Clinical trial NCT04014790
Conditions: Graft Vs Host Disease Graft-versus-host-disease Acute-graft-versus-host Disease Prevention of aGVHD
Sponsor: Regimmune Corporation
Start date: 2019-11-25; Completion date: 2023-04-03
Enrollment: 49 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This Phase II open label study will evaluate the safety and efficacy of repeat doses of RGI-2001 in combination with standard of care treatment for the prevention of acute graft-vs-host-disease (aGvHD) in subjects following Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT). These subjects will be compared to contemporary controls.

Detailed description:
This is an open-label, multi-center, single-arm study to evaluate six weekly doses of RGI-2001 in combination with standard of care treatment for the prevention of aGvHD in subjects following alloHSCT. The study will include a Safety Run-in Phase to assess the safety and tolerability of 6 weekly doses of RGI-2001 followed by an Expansion Phase in which the potential efficacy of 6 weekly doses of RGI-2001 in addition to standard of care for GvHD prophylaxis will be assessed. Comparison will be made to a contemporaneous control group.

Arms: arm 1: Subjects will be administered RGI 2001 in combination with standard of care treatment
Interventions: intervention 1: RGI-2001 intervention 2: Standard of Care
Intervention descriptions: intervention 1: Subjects will receive 6 weekly doses of RGI 2001, 100 μg/kg via IV administration after completion of alloHSCT intervention 2: Standard of care prophylaxis regimen will be administered according to institutional guidelines

Protocol documents:
Prot_000.pdf: 
RGI-2001-003 
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CLINICAL STUDY PROTOCOL 
Protocol Title: 
An Open Label, Non-Randomized Multicenter Phase 
2b, Study with a Safety Run-in to Evaluate the Safety 
and Efficacy of RGI-2001 for the Prevention of Acute 
Graft-Versus-Host Disease (aGvHD) Compared to 
Contemporary Controls in Subjects Following 
Allogeneic Hematopoietic Stem Cell Transplantation 
(alloHSCT) 
Protocol Number: 
RGI-2001-003 
Investigational Product: 
RGI-2001 
IND Number/NCT Number: 
102,285/ NCT04014790 
Sponsor: 
REGiMMUNE Corporation 
35-3 Nihonbashi Hakozaki-cho BRICK GATE 5F,
Chuou-ku, Tokyo 103-0015 Japan
Protocol Date and Version: 
Original: 18 March 2019, Version 1.0 
Amendment #1: 06 March 2020, Version 2.0 
CONDUCT 
This study will be conducted according to the protocol and in compliance with Good Clinical 
Practice (GCP), the ethical principles stated in the Declaration of Helsinki, and other 
applicable regulatory requirements. 
CONFIDENTIAL INFORMATION 
This is a REGiMMUNE Corporation document that contains confidential information. It is 
intended solely for the recipient clinical investigator(s) and must not be disclosed to any 
other party. This material may be used only for evaluating or conducting clinical 
investigations; any other proposed use requires written consent from REGiMMUNE 
Corporation. 


 
 
 
 
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PROTOCOL APPROVAL SIGNATURE PAGE 
 
Protocol Title: 
An Open Label, Non-Randomized Multicenter Phase 2b, Study 
with a Safety Run-in to Evaluate the Safety and Efficacy of 
RGI-2001 for the Prevention of Acute Graft-Versus-Host 
Disease Compared to Contemporary Controls in Subjects 
Following Allogeneic Hematopoietic Stem Cell Transplantation 
(alloHSCT) 
 
 
 
Protocol Number: 
RGI-2001-003 
 
 
 
 
 
 
Date: 
06 March 2020 
 
 
 
 
 
 
 
 
 
Date 
 
 


 
 
 
 
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INVESTIGATOR SIGNATURE PAGE 
 
Protocol Title: An Open Label, Non-Randomized Multicenter Phase 2b, Study with a Safety 
Run-in to Evaluate the Safety and Efficacy of RGI-2001 for the Prevention of Acute Graft-
Versus-Host Disease Compared to Contemporary Controls in Subjects Following Allogeneic 
Hematopoietic Stem Cell Transplantation (alloHSCT) 
 
Date: 06 March 2020 
 
 
Signature on this page assures the Sponsor that, to the best of the investigator’s knowledge, the 
affiliated Institutional Review Board (IRB) operates in accordance with the governing 
regulations, and that the investigator understands, and agrees to conduct this study in 
accordance with the protocol and according to the Declaration of Helsinki, the Code of Federal 
Regulations on the Protection of Human Subjects (45 CFR Part 46), the International Council 
for Harmonization (ICH) E6 Guideline for Good Clinical Practice (GCP), and all applicable 
regulatory requirements. All study site personnel involved in the study will be under their 
direction and informed about the contents of this study protocol and will receive all necessary 
instructions for conducting the study in accordance with the study protocol.  
 
 
________________________________________  
_______________________ 
Investigator’s Signature  
 
 
 
 
 
Date  
 
_______________________________________ 
Name (printed) 
 
 


 
 
 
 
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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ..................................................................................................1 
PROTOCOL APPROVAL SIGNATURE PAGE ...........................................................................2 
INVESTIGATOR SIGNATURE PAGE .........................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
TABLE OF TABLES ......................................................................................................................7 
TABLE OF FIGURES .....................................................................................................................7 
1 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .........................................8 
2 
PROTOCOL SYNOPSIS......................................................................................................11 
3 
SCHEDULE OF ASSESSMENTS .......................................................................................21 
4 
INTRODUCTION ................................................................................................................24 
4.1 
Background ................................................................................................................24 
4.1.1 
Graft Versus Host Disease ..........................................................................24 
4.1.2 
CD4+Foxp3+ Regulatory T-cells ................................................................25 
4.2 
Investigational Product ...............................................................................................26 
4.3 
Study Rationale ..........................................................................................................26 
4.4 
Summary of Nonclinical Data ....................................................................................27 
4.5 
Summary of Clinical Data ..........................................................................................29 
4.6 
Risks/Benefits ............................................................................................................30 
4.7 
Dose Regimen and Treatment Period Rationale ........................................................32 
5 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................34 
6 
STUDY DESIGN..................................................................................................................36 
6.1 
Safety Run-in Phase ...................................................................................................37 
6.1.1 
Definition of Dose-limiting Toxicities ........................................................38 
6.2 
Expansion Phase .........................................................................................................39 
6.3 
Control Group ............................................................................................................39 
6.4 
Safety Review Committee ..........................................................................................39 
6.5 
Number of Sites ..........................................................................................................39 
6.6 
Number of Subjects ....................................................................................................40 
6.7 
Study Duration ...........................................................................................................40 
7 
SUBJECT POPULATION....................................................................................................41 
7.1 
Inclusion Criteria ........................................................................................................41 
7.2 
Exclusion Criteria .......................................................................................................42 
7.3 
Eligibility for the Control Arm...................................................................................43 
7.4 
Donor Screening .........................................................................................................43 
7.5 
Withdrawal/Discontinuation from Treatment, Procedures and Study .......................44 
7.5.1 
Study Discontinuation .................................................................................44 


 
 
 
 
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7.5.2 
Subjects’ Decision to Withdraw ..................................................................44 
7.5.3 
Discontinuation of Study Treatment and/or Withdrawal of Subjects 
Prior to Study Completion ...........................................................................45 
7.6 
Replacement of Subjects ............................................................................................45 
8 
STUDY DRUG .....................................................................................................................46 
 
 
8.2 
Packaging and Labeling .............................................................................................46 
8.3 
Storage ........................................................................................................................46 
8.4 
Study Drug Accountability.........................................................................................46 
8.5 
Return and Disposition of Study Drug .......................................................................46 
8.6 
Administration and Dosing Regimen .........................................................................47 
8.7 
Randomization and Blinding ......................................................................................47 
8.8 
Prior and Concomitant Medications ...........................................................................47 
8.9 
Dietary or Other Protocol Restrictions .......................................................................48 
8.10 Dose Modification/Treatment Cessation ....................................................................48 
8.10.1 
Safety Run-in Phase ....................................................................................48 
8.10.2 
Expansion Phase ..........................................................................................48 
8.11 Management of Cytokine Release Syndrome ............................................................49 
9 
STUDY ASSESSMENTS AND PROCEDURES ................................................................51 
9.1 
General Study Procedures ..........................................................................................51 
9.1.1 
Informed Consent ........................................................................................51 
9.1.2 
Demographics ..............................................................................................51 
9.1.3 
Medical/Cancer/Surgical History ................................................................51 
9.2 
Efficacy Assessments .................................................................................................52 
9.3 
Evaluation of GvHD...................................................................................................52 
9.3.1 
Tumor Assessment ......................................................................................52 
 
 
 
 
 
 
9.4 
Safety Assessments ....................................................................................................53 
9.4.1 
Marrow Engraftment and Graft Failure .......................................................53 
9.4.2 
Dose Limiting Toxicities .............................................................................53 
9.4.3 
Adverse Events ............................................................................................53 
9.4.4 
Concomitant Medications ............................................................................53 
9.4.5 
Weight and Height .......................................................................................54 
9.4.6 
Physical Examinations, Vital Signs and Karnofsky Performance 
Status ...........................................................................................................54 
9.4.7 
Electrocardiogram .......................................................................................54 


 
 
 
 
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9.4.8 
Clinical Laboratory Assessments ................................................................54 
10 
ADVERSE EVENTS ............................................................................................................57 
10.1 Definitions ..................................................................................................................57 
10.1.1 
Serious Adverse Event ................................................................................57 
10.2 Adverse Event Reporting ...........................................................................................58 
10.2.1 
Laboratory Test Abnormalities ...................................................................58 
10.2.2 
Adverse Event Severity ...............................................................................59 
10.2.3 
Adverse Event Causality .............................................................................60 
10.3 Serious Adverse Events ..............................................................................................61 
10.3.1 
Serious Adverse Events Reporting ..............................................................61 
10.4 Reporting of Disease Progression ..............................................................................62 
10.5 Reporting of GvHD ....................................................................................................62 
10.6 Medication Errors .......................................................................................................62 
10.7 Pregnancy ...................................................................................................................63 
11 
REGISTRATION OF CIBMTR SUBJECTS FOR THE CONTROL GROUP ...................64 
11.1 Selection of Control Arm Transplant Centers ............................................................64 
11.2 Enrollment Procedure for the Transplant Subjects in the Control Arm via the 
CIBMTR ....................................................................................................................64 
12 
STATISTICS ........................................................................................................................65 
 
12.2 Demographics and Baseline Characteristics ..............................................................65 
12.3 Analysis Population, Handling of Dropouts, and Missing Data ................................65 
12.3.1 
Analysis of Efficacy Data ............................................................................66 
12.4 Suspension Rules Based on Safety (RRT, Graft Failure, and NRM) ........................66 
13 
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS .............................................68 
13.1 Ethics ..........................................................................................................................68 
13.2 Compliance Statement................................................................................................68 
13.3 Institutional Review Board ........................................................................................68 
13.4 Informed Consent and Human Subject Protection .....................................................68 
13.4.1 
Direct Access to Source Data/Source Documents ......................................68 
13.4.2 
Data Quality Control and Quality Assurance: Data Handling and 
Recordkeeping .............................................................................................69 
13.4.3 
Confidentiality .............................................................................................69 
14 
FINAL STUDY REPORT AND PUBLICATION POLICY ...............................................70 
REFERENCES ..............................................................................................................................71 
15 
APPENDICES ......................................................................................................................73 
Appendix 1 
PHARMACOKINETICS (RGI-2001) AND 
PHARMACODYNAMICS SAMPLING SCHEDULE ..............................74 


 
 
 
 
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Appendix 2 
MAGIC GVHD ASSESSMENT CRITERIA .............................................75 
Appendix 3 
MODIFIED KEYSTONE CRITERIA FOR ACUTE GVHD ....................77 
Appendix 4 
NIH DEFINED DIAGNOSTIC OR DISTINCTIVE FEATURES OF 
CHRONIC GVHD 2014 .............................................................................78 
Appendix 5 
KARNOFSKY PERFORMANCE STATUS SCORES ..............................81 
Appendix 6 
CONTRACEPTIVE GUIDANCE AND COLLECTION OF 
PREGNANCY INFORMATION ................................................................82 
TABLE OF TABLES 
Table 1 
Medical Guidelines for Cytokine Release Reactions .............................................................. 49 
Table 2 
Clinical Laboratory Tests ........................................................................................................ 55 
Table 3 
Suspension Rules for Grade 4-5 RRT, Graft Failure, and Day-100 NRM .............................. 67 
Table 4 
Operating Characteristics of Suspension Rules ....................................................................... 67 
 
TABLE OF FIGURES 
Figure 1 
Study Design Schema .............................................................................................................. 37 
Figure 2 
DLT Schema ........................................................................................................................... 38 
 


 
 
 
 
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1 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
aGvHD 
Acute Graft versus Host Disease 
ADME 
Absorption, Distribution, Metabolism and Excretion 
AE 
Adverse Event 
alloHSCT 
Allogeneic hematopoietic Stem Cell Transplantation 
α-GalCer 
α-galactosylceramide 
ALT 
Alanine Aminotransferase 
APC 
Antigen Presenting Cell 
API 
Active Pharmaceutical Ingredient 
aPTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Aminotransferase 
ATG 
Anti-Thymocyte Globulin 
AUC 
Area Under the Curve 
BMT 
Bone Marrow Transplantation 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
cGvHD 
Chronic Graft versus Host Disease 
Cmax 
Maximum Concentration 
Cmin 
Minimum Concentration 
CBC 
Complete Blood Count 
CFR 
Code of Federal Regulations 
CIBMTR 
Center for International Blood and Marrow Transplant Research 
CRA 
Clinical Research Associate 
CR 
Complete Remission 
CRF 
Comprehensive Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DC 
Dendritic Cell 
DCregs 
Regulatory Dendritic Cells 
DLT 
Dose-Limiting Toxicity 
DST 
Donor-Specific Transfusion 
ET 
Early Termination 
ECGs 
Electrocardiograms 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
FIH 
First-In-Human 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte Colony Stimulating Factor 
GLP 
Good Laboratory Practice 
GRFS 
Graft vs Host disease free, relapse free survival 


 
 
 
 
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Abbreviation 
Definition 
GvHD 
Graft versus Host Disease 
GvL 
Graft vs Leukemia 
HBV 
Hepatitis B Virus 
Hct 
Hematocrit 
HEENT 
Head, ears, eyes, nose and throat 
HCV 
Hepatitis C Virus 
HED 
Human Equivalent Dose 
Hgb 
Hemoglobin 
HIV 
Human Immunodeficiency Virus 
HLA 
Human Leukocyte Antigen 
HNSTD 
Highest non-severely toxic dose 
HR 
Heart Rate 
HSCs 
Hematopoietic stem cells 
HSCT 
Hematopoietic stem cell transplant 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IL 
Interleukin 
iNKT 
Invariant Natural Killer T (cells) 
INR 
International Normalized Ratio 
IP(s) 
Investigational Product(s) 
IRB 
Institutional Review Board 
iTCR 
Invariant T-cell Receptor 
IUD 
Intra-uterine Device 
IV 
Intravenously 
KPS 
Karnofsky Performance Status 
LDH 
Lactate Dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFD 
Maximum Feasible Dose 
MHC 
Major Histocompatibility Complex 
MMF 
Mycophenolate Mofetil 
MTD 
Maximum Tolerated Dose 
MTX 
Methotrexate 
NCI 
National Cancer Institute 
NKT 
Natural killer T (cell) 
NRM 
Nonrelapse Mortality 
OS 
Overall Survival 
OTC 
Over-the-counter 
PBSCT 
Peripheral Blood Stem Cell Transplant 
PBMC 
Peripheral Blood Mononuclear Cell 


 
 
 
 
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Abbreviation 
Definition 
PD 
Pharmacodynamic 
PE 
Physical Examination 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PT 
Prothrombin Time 
QTcF 
QTc interval using Frederica’s correction 
RBC 
Red Blood Cell 
RR 
Respiratory Rate 
RRT 
Regimen-related toxicity 
SAEs 
Serious Adverse Events 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
SOC 
Standard of Care 
SRC 
Safety Review Committee 
STD 
Severely toxic dose 
T1/2 
Half-life 
TEAE 
Treatment emergent adverse event 
TK 
Toxicokinetic 
Tmax 
Time to Cmax 
TNF-α 
Tumor Necrosis Factor-alpha 
Tregs 
Regulatory T Cells 
ULN 
Upper Limit of Normal 
WBC 
White Blood Cell 
 


 
 
 
 
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2 
PROTOCOL SYNOPSIS  
Name of Sponsor 
REGiMMUNE Corporation (JAPAN) 
35-3 Nihonbashi Hakozaki-cho BRICK GATE 5F, Chuou-ku, 
Tokyo 103-0015 Japan  
Protocol Title 
An Open Label, Non-Randomized Multicenter Phase 2b, 
Study with a Safety Run-in to Evaluate the Safety and 
Efficacy of RGI-2001 for the Prevention of Acute Graft-
Versus-Host Disease Compared to Contemporary 
Controls in Subjects Following Allogeneic 
Hematopoietic Stem Cell Transplantation (alloHSCT) 
Name of Investigational Product 
RGI-2001 
Protocol Number 
RGI-2001-003 
Phase 
Phase 2 
Indication 
Prevention of Acute Graft–versus-Host Disease following 
alloHSCT 
Study Centers 
This study will be conducted at 8-12 sites in the United 
States.  
Study Rationale: 
Despite efforts to date, the incidence of acute GvHD remains 
high. Thus, improvements in the prevention of the disease 
constitutes a high unmet medical need. 
Studies in both humans and mice have confirmed the pivotal 
role CD4+Foxp3+ Treg cells play in controlling GvHD 
(Socié 2009). However, the development of Treg cell-based 
therapeutic modalities has been hampered, in part, by the small 
numbers of these cells. RGI-2001 is a liposomal form 
designed to deliver RGI-7000, which is an immunomodulatory 
compound that may promote the proliferation of Tregs in 
donor bone marrow and the development of tolerance to 
alloantigens and therefore constitutes a novel approach to the 
prevention of GvHD. 
Objectives 
Endpoints 
Primary 
• 
To assess the potential efficacy of 
RGI-2001 in addition to standard 
of care (SOC) vs SOC for the 
prevention of acute GvHD 
(aGvHD) 
• 
To characterize the safety and 
tolerability of 6 weekly 
intravenous (IV) infusions of 
• 
Efficacy: Grades II-IV aGvHD by Day 100 according to 
the Modified Keystone Criteria (Przepiorka 1995) 
• 
Safety: Incidence, nature, and severity of 
treatment-emergent AEs, SAEs, laboratory test values, 
vital-sign measures, and graft failure  


 
 
 
 
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RGI-2001 in subjects following 
alloHSCT  
Secondary 
• 
To assess the potential efficacy of 
RGI-2001 in addition to SOC vs 
SOC for the prevention of 
chronic GvHD (cGvHD) 
according to the secondary 
endpoints listed 
• 
To assess the survival of subjects 
who received RGI-2001 in 
addition to SOC vs SOC  
• 
To evaluate the 
pharmacodynamics (PD) effects 
of weekly dosing of RGI-2001 
• 
Grades II-IV aGvHD by Day 180 according to the 
Modified Keystone Criteria 
• 
Total and moderate-severe cGvHD at 6 months and 1 year 
according to the 2014 NIH criteria for cGvHD  
• 
Non-relapse mortality (NRM) rates at Day 100, 6 months 
and 1 year  
• 
Disease-free survival (DFS) at 6 months and 1 year  
• 
GvHD-free, relapse free survival (GRFS) at 6 months and 
1 year  
• 
Overall survival (OS) at 6 months and 1 year  
• 
Change from baseline in the percentage of 
CD4+CD25+CD45RA+ CD127-LO T cells (naive Tregs) 
on Days 14, 28, 42, 60, 100, 180 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
Study Design 
This is an open-label, multi-center, single-arm study to 
evaluate six weekly doses of RGI-2001 in combination with 
SOC treatment for the prevention of aGvHD in subjects 
following alloHSCT. Study subjects will be compared to a 
contemporaneous set of controls from the Center for 
International Bone and Marrow Transplant Research 
(CIBMTR) that is derived using the same eligibility criteria 


 
 
