study drug or study-related procedures  
• 
Action taken 
• 
Outcome 
Follow-up of non-serious AEs will continue through the last day on the study and/or until a 
definitive outcome (e.g., resolved, resolved with sequelae, lost to follow-up) is achieved. 

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When a subject is withdrawn from the study because of a non-serious AE, the Sponsor and/or 
designee must be notified by e-mail or phone within 48 hours. 
7.5.2. 
Reporting Procedures Serious Adverse Events 
The investigator is responsible for ensuring that all SAEs observed by the investigator or reported 
by the subject are promptly assessed and reported to the Sponsor and/or designee.  The investigator 
must assess whether the SAE is related to study drug or any study-related procedure. 
The procedures for reporting SAEs are as follows: 
• 
Record the SAE on the AE eCRF and complete the “Serious Adverse Event Report” form. 
• 
Within 24 hours of the investigator’s knowledge of the event, e-mail, fax and/or enter via the 
electronic CRF the SAE Report form to the attention of the Sponsor and/or designee.  
Additional contact numbers and AE/SAE reporting instructions will be provided in the Study 
Manual. 
• 
For fatal or life-threatening events, also e-mail and/or fax copies of hospital case reports, 
autopsy reports, and other documents, when requested and applicable.  Transmission of such 
documents should occur with personal subject details de-identified, without losing the 
traceability of a document to the subject identifiers.  Transmission of the initial report of the 
event should not be delayed in order to include these additional documents. 
• 
The Sponsor or/or designee may request additional information from the investigator to 
ensure the timely completion of accurate safety reports. 
The investigator must take all therapeutic measures necessary for resolution of the SAE.  Any 
medications or therapies necessary for treatment of the SAE must be recorded in the event 
description section of the SAE form and the concomitant medication eCRF. 
Follow-up of SAEs will continue through the last day on the study and/or until a definitive 
outcome (e.g., resolved, resolved with sequelae, lost to follow-up, fatal) is achieved. 
While pregnancy is not considered an AE, all cases of fetal drug exposure via a maternal parent 
as study subject or pregnancy of a partner of a male study subject will be reported immediately 
to the Sponsor or its designee.  Information related to the pregnancy must be documented on a 
“Pregnancy Confirmation and Outcome” form, provided by the Sponsor or its designee, and the 
pregnancy should be followed until a definitive outcome has been determined. 
Some SAEs will qualify for reporting to the FDA as applicable via the MedWatch reporting 
system in accordance with FDA and other applicable regulations.  The Sponsor or its designee 
will report SAEs as required to regulatory authorities, investigators in compliance with all 
reporting requirements according to local regulations and Good Clinical Practice (GCP). 
The investigator will notify the appropriate IRB of SAEs occurring at the study site and other AE 
reports received from the Sponsor, in accordance with local procedures and statutes.  The 
investigator or designee at each study site is responsible for submitting Investigational New 

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Drug (IND) safety reports (initial and follow-up) and other safety information (e.g., revised 
Investigator’s Brochure) to the IRB and for retaining a copy in the study files. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8. 
STUDY ACTIVITIES 
Please refer to the Appendices, Section 12, for additional details.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 EQ001 T cell stimulation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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tments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8.13. Unscheduled Visit 
If at any time up to Study Day 169, a subject has an unscheduled study visit, all procedures that 
were conducted at the visit will be collected in the eCRF as an unscheduled visit.  If a subject 
experiences disease progression or recurrence, the subject should complete an unscheduled visit 
that includes disease assessments and grading. 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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9. 
PLANNED STATISTICAL METHODS 
A detailed description of data analysis and statistical methods to be used will be outlined 
separately in a Statistical Analysis Plan (SAP). 
9.1. 
General Considerations 
Data will be summarized using descriptive statistics (n, mean, median, standard deviation, 
minimum, maximum) for continuous variables and frequencies and percentages for discrete 
variables.  All data summaries will be displayed by cohort in Part A and by treatment group in 
Part B.  A total column will also be included.  By-subject listings of the data will also be 
provided.  All data summaries and listings will be produced using the SAS® software Version 9.3 
or higher.  A separate SAP will be prepared describing the details of the analyses mentioned 
below and the analyses of the exploratory efficacy endpoints. 
 
 
 
 
 
 
 
 
 
 
 
 
9.3. 
Analysis Populations 
9.3.1. 
Safety Population 
Safety population consists of all subjects who receive any study medication.  All data summaries 
except PK and PD data related summaries will use this population. 
9.3.2. 
Pharmacokinetic Analysis Population 
 
Subjects in the safety population who have at least one (1) measurable post-EQ001exposure 
concentration will be included in the PK analysis population. 
 
 
 
 

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Clinical laboratory data will be summarized descriptively, these summaries will include observed 
values at collection timepoints and change from baseline.  All laboratory parameters that can be 
graded using the CTCAE will be graded.  
 
 
 
 
 
 
 
 
 
 
 
. 
9.9. 
Efficacy Analyses 
  
All efficacy data summaries for Part A will use the safety population, whereas Part B will use the 
efficacy population for Part B.  Clinical activity will be assessed by change from baseline in: 
aGVHD Organ Stages and Overall Clinical Grading and aGVHD-AI.  Corticosteroid and 
immunosuppressive agent usage will be compared between groups.  Overall mortality and 
nonrelapse-mortality at 12 months, overall response rate (proportion of subjects with a best 
response of PR or better during the 12-month assessment period compared to last pre-dose 
assessment) and Kaplan-Meier estimates of progression-free survival will also be calculated.  In 
general, changes from baseline in numeric variables will be compared between the two groups 
using an analysis of covariance model with baseline value as a covariate.  Proportions will be 
compared between the groups using the Fisher’s Exact test.  Time to event data will be compared 
using the log-rank test. 
 
 
 
 
 

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10. 
ADMINISTRATIVE CONSIDERATIONS 
10.1. Investigator Responsibilities 
The investigator is responsible for complying with all local, state, and federal regulations relating 
to performing clinical research with an investigational product.  The investigator is responsible 
for ensuring that the investigation is conducted according to the signed Investigator Agreement 
(FDA Form 1572), the approved protocol, and applicable regulations for protecting the rights, 
safety, and welfare of study subject under the investigator's care.  The investigator is additionally 
responsible for the control of investigational product and for providing accurate and verifiable 
data to the Sponsor. 
The investigator must obtain the Informed Consent and HIPAA authorization of each subject 
before participation in the study.  The investigator must assure initial and continuing review of 
the study by an IRB that complies with applicable national and local regulations.  
The investigator will maintain minutes of meetings with study staff and document training of 
research study personnel for conduct of the study, including qualifications, experience, and study 
role. 
The investigator will be given a copy of the most current version of the EQ001 Investigator’s 
Brochure and appropriate study process manuals and plans.  The investigator is obligated to 
become familiar with all sections of these documents prior to initiation of the study. 
Other investigator responsibilities relative to the IRB include the following: 
• 
Submit to the IRB for review any advertisements that will be used to recruit subjects 
• 
Submit all protocol amendments, revisions of the Investigator’s Brochure, or revisions of the 
Informed Consent to the IRB for review 
• 
If Sponsor notifies the investigator about SAEs reported in other studies associated with this 
investigational product, report that information to the IRB 
• 
Provide the IRB with any other information it requests before or during the conduct of the 
study 
• 
Report to the IRB all adverse drug reactions that are serious, unexpected, and related to 
investigational product 
• 
Maintain a file of study-related information 
• 
Update the IRB on a minimum of a yearly basis 
10.2. Institutional Review Board (IRB) Approval 
Before initiation of the study at a study site, the protocol, including the final version of the ICF, 
the subject information sheet (if applicable), and any other relevant study documentation will be 
submitted to the appropriate IRB.  In addition, the IRB must approve all advertising used to 
recruit subjects for the study.  Written approval of the study documentation, including any 
proposed postings or advertising, must be obtained and sent to the Sponsor or its designee before 
the study site can be initiated or the study drug can be released to the investigator.  