 
 
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used for this study. The study will include a Safety Run-in 
Phase and an Expansion Phase.  
Safety Run-in Phase: 
Subjects will receive open-label RGI-2001 at a dose of 100μg 
/kg, via 30-minute intravenous (IV) infusion on a weekly basis 
for 6 doses in addition to a standard of care (SOC) GvHD 
prophylactic regimen. The first dose will be administered on 
Day 0, approximately 30 minutes and no later than 1 hour after 
hematopoietic stem cell transplant (HSCT) infusion. 
Subsequent doses will be administered weekly, on Days 7, 14, 
21, 28 and 35. 
Up to two cohorts of 3 subjects each will be enrolled to the 
Safety Run-in Phase. Initially, 3 subjects will be enrolled, 
treated and assessed for dose-limiting toxicities through Day 
30 (dose limiting toxicity [DLT] window). A safety review 
committee (SRC) will examine all relevant safety data after 
the 3rd subject has reached Day 30. As a rough guide, a DLT 
rate on the order of 20% or less would be considered as 
acceptable. Therefore, if 0 subjects are reported to have a DLT 
among the first 3 subjects, consideration will be given to 
enrolling up to 3 additional subjects. However, this decision 
will not be made solely on the observed occurrence (or lack 
of) DLTs; rather the SRC will consider the totality of the 
safety data before arriving at a definitive conclusion regarding 
enrollment of additional subjects at the dose of 100μg /kg. If 
within the first 3 subjects, 1 or more DLT are observed, then 
consideration will be given to use of an alternative dose and/or 
dosing schedule, with the ultimate decision being made by the 
SRC. If an alternate dose and/or schedule is used, the same 
process as described above will be used. If the additional 3 
subjects (beyond the initial 3) are allowed to enroll at the dose 
of 100μg /kg or a lower dose and/or alternative schedule, 
safety data after the 6th subject has completed all 6 doses, as 
well as initial efficacy, PK and PD data will be evaluated in 
coming to a recommendation regarding proceeding to the 
Expansion Phase, with this recommendation made by the 
SRC.  
Definition of Dose-limiting Toxicities  
The following DLT criteria apply to the Safety Run-in Phase 
of the study. A DLT is defined as any treatment-related AE 
that is not attributable to an extraneous cause (e.g., disease 
progression, preparatory regimen or HSCT infusion) and also 
excludes any signs and symptoms of GvHD. A DLT is an 
adverse event occurring in the period of 30 days after the first 
dose of RGI-2001 administration, and meeting at least 1 of the 
following NCI CTC (Version 5.0) criteria: 
• 
Grade 3+ infusion-related/cytokine release reactions  


 
 
 
 
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• 
Graft failure (as defined in Section 9.4.1) 
• 
Any Grade 4-5 non-hematological AE 
• 
Delay in dosing by > 2 weeks due to treatment-related AE 
that is not attributable to an extraneous cause 
Expansion Phase: 
Once a dose/schedule is determined by the SRC to have an 
acceptable safety/PK profile, enrollment will continue in the 
Expansion Phase and be extended to all sites.  
Accrual is targeted at 50 subjects who receive the dose 
deemed as acceptable from the Safety Run-in Phase (44 in the 
Expansion Phase, 6 from the Safety Run-in Phase at the dose 
used in expansion).  
Subjects will receive open-label RGI-2001 at a dose of 
100μg/kg, via 30-minute intravenous (IV) infusion on a 
weekly basis for 6 doses (or an alternative dose/schedule as 
determined in the run-in phase) in addition to a SOC GvHD 
prophylactic regimen. The first dose will be administered on 
Day 0 at approximately 30 minutes and no later than 1 hour 
after HSCT infusion. Subsequent doses will be administered 
weekly, on Days 7, 14, 21, 28 and 35. 
Control Group: 
A non-randomized, contemporary control group from the 
CIBMTR database will be derived for comparison. Control 
subjects will be chosen so as to meet all eligibility 
requirements for the clinical trial, have received a transplant in 
the same time window as the study subjects, and have been 
transplanted in a center that participates in this study. Consent 
will be obtained via the CIBMTR to participate in this study. 
Number of Subjects 
A total of 50 subjects will be enrolled. It is anticipated that a 
minimum of 250 subjects will be included in the control 
group. 
Study Duration 
Individual subject participation is expected to last up to 1 year 
following alloHSCT, including a 6-week treatment period and 
a 42-week follow-up period. In addition, there is a screening 
period lasting approximately 2 weeks.  
Inclusion Criteria 
All subjects (including CIBMTR control group, except where 
noted) must meet the following criteria: 
1. Ages > 18 and < 65 years of age 
2. Has a hematologic malignancy as defined below and is 
considered a candidate for alloHSCT: 
a. Acute myelogenous leukemia (AML) in first or 
subsequent morphologic complete remission (CR) 
b. T or B cell acute lymphoblastic leukemia (ALL) in 
first or subsequent complete morphologic remission  


 
 
 
 
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c. Myelodysplastic syndrome (MDS), chronic 
myelomonocytic leukemia (CMML), 
myeloproliferative disorder (MPD) including myeloid 
metaplasia and myelofibrosis and are currently with 
< 10% blasts in bone marrow 
d. CML subjects who have received prior treatment 
including at least one tyrosine kinase inhibitor and are 
currently in chronic phase or with a complete 
hematologic remission but with evidence of 
cytogenetic or molecular relapse  
3. Must have adequate organ function as defined below 
(RGI-2001treatment group only): 
a. Cardiac function: Left ventricular ejection 
fraction at rest ≥ 45% 
b. Liver function: total bilirubin < 1.5 x upper 
limit of normal (ULN); alanine 
aminotransferase (ALT) and aspartate 
aminotransferase (AST) < 2.5 x the ULN. 
Patients who have been diagnosed with 
Gilbert’s Disease or malignant involvement 
are allowed to exceed the defined bilirubin 
value of 1.5 x the ULN 
c. Serum creatinine < 2 mg/dL or estimated 
creatinine clearance > 50mL/min calculated 
using the Cockcroft-Gault equation 
d. Pulmonary: DLCO (corrected for 
hemoglobin) and/or FEV1 ≥ 50 % 
4. Considered suitable candidate for a myeloablative 
allogeneic or unrelated donor transplant based on 
institutional criteria  
5. Subject must be receiving first allogeneic transplant 
from a single donor. Prior autologous transplant is 
acceptable 
6. Transplant Donor: 
a. Matched related donor (8/8): Molecular 
identity at HLA-A, -B, -C and -DRB1 by 
high-resolution typing 
b. Unrelated donor (≥ 7/8 allelic match): high 
resolution molecular typing at the following 
loci is required HLA -A, -B, -C and -DRB1 
c. Meets institutional criteria for bone marrow or 
PBSC donation (see Section 7.4) 
7. Source of the allograft; unmodified bone marrow or 
mobilized peripheral blood stem cell (PBSC) 
transplant, using granulocyte colony stimulating factor 


 
 
 
 
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(G-CSF) as the mobilizing agent. Cord blood is not 
allowed. 
8. KPS ≥ 60 
9. Is a candidate for anti-graft-vs-host-disease (GvHD) 
prophylaxis that includes a calcineurin inhibitor (either 
tacrolimus [FK 506] or cyclosporine A), in 
combination with either methotrexate (MTX), 
mycophenolate mofetil (MMF).  
10. Ability to understand and willingness to sign a written 
informed consent form  
Inclusion criteria pertaining specifically for subjects scheduled 
to receive RGI-2001: 
11. If female of childbearing potential, must have had a 
negative serum pregnancy test prior to enrollment and 
must have agreed to use a double barrier method of 
contraception for 90 days following the last dose of 
RGI-2001 
12. If male, must be sterile or willing to use an approved 
method of contraception from the time of informed 
consent to 90 days after the last dose of RGI-2001 
Exclusion Criteria 
Any subjects (including CIBMTR control group) who meet 
any of the following criteria will be excluded from study 
entry: 
1. Has had any other prior organ transplantation 
2. Planned procedure to deplete regulatory T-cells from 
donor transplant materials  
3. Planned reduced intensity conditioning 
4. Planned use of any additional or alternative drug(s) for 
GvHD prophylaxis than listed in the inclusion criteria 
(e.g., rapamycin, cyclophosphamide, steroids)  
5. Has had prior treatment with anti-CD3, other T cell 
depleting antibodies, or anti-thymocyte globulin within 
12 months prior to alloHSCT procedure 
6. Is participating in a trial (other than RGI-2001-003) 
involving an investigational agent/non-standard of care 
drug  
7. Has progressive underlying malignant disease 
including post-transplant lymphoproliferative disease 
8. Has evidence of active central nervous system (CNS) 
disease including known brain or leptomeningeal 
disease (CT or MRI scan of the brain required only in 
case of clinical suspicion of CNS involvement)  
9. Patients with active bacterial, viral or fungal infections 
(currently taking medication(s) and with progression or 
no clinical improvement) 


 
 
 
 
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10. Known history of human immunodeficiency virus 
(HIV) 
11. Active infection with hepatitis C virus (HCV) or 
hepatitis B virus (HBV) (control group only).  
12. Is female and pregnant or lactating 
Exclusion criteria pertaining specifically to subjects scheduled 
to receive RGI-2001: 
13. Has undergone major surgery within 1 month before 
Day 0. Indwelling catheter placement is allowed 
14. Hepatitis B virus (HBV) or hepatitis C virus (HCV) 
infection with viral load above the limit of 
quantification. Subjects that are on study with HBV or 
HCV infection should have titers checked regularly, as 
per institutional standard of care 
15. Has had any other condition that, in the opinion of the 
Investigator, renders the subject unsuitable for study 
participation 
16. Has a documented history of uncontrolled autoimmune 
disease or on active treatment 
17. Vaccinated with live, attenuated vaccines within 4 
weeks of first dose of study drug. 
18. History of myocardial infarction, unstable angina, or 
acute coronary syndrome within 6 months prior to 
receiving study drug 
19. Has received an investigational agent within 4 half-
lives or 14 days prior to HSCT, whichever is shorter 
Investigational Product;  
Dose; Route of Administration 
RGI-2001 for Injection is supplied as a sterile liquid 
suspension filled into depyrogenated USP Type 1, 5-mL glass 
vials with a 2.5 mL fill volume. 
All subjects will receive 6 weekly doses of RGI-2001, 100 
μg/kg via IV administration over 30 minutes. The dosage of 
RGI-2001 will be diluted in 50 mL 0.9% normal saline and the 
first dose will administered intravenously (IV) at 
approximately 30 minutes and no later than 1 hour after 
completion of the alloHSCT on Day 0. 


 
 
 
 
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Conditioning, Prophylactic and 
Concomitant Therapy 
Concomitant medications are any prescription or over-the-
counter (OTC) preparations used from 2 days prior to the 
preparatory regimen before Day 0 through the end of the 
subject’s study participation. 
Standard myeloablative preparatory regimens, (i.e., 
experimental regimens or drugs are not allowed), HSCT, and 
standard supportive care/ prophylactic treatments (including 
but not limited to colony stimulating factors, transfusions, 
antibiotics/ anti-virals/ anti-fungals) per institutional 
guidelines for optimal medical care shall be permitted during 
participation in this study. The dose of steroids that are 
required for reasons unrelated to the underlying malignancy or 
HSCT process or sequelae must not be higher than physiologic 
doses (the equivalent of 20 mg of prednisone). No anti-
thymocyte globulin is allowed in the conditioning regimen. 
GvHD prophylaxis must consist of a calcineurin inhibitor 
(cyclosporine or tacrolimus) in combination with MTX or 
MMF. Dosing, schedule and monitoring of the GvHD regimen 
should follow institutional guidelines. Please see respective 
prescribing information for safety information. Steroids, 
sirolimus, post-transplant cyclophosphamide, other GvHD 
prophylactic agents (including investigational agents) or 
manipulation of the graft to reduce GvHD are not allowed.  
Post transplant maintenance therapy that includes an 
investigational agent (ie, not an FDA approved drug for any 
indication), or any treatments that can be used for GvHD is not 
allowed. Maintenance therapy for actionable targeted 
mutations (e.g., FLT3 inhibitors) or with FDA approved 
agents in any indication, should not be initiated prior to Day 
42 post alloHSCT. 
Treatment of GvHD should follow institutional guidelines and 
may include steroid treatment at supra-physiologic doses.  
Statistical Considerations 
The primary objective of this study is to assess the potential 
efficacy of RGI-2001. The primary endpoint for these 
purposes is grades II-IV acute GvHD, and the study subjects 
will be compared to a control group of subjects supplied by the 
CIBMTR. Control subjects will be chosen so as to meet all 
eligibility requirements for the clinical trial, have received a 
transplant in the same time window as the study subjects, and 
have been transplanted in a center that participates in this 
study.  
 
 
 
 
 
  


 
 
 
 
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We consider a one-sided significance level of .10 to be 
sufficient evidence of a signal for moving forward.  
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Based on these estimates, it is anticipated that a total of 50 
subjects who receive at least one dose of RGI-2001 will be 
enrolled, this including subjects from the run-in stage treated 
at the dose moved forward to the Expansion Phase. It is 
anticipated that a minimum of 250 subjects will be included in 
the control group.  
Demographics and Baseline Characteristics 
Categorical factors will be summarized with proportions, and 
continuous variables will be summarized using means and 
medians. 
Analysis Population, Handling of Dropouts, and Missing Data 
All subjects who receive at least one dose of RGI-2001 will be 
used for comparison to the CIBMTR subjects.  
Analysis of Efficacy Data 
The primary endpoint grades II-IV acute GvHD by Day 100 
according to the Modified Keystone Criteria will be compared 
between the study group and CIBMTR controls using logistic 
regression. The factors that will be considered for adjustment 
in this model include subject age, gender, donor age, type of 
donor (MRD, 8/8 URD 7/8 URD), source of allograft, 
diagnosis (AML, ALL, MDS, MPD including CMML), 
preparative regimen, GvHD prophylaxis regimen. 
Secondary endpoints that will be modeled as binary outcomes 
will similarly be compared using logistic regression. 
Secondary endpoints that will be modeled as time-to-event 
outcomes will be compared using Cox regression. 
Potential interactions of RGI-2001 and various factors will be 
examined by including appropriate factors into regression 
models. 
Given that this is not a randomized study and that the intention 
is only to assess outcomes for a potential signal, no 


 
 
 
 
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adjustments will be made for multiple comparisons. As such, a 
Type II error (or a false negative) is prioritized over a Type I 
error (or a false positive). 
Binary exploratory outcomes will be summarized with 
proportions, continuous outcomes with means and medians, 
and time-to-event outcomes with Kaplan-Meier estimates or 
cumulative incidence estimates for endpoints with competing 
risks.  
 


 
 
 
 
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3 
SCHEDULE OF ASSESSMENTS 
ASSESSMENTS 
Screeninga 
Prior 
to 
HSCT 
HSCT/ 
RGI-2001 
Infusion 
Treatment Period 
Follow-up Safety Period 
Early 
Termination 
(ET)b 
Unscheduled 
Visitc 
Day 
 
 
-14 to -1 
0 
0 
7 
14 
21 
28 
35 
42 
60 
100 
180 
274 
(9mo) 
365 
(12mo) 
 
 
Visit Window 
 
0 
0 
(± 
1) 
(± 
1) (± 1) (± 1) (± 1) (± 3) (± 3) (± 5)  (± 5) 
(± 7) 
(± 7) 
 
 
Informed consentd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/cancer/ surgical 
historye 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs/KPSf 
X 
X 
 
X
X
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight/heightg 
X 
X 
 
X 
X 
X 
X 
X 
 
 
X 
X 
 
X 
X 
 
Physical examh 
X 
X 
 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Hematologyi 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum chemistryj 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation testingk 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Urinalysisl 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Serum pregnancy testm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
Allogeneic HSCT 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
RGI-2001 administrationo 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
RGI-2001 PK samples 
 
 
Blood for 
immunophenotyping 
 
 
 
 
 
 
 
GvHD assessmentp 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor assessmentsq 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
X 
X 
X 
Adverse eventsr 
X 
X 
 
X 
X 
Concomitant medicationss 
X 
X 
X 
Abbreviations: ET = early termination, HSCT = hematopoetic stem cell transplant, KPS = karnofsky performance status, ECG = electrocardiogram, PK= pharmacokinetics, GvHD = 
graft vs host disease 
a 
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specified. Informed consent, results of screening hepatitis, HIV tests, and tumor assessment (provided that no intervening therapy for their malignancy has been administered) 
may be obtained up to 42 days before initiation of the preparatory regimen.  PFTs and ECHO may be obtained as per institutional standard of care criteria within 84 days prior 
to the preparatory regimen provided no intervening therapy for their malignancy has been administered. Pregnancy test must be conducted within 7 days before preparatory 
regimen. Results of standard of care tests/procedures, performed prior to the subject signing the informed consent form (ICF) can be used as part of the screening assessments 
as long as the tests/procedures are performed within the appropriate screening window, unless otherwise specified. Screening assessments do not need to be repeated due to 
minor delays in procurement of donor HSC’s. 
b 
Subjects who are permanently discontinued from the study, either during the treatment period or follow up period, should complete the Early Termination Visit and, if 
applicable, monitor adverse event through 30 days of last RGI-2001 dose. 
c 
Unscheduled visits and procedures may be performed as clinically indicated. 
d 
Written informed consent must be signed by the subject before any protocol required procedures and assessments are performed. Results of standard of care tests/procedures, 
performed prior to the subject signing the informed consent form (ICF) can be used as part of the screening assessments as long as the tests/procedures are performed within 
the appropriate screening window unless otherwise specified. Screening assessments do not need to be repeated due to minor delays in procurement of donor HSC’s. 
e 
Prior cancer history includes: (i) date of diagnosis, (ii) prognostic score if applicable (iii) all previous therapies (i.e., chemotherapy, immunotherapy, biologic or targeted 
agents, experimental therapies, radiotherapy, and surgery), (iv) previous therapy details (i.e., regimen, start and stop dates), (v) best response for each regimen. 
f 
Vital signs, including temperature, blood pressure (systolic/diastolic), heart rate (HR), and respiratory rate (RR) should be taken in supine or seated position. Vital 
signs should be obtained within 15 minutes prior to RGI-2001 infusion and should be repeated within 30 minutes after the infusion. Additional vital signs measurements 
should be obtained as clinically indicated. 
g 
Height (without shoes) should be obtained prior to initiation of the preparatory regimen only. Weight should be taken within one day of dosing and the dosage of RGI-2001 
should be verified to be the same as the planned dose. 
h 
A complete physical exam should be performed during screening and should include HEENT, dermatologic, cardiovascular, respiratory, GI (including assessments of liver 
and spleen), musculoskeletal, neurological, and lymphatic systems. Physical examinations at all other time points should be a limited review of body systems as well as 
symptom-directed physical examinations of an AE or SAE. 
i 
A complete blood count including red blood cell (RBC) and white blood cell (WBC) count with differential, hemoglobin, hematocrit, and platelet count.  
j 
A comprehensive chemistry panel includes sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, albumin, total protein, calcium, 
phosphorus, magnesium, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase 
(LDH) and gamma glutamyl transferase (GGT). 
k 
Coagulation tests including prothrombin time (PT) or INR, and aPTT should be obtained at baseline and prior to HSCT infusion. Additional tests may be obtained as 
clinically indicated. 
l 
Urinalysis, including protein, glucose, ketones, blood, bilirubin, urobilinogen, pH, specific gravity and nitrates, with microscopic examination of sediment in the event 
of an abnormal reading on the dipstick. 
m 
Serum pregnancy test (women of child-bearing potential) – within 7 days prior to preparatory regimen. 
n 
Single ECG to be performed.  If abnormal, including QTc > 450 msec, perform in triplicate approximately 30 seconds apart, using the average of the three. 
o 
RGI-2001 should be administered intravenously over 30 minutes. On Day 0, the infusion should occur approximately 30 minutes and no later than 1 hour following the 
completion of HSCT. If cytokine reaction occurs with HSCT, subject should have resolved symptoms prior to the administration of RGI-2001. 
p 
Assessment for GvHD should be performed during every examination or per institutional guidelines from the time of engraftment to end of study. Documentation of the 
timing, severity is required including any biopsies obtained. Treatment for GvHD and outcome should be documented.  
q 
Evaluation of status of hematologic malignancy should be conducted as per institutional guidelines but should include a bone marrow aspirate and biopsy with cytogenetics, 
molecular diagnostics and chimerism as appropriate based on disease histology at baseline, and at time intervals close to Days 100, 180 and 365. 


 
 
 
 
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r 
Adverse events (AEs) must be recorded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v. 5.0) where possible. The 
reporting period for non-serious AEs starts after the first administration of study drug on Day 0. The reporting period for serious AEs starts after the informed consent form 
(ICF) has been signed. Adverse event monitoring should be continued for at least 30 days following the last dose of study drug. Infections should be recorded throughout the 
study. See Section 10 for further details. 
s 
Review of all medications, including over-the-counter (OTC) preparations and herbal products. Concomitant medications used from 2 days prior to the preparatory regimen 
before Day 0 through the end of the subject’s study participation, should be recorded. Maintenance therapy should be documented as a concomitant medication.


 
 
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4 
INTRODUCTION 
4.1 
Background  
4.1.1 
Graft Versus Host Disease 
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an important therapeutic 
option, and, in some indications, the only potentially curative therapy, for the treatment of a 
variety of hematologic malignancies, including acute myelogenous leukemia (AML), acute 
lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML) and myelodysplastic 
syndrome (MDS). In the U.S. approximately 8,500 subjects underwent allogeneic HSCT for a 
variety of indications in 2016. 
The success of myeloablative alloHSCT derives both from the ability to treat subjects with 
intensive chemo radiotherapy and from potent graft-versus-leukemia (GVL) effects mediated by 
donor immunity. Donor T cells in the infused stem cell graft are used to attack malignant cells, 
but may also strike normal host tissues and organs, resulting in graft versus host disease (GvHD). 
Despite the use of immunosuppressive agents, GvHD, acute or chronic, is one of the leading 
causes of morbidity and mortality from alloHSCT.  
Five phases of the development of acute GvHD have been described (Socié 2019). The first 
phase, priming of the immune response, is initiated by the underlying disease and the 
conditioning regimen used to prepare for transplantation. Damage to host tissues results in the 
secretion of pro-inflammatory cytokines that can increase the expression of adhesion molecules, 
co-stimulatory molecules, major histocompatibility complex (MHC) antigens and chemokines - 
all of which activate host antigen presenting cells (APCs). The second phase, T-cell activation 
and co-stimulation occur when donor T cells proliferate and differentiate in response to host 
APCs. The incidence of acute GvHD is directly related to the degree of mismatch in human 
leukocyte antigen (HLA) determinants such as MHC class II and I and minor histocompatibility 
antigens (MiHA). Additional donor/host differences, such as polymorphisms in proteins 
connected with innate immunity (NOD2), in the Toll-like receptor family, and in cytokine genes, 
are also believed to contribute to acute GvHD risk. The third and fourth phases of acute GvHD 
include alloreactive T-cell expansion and differentiation followed by the migration of activated 
T-cells to GvHD target tissues such as the gut, liver, skin, and lung and the recruitment of other 
effector leukocytes. In the last phase of acute GvHD development, effector T-cells initiate the 
destruction of target tissues via exposure to the cell surface and the release of soluble immune 
effectors. The resultant tissue damage leads to an increase in inflammatory signals and 
propagation of the cytokine storm. 
Classic acute GvHD generally develops within the first 100 days after myeloablative HSCT and 
typically affects the skin, gastrointestinal (GI) tract, and liver. In the setting of prophylaxis with 
immunosuppressants, Grade II-IV acute GvHD occurs in 25-60% of matched related transplant 
recipients and in 45-70% of matched unrelated recipients (Ho 2001). Although less common 
with myeloablative transplants, late onset acute GvHD may occur after 100 days post HSCT. The 
incidence of acute GvHD increases with increasing HLA mismatch between donor and recipient, 
unrelated donor transplant, female donor to male recipient and use of a total body irradiation 
(TBI) containing preparatory regimen. The development of Grade III/IV acute GvHD is 


 
 
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associated with a decrease in survival in subjects undergoing allogeneic transplantation. Steroids, 
primarily prednisone and methylprednisolone, constitute the first line of treatment for 
Grade III-IV acute GvHD. Complete responses can be expected in 25-35% of subjects, with an 
additional 15% achieving a partial response. Failure to respond to steroid therapy portends a poor 
prognosis. Second line treatment for acute GvHD include other immunosuppressive agents, such 
as tacrolimus, and anti-thymocyte globulin (ATG), as well as agents targeting TNF-α and the 
IL-2 receptor (Paczesny 2010). These therapeutic approaches are complicated by broad 
immunosuppression that results in enhanced susceptibility to infection and the risk of recurrence 
of the underlying malignancy. 
4.1.2 
CD4+Foxp3+ Regulatory T-cells 
A number of approaches, both pharmaceutical and cellular, in the prophylaxis of acute GvHD are 
being studied. The mainstay of prophylaxis therapy is a combination of a calcineurin inhibitor 
(cyclosporine and tacrolimus) plus either a short course of methotrexate or mycophenolate 
mofetil. More recently, sirolimus, which has been successful in the prevention of organ 
transplantation, has been utilized for acute GvHD. To date, no single combination has proved 
superior in the prevention of acute GvHD, and the incidence of acute GvHD remains high. 
Cellular approaches have included T-cell depletion, either ex vivo or in vivo and the positive 
selection of stem cells (to facilitate the exclusion of T-cells). While these efforts have had an 
impact on the incidence of acute GvHD, when used aggressively, these techniques have been 
associated with higher disease relapse rates (Paczesny 2010).  
More recently, efforts have been made to understand the function of regulatory T cells in 
transplantation. CD4+Foxp3+ Treg cells are considered a key player in maintaining peripheral 
tolerance (Wing 2001, Sagoo 2008, Paczesny 2010). Animal studies have demonstrated that 
these cells prevent or ameliorate various T-cell mediated diseases, including autoimmune disease 
and GvHD, by restoring immune tolerance to self-antigens as well as alloantigens (Wolff 2009). 
Studies in both humans and mice have confirmed the pivotal role Treg cells play in controlling 
GvHD (Socié 2019). However, the development of Treg cell-based therapeutic modalities has 
been hampered, in part, by the small numbers of these cells. RGI-2001 can expand these Treg 
cells in vivo and thus constitutes a novel approach to the treatment of GvHD.  
The relationship between Treg cells and acute GvHD in clinical allogeneic bone marrow 
transplantation (BMT) recipients has been assessed clinically. A prospective analysis of 
peripheral blood Treg cells as determined by the frequency of CD4+CD25hiFoxp3+ 
lymphocytes was conducted in 215 BMT subjects (Magneau 2010). Autologous BMT subjects 
(N = 90) and allogeneic BMT subjects without GvHD (N = 65) had similar cell frequencies, 
whereas allogeneic subjects with GvHD (N = 60) had Treg cell frequencies that were 40% less 
than those without GvHD. Treg cell frequencies decreased linearly with increasing grades of 
GvHD at onset, and correlated with the eventual maximum grade of GvHD (P < 0.001). In 
addition, the number of Treg cells at onset of GvHD predicted the response to GvHD treatment 
(P < 0.003). Subjects with Treg cell frequencies less than the median had higher non-relapse 
mortality than subjects with Treg cells greater than the median, but experienced equivalent 
relapse mortality, resulting in an inferior survival at 2 years (38% versus 63%, P < 0.03). Treg 


 
 
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cell frequency may therefore have important prognostic value as a biomarker of acute GvHD 
(Magneau 2010). 
4.2 
Investigational Product 
RGI-2001 is a liposomal formulation of the compound known as RGI-7000. RGI-7000 is a 
synthetic glycolipid composed of a galactose and a ceramide moiety linked in an 
α-configuration, a derivative of α-galactosylceramide (α-GalCer), a glycolipid originally 
extracted from a marine sponge (Natori 1993). It serves as a ligand for the CD1d molecule, 
expressed on APCs (Kawano 1997, Brossay 1998). The CD1d molecule is a non-polymorphic, 
MHC class I–like antigen-presenting molecule with an antigen-binding groove adapted for the 
presentation of lipid antigens (Moody 2005, Brigl 2004).
 
 
 
 
Refer to the current edition of the Investigator’s Brochure (IB) for additional information related 
to the physical, chemical and pharmaceutical properties and formulation of RGI-2001. 
4.3 
Study Rationale 
Despite efforts to date, the incidence of acute GvHD remains high. Thus, improvements in the 
prevention of the disease constitutes a high unmet medical need. 
Studies in both humans and mice have confirmed the pivotal role CD4+Foxp3+ Treg cells play 
in controlling GvHD (Socié 2009). However, the development of Treg cell-based therapeutic 
modalities has been hampered, in part, by the small numbers of these cells. RGI-2001 is a 
liposomal form designed to deliver RGI-7000, which is an immunomodulatory compound that 
may promote the proliferation of Tregs in donor bone marrow and the development of tolerance 
to alloantigens and therefore constitutes a novel approach to the prevention of GvHD. 
Preclinical studies suggest that the effects of RGI-2001 treatment are immunologically selective, 
affecting responses against specific antigens without causing generalized immunosuppression or 
the depletion of B- or T-cell function or numbers, and that RGI-2001 does not compromise 
beneficial GvL. In vitro and in vivo studies using model antigens have determined the 
mechanism for RGI-2001’s immunomodulatory activity. These studies have shown that 
RGI-2001 activates a tolerogenic cellular pathway, which ultimately leads to the activation of 
cellular cascades including regulatory dendritic cells (DCreg) and Tregs. These antigen-specific 
Tregs have been shown to down regulate the immune response directed toward specific antigens 
without causing generalized immunosuppression. In vivo experiments have also shown that 
primary antibody (humoral) responses were suppressed when mice were exposed to a prototypic 
preparation of liposomal RGI-7000 at or around the time an antigen was introduced (Ishii 2008). 
Furthermore, in a murine model of acute GvHD, treatment with RGI-2001 resulted in a 
statistically significant prolongation of survival in animals treated at doses ranging from 0.1 to 
100 µg/kg. In the treated animals, significantly higher levels of host alloantigen-specific Tregs 


 
 
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were observed after hematopoietic cell transplantation when compared with untreated animals. 
Immune responses against host alloantigens were suppressed in these treated mice, but 
responsiveness to third-party alloantigens remained intact. Additionally, in a mouse model of 
graft-versus-leukemia (GvL), treatment with RGI-2001 at the time of allogeneic bone marrow 
transplant was clearly shown to suppress GvHD without abrogating GvL effects 
(Duramad 2011). 
4.4 
Summary of Nonclinical Data 
RGI-2001 is anticipated to elicit antigen-specific immune tolerance. In vitro and in vivo studies 
have demonstrated the biological activity of RGI-2001 as follows: 
• RGI-2001 has been shown in vitro to be effectively taken up by B cells.  
• In peripheral blood mononuclear cell (PBMC) and whole blood studies to assess 
cytokine induction, RGI-2001 at clinically relevant concentrations, did not induce 
significant levels of pro-inflammatory cytokines in either human PBMCs or whole 
blood, demonstrating the low potential for inducing cytokines that may play an 
inciting role in GvHD (e.g., IL-12, IFN-γ or TNF-α).  
• In an acute GvHD model, RGI-2001 induced host-specific tolerance by promoting 
significant and dose dependent expansion of donor-derived CD4+Foxp3+ Tregs 
following allogeneic bone marrow and whole spleen cell (WSC) transplantation. The 
expansion of Tregs was also associated with a significant survival benefit and 
improvement in clinical signs of GvHD without compromise of GvL effects. 
• Concurrent treatment of normal mice with RGI-2001 and allogeneic donor spleen 
cells resulted in tolerance specific to the donor alloantigens through expansion of 
DCreg and Treg cells in a donor-specific transfusion (DST) mouse model 
(REGiMMUNE internal report. 
• In the GvHD efficacy studies a highly significant survival benefit was seen in mice 
treated with single injections of RGI-2001 at doses as low as 0.1 μg/kg. A dose-
dependent donor derived CD4+Foxp3+ Treg expansion was observed at doses 
ranging from 0.01 to 100 μg/kg. The survival benefit in these models reached 
significance at approximately 0.1 ug/kg. Thus, the minimum pharmacologically 
active dose (PAD) in the mouse GvHD model was defined as 0.1 μg/kg based on both 
survival and Treg expansion. 
In good laboratory practice (GLP) toxicology studies in the mouse (doses of 0.25, 3.5, or 
50 mg/kg every 3 days) and monkey (doses of 0.1, 1.5, or 20 mg/kg every 3 days), doses up to 
50 mg/kg and 20 mg/kg of RGI-2001 respectively, the maximum feasible doses (MFD), did not 
result in significant toxicity or dose limiting adverse effects. RGI-2001 was administered 
intravenously every 3 days to mice and monkeys for a period of up to 2 weeks, for a total of 
5 doses. These repeat dose studies included complete clinical, as well as morphological 
evaluations in addition to immunophenotypic analyses. Although the severely toxic dose – 10 
(STD-10) or the highest non-severely toxic dose (HNSTD) was not reached in the mouse or 
monkey repeat dose toxicology studies, the highest dose was considered the no observed adverse 


 
 
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effect level (NOAEL). The human equivalent dose (HED) of the NOAEL in the mouse 
(50 mg/kg) is 4400 µg/kg and the HED of the NOAEL in the monkey (20 mg/kg) is 6450 µg/kg. 
These HEDs are 44- to 65-fold higher than the dose planned in study RGI-2001-003 (100 µg/kg), 
To supplement the general toxicology studies a single primate GLP safety pharmacology study 
encompassing CNS, cardiovascular, and respiratory evaluations was conducted. This study 
assessed intravenous doses of up to 20 mg/kg (the same doses evaluated in the definitive 
toxicology study in the monkey), employing telemetry to monitor cardiovascular responses. 
Cardiovascular parameters were also monitored in the repeat-dose GLP toxicology study in 
monkeys. 
RGI-2001 administration did not result in any mortality and was without effect on functional 
observational battery (FOB) parameters. In addition, there were no significant effects on; body 
weight, body temperature, PR interval, QRS duration, QTc interval, QT vs. RR or QTc vs. RR 
interval plots, electrocardiographic morphology evaluations, respiratory rate, minute volume, or 
tidal volume. 
Toxicokinetic (TK) evaluations were performed for each of the pivotal toxicology studies in 
mice and monkeys and demonstrated adequate exposure throughout the course of the studies. 
Mass balance (i.e., excretion into urine and feces) studies were conducted in mice and monkeys 
using radiolabeled RGI-2001. In addition, a tissue distribution and expired air study was 
conducted in mice.  
In both mice and monkeys, radioactivity following [14C]RGI-2001 administration was associated 
more with plasma than blood cells over the first several hours post-treatment, but the terminal 
half-life (T ½) in cells (> 250 hours) was much longer than in plasma (~ 50 hours).  
After administration of [14C]RGI-2001 to mice, different tissues reached peak radioactivity levels 
at different times with widespread distribution of radioactivity to tissues still observed at 
168 hours post-dose. Tissues with notably high radioactivity levels were the spleen, liver, bone 
marrow, lung, and adrenal gland. These distribution data were consistent with established 
clearance mechanisms for liposomes through the reticuloendothelial system (Ishida 2002). Some 
of the tissues with the highest radioactivity were those associated with histopathologic alterations 
in the mouse toxicology study. Tissues with notably low radioactivity were the central nervous 
system (CNS), ocular tissues, bone, skeletal muscle and reproductive tissues.  
Excretion studies in both mice and monkeys demonstrated that very little RGI-2001 was 
eliminated in the urine and feces. In monkeys, 2.88% was eliminated in the urine and 0.91% in 
the feces. In mice < 6% was eliminated in urine and feces combined. In bile duct-cannulated 
mice, it was shown that only 0.11% of the injected radioactivity was collected in bile over 
24 hours. Collection of expired air yielded 64.68% of the injected dose as CO2, indicating the 
major route of elimination was conversion of [14C]RGI-2001 to CO2. 
The species used in the absorption, distribution, metabolism and excretion 
(ADME)/toxicokinetic evaluations of RGI-2001 were the same species employed in the 
pharmacological evaluations (mouse, cynomolgus monkey) and definitive toxicology studies. To 
date, no metabolism studies of RGI-2001 have been conducted. The expected consequence of the 
metabolism of liposomal products such as RGI-2001 is degradation to the individual 
phospholipid components and/or triglycerides (Seltzer 1984). 


 
 
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An in vitro study was performed with appropriate positive and negative controls to determine if 
RGI-7000, the active pharmaceutical ingredient (API) of RGI-2001, inherited human cytochrome 
P450 enzymes. This study was conducted with RGI-7000 rather than RGI-2001 because it was 
considered a more sensitive means with which to assess inhibitory potential. Under experimental 
conditions, there was little or no evidence that RGI-7000 inhibited CYP1A2, CYP2B6, CYP2C8, 
CYP2C9, CYP2C19, CYP2D6 or CYP3A4/5 in either a direct, time-dependent without 
metabolism or metabolism-dependent manner.  
The protein binding capacity of RGI-2001 and RGI-7000 was assessed in mouse, monkey, and 
human plasma. 
 
 
 
Refer to the current edition of the RGI-2001 IB for additional information related to RGI-2001 
clinical experience. 
4.5 
Summary of Clinical Data 
The first in human (FIH) study of RGI-2001 was a Phase 1/2a multicenter, open-label, dose 
escalation study whose primary objective was to evaluate the safety, tolerability, and 
pharmacokinetic profile of a single dose of RGI-2001 in subjects undergoing alloHSCT, with 
radiation or non-radiation containing myeloablative or reduced intensity preparative treatments 
based on institutional practices. GvHD prophylaxis consisted of a calcineurin inhibitor and one 
of the following (based on institutional practices): methotrexate, mycophenolate mofetil, or 
sirolimus. The study was divided into 2 parts: Part 1 was the dose-escalation phase and Part 2 
was the dose-expansion Phase. Eligible subjects were enrolled at 7 centers. A total of 
68 subjects, 57 RGI-2001 treated subjects as well as 11 control subjects participated in the study. 
In Part 1 of the study, a total of 28 subjects with a variety of hematologic diseases received a 
single dose of RGI-2001, administered approximately 30 minutes and no later than 1 hour after 
alloHSCT with an unrelated peripheral blood or bone marrow donor graft. The dose ranged from 
0.001 ug/kg to 100 ug/kg. Based on the results of the Part 1 study, 2 doses, were selected to 
further study in the Part 2 for the dose-expansion. The maximal administered dose that had no 
significant toxicity and had some signal of effect was 100 μg/kg. A dose 2 logs lower (1 μg/kg) 
was chosen to evaluate the potential dose response between the 1 μg/kg and 100 μg/kg doses in 
an effort to see a dose response in Part 2 of the study.  
In the Part 2 dose-expansion phase of the study, 29 subjects receiving matched related or 
unrelated donor grafts were randomized to receive a single infusion of either 1.0 ug/kg or 
100 ug/kg RGI-2001 administered approximately 30 minutes and no later than 1 hour after 
alloHSCT. Fourteen subjects received a dose of 1.0 ug/kg and 15 subjects received a dose of 
100 ug/kg of RGI-2001. An additional 11 subjects were enrolled as control subjects. A subset of 
subjects comprised of 4 subjects from each cohort, (8 of 29, 28%) responded to RGI-2001 by 
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Ki-67 index and were almost exclusively Helios+ and Foxp3+, indicating that their accumulation 
was due to expansion of natural Tregs. Notably, the incidence of grade 2 to 4 GvHD in the 8 
subjects who responded to RGI-2001 was 12.5%, compared with 52.4% in the 21 subjects who 
did not respond. No grade 3 or 4 GvHD was observed in the responder group, compared with a 
9.5% incidence among nonresponders (Chen 2017).  
The expansion of Treg cells was observed through Day 22 relative to the control group. Treg 
increases appeared to be inversely related to the severity of GvHD. There was no impact on 
myeloid or platelet engraftment noted. 
In general, the mean Cmax was increased as the dose of RGI-2001 increased. For most cohorts 
and for the subjects who received either the 1 μg/kg or 100 μg/kg dose of RGI-2001 in Part 2, the 
median times to Tmax were between 0.5 and 0.7 hours. 
RGI-2001 was well tolerated and without infusion reactions or cytokine release syndrome up to a 
dose level of 100 μg/kg administered as a single intravenous infusion in subjects who underwent 
allogeneic transplantation. There were no notable adverse effects across a variety of conditioning 
regimens and regimens for GvHD prophylaxis.  
This study served as the proof of concept for further exploring the potential of RGI-2001 for 
repeat administration to reduce or prevent GvHD during the critical phase post-transplantation. 
Refer to the current edition of the RGI-2001 IB for additional information related to RGI-2001 
clinical experience. 
4.6 
Risks/Benefits 
Despite utilization of doublet prophylactic regimens, GvHD remains the largest factor 
influencing outcome from HSCT. Transplant related mortality rates increase with increasing 
severity of acute GvHD. Thus, additional treatments are needed. RGI-2001 has demonstrated the 
potential for Treg expansion and a subsequent decrease in acute GvHD without significant 
toxicity. 
Clinical experience consists of the Phase 1 study which is described in Section 4.5. The MTD 
was not reached in doses ranging from 0.001 µg/kg to 100 µg/kg. 
There were no notable adverse effects across a variety of conditioning and GvHD prophylaxis 
regimens. The expansion of regulatory T-cells was observed up through Day 22 as compared to 
the control group. Correlation of regulatory T cell increase appeared to be in inverse relation 
with severity of GvHD.  
All subjects achieved myeloid engraftment within 30 days following RGI-2001 administration. 
Two subjects (both in cohort 2 [0.01 µg/kg]) did not achieve platelet engraftment within the time 
period; platelet engraftment for 2 other subjects was unknown (1 in the 1.0 µg/kg group and 1 in 
the 100 µg/kg group). Three subjects in the control group did not have platelet engraftment 
within 30 days following RGI-2001 administration. 
All of the subjects who received RGI-2001 reported at least 1 treatment-emergent adverse event 
(TEAE) during the protocol-specified reporting period. There were no TEAEs that led to 