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The investigator is responsible for informing the IRB of any amendments to the protocol, ICF, 
written information provided to subjects, and/or other procedures in accordance with local 
requirements.  The protocol must be re-approved by the IRB upon receipt of amendments, in 
accordance with applicable law.  The investigator must send a copy of the approval letter from 
the IRB to the Sponsor or its designee. 
The investigator will report promptly to the IRB and the Sponsor any new information that may 
adversely affect the health or safety of past or current subjects or the conduct of the study, 
including deviations from the protocol or reports of any reportable SAEs, during and for two (2) 
years after completion of the study.  
The investigator should submit written reports of clinical study status to their IRB annually or 
more frequently if required.  A final study notification will also be forwarded to the IRB after the 
study is completed or in the event of premature termination of the study in accordance with the 
applicable regulations.  After completion of the study, the investigator will provide the IRB with 
a report of the outcome of the study.  Copies of all contact with the IRB should be maintained in 
the study file.  Copies of clinical study status reports (including termination) should be provided 
to the Sponsor. 
10.3. Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol; GCP guidelines, including 
International Council for Harmonisation (ICH) of Technical Requirements for Registration of 
Pharmaceuticals for Human Use Guidelines (ICH E6); and FDA regulatory requirements.  In 
addition, the study will be conducted in compliance with any and all current laws, requirements, 
regulations (including, but not limited to, HIPAA) of local, state, federal and foreign authorities 
and agencies having jurisdiction over the subject matter and performance of, and the study 
(referred to herein as “applicable law”). 
Investigators and all sub-investigators will comply with 21 Code of Federal Regulations (CFR), 
Part 54, 1998 and similar conflicts of interest laws requiring documentation of financial interests 
or arrangements with the Sponsor, or proprietary interests in the drug under study.  Any required 
documentation must be provided prior to the investigator’s (and any sub-investigator’s) 
participation in the study.  The investigator and sub-investigator(s) will notify the Sponsor or its 
designee of any change in reportable interests during the study and for 1 year following 
completion of the study.  Study completion is defined as the date when the last subject completes 
all protocol-defined activities. 
10.4. Subject Information and Consent 
Prior to conducting any study-related procedures, the investigator must obtain written informed 
consent from each subject or legally authorized representative, in accordance with applicable 
law.  Consent will be documented on a written ICF.  The ICF must be approved both by the 
Sponsor and by the reviewing IRB prior to presenting it to a subject.  Each ICF must comply 
with the ICH GCP Guidelines, FDA requirements, and local regulatory requirements. 

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Investigators may discuss study availability and the possibility for entry with a potential subject 
without first obtaining consent.  However, informed consent must be obtained and documented 
prior to initiation of any procedures that are performed solely for the purpose of determining 
eligibility for research, including withdrawal from current medication(s).  The informed consent 
process should take place under conditions where the subject has adequate time to consider the 
risks and benefits associated with his/her participation in the study.  The investigator or qualified 
designee must explain to each subject or legally authorized representative the aims, methods, 
reasonably anticipated benefits, and potential hazards of the study. 
Once appropriate essential information has been provided and fully explained in layman’s 
language to the subject by the investigator (or a qualified designee), the approved ICF will be 
signed and dated by both the subject and the person obtaining consent (investigator or designee), 
as well as by any other parties required by the IRB.  The subject will receive a copy of the signed 
ICF; the original will be retained in the study files.  The investigator must document the consent 
interview and place the record in the study files.  The investigator shall also maintain a log of all 
subjects who sign the ICF and indicate if the subject was enrolled into the study or reason for 
non-enrollment. 
10.5. Confidentiality 
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties.  Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB, or laboratory.  Laboratory specimens 
must be labeled in such a way as to protect subject identity while allowing the results to be 
recorded to the proper subject.  Refer to specific laboratory instructions (or in accordance with 
local regulations).  NOTE: The investigator must keep a screening log showing codes, names, 
and addresses for all subjects screened and for all subjects enrolled in the study.  Subject data 
will be processed in accordance with all applicable regulations.  (Some studies may require 
double-coding of samples; insert language as appropriate.) 
The investigator agrees that all information received from the Sponsor, including but not limited 
to the Investigator’s Brochure, this protocol, CRF/eCRF, the study 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.  In compliance with applicable law and/or ICH GCP 
Guidelines, the investigator will permit the Sponsor’s representatives and, when necessary, 
representatives of the FDA or other regulatory authorities’ direct access to any medical records 
relevant to the study for verification of study-related procedures and data.  Direct access includes 
examining, analyzing, verifying, and reproducing any records and reports that are important to 
the evaluation of the study. 