 
 
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discontinuation from the study. No cytokine reactions or infusion-related reactions were 
observed.  
The most frequently reported adverse events for all cohorts (those occurring in > 15% of the 
subjects who received RGI-2001) were diarrhea (63.2%); nausea (61.4%); mucosal inflammation 
(56.1%); fatigue (54.4%); febrile neutropenia (43.9%); vomiting (36.8%); hypertension (33.3%); 
rash and headache (31.6% each); peripheral edema (29.8%); constipation (28.1%); muscular 
weakness (24.6%); dyspnea, abdominal pain, and increased AST (22.8% each); pyrexia and 
stomatitis (21.1% each); tachycardia and chills (19.3% each); decreased appetite and myalgia 
(17.5% each); and increased blood creatinine and hypomagnesemia (15.8% each).  
The TEAEs considered related to RGI-2001 (those occurring in ≥ 4 subjects in the all RGI-2001 
group) were nausea (10/57 subjects, 17.5%); diarrhea and increased AST (9/57 subjects each, 
15.8% each); febrile neutropenia (8/57 subjects, 14.0%); vomiting, increased ALT, and increased 
alkaline phosphatase (6/57 subjects each, 10.5% each); chills, fatigue, increased bilirubin, 
increased creatinine, and headache (5/57 subjects each, 8.8% each); and peripheral edema, 
myalgia, dizziness, and rash (4/57 subjects each, 7.0% each) 
Grade 3 TEAEs (those occurring in ≥ 4 subjects in the all RGI-2001 group) were febrile 
neutropenia (24/57 subjects, 42.1%), mucosal inflammation (13/57 subjects, 22.8%), 
hypertension (10/57 subjects 17.5%), diarrhea (7/57 subjects, 12.3%), stomatitis (6/57 subjects, 
10.5%), and nausea (5/57 subjects, 8.8%). Grade 4 TEAE included sepsis in 1 subject (100 µg/kg 
group), and septic shock and respiratory failure in another subject (100 µg/kg group). 
The following SAEs occurred in ≥ 2 subjects in the all RGI-2001 group: pyrexia, GvHD, and 
venoocclusive disease (3 subjects each); and diarrhea, sepsis, and staphylococcal bacteremia 
(2 subjects each).  
Based on the nonclinical safety data available for RGI-2001, potential side effects associated 
with the administration of RGI-2001 include: 
• 
 Extramedullary hematopoiesis and splenomegaly; observed in animals receiving 
multiple high dose injections of RGI-2001. Although extramedullary hematopoiesis is 
rare in humans, subjects will be monitored closely with complete blood counts (CBC) 
and physical exam for evaluation of splenomegaly. 
• Microgranulomas; observed in the liver of animals receiving multiple high dose 
injections of RGI-2001. Subjects will have liver function tests monitored frequently 
throughout the course of the study. 
• Changes in RBCs, reticulocytes, WBC, leukocytes and various T- and B-cell 
lymphocyte subsets. Decline in RBCs may result in anemia, while decline in 
lymphocyte subsets may increase susceptibility to some types of infection. Subjects 
will have frequent CBCs to monitor for significant changes in red and white blood 
cell populations. 
• A mild decline in triglycerides; observed in preclinical safety studies. It is anticipated 
that such a decline will have little impact on safety in subjects.  


 
 
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The pharmacologic actions of RGI-2001, manifested by a decrease in iNKT cells, could result in 
an impaired immune response to various pathogens and in absolute changes in T-cell or B-cell 
lymphocyte counts. Additionally, the ability of RGI-2001 to induce a tolerogenic state could 
result in undesirable tolerance to antigens to which subjects are exposed in the interval 
surrounding the administration of RGI-2001. 
Literature reports have linked the activation of iNKT cells with the progression of atherosclerosis 
in murine models of atherogenesis (Tupin 2004). The role of iNKT cells in the development of 
atherosclerotic lesions in humans is unknown; however, inflammation and the innate immune 
response are believed to contribute to the progression of atherosclerosis. Pharmacologically 
active doses of RGI-2001 are expected to activate iNKT cells and theoretically could, as a result, 
aggravate underlying atherosclerotic disease. Only subjects with adequate cardiovascular 
function without ischemia or myocardial infarction in the previous six months will be enrolled in 
the clinical study. 
4.7 
Dose Regimen and Treatment Period Rationale 
The dose and dose schedule for the Phase 2 study is 100 µg/kg, weekly for a duration of 5 weeks 
(6 doses). This dose was selected based on nonclinical pharmacology and toxicology information 
and the safety and exploratory efficacy results of the Phase 1/2a FIH study. 
In murine models of GvHD, doses as low as 2 µg/mouse (approximately 100 µg/kg) prolonged 
the survival of mice. Additional studies showed prolongation of survival in these murine models 
was noted over a dose range of 0.1 to 10 µg/kg. As there was no sign of decreasing efficacy with 
dose, these mouse models suggested a dose of 100 µg/kg was toward the top of a wide range of 
effective doses. 
In 2-week GLP toxicity studies of RGI-2001 in the mouse and monkey, the NOAEL was the 
highest dose tested in each species, 50 and 20 mg/kg, respectively. The HED of these doses are 
44-fold and 65-fold higher than the planned dose of 100 µg/kg in study RGI-2001-003. Exposure 
of mice and monkeys at the NOAEL, based AUC0-t was very large, 2,155,000 ng*h/mL and 
12,950,000 ng*h/mL, respectively. These exposures are over 10,000-fold higher than the human 
AUC0-t associated with a dose of 100 µg/kg (133 ng*h/mL, n = 15, study RGI-2001-002, 
Part 2). 
Longer term toxicity of the active agent (RGI-7000) given by daily IV injection has been 
evaluated in GLP studies in rats (50, 100, 200, and 400 µg/kg/day for 26 weeks) and monkeys 
(30, 60, 200, and 600 µg/kg/day for 15 weeks), with a toxicity pattern similar to that of 
RGI-2001 suggesting there is no change in the toxicity of the active agent of RGI-2001 with 
longer duration of treatment. 
Further support for the selection of 100 µg/kg comes from the clinical safety seen in study 
RGI-2001-002, in which RGI-2001 was safe and well tolerated up to 100 μg/kg administered as 
a single intravenous infusion for subjects who received allogeneic transplantation. There were no 
notable adverse effects across a variety of conditioning regimens and GvHD prophylaxis. 
Possible efficacy was observed in subjects during Part 1 (dose escalation) of the study but the 
differences between doses were not clear because of the small sample sizes. In Part 2 (dose 
expansion), both doses at 1.0 µg/kg and 100 µg/kg dose level showed some signal of effect and 


 
 
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there was no increase toxicity at the highest dose evaluated. There were no trends in toxicity with 
dose escalation across all the cohorts. Therefore, RGI 2001 at 100 ug/kg was selected to further 
evaluated for repeat dosing for the clinical development program.  
Potential signals of efficacy from a single dose of RGI-2001 in study RGI-2001-002 support 
further testing of repeated (weekly) doses of RGI-2001 in this study. The weekly interval was 
selected to extend the exposure seen in the single dose clinical trial RGI-2001-002, while 
minimizing subject inconvenience with clinic visits. 


 
 
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5 
STUDY OBJECTIVES AND ENDPOINTS  
Objectives 
Endpoints 
Primary 
 
• 
To assess the potential efficacy of RGI-
2001 in addition to standard of care 
(SOC) vs SOC for the prevention of 
aGvHD 
• 
To characterize the safety and 
tolerability of 6-weekly IV infusions of 
RGI-2001 in subjects following 
alloHSCT  
• 
Efficacy: Grades II-IV aGvHD by Day 100 according 
to the Modified Keystone Criteria (Przepiorka 1995)  
• 
Safety: Incidence, nature, and severity of 
treatment-emergent AEs, SAEs, laboratory test values, 
vital sign measures, and graft failure  
Secondary 
 
• 
To assess the potential efficacy of RGI-
2001 in addition to SOC vs SOC for the 
prevention of chronic GvHD (cGvHD) 
according to the secondary endpoints 
listed 
• 
To assess the survival of subjects who 
received RGI-2001 in addition to SOC 
vs SOC  
• 
To evaluate the pharmacodynamics 
effects of weekly dosing of RGI-2001 
• 
Grades II-IV aGvHD by Day 180 according to the 
Modified Keystone Criteria  
• 
Total and moderate-severe cGvHD at 6 months and 
1 year according to 2014 NIH criteria  
• 
Non-relapse mortality (NRM) rates at Day 100, 
6 months and 1 year  
• 
Disease-free survival (DFS) at 6 months and 1 year  
• 
GvHD-free, relapse free survival (GRFS)a at 6 months 
and 1 year  
• 
Overall survival (OS) at 6 months and 1 year  
• 
Change from baseline in the percentage of 
CD4+CD25+CD45RA+ CD127-LO T cells (naive 
Tregs) on Days 14, 28, 42, 60, 100, 180 
 
 
• 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  


 
 
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Objectives 
Endpoints 
•
 
 
  
 
 
  
a 
A GRFS event includes grade III-IV acute GVHD, chronic GvHD requiring systemic immunosuppressive 
treatment, disease relapse or progression, or death by any cause. 
 


 
 
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6 
STUDY DESIGN 
This is an open-label, multi-center, single-arm study to evaluate six weekly doses of RGI-2001 in 
combination with SOC treatment for the prevention of aGvHD in subjects following alloHSCT. 
The study will include a Safety Run-in Phase of up to 6 subjects to assess the safety and 
tolerability of 6 weekly doses of RGI-2001. If the safety profile in this run-in is deemed 
acceptable (see Section 6.1), an Expansion Phase in which the potential efficacy of 6 weekly 
doses of RGI-2001 in addition to SOC for GvHD prophylaxis will be assessed. Comparison will 
be made to a contemporaneous control group of subjects from the CIBMTR database in which 
SOC GvHD prophylaxis was administered (details in Section 11).  
All subjects will be assessed for suitability of alloHSCT based on institutional practice, using 
either a matched-related donor (MRD) or unrelated donor (URD), and will be enrolled after 
meeting inclusion/exclusion criteria for this study. Preparatory regimens will be based on 
institutional practice for the disease subtype. Either bone marrow or peripheral stem cell grafts 
mobilized with G-CSF will be used. GvHD prophylaxis must consist of a calcineurin inhibitor 
(tacrolimus or cyclosporine) and a second agent (methotrexate or mycophenolate mofetil. 
All subjects will be assessed for GvHD as per institutional practices but at minimum Day +100, 
+180 and 1-year post alloHSCT. Assessment of cGvHD will likewise occur at regular intervals 
as per institutional guidelines. Similar to the methodology employed by CIBMTR for the control 
subjects, cumulative data will be captured at regular intervals as outlined in the Schedule of 
Assessments (SoA). 
• Safety will be assessed with periodic vital signs, physical exams, laboratory 
assessments and by reporting of AEs. 
• Disease status will be assessed via regular laboratory and bone marrow assessments. 
The study design is presented in Figure 1. 


 
 
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Figure 1 
Study Design Schema 
 
6.1 
Safety Run-in Phase 
A Safety Run-in Phase will be used to assess the safety profile and tolerability of repeat doses of 
RGI-2001 prior to the Expansion Phase. This portion of the study will be conducted at a limited 
number of sites. 
Subjects will receive open-label RGI-2001 at a dose of 100μg /kg, via 30-minute intravenous 
(IV) infusion on a weekly basis for 6 doses in addition to a SOC GvHD prophylactic regimen. 
The first dose will be administered on Day 0 at approximately 30 minutes and no later than 1 
hour after HSCT infusion (see Section 8.6 on Dose Administration). Subsequent doses will be 
administered weekly, on Days 7, 14, 21, 28 and 35. 
Up to two cohorts of 3 subjects each will be enrolled to the Safety Run-in Phase. Initially, 
3 subjects will be enrolled, treated and assessed for dose-limiting toxicities (as defined below in 
Section 6.1.1) through Day 30 (DLT window). A safety review committee (SRC) will examine 
all relevant safety data after the 3rd subject has reached Day 30. As a rough guide, a DLT rate on 
the order of 20% or less would be considered as acceptable. Therefore, if 0 subjects are reported 
Screening Phase
AML/ALL/MDS/CMLL/MPD/CML
Enrollment Phase
Safety Run-in: n=6
Expansion: n=44
Conditioning Regimen: Myeloablative Conditioning
AlloHSCT
Donor Source: PMBC or BM
GVHD Prophylaxis Regimen: Calcineurin Inhibitor + MTX or MMF
Treatment Phase
RGI 100ug/kg IV infusion Days 0, 7, 14, 21, 28, 35 
Follow-up Phase 
until end of study or early termination


 
 
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to have a DLT among the first 3 subjects, consideration will be given to enrolling up to 3 
additional subjects. However, this decision will not be made solely on the observed occurrence 
(or lack of) DLTs; rather the SRC will consider the totality of the safety data before arriving at a 
definitive conclusion regarding enrollment of additional subjects at the dose of 100 μg /kg. If 
within the first 3 subjects, 1 or more DLTs are observed, then consideration will be given to use 
of an alternative dose and/or dosing schedule, with the ultimate decision being made by the SRC. 
If an alternate dose and/or schedule is used, the same process as described above will be used. If 
the additional 3 subjects (beyond the initial 3) are allowed to enroll at the dose of 100 μg /kg or a 
lower dose and/or alternative schedule, safety data after the 6th subject has completed all 6 doses, 
as well as initial efficacy, PK and PD data will be evaluated in coming to a recommendation 
regarding proceeding to the Expansion Phase, with this recommendation made by the SRC. Once 
the study extends to the Expansion Phase, enrollment will be open to all sites (Figure 2).  
6.1.1 
Definition of Dose-limiting Toxicities  
All subjects are expected to experience hematologic toxicity as part of the myeloablative 
alloHSCT procedure. Therefore, hematologic toxicities (e.g., leukopenia and thrombocytopenia) 
will not be useful measures of drug-induced toxicity, and DLTs are defined by non-hematologic 
toxicities. 
The following DLT criteria apply to the Safety Run-in Phase of the study. A DLT is defined as 
any treatment-related AE that is not attributable to an extraneous cause (i.e., disease progression, 
preparatory regimen or HSCT infusion) and also excludes any signs and symptoms of GvHD. 
DLT is an adverse event occurring in the period of 30 days after the first dose of RGI-2001 
administration, and meeting at least one of the following NCI CTC (Version 5.0) criteria: 
• Grade 3+ infusion-related/cytokine release reactions 
• Graft failure (as defined in Section 9.4.1.) 
• Any Grade 4-5 non-hematological AE 
• Delay in dosing by > 2 weeks due to treatment-related AE that is not attributable to an 
extraneous cause as defined above 
Subjects who do not complete the DLT window for reasons other than toxicity may be replaced. 
Similarly, if a subject receives ≤ 50% of planned doses of RGI-2001 for reasons other than 
toxicity considered related to RGI-2001, this subject may be replaced. 
Figure 2 
DLT Schema 
 


 
 
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6.2 
Expansion Phase 
Once a dose/schedule is determined by the SRC to have an acceptable safety/PK profile, 
enrollment will continue in the Phase 2 Expansion Phase and be extended to all sites.  
Accrual is targeted at 50 subjects who receive the dose deemed as acceptable from the Safety 
Run-in Phase (44 in the Expansion Phase, 6 from the Safety Run-in Phase at the dose used in 
expansion). All subjects in the Expansion Phase who receive at least one dose will be considered 
in all efficacy and safety analyses.  
Subjects will receive open-label RGI-2001 at a dose of 100μg/kg (unless an alternative dose 
and/or schedule is chosen by SRC), via 30-minute intravenous (IV) infusion on a weekly basis 
for 6 doses (or an alternative dose/schedule as determined in the run-in phase) in addition to a 
SOC GvHD prophylactic regimen. The first dose will be administered on Day 0 at approximately 
30 minutes and no later than 1 hour after HSCT infusion. Subsequent doses will be administered 
weekly, on Days 7, 14, 21, 28 and 35. 
6.3 
Control Group 
A non-randomized, contemporary control group from the CIBMTR database will be derived for 
comparison. Control subjects will be chosen so as to meet all eligibility requirements for the 
clinical trial, have received a transplant in the same time window as the study subjects, and have 
been transplanted in a center that participates in this study. Consent will be obtained via the 
CIBMTR to participate in this study (Section 11). 
6.4 
Safety Review Committee 
As noted above, a safety review committee will be used in this study. The SRC will serve 
3 primary roles: 1) assessment of DLTs, other safety measures, and PK/PD in the initial 
3 subjects to determine whether dose and schedule appropriate to enroll another 3 subjects 
2) assessment of safety and PK/PD data to determine suitability to proceed to dose expansion 
3) ongoing monitoring of both safety and aggregated efficacy data. The SRC will develop and 
follow a data and Safety Monitoring Plan and charter. 
The SRC will be composed of, at a minimum the Sponsor or designee members including the 
Medical Monitor, Statistician, Safety Scientist, and the Lead Principal Investigator (PI). SRC 
meetings will occur in accordance with the SRC charter. 
Depending on the results of safety reviews, the SRC may provide recommendations on the future 
continuation of the study and other relevant steps, including prophylactic pre-medications in all 
or some current and future subjects. 
6.5 
Number of Sites 
This study will be conducted at 8-12 sites in the United States.  


 
 
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6.6 
Number of Subjects 
Anticipated accrual is 50 patients who receive at least one dose of RGI-2001, with at least 
6 subjects in the Safety Run-in Phase, and up to 44 subjects in the Expansion Phase. It is 
anticipated that a minimum of 250 subjects will be included in the control group. 
6.7 
Study Duration 
Individual subject participation is expected to last up to one year following alloHSCT, including 
a 6-week treatment period and a 42-week follow-up period. In addition, there is a screening 
period lasting approximately 2 weeks.  


 
 
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7 
SUBJECT POPULATION 
7.1 
Inclusion Criteria 
All subjects (including CIBMTR control group, except where noted) must meet the following 
criteria: 
1. Ages > 18 and ≤ 65 years of age 
2. Has a hematologic malignancy as defined below and is considered a candidate for allo 
HSCT: 
a. Acute myelogenous leukemia (AML) in first or subsequent morphologic complete 
remission 
b. T or B cell acute lymphoblastic leukemia (ALL) in first or subsequent complete 
morphologic remission  
c. Myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), 
myeloproliferative disorder (MPD) including myeloid metaplasia and myelofibrosis 
and are currently with <10% blasts in bone marrow 
d. CML subjects who have received prior treatment including at least one tyrosine 
kinase inhibitor and are currently in chronic phase or with a complete hematologic 
remission but with evidence of cytogenetic or molecular relapse  
3. Must have adequate organ function as defined below (RGI-2001treatment group only): 
a. Cardiac function: Left ventricular ejection fraction at rest ≥ 45% 
b. Liver function: total bilirubin < 1.5 x upper limit of normal (ULN); alanine 
aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x the ULN. 
Patients who have been diagnosed with Gilbert’s Disease or malignant involvement 
are allowed to exceed the defined bilirubin value of 1.5 x the ULN 
c. Serum creatinine < 2 mg/dL or estimated creatinine clearance >50mL/min calculated 
using the Cockcroft-Gault equation 
d. Pulmonary: DLCO (corrected for hemoglobin) and/or FEV1 ≥ 50 % 
4. Considered suitable candidate for a myeloablative allogeneic or unrelated donor transplant 
based on institutional criteria  
5. Subject must be receiving first allogeneic transplant from a single donor. Prior autologous 
transplant is acceptable 
6. Transplant Donor: 
a. Matched related donor (8/8): Molecular identity at HLA-A, -B, -C and -DRB1 by 
high-resolution typing 
b. Unrelated donor (≥ 7/8 allelic match): high resolution molecular typing at the 
following loci is required HLA -A, -B, -C and -DRB1 
c. Meets institutional criteria for bone marrow or PBSC donation (see Section 7.4) 


 
 
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7. Source of the Allograft: 
a. Unmodified bone marrow or mobilized peripheral blood stem cell (PBSC) transplant, 
using granulocyte colony stimulating factor (G-CSF) as the mobilizing agent. Cord 
blood is not allowed 
8. KPS ≥ 60 
9. Is a candidate for anti-graft-vs-host-disease (GvHD) prophylaxis that includes: 
a. A calcineurin inhibitor (either tacrolimus [FK 506] or cyclosporine A), in 
combination with either methotrexate (MTX), mycophenolate mofetil (MMF)  
10. Ability to understand and willingness to sign a written informed consent form  
Inclusion criteria pertaining specifically for subjects scheduled to receive RGI-2001: 
11. If female of childbearing potential, must have had a negative serum pregnancy test prior to 
enrollment and must have agreed to use a double barrier method of contraception for 
90 days following the last dose of RGI-2001 
12. If male, must be sterile or willing to use an approved method of contraception from the 
time of informed consent to 90 days after the last dose of RGI-2001  
7.2 
Exclusion Criteria 
Any subjects (including CIBMTR control group) who meet any of the following criteria will be 
excluded from study entry: 
1. Has had any other prior organ transplantation 
2. Planned procedure to deplete regulatory T-cells from donor transplant materials  
3. Planned reduced intensity conditioning 
4. Planned use of any additional or alternative drug(s) for GvHD prophylaxis than listed in 
the inclusion criteria (e.g., rapamycin, cyclophosphamide, steroids)  
5. Has had prior treatment with anti-CD3, other T cell depleting antibodies, or 
anti-thymocyte globulin within 12 months prior to alloHSCT procedure 
6. Is participating in a trial (other than RGI-2001-003) involving an investigational 
agent/non-standard of care drug.  
7. Has progressive underlying malignant disease including post-transplant 
lymphoproliferative disease. 
8. Has evidence of active central nervous system (CNS) disease including known brain or 
leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical 
suspicion of CNS involvement).  
9. Known history of human immunodeficiency virus (HIV) 
10. Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) (control group 
only) 


 
 
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11. Is female and pregnant or lactating 
12. Patients with active bacterial, viral or fungal infections (currently taking medication(s) 
and with progression or no clinical improvement) 
Exclusion criteria pertaining specifically for subjects scheduled to receive RGI-2001: 
13. Has undergone major surgery within 1 month before Day 0. Indwelling catheter placement 
is allowed 
14. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the 
limit of quantification.  Subjects that are on study with HBV or HCV infection should 
have titers checked regularly, as per institutional standard of care. 
15. Has had any other condition that, in the opinion of the Investigator, renders the subject 
unsuitable for study participation 
16. Has a documented history of uncontrolled autoimmune disease or on active treatment 
17. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug. 
18. History of myocardial infarction, unstable angina, or acute coronary syndrome within 
6 months prior to receiving study drug 
19. Has received an investigational agent within 4 half-lives or 14 days prior to HSCT, 
whichever is shorter 
7.3 
Eligibility for the Control Arm 
Subjects in the control arm will be identified from subjects reported to the CIBMTR from U.S. 
centers and which agree to participate in this study. Control subjects must satisfy the inclusion 
and exclusion criteria of this study according to Section 7.  
Data for all eligible subjects in centers agreeing to participate in the study will be used to 
constitute the control database for this study.  
7.4 
Donor Screening 
Stem cell or bone marrow donors will be evaluated according to institutional protocol. A bone 
marrow transplant physician and/or nurse practitioner will perform a complete medical history 
and physical exam, donor health history questionnaire and Zika virus screening. Required testing 
will include hematology studies, evaluation of risk for hemoglobinopathy as clinically indicated, 
chemistry studies, infectious disease testing, EKG, and chest x-ray. Bone marrow donors will 
also require evaluation and clearance by an anesthesiologist as per institutional practices. 
Donors will be considered eligible if screening shows that the donor is free from risk factors for, 
and clinical evidence of, infection due to relevant communicable disease agents and diseases, 
and is free from communicable disease risks associated with transplantation (test results for 
relevant communicable disease agents are negative or nonreactive).  


 
 
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7.5 
Withdrawal/Discontinuation from Treatment, Procedures and Study  
7.5.1 
Study Discontinuation 
The Sponsor has the right to terminate this study at any time. Reasons for terminating the study 
overall or at a specific study site may include, but are not limited to the following: 
1. The incidence or severity of adverse events (AEs) in this or other RGI-2001 studies 
indicates a potential health hazard to subjects 
2. Subject enrollment is unsatisfactory 
3. Data recording is inaccurate or incomplete 
4. Investigator does not adhere to the protocol or applicable regulatory guidelines in 
conducting the study 
5. The safety review committee (SRC) recommends termination of the study due to revealed 
safety concerns. 
7.5.2 
Subjects’ Decision to Withdraw 
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution. 
Subjects can decline to continue receiving investigational product and/or other protocol-required 
therapies or procedures at any time during the study but continue participation in the study. 
If this occurs, the investigator is to discuss with the subject the appropriate process for 
discontinuation from investigational product or other protocol-required therapies and must 
discuss with the subject the options for continuation of the Schedule of Assessments and 
collection of data, including endpoints and adverse events. The investigator must document the 
level of follow-up that is agreed to by the subject (e.g., in person, by telephone/mail, through 
family/friends, in correspondence/communication with other physicians, from review of the 
medical records). 
Withdrawal of consent from a study means that the subject does not wish to receive further 
protocol-required therapies or procedures, and the subject does not wish to or is unable to 
continue further study participation. Subject data up to withdrawal of consent will be included in 
the analysis of the study, and where permitted, publicly available data can be included after 
withdrawal of consent. The investigator is to discuss with the subject appropriate procedures for 
withdrawal from the study. 
If a subject fails to return for scheduled visits, a documented effort must be made to determine 
the reason. If the subject cannot be reached by telephone after two attempts, a certified letter 
should be sent to the subject (or the subject’s legally authorized representative, if appropriate) 
requesting contact with the Investigator. Attempts to contact the subject should be documented in 
the study records. 


 
 
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7.5.3 
Discontinuation of Study Treatment and/or Withdrawal of Subjects Prior to Study 
Completion 
The investigator and/or Sponsor can decide to withdraw a subject(s) from investigational product 
and/or other protocol-required therapies, protocol procedures, or the study as a whole at any time 
prior to study completion. Reasons for removal from protocol-required investigational product or 
procedural assessments include any of the following: 
1. Subject withdrawal of consent  
2. Safety concern (e.g., due to an adverse event including those defined as DLT criteria, 
ineligibility determined, significant protocol deviation, noncompliance, requirement for 
alternative therapy, pregnancy) 
3. Death 
4. Lost to follow-up 
If a subject develops acute GvHD prior to completing all six RGI-2001 doses, the subject is still 
permitted to receive any remaining RGI-2001 doses with written approval by the Medical 
Monitor and if no experimental GvHD treatment is planned. 
Subjects who permanently discontinue RGI-2001 prior to receiving all six doses should be 
encouraged to remain in the study and follow the SOA (see Section 3) for all remaining study 
visits primarily for assessment of secondary endpoints. 
Subjects who are permanently discontinued from the study, either during the treatment period or 
follow up period, should complete the Early Termination Visit as per the SOA (Section 3) and, if 
applicable, monitor adverse event through 30 days of last RGI-2001 dose. 
7.6 
Replacement of Subjects 
Subjects in the Safety Run-in Phase who do not complete the DLT window for reasons other 
than toxicity may be replaced. Similarly, if a subject in the Safety Run-in Phase receives ≤ 50% 
of planned doses of RGI-2001 for reasons other than toxicity considered related to RGI-2001, 
this subject may be replaced. All subjects who receive at least one dose of RGI-2001 in the 
Expansion Phase will be considered evaluable. 
Subjects who have cancelled alloHSCT will also be replaced. 


 
 
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8 
STUDY DRUG 
Refer also to the current sponsor approved study Pharmacy Manual for details. 
8.1 
Physical Description 
 
 
 
 
8.2 
Packaging and Labeling 
RGI-2001 for Injection is supplied as a sterile liquid suspension filled into depyrogenated USP 
Type 1 5-mL glass vials with a 2.5 mL fill volume, using a closure system consisting of 
sterilized rubber stoppers (22 mm) with aluminum royal blue seals and flip-off caps. The dosing 
is based on the dose of the liposome-encapsulated ingredient, RGI7000. Each vial contains 
5 mg/mL of RGI7000 and 50 mg/mL of lipid blend in a 10% sucrose solution containing 
20 mM Histidine.  
The product is for single-use only and does not contain a preservative. 
8.3 
Storage 
RGI-2001 should be stored at 2°–8°C, protected from freezing and exposure to light. 
8.4 
Study Drug Accountability 
The PI or designee is responsible for maintaining accurate records (including dates and 
quantities) of IP received, subjects to whom IP is dispensed (subject-by- subject dose specific 
accounting), and IP lost or accidentally or deliberately destroyed. The PI or designee must 
retain all unused or expired study supplies until a Sponsor-designated Clinical Research 
Associate (CRA) has confirmed the accountability data.   
8.5 
Return and Disposition of Study Drug 
Unused study drug must be kept in a secure location for accountability and reconciliation by the 
Sponsor-designated CRA. The Investigator or designee must provide an explanation for any 
destroyed or missing study drug or study materials. 
Unused study drug may be destroyed on site, per the site’s standard operating procedures, but 
only after Sponsor or its designee has granted approval for drug destruction. The 
Sponsor-designated CRA must account for all study drug in a formal reconciliation 
process prior to study drug destruction. All onsite study drug destruction must be documented. 
Documentation must be provided to the Sponsor or its designee and the original retained in 
the PI’s study files. If a site is unable to destroy study drug appropriately, the site can return 
unused study drug to Sponsor’s designee upon request. 


 
 
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All study drug and related materials should be stored, inventoried, reconciled, and destroyed or 
returned, according to applicable state and federal regulations and study procedures. 
8.6 
Administration and Dosing Regimen 
All subjects will receive 6 weekly doses of RGI-2001 100 μg/kg via IV administration over 
30 minutes. Weight should be taken within one day of dosing and the dosage of RGI-2001 
should be verified to be the same as the planned dose. The dosage of RGI-2001 will be diluted in 
50 ml 0.9% normal saline and the first dose will administered intravenously at approximately 
30 minutes and no later than 1 hour after completion of the allogeneic HSCT on Day 0 (study 
Day 1 if transplant occurs over 2 days). If cytokine release/infusion reaction is observed during 
or after HSCT, then RGI-2001 should be postponed until at least 30 minutes after the reaction 
has resolved. Subsequent RGI-2001 administrations should be administered on Days 7, 14, 21, 
28, and 35 + /- 1 day. Pre-medications should not be administered prophylactically. However, if 
a grade 2 cytokine release is observed, pre-medication with an antihistamine (e.g., 
diphenhydramine), an anti-pyretic (e.g. acetaminophen) and corticosteroids (e.g., 4 mg 
dexamethasone or equivalent) should be administered. Consideration may be made to administer 
premedication for Grade 1 cytokine release, depending on the constellation of symptoms. In 
addition, the SRC may recommend pre-medications in all current and future subjects depending 
on safety reviews. 
8.7 
Randomization and Blinding 
This is an open-label study and there is no randomization or blinding. 
8.8 
Prior and Concomitant Medications 
Please see exclusion criteria for prohibited medications. 
Concomitant medications are any prescription or over-the-counter preparations used from 
2 days prior to the preparatory regimen before Day 0 through the end of the subject’s study 
participation. 
Standard myeloablative preparatory regimens, (i.e., reduced intensity conditioning, non 
myeloablative conditioning, experimental regimens or drugs are not allowed), HSCT and 
standard supportive care/ prophylactic treatments (including but not limited to colony stimulating 
factors, transfusions, antibiotics/anti-virals/anti-fungals) per institutional guidelines for optimal 
medical care shall be permitted during participation of this study. The dose of steroids that are 
required for reasons unrelated to the underlying malignancy or HSCT process or sequelae must 
not be higher than physiologic doses (the equivalent of 20 mg/day of prednisone). No anti-
thymocyte globulin (ATG) is allowed in the conditioning regimen. 
GvHD prophylaxis must consist of a calcineurin inhibitor (cyclosporine or tacrolimus) in 
combination with MTX or MMF. Dosing, schedule and monitoring of the GvHD regimen should 
follow institutional guidelines. Please see respective prescribing information for safety 
information. Steroids, sirolimus, post-transplant cyclophosphamide, ATG, other GvHD 


 
 
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prophylactic agents (including investigational agents) or manipulation of the graft to reduce 
GvHD are not allowed.  
Post transplant maintenance therapy that includes an investigational agent, or any treatments that 
can be used for GvHD are not allowed. Maintenance therapy for actionable targeted mutations 
(e.g., FLT3 inhibitors) or with FDA approved agents in any indication should not be initiated 
prior to Day 42 post alloHSCT. 
Treatment of GvHD should follow institutional guidelines and may include steroid treatment at 
supra-physiologic doses. See Section 7.5.3 for development of GVHD prior to completion of 
RGI-001 dosing. 
The investigator may prescribe additional medications during the study, as long as the prescribed 
medication is not prohibited by the protocol. In the event of an emergency, any needed 
medications may be prescribed without prior approval, but the Medical Monitor must be notified 
of the use of any medications, except acetaminophen, immediately after use. Any concomitant 
medications added or discontinued during the study should be recorded on the electronic case 
report form (eCRF.) 
8.9 
Dietary or Other Protocol Restrictions 
Dietary restrictions per institutional guidelines (e.g. neutropenic diet) may be imposed on study 
subjects. Alcohol and tobacco use should be limited as per institutional guidelines. 
8.10 
Dose Modification/Treatment Cessation 
If a subject permanently discontinues treatment in the Safety Run-in or Expansion Phase as 
specified below, see Section 7.5.3 Discontinuation of Study Treatment and/or Withdrawal of 
Subjects Prior to Study Completion, for further details. 
8.10.1 
Safety Run-in Phase 
RGI-2001 will be administered at a dose of 100 μg/kg IV weekly for 6 doses. There are no dose 
reductions or escalations in this portion of the study except as recommended by the SRC at the 
end of the run-in period. Each individual infusion is allowed to be delayed up to 2 weeks for 
ongoing grade 3+ AEs, regardless of causality. However, if a subject enrolled in the run-in 
period is not able to receive at least 50% of RGI-2001 doses during the DLT window for reasons 
other than toxicity, then that subject will be replaced. Subjects requiring delay of an infusion of 
> 2 weeks should be discontinued from treatment. 
Subjects enrolled in the Run-in Phase beyond the DLT window who meet DLT criteria should be 
discontinued from study treatment. Supportive care should be administered as appropriate. 
8.10.2 
Expansion Phase 
RGI-2001 will be administered at the dose and schedule agreed upon by the SRC at the 
completion of the Safety Run-In Phase. No dose escalations will be allowed. 


 
 
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If a subject has a treatment related Grade 3 adverse event (excluding any hematologic AE or 
CRS) that is not considered to be related to extraneous cause ((i.e. disease progression, 
preparatory regimen, HSCT infusion), subsequent doses will be held until the toxicity returns to 
≤ Grade 2 or baseline. RGI-2001 may be restarted at a dose of 10 µg/kg IV infusion. 
Subjects who meet DLT criteria (including Grade 3+ CRS) at any point in the study should be 
permanently discontinued from study treatment. Supportive care should be administered as 
appropriate. 
If subject has a 2nd occurrence of Grade 3 adverse event, RGI-2001 will be held until the toxicity 
returns to ≤ Grade 2 or baseline. RGI-2001 will be restarted at a dose of 1 µg/kg IV infusion. 
If a subject experiences a Grade 4 adverse event that is related or continues to have recurrence of 
Grade 3 adverse events beyond the 2nd instance, discontinue RGI-2001 permanently. 
If a subject does not demonstrate evidence of myeloid engraftment by Day 28, discontinue 
RGI-2001 permanently. 
8.11 
Management of Cytokine Release Syndrome 
Pre-medications for RGI-2001 will not be administered initially as no signs of cytokine release 
were observed in the Phase 1 study. If symptoms suggestive of cytokine release (fever, chills, 
etc.) are observed with administration of RGI-2001, subjects should be treated according to 
institutional guidelines. The SRC may provide additional recommendations for such 
situations (please refer to Section 6.4). For Grade 2 AEs, acetaminophen, diphenhydramine 
and/or steroids may be administered. Premedication for subsequent RGI-2001 infusions may 
consist of intravenous or oral dexamethasone (4 mg), acetaminophen and diphenhydramine prior 
to each administration of RGI-2001. Details should be discussed with the Medical Monitor prior 
to the next infusion. For subjects with Grade 3–4 infusion reaction/cytokine release 
symptoms should be discontinued from further RGI-2001 therapy regardless of whether 
prophylactic treatment was administered.  
Table 1 
Medical Guidelines for Cytokine Release Reactions 
Grade 1 
• 
Continue to monitor subject carefully.  
• 
No treatment is needed unless symptoms worsen 
• 
Consider pre-medications for subsequent infusions depending on the 
presentation. 
Grade 2 
• 
Hold infusion until symptoms resolve.  
• 
Supportive care as per institutional guidelines. May include but not limited to 
acetaminophen, diphenhydramine, H2 blockers, dexamethasone or equivalent, 
oxygen, demerol or equivalent, IV fluids, anti-emetics  
• 
For subsequent RGI-2001 infusions, premedicate with acetaminophen, 
diphenhydramine, dexamethasone 4mg or equivalent 


 
 
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Grade 3-4 
• 
Discontinue RGI-2001 treatment 
• 
Supportive care as per institutional guidelines. May include but not limited to 
acetaminophen, diphenhydramine, H2 blockers, dexamethasone or equivalent, 
oxygen, demerol or equivalent, IV fluids, anti-emetics, vasopressors, 
mechanical ventilation. 
 