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Investigators will obtain authorization from the subject to permit access to study-related records, 
including personal information.  
The Sponsor will ensure that the use and disclosure of protected health information obtained 
during the study complies with HIPAA and related privacy laws, including the Health 
Information Technology for Economic and Clinical Health Act, where these rules are applicable.  
Authorization is required from each subject (i.e., specific permission granted by such individual 
to a covered entity for the use or disclosure of an individual's protected health information).  The 
investigator and institution must obtain such waiver/authorization in writing from the subject or 
legally authorized representative.  Valid authorization must meet the implementation 
specifications under the applicable privacy laws.  Authorization may be combined in the ICF 
(approved by the IRB), or it may be a separate document (approved by the IRB) or provided by 
the investigator or Sponsor (without IRB approval). 
10.6. Study Initiation 
Before the study drug can be shipped to the study site and before the study can begin, the 
following documents must be submitted and received by the Sponsor: 
• 
Original US FDA Form 1572 signed by the investigator 
• 
Documentation of the IRB approval of the protocol and Informed Consent 
• 
A copy of the IRB-approved Informed Consent and HIPAA authorization that will be used 
• 
Copy of current curriculum vitae and medical licenses of the investigator 
• 
A membership list of the IRB 
• 
Investigator’s financial disclosure form 
The Sponsor will notify the site when the study can begin.  
10.7. Case Report Forms and Study Records 
The investigator will comply with the requirements for all assessments and data collection for 
each subject, as specified in the protocol. 
During each subject’s visit to the clinic, the investigator or qualified designee will record 
progress notes in the subject’s medical record to document all significant observations.  At a 
minimum, these notes will contain the following: 
• 
Documentation of the informed consent process, including any revised consents. 
• 
The date of the visit and the corresponding visit or day in the study schedule. 
• 
General subject status remarks, including any significant medical findings.  The severity, 
frequency, and duration of any AEs and the investigator's assessment of relationship to study 
drug must also be recorded. 
• 
Any changes in concomitant medications. 
• 
A general reference to the procedures completed. 
• 
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In addition, any contact with the subject via telephone or other means that provides significant 
clinical information will also be documented in the progress notes, as described above. 
Data for this study will be captured in electronic eCRFs.  Study auditing, data entry, verification 
and validation, and subsequent analysis will be performed by the Sponsor, or its designees, in 
accordance with GCPs and established Standard Operating Procedures. 
Clinical data (including AEs, concomitant medications, and clinical laboratory data) will be 
entered into a database.  The creation and validation of the database, data entry, validation, and 
verification will be performed according to 21 CFR and other applicable local regulations.  The 
data system includes password protection and internal quality checks, such as automatic range 
checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
10.8. Study Monitoring 
The Sponsor or designee will assign monitors who will perform on site monitoring as frequently 
as necessary and in accordance with ICH GCP. 
Source documents and eCRFs will be reviewed at monitoring visits and any findings will be 
discussed with the investigational staff.  The Sponsor expects that at monitoring visits study 
documents and staff will be available and a suitable space will be provided for review of the 
study documents.  The monitor will meet with the investigator on a regular basis to provide 
feedback on the conduct of the study. 
For Part B, another monitor who is unblinded to subject treatment assignment will perform 
on-site monitoring of the drug accountability records. 
10.9. Access to Source Documentation 
The study may be subject to audit by the Sponsor, its designee, or by regulatory authorities.  If 
such an audit occurs, the investigator must agree to allow access to required subject records.  The 
investigator should notify the Sponsor promptly of regulatory authority audits that are scheduled 
and must forward copies of any findings or audit reports to the Sponsor promptly. 
By signing this protocol, the investigator grants permission to personnel from the Sponsor, its 
representatives, and appropriate regulatory authorities for on-site monitoring and review of all 
appropriate study documentation, as well as on-site review of the procedures employed in data 
collection, where clinically appropriate. 
10.10. Study or Study Site Termination 
The Sponsor may suspend or stop the study at all centers or at specific study centers due to (but 
not limited to) the discovery of an unexpected, serious, or unacceptable risk to the subjects 
enrolled in the study, a decision on the part of the Sponsor to suspend or discontinue 
development of the product, failure of the investigator to enroll subjects into the study at an 
acceptable rate, failure of the investigator to comply with regulatory authority or ICH 
Guidelines, or submission of knowingly false information. 

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10.13. Quality Assurance 
Authorized representatives of the Sponsor, a regulatory authority, or IRB may visit the study site 
to perform audits or inspections, including source data verification.  The purpose of any such 
audit or inspection is to systematically and independently examine all study-related activities and 
documents to determine whether these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, ICH GCP guidelines, and any other 
applicable regulatory requirements. 

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The investigator should contact the Sponsor immediately if contacted by a regulatory agency 
about an inspection. 
It is important that the investigator and relevant personnel are available during the possible audits 
or inspections and that sufficient time is devoted to the process. 
10.14. Retention of Data 
When the study is completed, the investigator must retain the essential documents for as long as 
needed to comply with regulatory guidelines and Sponsor requirements.  The investigator will 
notify the Sponsor prior to moving or destroying any of the study documents.  It is the 
responsibility of the Sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained.  The investigator should take measures to prevent any accidental or 
premature destruction of these documents. 
10.15. Study Report and Publications 
A clinical study report (CSR) 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. 
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after written consent has been obtained from the Sponsor. 
The investigator will submit to the Sponsor any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 60 days before submission of the 
publication or presentation.  
No such communication, presentation, or publication will include the Sponsor’s confidential 
information (see Section 10.5). 
The investigator will comply with the Sponsor’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary. 

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