 
 
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9 
STUDY ASSESSMENTS AND PROCEDURES 
The Schedule of Assessments in Section 3 describes the frequency and timing of the study 
assessments and procedures. The schedule of PK and PD sample collection is provided in 
Appendix 1. All enrolled subjects will undergo the same study procedures unless otherwise 
noted. 
All screening evaluations must be completed and reviewed to confirm a potential subject meets 
all eligibility criteria prior to alloHSCT, including the preparatory regimen. Investigators are to 
maintain a screening log of all potential subjects.  
Screening assessments must be performed within 14 days prior to initiation of any 
treatments related to the HSCT including the preparatory regimen unless otherwise specified. 
Informed consent, screening hepatitis, HIV tests, and tumor assessment (provided that no 
intervening therapy for their malignancy has been administered) may be obtained up to 42 days 
before the preparatory regimen.  PFTs and ECHO may be obtained as per institutional standard 
of care criteria within 84 days prior to the preparatory regimen provided no intervening therapy 
for their malignancy has been administered. Pregnancy test must be conducted within 7 days 
before preparatory regimen. Standard of care tests/procedures, performed prior to the subject 
signing the informed consent form (ICF) can be used as part of the screening assessments as long 
as the tests/procedures are performed within the appropriate screening window. Screening 
assessments do not need to be repeated due to minor delays in procurement of donor HSC’s. 
9.1 
General Study Procedures 
9.1.1 
Informed Consent 
Except as noted in Section 9, informed consent must be obtained before conducting any study-
specific activities/procedures and documented in the subject’s source documents. 
9.1.2 
Demographics 
Subject demographics (including date/year of birth, sex, race, ethnicity, and age at the time of 
consent) will be collected. 
9.1.3 
Medical/Cancer/Surgical History 
A complete medical, cancer and surgical history starting prior to enrollment through the time of 
consent will be obtained from each subject at the Screening visit. 
Prior cancer history includes: (i) date of diagnosis, (ii) prognostic score if applicable (iii) all 
previous therapies (i.e., chemotherapy, immunotherapy, biologic or targeted agents, experimental 
therapies, radiotherapy, and surgery), (iv) previous therapy details (i.e., regimen, start and stop 
dates), (v) best response for each regimen 
Data from SOC procedures will be part of the subject's medical history and may be used for 
study purposes. 


 
 
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9.2 
Efficacy Assessments 
Efficacy evaluations will be performed as described below. Refer to the SoA, Section 3 for the 
timing of all efficacy evaluations. 
9.3 
Evaluation of GvHD 
The frequency of acute and chronic GvHD will be assessed in both parts of the study. 
Assessment for GvHD should be performed during every examination or per institutional 
guidelines from the time of engraftment to end of study. Documentation of the timing, severity 
treatment for GvHD and outcome including any biopsies should be obtained at regular intervals 
per the SoA.  
The clinical activity of RGI-2001 will be evaluated by assessment of GvHD according to the 
MAGIC Criteria and Modified Keystone Criteria for grading acute GvHD (Appendix 2 and 
Appendix 3) NIH 2014 criteria will be used to assess chronic GvHD. 
9.3.1 
Tumor Assessment 
Evaluation of status of hematologic malignancy should be conducted as per institutional 
guidelines but should include a bone marrow aspirate and biopsy with cytogenetics, molecular 
diagnostics and chimerism as appropriate based on disease histology. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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9.4 
Safety Assessments 
Safety will be assessed by clinical laboratory studies, time to myeloid and platelet engraftment 
and by monitoring of AEs.  
Potential safety issues associated with the route of administration or the pharmacology of 
RGI-2001 include hypersensitivity to RGI-2001, organomegaly, microgranuloma, and 
infections. Subjects will be monitored closely for hypersensitivity reactions to RGI-2001. 
Infections will be recorded throughout the study. Subjects will be followed for 30 days 
following end of treatment and monitored for the occurrence of adverse events by means of 
physical examination, and laboratory testing, including hematology, T-cell, 
immunophenotyping, other serum chemistry, urinalysis and liver function tests. 
9.4.1 
Marrow Engraftment and Graft Failure 
Myeloid engraftment will be defined as the first of 3 consecutive days when the absolute 
neutrophil counts (ANC) exceeds 0.5 x109/L and platelet engraftment will be defined as the first 
of 3 consecutive days when the platelet count exceeds 20 x x109/L without transfusion support. 
Graft failure will be defined as the lack of myeloid engraftment in subjects surviving in 
remission for at least 28 days after transplantation.  
9.4.2 
Dose Limiting Toxicities 
Subjects enrolled in the Safety Run-in Phase will be monitored for DLTs (Section 4.1).  
9.4.3 
Adverse Events 
Information regarding AEs and SAEs will be collected as per Section 10. 
9.4.4 
Concomitant Medications  
Concomitant medications will be documented for each subject at each scheduled visit. All 
concomitant medications including prescription or OTC preparations used from 2 days prior to 
the preparatory regimen before Day 0 through the end of the subject’s study participation, 
including changes is medication, should be recorded. 


 
 
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9.4.5 
Weight and Height 
Weight (indoor clothing without shoes) in kilograms, should be taken within 1 day of dosing and 
the dosage of RGI-2001 should be verified to be the same as the planned dose. Height (without 
shoes) in centimeters, should be obtained prior to initiation of the preparatory regimen only. 
9.4.6 
Physical Examinations, Vital Signs and Karnofsky Performance Status 
A complete physical examination will be performed by the investigator or designee at time 
points specified in the Schedule of Assessments Section 3. Examination at screening should 
include HEENT, dermatologic, cardiovascular, respiratory, GI (including assessments of liver 
and spleen), musculoskeletal, neurological, and lymphatic systems. Physical examinations at all 
other time points should be limited, symptom-directed physical examinations of an AE or 
SAE,  including body systems as appropriate.  
Please also refer to Efficacy Assessments Section 9.3 for description of MAGIC and Modified 
Keystone Criteria symptom assessments for GvHD. 
Vital signs and KPS will be performed as indicated in the SoA. Vital signs including systolic 
and diastolic blood pressure (BP), body temperature, heart rate, and respiratory rate should be 
taken in supine or seated position. Vital signs should be obtained within 15 minutes prior to 
RGI-2001 infusion and should be repeated within 30 minutes after the infusion. Additional vital 
signs measurements should be obtained as clinically indicated.  
KPS will be assessed as per Appendix 5. 
9.4.7 
Electrocardiogram  
A single, 12-lead ECG will be performed at the time point specific in the SoA (Section  3). 
The subject must be in a supine position in a rested and calm state for at least 5 minutes before 
ECG assessment is conducted. If the subject is unable to be in the supine position, the subject 
should be in the most recumbent position possible.  
The electrocardiogram should be performed in a standardized method, prior to blood draws or 
other invasive procedures. The ECG must include the following measurements: QRS, QT, QTc 
using Fredericia’s formula, RR, and PR intervals. If the ECG is abnormal, including QTc >450 
msec, perform in triplicate approximately 30 seconds apart, and record the average of the three 
readings. 
The PI or designated site physician will review all ECGs. Standard ECG machines should be 
used for all study-related ECG requirements.  
9.4.8 
Clinical Laboratory Assessments 
Blood samples for safety laboratory tests, which include clinical chemistry, hematology and 
coagulation, will be collected according to the SoA (Section 3). Additional laboratory 
assessments include pregnancy test, hepatitis B and C testing. All clinical laboratory analyses 
will be performed by the site local laboratory unless otherwise indicated. Reference ranges will 


 
 
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be supplied by the laboratory and used to assess the data for clinical significance and out-of-
range values. Biomarker and pharmacokinetic samples will be shipped to a specialty laboratory. 
Screening laboratory assessments used to determine subject eligibility may be repeated once (up 
to a total of 2 times during the 14 day screening period), if necessary. 
Clinical laboratory tests will be performed as indicated in Table 2: 
Table 2 
Clinical Laboratory Tests 
Chemistry  
Coagulation  
Urinalysis  
Hematology  
Other Labs  
Sodium  
Potassium  
Chloride  
Bicarbonate  
Total protein  
Albumin  
Calcium  
Magnesium  
Phosphorus  
Glucose  
BUN or Urea  
Creatinine  
Total bilirubin  
Direct bilirubin  
Alk phos  
LDH  
AST  
ALT 
GGT  
PT/INR aPTT or 
PTT  
  
Specific gravity 
pH  
Blood  
Protein  
Glucose  
Bilirubin 
Ketones 
Urobilirubin 
  
RBC  
Hemoglobin 
Hematocrit 
Platelets  
WBC  
Differential  
Neutrophils  
Eosinophils  
Basophils  
Lymphocytes  
Monocytes 
Blasts  
  
Hep B surface antigen 
Hep C antibody  
Hep B total core 
antibody  
Hep B viral load 
Hep C viral load 
Pregnancy test  
Bone marrow aspirate 
and biopsy 
Cytogenetics 
Molecular markers 
Chimerism 
  
  
Immunophenotyping 
 
Alk phos: ALT: alanine transaminase; AST: aspartate transaminase; BUN: blood urea nitrogen; GGT: gamma-
glutamyl transferase; LDH: lactate dehydrogenase; PTT: partial thromboplastin time; PT: prothrombin time; aPTT: 
abbreviated partial prothromboplastin time; RBC: red blood cell; WBC: white blood cell 
The maximum amount of blood collected from each subject over the duration of the study, 
including any extra assessments that may be required, will not exceed local guidance/regulations. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. Further information around blood volumes can be found in the Laboratory Manual.  
Any abnormal clinical laboratory test results that lead to a change in subject management 
(ie dose delay, clinical condition, need for additional medication or monitoring) are considered 
clinically significant. The diagnosis, if known, associated with abnormalities in clinical 
laboratory tests that are considered clinically significant by the Investigator will be recorded on 
the AE eCRF. Any abnormal clinical laboratory test result determined to be clinically significant 
by the Investigator should be repeated (at the Investigator’s discretion) until the cause of the 


 
 
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abnormality is determined, the value returns to baseline or to within normal limits, or the 
Investigator determines that the abnormal value is no longer clinically significant. 
9.4.8.1 
Donor/Host Chimerism 
Donor/host chimerism for the evaluation of engraftment status of the stem cell transplantation 
will be evaluated at the local laboratory. 
9.4.8.2 
Pregnancy Testing 
A serum pregnancy test will be performed on each female subject of childbearing potential at the 
screening visit. A negative pregnancy test must be documented prior to administration of study 
drug. 


 
 
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10 
ADVERSE EVENTS 
10.1 
Definitions 
According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical 
occurrence in a patient or clinical investigation subject administered a pharmaceutical product 
and which does not necessarily have a causal relationship with this treatment. An AE can 
therefore be any of the following: 
• Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not considered related to the medicinal 
(investigational) product 
• Any new disease or exacerbation of an existing disease (a worsening in the character, 
frequency, or severity of a known condition),  
• Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline 
• Any deterioration in a laboratory value or other clinical test (e.g., ECG, X-ray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study drug 
• AEs that are related to a protocol-mandated intervention, including those that occur 
prior to assignment of study treatment (e.g., screening invasive procedures such as 
biopsies) 
10.1.1 
Serious Adverse Event  
A serious adverse event is any adverse event that at any dose meets any of the following criteria:  
• Fatal (i.e., the adverse event actually causes or leads to death)  
• Life threatening (i.e., the adverse event, in the view of the Investigator, places the 
patient at immediate risk of death). This does not include any adverse event that had it 
occurred in a more severe form or was allowed to continue might have caused death.  
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient’s ability to conduct normal life 
functions)  
• Congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug  
• Significant medical event. An important medical event is an event that may not 
result in death, be life-threatening, or require hospitalization but may be considered 
an SAE when, based upon appropriate medical judgment by the Investigator or the 
Sponsor, it may jeopardize the patient and may require medical or surgical 


 
 
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intervention to prevent one of the outcomes listed in the definitions for SAEs. 
Examples of such medical events include second primary malignancies developed 
months after the end of the study treatment, or convulsions that do not result in in- 
patient hospitalization. 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an 
adverse event (rated as mild, moderate, or severe, or according to NCI CTCAE criteria v. 5.0; 
see Section 10.2.2); the event itself may be of relatively minor medical significance (such as 
severe headache without any further findings).  
Severity and seriousness need to be independently assessed for each adverse event recorded on 
the eCRF. 
10.2 
Adverse Event Reporting 
The reporting period for non-serious adverse events starts at the commencement of the infusion 
of RGI-2001 on Day 0 and continues for at least 30 days following the last dose of study drug. 
Medical conditions that start after the ICF is signed, but before the first dose of study drug 
should be recorded on the medical history eCRF. 
If an AE remains unresolved 30 days following the last dose of study drug, the subject will be 
followed, at the investigator’s discretion, until resolution of the event. Resolution is defined as 
return to baseline status or stabilization of the condition with the expectation that it will remain 
chronic. 
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than individual underlying signs and symptoms. 
When a clear diagnosis cannot be identified, each sign or symptom should be recorded as a 
separate AE. 
The Investigator should ask the subject non-leading questions to determine if any AEs have 
occurred during the study, since the last study visit. Adverse events may also be recorded when 
they are volunteered by the subject, or through physical examination, laboratory tests, or other 
clinical assessments. 
10.2.1 
Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (i.e., are considered to be 
clinically significant, induce clinical signs or symptoms, require concomitant therapy, or require 
changes in study drug), should be recorded on the Adverse Events eCRF. Whenever possible, a 
diagnosis, rather than a symptom should be provided (e.g., anemia instead of low hemoglobin). 
Laboratory abnormalities that meet the criteria for an AE should be followed until they have 
returned to baseline levels (as measured during the Screening visit) or an adequate explanation of 
the abnormality is identified. When an abnormal laboratory or test result corresponds to a 
sign/symptom of an already reported AE, it is not necessary to separately record the 
laboratory/test result as an additional event. 


 
 
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Not every laboratory or ECG abnormality qualifies as an AE. A laboratory or ECG test result 
must be reported as an AE if it meets any of the following criteria:  
• Accompanied by clinical symptoms 
• Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
• Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy 
• Clinically significant in the Investigator’s judgment 
It is the Investigator’s responsibility to review all laboratory abnormality. Medical and scientific 
judgment should be exercised in deciding whether an isolated laboratory abnormality should be 
classified as an AE. 
If a clinically significant laboratory or ECG abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5 × the ULN associated with cholecystitis), only the 
diagnosis (i.e., cholecystitis) should be recorded on the AE eCRF. 
If a clinically significant laboratory or ECG abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the AE eCRF, along with a descriptor indicating if 
the test result is above or below the normal range (e.g., "elevated potassium," as opposed to 
"abnormal potassium"). If the laboratory abnormality can be characterized by a precise clinical 
term per standard definitions, the clinical term should be recorded as the AE. For example, an 
elevated serum potassium level of 7.0 mEq/L should be recorded as “hyperkalemia.” 
10.2.2 
Adverse Event Severity 
The term “severe” is used to describe the intensity of an AE; the event itself could be of 
relatively minor clinical significance (e.g., ‘severe’ headache). This is not the same as a “serious” 
AE. 
The severity of the AE will be graded by the Investigator according to the NCI CTCAE Grading 
Scale, v.5.0  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf 
If there is not a specific NCI CTCAE grading scale for an AE, the severity will be characterized 
as mild, moderate, severe, or life-threatening, according to the following definitions: 
Grade 
Description 
1 (Mild) 
Asymptomatic or mild symptoms, clinical or diagnostic observations 
only, intervention not indicated No limitation of usual daily activities 
2 (Moderate) 
Some limitation of usual daily activities 
Minimal, local or non invasive intervention indicated, limiting 
instrumental activities of daily activities  


 
 
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Grade 
Description 
3 (Severe) 
Severe or Medically significant but not immediately life threatening, 
hospitalization or prolongation of hospitalization indicated, disabling. 
Intervention typically required. 
4 (Life Threatening) 
Events that are considered life-threatening, urgent intervention 
indicated 
5 (fatal) 
Death*  
*Grade 5 events must be reported as SAEs (see Section 10.3.1 for reporting instructions), per the definition of an 
SAE in Section 10.1.  
10.2.3 
Adverse Event Causality 
The Investigator should use their knowledge of the study subject, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether or not an 
adverse event is considered to be related to the study drug. The following guidance should be 
taken into consideration. Discuss with medical monitor if needed:  
• Temporal relationship of event onset to the initiation of study drug  
• Course of the event, considering especially the effects of dose reduction, 
discontinuation of study drug, or reintroduction of study drug (where applicable)  
• Known association of the event with the study drug or with similar treatments  
• Known association of the event with the disease under study  
• Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event  
• Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event 
Relationship 
Description 
Not Related 
Exposure to the investigational product has not occurred, or the occurrence of 
the AE is not reasonably related in time, or the event is readily and more likely 
explained by the subject’s clinical state or by other modes of therapy 
administered to the subject. 
Note: per your institution standard, if relationship is determined to be unlikely, it 
should be classified as Not Related unless the investigator determines possibly 
related or probably related are more appropriate with the definitions below. 
Possibly Related 
The administration of the IP and the occurrence of the AE are reasonably related 
in time, and 
The AE could be explained equally well by factors or causes other than exposure 
to the IP. 
Follows a reasonable temporal sequence from study drug administration; but 
could have been produced by the subject’s clinical state or by other modes of 
therapy administered to the subject. 


 
 
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Relationship 
Description 
Probably Related 
The study treatment and the AE were reasonably related in time, 
and the AE is more likely explained by exposure to the study product than by 
other causes, or the investigational product was the most likely cause of the AE 
10.3 
Serious Adverse Events 
SAEs that occur at any time between the signing of the ICF up to the first dose of study drug 
must be reported (in addition to SAEs that occur after the first dose of study drug). 
Important medical events that may not result in death, are not life-threatening, or do not require 
hospitalization may be considered SAEs when, based on 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. See definition of SAE in Section 10.1. 
Elective hospitalizations to administer, or to simplify trial treatment or trial procedures (e.g., an 
overnight stay to facilitate 24-hour urine collection) or other medical procedures are not 
considered SAEs. A ‘serious’ hospitalization is defined as any inpatient hospital admission into 
the ward on the floor that includes a minimum of an overnight stay in a health care facility. An 
emergency room visit is not considered a hospitalization unless it results in an official admission 
as an inpatient to the hospital (e.g., undesirable effects of any administered treatment) and must 
be documented as an SAE. 
10.3.1 
Serious Adverse Events Reporting 
SAEs that occur at any time between the signing of the ICF until at least 30 days after the subject 
has stopped study drug must be reported regardless of the casual relationship to the study drug.  
SAEs will be reported immediately (within 24 hours of learning of the event) to the Sponsor or 
its designee by email using the study-specific SAE Report Form and recorded in the eCRF. In 
addition to the outcome of the SAE, any medication or other therapeutic measures used to treat 
the event will be recorded on the appropriate eCRF page(s). Investigators should not wait to 
collect additional information that fully documents the event before notifying Sponsor or its 
designee of an SAE. Sponsor may be required to report certain SAEs to regulatory authorities 
within 7 calendar days of being notified about the event; therefore, it is important that 
Investigators submit additional information requested by Sponsor or its designee as soon as it 
becomes available. 
Reporting of SAEs to the IRB will be done in compliance with the standard operating 
procedures and policies of the IRB and with applicable regulatory requirements. Adequate 
documentation must be obtained by Sponsor or its designee showing that the IRB was properly 
and promptly notified as required. 
The SAE form should be emailed to: sae.regimmune@clindatrix.com 


 
 
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The Investigator is encouraged to discuss with the medical monitor any AEs for which the issue 
of seriousness is unclear or questioned. Contact information for the Medical Monitor is as 
follows: 
 
 
 
Any SAE observed after the 30-day follow-up period should only be reported to the Sponsor if 
the Investigator suspects that the SAE has a causal relationship to the study drug. An SAE should 
be followed until its resolution or until it is judged to be stable. An assessment should be made at 
each study visit (or more frequently, if necessary) of any changes in severity of the event, the 
suspected relationship to the study drug, the interventions required to treat the event, and the 
outcome of the event. 
Recurrent episodes, complications, or progression of the initial SAE must be reported, as 
follow-up to the original episode, within 24 hours of the Investigator receiving the follow-up 
information. 
10.4 
Reporting of Disease Progression 
Progression of the malignancy/disease (including fatal outcomes) should NOT be reported as an 
SAE during the study or within the safety reporting period. Any sudden or unexplained death 
should be reported as an SAE. However, the underlying disease or condition, which led to the 
fatal outcome, should be used as an SAE term. Death as an SAE term should be avoided, with 
the exception of rare situations when the cause of death is unknown. If there is any uncertainty 
about a finding being due solely to progression of malignancy/disease, the finding should be 
reported as an AE or SAE, as appropriate. 
10.5 
Reporting of GvHD 
The event of GvHD disease is a criterion for assessment of clinical activity and is therefore not 
considered to be an AE. GvHD should be reported within the eCRF. AEs and SAEs that occur in 
relation to GvHD that are not consistent with the nature and natural progression of the subject’s 
disease should be recorded as AE/SAE. Death due to GvHD that is consistent with the nature and 
natural progression of the subject’s disease is not recorded as an AE/SAE.  
10.6 
Medication Errors 
Any dose or route of administration of RGI-2001 that was not administered as prescribed in the 
protocol should be reported as an AE in the eCRF regardless of whether or not there is an 
associated AE. Medication errors that meet the definition of an SAE will be reported per the 
SAE reporting guidelines.  


 
 
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10.7 
Pregnancy 
Although pregnancy is not considered an AE or SAE, all pregnancies occurring in subjects 
enrolled in this study or in a female partner of a male subject in this study must be reported to the 
Sponsor within 24 hours of becoming aware, and followed to outcome, even after the end of the 
study. If a female subject inadvertently becomes pregnant while on study treatment, the subject 
will immediately be removed from the study. Any pregnancies that occur within 150 days for 
females or 90 days for males following the last dose of study treatment must be reported to the 
Sponsor.  
Refer to Appendix 6 for complete information regarding pregnancies including highly effective 
contraceptive methods and recording and reporting guidelines in the event of a pregnancy. 


 
 
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11 
REGISTRATION OF CIBMTR SUBJECTS FOR THE CONTROL GROUP 
This clinical trial will compare certain outcome parameters from subjects enrolled in the 
RGI-2001 treatment study to a contemporaneous control group obtained from the CIBMTR. 
(refer to Section 12) 
11.1 
Selection of Control Arm Transplant Centers 
The CIBMTR will be contracted with the Sponsor to provide transplant subject data for the 
control group. Only CIBMTR research centers participating in the treatment protocol with 
experience in submitting comprehensive report forms to the CIBMTR will be eligible to 
participate in the study. Additionally, participating centers will need to agree to participate in this 
study and submit all CIBMTR report forms required for this study according to the CIBMTR 
pre-specified time schedule. 
11.2 
Enrollment Procedure for the Transplant Subjects in the Control Arm via the 
CIBMTR 
Data reported on pre-transplant Transplant Essential Data (TED) forms to the CIBMTR by 
participating centers will be monitored to screen subjects who fulfill the eligibility criteria 
(Section 7). Control subjects who fulfill eligibility criteria and who have a signed ICF to allow 
their data to be used for research will be assigned to the CIBMTR comprehensive data reporting 
track (CRF-track) and centers will be notified. Forms due requirements for the case report form 
(CRF) track will be implemented.  
It is anticipated that a minimum of 250 transplant subjects will be enrolled to ensure sufficient 
subjects are comparable to the RGI-2001 treatment population. 


 
 
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12 
STATISTICS 
The primary objective of this study is to assess the potential efficacy of RGI-2001. The primary 
endpoint for these purposes is grades II-IV acute GvHD, and the study subjects will be compared 
to a control group of subjects supplied by the CIBMTR. Control subjects will be chosen so as to 
meet all eligibility requirements for the clinical trial, have received a transplant in the same time 
window as the study subjects, and have been transplanted in a center that participates in this 
study.  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Based on these estimates, it is anticipated that a total of 50 subjects who receive at least one dose 
of RGI-2001 will be enrolled, this including subjects from the run-in stage treated at the dose 
moved forward to the Expansion Phase. It is anticipated that a minimum of 250 subjects will be 
included in the control group.  
12.2 
Demographics and Baseline Characteristics 
Categorical factors will be summarized with proportions, and continuous variables will be 
summarized using means and medians. 
12.3 
Analysis Population, Handling of Dropouts, and Missing Data 
All subjects who receive at least one dose of RGI-2001 will be used for comparison to the 
CIBMTR subjects.  


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12.3.1 
Analysis of Efficacy Data 
The primary endpoint grades II-IV acute GvHD by Day 100 according to the MAGIC criteria 
will be compared between the study group and CIBMTR controls using logistic regression. The 
factors that will be considered for adjustment in this model include subject age, gender, donor 
age, type of donor (MRD, 8/8 URD 7/8 URD), source of allograft, diagnosis (AML, ALL, MDS, 
MPD including CMML), preparative regimen, GvHD prophylaxis regimen. 
Secondary endpoints that will be modeled as binary outcomes will similarly be compared using 
logistic regression. Secondary endpoints that will be modeled as time-to-event outcomes will be 
compared using Cox regression. 
Potential interactions of RGI-2001 and various factors will be examined by including appropriate 
factors into regression models.  
Given that this is not a randomized study and that the intention is only to assess outcomes for a 
potential signal, no adjustments will be made for multiple comparisons. As such, a Type II error 
(or a false negative) is prioritized over a Type I error (or a false positive). 
Binary exploratory outcomes will be summarized with proportions, continuous outcomes with 
means and medians, and time-to-event outcomes with Kaplan-Meier estimates or cumulative 
incidence estimates for endpoints with competing risks. 
12.4 
Suspension Rules Based on Safety (RRT, Graft Failure, and NRM) 
Careful monitoring of safety will take place beyond the Safety Run-in Phase, with safety 
encompassing the outcomes grade 4-5 regimen-rated toxicity (RRT), graft failure, and NRM.  
The study will be suspended pending SRC review if there is sufficient evidence to suggest that 
the true failure rate for any of these outcomes is excessive. A true graft failure (as defined in 
Section 9.4.1) rate of 5% or higher is considered excessive (Olsson et al), a true Day-100 NRM 
rate of 10 or higher is considered excessive (Styczyński et al), and a true Day 30 grade 4-5 RRT 
rate of 50% or higher is considered excessive (defined as any non-hematologic toxicity that 
occurs as a result of the transplant process including the preparatory regimen or RGI-2001 
infusions).  This rate is extrapolated from published results of D30 NRM (Styczyński et al) and 
increased further to encompass grade 4 events in the allogeneic myeloablative setting based on 
site experience.  Sufficient evidence will be taken to be a lower limit to the one-sided 80% 
confidence interval associated with an estimated failure rate that exceeds the appropriate level 
listed above.  Table 3 below shows observed outcomes that would trigger suspension, and 
Table 4 below summarizes the operating characteristics of the listed suspension rule separately 
for each safety endpoint (e.g., separately for Day 30 grade 4-5 RRT, graft failure, Day-100 
NRM).   


 
 
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Table 3 
Suspension Rules for Grade 4-5 RRT, Graft Failure, and Day-100 NRM  
Safety outcome 
Occurrences that would trigger suspension rule and SRC review 
Day 30 grade 4-
5 RRT 
3 RRT of first 3 pts, 4 RRT of first 5 or fewer pts, 5/6, 6/7-8, 7/9-10, 8/11-
12, 9/13, 10/14-15, 11/16-17, 12/18-19, 13/20-21, 14/22, 15/23-24, 16/25-
26, 17/27-28, 18/29-30, 19/31-32, 20/33-34, 21/35, 22/36-37, 23/38-39, 
24/40-41, 25/42-43, 26/44-45, 27/46-47, 28/48-49, 29/50 
Graft Failure 
2 failures of first 16 pts or fewer, 3/17-30, 4/31-46, 5/47-50 
Day-100 NRM 
2 failures of first 8 pts or fewer, 3/9-15, 4/16-23, 5/24-31, 6/32-39, 7/40-47, 
8/48-50 
Table 4 
Operating Characteristics of Suspension Rules 
Safety outcome 
True probability 
of failure 
Number of 
patients 
Probability of suspension rule 
being triggered after listed 
number of patients 
Grade 4-5 RRT 
.30 
10 
25 
45 
.05 
.05 
.10 
Grade 4-5 RRT 
.70 
10 
25 
45 
.72 
.94 
.99 
Graft Failure 
.02 
10 
25 
45 
.02 
.04 
.05 
Graft Failure 
.12 
10 
25 
45 
.36 
.68 
.88 
Day-100 NRM 
.05 
10 
25 
45 
.06 
.08 
.08 
Day-100 NRM 
.20 
10 
25 
45 
.51 
.78 
.91 


 
 
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13 
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS 
13.1 
Ethics 
The procedures set out in this protocol, pertaining to the conduct, evaluation, and documentation 
of this study, are designed to ensure that the Sponsor and investigator abide by Good Clinical 
Practice (GCP) and International Conference on Harmonization (ICH) guidelines. The study will 
also be carried out in keeping with applicable local laws and regulations. 
13.2 
Compliance Statement 
This study will be conducted in accordance with the protocol and with GCP and ICH guidelines, 
as well as all applicable regulatory requirements. The investigator is responsible for ensuring that 
this protocol, the site’s informed consent form, and any other information that will be presented 
to potential subjects are reviewed and approved by the appropriate Institutional Review Board 
(IRB) prior to the enrollment of any study subjects. 
13.3 
Institutional Review Board 
The investigator will submit this protocol, the informed consent, investigator’s brochure (IB), 
and any other relevant supporting information to the appropriate IRB and the local regulatory 
agency for review and approval prior to study initiation. A letter confirming IRB approval of the 
protocol and informed consent, a statement that the IRB is organized and operates according to 
GCP and the applicable laws and regulations, and financial disclosures must be forwarded to the 
Sponsor prior to screening subjects for the study. 
Amendments to the protocol must also be approved by the IRB and the local regulatory agency, 
as appropriate, prior to the implementation of changes in this study. However, the investigator 
may implement a deviation from, or a change of, the protocol to eliminate an immediate 
hazard(s) to the study subjects without prior IRB/Sponsor approval/favorable opinion. As soon 
as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the 
proposed protocol amendment, should be submitted to the IRB/Sponsor. Any deviations from the 
protocol must be fully explained and documented by the investigator. 
13.4 
Informed Consent and Human Subject Protection 
13.4.1 
Direct Access to Source Data/Source Documents 
The study will be carried out in keeping with applicable local laws and regulations. This may 
include an inspection by Sponsor representatives/designees, and/or regulatory authority 
representatives at any time. The investigator/institution must agree to the inspection of 
study-related records by the regulatory authority/Sponsor representatives/designees, and must 
allow direct access to source documents to the regulatory authority/Sponsor representatives/ 
designees/IRB. The investigator must allocate time (investigator and study staff) to discuss 
findings and relevant issues with the regulatory authority/Sponsor representatives. 


 
 
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13.4.2 
Data Quality Control and Quality Assurance: Data Handling and Recordkeeping 
Data collection will involve the use of the electronic data capture (EDC) system, to which only 
authorized personnel will have access. Entries made on the electronic case report form (eCRF) 
must be verifiable against source documents. In addition to periodic monitoring occurring within 
the system by study monitors, programmatic edit checks and data listings will be used to review 
the data for completeness, logic, and adherence to study protocol. As a result of this monitoring 
and these checks, queries may be electronically issued to the clinical study sites and 
electronically resolved by those sites. The identifying information (assigned username, date, and 
time) for both the originator of the query (if created during the monitoring and data reviewing 
process) and the originator of the data change (if applicable), as well as the PI’s approval of all 
changes performed on his/her subjects’ data, will be collected. 
All data collected in the context of this study will be stored and evaluated per regulatory 
requirements and applicable guidance for electronic records. Also, data will be stored and 
evaluated in such a way as to guarantee subject confidentiality in accordance with the legal 
stipulations applying to confidentiality of data. Study records (e.g., copies of eCRFs, regulatory 
documents) will be retained at the study site, along with adequate source documentation, 
according to FDA and ICH requirements. The study file and all source data should be retained 
until written notification is given by the sponsor or designee for destruction. 
13.4.3 
Confidentiality 
All records identifying the subject will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available. 
Subject names will not be supplied to the Sponsor. Only the subject number and initials will be 
recorded on the case report form (eCRF). If the subject name appears on any other document 
(e.g., pathologist report) or study materials (e.g., biopsy tissue slides), then that information must 
be deleted before a copy of the document is supplied to the sponsor. Study data stored on a 
computer will be stored in accordance with local data protection laws. Subjects will be informed 
in writing that representatives of the sponsor, IRB, or regulatory authorities may inspect their 
medical records to verify the information collected, and that all personal information made 
available for inspection will be handled in strictest confidence and in accordance with local data 
protection laws. 
If the results of the study are published, the subject’s identity will remain confidential. 
The investigator will maintain a list to enable subjects’ records to be identified. 


 
 
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14 
FINAL STUDY REPORT AND PUBLICATION POLICY 
A study report will be prepared by the Sponsor. Independent analysis and/or publication of these 
data by the investigator(s) or any member of their staff will comply with the terms of the clinical 
Trial Agreement between the Sponsor, and the investigational site and/or investigator. 
The Sponsor will comply with applicable laws regarding the requirements for publication of 
study results. 


 
 
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Ishii Y, Nozawa R, Takamoto-Matsui Y, Teng A, Katagiri-Matsumura H, Nishikawa H, et al. 
Alpha-galactosylceramide-driven immunotherapy for allergy. Front Biosci 
2008,13:6214–28. PMID 18508655 
Kawano T, Cui J, Koezuka Y, et al. CD1d-restricted and TCR-mediated activation of valpha14 
NKT cells by glycosylceramides. Science. 1997;278:1626-1629. PMID 9374463 
Magenau J, Qin X, Tawara I, Rogers C, Kitko C, Schlough M, Bickley D, Braun TM, Jang PS, 
Lowler KP, Jones DM, Choi SW, Reddy P, Mineishi S, Levine JE, Ferrara JL, Paczesny 
S. Frequency of CD4(+)CD25(hi)FOXP3(+) regulatory T cells has diagnostic and 
prognostic value as a biomarker for acute graft-versus-host-disease. Biol Blood Marrow 
Transplant. 2010 16(7):907-14. PMID 20302964 
Moody DB, Zajonc DM, Wilson IA. Anatomy of CD1-lipid antigen complexes. Nat Rev 
Immunol. 2005;5:387-399. PMID 15864273 


 
 
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Natori T, Koezuka, Y. & Higa, T. Agelasphins, novel α-galactosylceramides from the marine 
sponge Agelas mauritianus. Tetrahedron Lett. 1993;34:5591-5592. 
Olsson RF, Logan BR, Chaudhury S, Zhu X, et al. Primary graft failure after myeloablative 
allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia. 
2015 Aug; 29(8): 1754-1762. 
Paczesny S, Hanauer D, Sun Y and Reddy P. Bone Marrow Transplantation. 2010; 45: 1–11. 
PMID19946340 
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 
Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 
Jun;15(6):825-8. 
Sagoo P, Lombardi G, Lechler RI. Regulatory T cells as therapeutic cells. Curr Opin Organ 
Transplant. 2008;13:645-653. PMID 19060557 
Seltzer S, Shulkin P, Adams D, Davis M, Hoey G, Hopkins R, Bosworth M. Usefulness of 
Liposomes Carrying Losefamate for CT Opacification of Liver and Spleen. AJR 1984; 
143: 575-579. PMID 6331738 
Socié G, Blazar BR. Acute graft-versus-host disease: from the bench to the bedside. Blood 
2009;114(20):4327–36. PMID 19713461 
Styczyński J, Tridello G, Koster L, Iacobelli S, et al. Death after hematopoietic stem cell 
transplantation: changes over calendar year time, infections and associated factors. Bone 
Marrow Transplant. 2020; 55:126-136. 
Taniguchi M, Harada M, Kojo S, Nakayama T, Wakao H. The regulatory role of Valpha14 NKT 
cells in innate and acquired immune response. Annu Rev Immunol. 2003;21:483-513. 
PMID 12543936 
Tupin E, Nicoletti A, Elhage R, Rudling M, Ljunggren HG, Hansson GK, et al.  
CD1d-dependent activation of NKT cells aggravates atherosclerosis. J Exp Med 
2004;199(3):417–22. PMID 14744994 
Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and 
autoimmunity. Nat Immunol. 2009;11:7-13. PMID 20016504 
Wolff D, Steiner B, Hildebrandt G, Edinger M, Holler E. Pharmaceutical and cellular strategies 
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15 
APPENDICES 


 
 
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APPENDIX 2 
MAGIC GVHD ASSESSMENT CRITERIA 
GvHD Target Organ Staging 
Stage 
Skina 
Liver (bilirubin) 
Upper GI 
Lower GI  
(stool output/day) 
0 
No active 
(erythematous) GvHD 
rash 
Total serum bilirubin < 
34 umol/L (< 2 mg/dL) 
No or intermittentb 
anorexia, nausea or 
vomiting 
Diarrhea <500mL per day 
or <3 episodes/day for 
adults c 
1 
Maculopapular rash < 
25% of BSA 
Total serum bilirubin 
34-50 umol/L (2 to 
3 mg/dL) 
Persistent anorexia 
or nausea or 
vomiting 
Diarrhea 500 -999 mL per 
day or 3-4 episodes per 
day for adults c  
2 
Maculopapular rash 
25 to 50% of BSA 
Total serum bilirubin 
51-102umol/L (3.1 to 
6 mg/dL) 
 
Diarrhea 1000–1500 mL 
per day or 5–7 episodes for 
adultsc 
3 
Maculopapular rash > 
50% of BSA 
Total serum bilirubin 
103-255 umol/L (6.1 to 
15 mg/dL) 
 
Diarrhea > 1500 mL per 
day or > 7 episodes for 
adults b 
4 
Generalized 
erythroderma (> 50% 
BSA) plus bullous 
formation and 
desquamation > 5% 
of BSA 
Total Serum bilirubin 
> 255umol/L 
(> 15 mg/dL) 
 
Severe abdominal pain 
with or without ileus or 
grossly bloody stools 
(regardless of stool 
volume) c 
BSA: body surface area, GI: gastro-intestinal tract, GvHD: Graft versus Host Disease MAGIC: Mount Sinai Acute 
GvHD International Consortium 
 
Overall Grade (based upon most severe target organ involvement 
0 
No stage 1-4 of any organ 
I 
Stage 1-2 skin without liver, upper GI or lower GI involvement 
II 
Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI 
III 
Stage 2-3 liver and/or stage 2-3 lower GI, with stage 0-3 skin and/or stage 0-1 upper GI 
IV 
Stage 4 skin, liver, or lower GI involvement, with stage 0-1 upper GI 
a 
Use the “rule of nines” or burn chart to determine extent of rash  
b 
To be suggestive for GvHD: anorexia should be accompanied by weight loss, nausea should last at least 3 days, 
or be accompanied by at least 2 vomiting episodes per day for at least 2 days 
c 
One episode of diarrhea is considered to be about 200 ml for an adult and 3 ml/kg for a child (< 50 kg) 
 


 
 
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Confidence Level Criteria 
Confidence 
Level 
Pathologic 
Evidence 
Clinician 
Assessment 
Treatment for 
Acute GvHD 
Comments 
Confirmed 
Unequivocal 
pathologic 
evidence of GvHD 
GvHD is the etiology 
for symptoms 
Not applicable 
GVHD is clearly present 
even if other etiologies 
may coexist 
simultaneously. 
Probable 
Not required 
GvHD most likely 
etiology for 
symptoms (as 
evidenced by 
treatment being 
provided) 
Yes 
GVHD is most likely 
present, but other 
etiologies may also 
explain the symptoms, and 
there is insufficient 
evidence to make a 
confirmed diagnosis. 
Possible 
Not required 
GvHD in differential 
diagnosis (but no 
treatment is being 
provided) 
No 
GVHD may be present, 
but other etiologies are 
favored to the degree that 
GVHD 
treatment is not initiated. 
Negative 
Unequivocal 
evidence of a 
diagnosis other 
than GvHD (e.g. 
drug rash 
GvHD is no 
considered as an 
explanation for the 
symptoms 
No and the 
symptoms resolve 
without GvHD 
treatment 
GVHD may be present, 
but other etiologies 
are favored to the degree 
that GVHD treatment is 
not initiated. 
 
Biopsy Results and Confidence Levels 
Pathology Results 
Target Organ Confidence Level 
Treated as 
GvHD 
Not treated but GvHD in 
Differential Diagnosis 
Not Treated and GvHD Not in 
Differential Diagnosis 
Positive 
Confirmed 
Confirmed 
Confirmed 
Equivocal 
Probable 
Possible 
Possible 
Nondiagnostic 
Probable 
Possible 
Negative 
Non-GvHD etiology 
Probable 
Negative 
Negative 
Source: Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, et al. International, multicenter 
standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute 
GVHD International Consortium. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 
2016;22:4-10 
 


 
 
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APPENDIX 3 
MODIFIED KEYSTONE CRITERIA FOR ACUTE GVHD 
GvHD Assessment 
Stage 
Skina 
Liverb,c 
Gutc 
0 
No GvHD rash 
Bilirubin < 2 mg/dL 
Diarrhea ≤ 500mL per day No 
anorexia or persistent nausea or 
anorexiad 
1 
Rash < 25% of skin 
Bilirubin 2 to 3 mg/dL 
Diarrhea > 500 mL per day or 
persistent nausea or nausead 
2 
Rash 25 to 50% of skin 
Bilirubin 3.1 to 6 mg/dL 
Diarrhea ≥ 1000 mL per day 
3 
Rash > 50% of skin 
Bilirubin 6.1 to 15 mg/dL 
Diarrhea ≥ 1500 mL per day 
4 
Generalized erythroderma 
with bullous formation 
Bilirubin > 15 mg/dL 
Severe abdominal pain with or 
without ileus 
 
Overall Gradee 
I 
Stage 1 to 2 
None 
None 
II 
Stage 3 or 
Stage 1 or 
Stage 1 
III 
– 
Stage 2 to 3 or 
Stage 2 to 4 
IVf 
Stage 4 or 
Stage 4 
– 
a 
The Rules of Nines or burn chart was used to determine the extent of rash. The percent of body surface area 
involved with rash: head and neck (9%), right arm (9%), left arm (9%), anterior trunk (18%), posterior trunk 
(18%), right leg (18%), left leg (18%), groin and perineum (1%). 
b 
Range given as total bilirubin. 
c 
For liver or gut, downgrade 1 stage if additional cause of elevated bilirubin or diarrhea had been documented. 
d 
Persistent nausea or anorexia, with histologic evidence of GvHD in the stomach or duodenum. 
e 
Criteria for grading given as minimum degree of organ involvement required to confer that grade. 
f 
Grade IV could have also included lesser organ involvement but with extreme decrease in performance 
Source: Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus 
Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8. 
 


 
 
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APPENDIX 4 
NIH DEFINED DIAGNOSTIC OR DISTINCTIVE FEATURES OF 
CHRONIC GVHD 2014  
Organ or 
Site 
Diagnostic  
(Sufficient to 
Establish the 
Diagnosis of Chronic 
GVHD) 
Distinctivea  
(Seen in Chronic GVHD, 
but Insufficient Alone to 
Establish a Diagnosis) 
Other Features or 
Unclassified Entitiesb 
Commonc 
(Seen with Both 
Acute and Chronic 
GVHD) 
Skin 
Poikiloderma  
Lichen planus-like 
features 
Sclerotic features 
Morphea-like features  
Lichen sclerosus-like 
features 
Depigmentation  
Papulosquaous lesions 
Sweat impairment 
Ichthyosis  
Keratosis pilaris 
Hypopigmentation 
Hyperpigmentation 
Erythema 
Maculopapular rash  
Pruritus 
Nails 
 
Dystrophy 
Longitudinal ridging, 
splitting, or brittle features 
Onycholysis 
Pterygium unguis 
Nail loss (usually symmetric; 
affects most nails) 
 
 
Scalp and 
body hair 
 
New onset of scarring or 
nonscarring scalp alopecia 
(after recovery from 
chemoradiotherapy) 
Loss of body hair,  
Scaling  
Thinning scalp hair, 
typically patchy, coarse, 
or dull (not explained by 
endocrine or other causes) 
Premature gray hair 
 
Mouth 
Lichen-type changes  
Xerostomia 
Mucoceles 
Mucosal atrophy 
Ulcers 
Pseudomembranes 
 
Gingivitis 
Mucositis 
Erythema 
Pain 
Eyes 
 
New onset dry, gritty, or 
painful eyes 
Cicatricial conjunctivitis 
Keratoconjunctivitis sicca 
Confluent areas of punctate 
keratopathy 
Photophobia 
Periorbital 
hyperpigmentation 
Blepharitis (erythema of 
the eyelids with edema) 
 
Genitalia 
 
 
Females 
 
Males 
Lichen planus-like 
features  
Lichen sclerosus-like 
features 
Vaginal scarring or 
clitoral/labial 
agglutination 
Phimosis or 
urethral/meatus 
scarring or stenosis 
Erosions 
Fissures 
Ulcers 
 
 


 
 
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Organ or 
Site 
Diagnostic  
(Sufficient to 
Establish the 
Diagnosis of Chronic 
GVHD) 
Distinctivea  
(Seen in Chronic GVHD, 
but Insufficient Alone to 
Establish a Diagnosis) 
Other Features or 
Unclassified Entitiesb 
Commonc 
(Seen with Both 
Acute and Chronic 
GVHD) 
GI tract 
Esophageal web 
Strictures or stenosis in 
the upper to mid third 
of the esophagus 
 
Exocrine pancreatic 
insufficiency 
Anorexia 
Nausea 
Vomiting 
Diarrhea 
Weight loss 
Failure to thrive 
(infants and 
children) 
Liver 
 
 
 
Total bilirubin, 
alkaline phosphatase 
> 2 ULN 
ALT or AST 
> 2 ULN 
Lung 
Bronchiolitis obliterans 
diagnosed with lung 
biopsy BOSd 
Air trapping and bronchiolitis 
obliterans on chest CT  
Cryptogenic organizing 
pneumonia 
Restrictive lung diseasee 
 
Muscles, 
fascia, joints 
Fasciitis 
Joint stiffness or 
contractures secondary 
to sclerosis 
Myositis or polymyositisf 
Edema 
Muscle cramps 
Arthralgia or arthritis 
 
Hematopoie
tic and 
immune 
 
 
Thrombocytopenia 
Eosinophilia 
Lymphopenia 
Hypo- or 
hypergammaglobulinemia 
Autoantibodies 
(AIHA and ITP) 
 
Other 
 
 
Pericardial or pleural 
effusions 
Ascites 
Peripheral neuropathy 
Nephrotic syndrome 
Myasthenia gravis 
Cardiac conduction 
abnormality or 
cardiomyopathy 
 
GVHD indicates graft-versus-host disease; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AIHA, 
autoimmune hemolytic anemia; ITP, idiopathic thrombocytopenic purpura. 
a 
In all cases, infection, drug effects, malignancy, or other causes must be excluded. 
b 
Can be acknowledged as part of the chronic GvHD manifestations if diagnosis is confirmed. 
c 
Common refers to shared features by both acute and chronic GVHD 
d 
BOS can be diagnostic for lung chronic GVHD only if distinctive sign or symptom present in another organ 
e 
Pulmonary entities under investigation or unclassified. 
f 
Diagnosis of chronic GVHD requires biopsy. 
Source: Jagasia, Madan H. et al. National Institutes of Health Consensus Development Project on Criteria for 
Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. 
Biology of Blood and Marrow Transplantation, 2015 March; 21 (3):389–401 


 
 
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NIH Global Severity of Chronic GvHD 
Mild chronic GvHD 
1 or 2 organs involved with no more than score 1 plus 
Lung score 0 
Moderate chronic GvHD 
3 or more organs involved with no more than score 1 
OR 
At least 1 organ (not lung) with a score of 2 
OR 
Lung score 1 
Severe chronic GvHD 
At least 1 organ with a score of 3 
OR 
Lung score of 2 or 3 
Key points: 
In skin: higher of the two scores are to be used for calculating global 
severity. 
In lung: FEV1 is used instead of clinical score for calculating global severity. 
If the entire abnormality in an organ is noted to be unequivocally explained 
by a non-GvHD documented cause, that organ is not included for calculation 
of the global severity. 
In the abnormality in an organ is attributed to multifactorial causes (GvHD 
plus other causes) the scored organ will be used for calculation of the global 
severity regardless of the contributing causes (no downgrading of organ 
severity score). 
Source: Jagasia, Madan H. et al. National Institutes of Health Consensus Development Project on Criteria for 
Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. 
Biology of Blood and Marrow Transplantation, 2015 March; 21 (3):389–401 
 


 
 
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APPENDIX 5 
KARNOFSKY PERFORMANCE STATUS SCORES  
Score (%) 
Karnofsky Performance Status 
100  
Normal; no complaints; no evidence of disease  
90  
Able to carry on normal activity; minor signs or symptoms of disease  
80  
Normal activity with effort; some signs or symptoms of disease  
70  
Cares for self; unable to carry on normal activity or to do active work  
60  
Requires occasional assistance, but is able to care for most personal needs  
50  
Requires considerable assistance and frequent medical care  
40  
Disabled; requires special care and assistance  
30  
Severely disabled; hospital admission is indicated although death not imminent  
20  
Very sick; hospital admission necessary; active supportive treatment necessary  
10  
Moribund; fatal processes progressing rapidly  
0  
Dead  
Source: Karnofsky DA, Burchenal JH. (1949). "The Clinical Evaluation of Chemotherapeutic Agents in Cancer." In: 
MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196.  
 


 
 
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APPENDIX 6 
CONTRACEPTIVE GUIDANCE AND COLLECTION OF 
PREGNANCY INFORMATION  
Definitions: 
Woman of Childbearing Potential (WCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below) 
Women in the following categories are not considered WCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.  
• Females on HRT and whose menopausal status is in doubt will be required to use 1 of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception Methods: 
Male patients 
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent 
• Agree to use a male condom plus partner use of a contraceptive method as described 
under highly effective contraceptive methods when having penile-vaginal intercourse 
with a woman of childbearing potential who is not currently pregnant. 
In addition, male patients must refrain from donating sperm for the duration of the study and for 
3 months after the last dose of study treatment. 
Male patients with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration from 
the start of study treatment until 90 days after study treatment. 


 
 
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Female patients 
Female patients of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception throughout the study and for 90 days after the end of study 
treatment.  
Highly effective methods include:  
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation 
− Oral  
− Intravaginal  
− Transdermal 
• Progestogen only hormonal contraception associated with inhibition of ovulation 
− Oral  
− Injectable 
− Implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomized partner 
• Sexual abstinence  
Pregnancy Testing: 
• WCBP must have a negative serum pregnancy test prior to initiation of study drug. 
Pregnancy Reporting Guidelines: 
Although pregnancy is not considered an AE or SAE, all pregnancies occurring in subjects 
enrolled in this study or in a female partner of a male subject in this study must be reported to the 
Sponsor on an expedited basis and followed to outcome, even after the end of the study.  
If a female subject inadvertently becomes pregnant while on study treatment, the subject will 
immediately be removed from the study. Any pregnancies that occur within 150 days for females 
or 90 days for males following the last dose of study treatment must be reported to the Sponsor.  
The investigator should report all pregnancies in clinical trial to the Sponsor within 24 hours of 
becoming aware. A Pregnancy Report Form must be completed and submitted to the Medical 
Monitor. If the pregnancy has occurred in the female partner of a male subject, the investigator 
should attempt to collect pregnancy information after obtaining the necessary signed ICF from 
the pregnant female partner directly.  


 
 
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The outcome of the pregnancy should be reported on a separate Pregnancy Outcome Report 
Form. 
Some complications of the pregnancy may constitute an SAE. Those include spontaneous and 
elective abortion, premature delivery, congenital anomaly or birth defect in an offspring, death of 
a newborn within 28 days of birth. In these cases, a separate SAE Report Form should be filled 
in and submitted on an offspring, along with the Pregnancy Outcome Report Form on the 
mother. 

SAP_001.pdf: 
Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
STATISTICAL ANALYSIS PLAN 
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
An Open-Label, Non-Randomized Multicenter Phase 2b, Study with a Safety Run-in to Evaluate 
the Safety and Efficacy of RGI-2001 for the Prevention of Acute Graft-Versus-Host Disease 
(aGvHD) Compared to Contemporary Controls in Subjects Following Allogeneic Hematopoietic 
Stem Cell Transplantation (alloHSCT). NCT04014790 
Author:
Document status:
Version dates:
Final
14 July 2023


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
Page i 
SIGNATURES / APPROVAL PAGE 
AUTHOR 
Date 
APPROVERS 
 
 
 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
Page ii 
Table of Contents 
1.0 
STUDY INTRODUCTION ................................................................................................. 2 
1.1 
Study Objectives and Endpoints ................................................................................... 2 
2.0 
STUDY DESIGN .................................................................................................................. 3 
2.1 
Overview of Study Design ........................................................................................... 3 
2.2 
Control Group ............................................................................................................... 3 
2.3 
Sample Size .................................................................................................................. 4 
2.4 
Study Population .......................................................................................................... 4 
2.5 
Randomization/Blinding............................................................................................... 4 
2.6 
Treatment Administration ............................................................................................ 4 
3.0 
ANALYSIS POPULATIONS ............................................................................................. 4 
4.0 
STATISTICAL METHODS OF ANALYSIS ................................................................... 4 
4.1 
Statistical Considerations ............................................................................................. 4 
4.2 
Methods for Handling Dose Changes........................................................................... 5 
4.3 
Methods for Handling Missing Data ............................................................................ 5 
4.4 
Interim Analysis ........................................................................................................... 5 
5.0 
STUDY SUMMARY ............................................................................................................ 6 
5.1 
Subject Disposition ....................................................................................................... 6 
5.2 
Protocol Deviations ...................................................................................................... 6 
6.0 
EVALUATION OF DEMOGRAPHICS, BASELINE CHARACTERISTICS, AND 
PROPHYLACTIC TREATMENT .............................................................................................. 6 
6.1 
Demographics ............................................................................................................... 6 
6.2 
Baseline Characteristics ................................................................................................ 6 
6.3 
Disease Status Prior to HSCT....................................................................................... 6 
6.4 
Graft Source and Donor Characteristics ....................................................................... 6 
6.5 
Preparative Conditioning Regimen .............................................................................. 6 
6.6 
Concomitant Medications ............................................................................................. 6 
7.0 
TREATMENT EXPOSURE ............................................................................................... 7 
8.0 
EVALUATION OF EFFICACY PARAMETERS ........................................................... 8 
8.1 
Acute GVHD ................................................................................................................ 8 
8.2 
Chronic GvHD.............................................................................................................. 9 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
Page iii 
8.3 
Overall Survival............................................................................................................ 9 
8.4 
Disease-Free Survival (DFS) ........................................................................................ 9 
8.5 
Non-Relapse Mortality (NRM) .................................................................................... 10 
8.6 
Acute GVHD-Free Survival (GFS) .............................................................................. 10 
8.7 
GvHD-Free, Relapse-Free Survival (GRFS) ................................................................ 10 
8.8 
Time to First Use of Systemic Therapy for GvHD ...................................................... 11 
9.0 
EVALUATION OF SAFETY PARAMETERS ................................................................ 11 
9.1 
Adverse Events ............................................................................................................. 11 
9.2 
Infections ...................................................................................................................... 12 
9.3 
Myeloid and Platelet Engraftment ................................................................................ 12 
9.4 
Vital Signs .................................................................................................................... 13 
9.5 
Karnofsky Performance Status ..................................................................................... 13 
9.6 
Evaluation of Laboratory Parameters ........................................................................... 13 
9.7 
Evaluation of Donor/Host Chimerism .......................................................................... 13 
9.8 
Evaluation of Other Safety Parameters ........................................................................ 13 
10.0 CONVENTIONS FOR CALCULATIONS AND TABULATIONS ............................... 14 
11.0 SPECIFICATIONS FOR ANALYSIS DISPLAYS .......................................................... 14 
11.1 Format........................................................................................................................... 15 
11.2 Summary Tables to Be Provided .................................................................................. 17 
11.3 Listings to Be Provided ................................................................................................ 20 
11.4 Figures to Be Provided ................................................................................................. 21 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 1 
LIST OF ABBREVIATIONS 
aGVHD 
Acute Graft-versus-host disease 
AE 
Adverse event 
alloHSCT 
alloHSCT Allogeneic Hematopoietic Stem Cell Transplantation 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
cGVHD 
Chronic Graft-versus-host disease 
CIBMTR 
Center for International Bone and Marrow Transplant Research 
CTCAE 
Common Terminology Criteria for Adverse Events 
DFS 
Disease-Free Survival 
DLT 
Dose-Limiting Toxicity 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
EOS 
End of Study 
GFS 
GVHD-free survival 
GRFS 
GVHD-free, relapse-free survival 
GVHD 
Graft-versus-Host Disease 
HSCT 
Hematopoietic Stem Cell Transplant 
iNKT 
invariant Natural Killer T 
ITT 
Intent-to-Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
Milligrams 
MRD 
Matched-related donor 
NRM 
Non-relapse Mortality 
OS 
Overall Survival 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PT 
Preferred Term 
RFS 
Relapse-free Survival 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SD 
Standard Deviation (statistical parameter) 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
Treg 
Regulatory T cells 
URD 
Unrelated donor 
WHO 
World Health Organization 
Note: The first occurrence of some abbreviations is not spelled out in the document (e.g. units of 
measure). 


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1.0 
STUDY INTRODUCTION 
This statistical analysis plan is based on the protocol “An Open-Label, Non-Randomized 
Multicenter Phase 2b, Study with a Safety Run-in to Evaluate the Safety and Efficacy of RGI-2001 
for the Prevention of Acute Graft-Versus-Host Disease (aGvHD) Compared to Contemporary 
Controls in Subjects Following Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)”, 
Version 2.0, dated 06 March 2020.  
1.1 
Study Objectives and Endpoints 
Type 
Objectives 
Endpoints 
Primary 
•
To assess the potential efficacy
of RGI-2001 in addition to
standard of care (SOC) vs SOC
for the prevention of acute
GvHD (aGvHD)
•
To characterize the safety
and tolerability of 6 weekly
intravenous (IV) infusions of
RGI-2001 in subjects
following alloHSCT
•
Efficacy: Grades II-IV aGvHD by Day 100
according to the Modified Keystone Criteria
•
Safety: Incidence, nature, and severity of
treatment-emergent AEs, SAEs, laboratory
test values, vital-sign measures, and graft
failure
Secondary 
•
To assess the potential efficacy
of RGI-2001 in addition to SOC
vs SOC for the prevention of
chronic GvHD (cGvHD)
according to the secondary
endpoints listed
•
To assess the survival of
subjects who received RGI-
2001 in addition to SOC vs
SOC
•
To evaluate the
pharmacodynamics (PD) effects
of weekly dosing of RGI-2001
•
Grades II-IV aGvHD by Day 180 according to
the Modified Keystone Criteria
•
Total and moderate-severe cGvHD at 6
months and 1 year according to the 2014 NIH
criteria for cGvHD
•
Non-relapse mortality (NRM) rates at Day
100, 6 months and 1 year
•
Disease-free survival (DFS) at 6 months and
1 year
•
GvHD-free, relapse-free survival (GRFS)a at
6 months and 1 year
•
Overall survival (OS) at 6 months and 1 year
•
Change from baseline in the percentage of
CD4+CD25+CD45RA+ CD127-LO T cells
(naive Tregs) on Days 14, 28, 42, 60, 100, 180
•


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• 
• 
a  A GRFS event includes Grade III-IV aGVHD, cmoderate-to-severe GvHD requiring systemic immunosuppressive
treatment, disease relapse or progression, or death by any cause. 
2.0 
STUDY DESIGN 
2.1 
Overview of Study Design 
This is an open-label, multi-center, single-arm study to evaluate six weekly doses of RGI-2001 in 
combination with SOC treatment for the prevention of aGvHD in subjects following alloHSCT. 
Subjects will be followed for safety and adverse events during a one-year follow-up period after 
alloHSCT, including a 6-week treatment period and a 42-week follow-up period. In addition, there 
is a screening period lasting approximately 2 weeks. 
Study subjects’ data will be compared to a contemporaneous set of control subjects’ data from the 
Center for International Bone and Marrow Transplant Research (CIBMTR). A description of and 
statistical plan for this comparison is contained in a SAP specific to that goal and separate from the 
current SAP. 
The visit schedule for the study is provided in the protocol, Section 3.  
2.2 
Control Group 
A non-randomized, contemporary control group from the CIBMTR database will be derived for 
comparison. Control subjects were selected based on eligibility requirements set forth in the 
protocol, Section 7.  As noted above, a SAP specific to this comparison is provided separate from 
the current SAP. 


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2.3 
Sample Size 
As described in Section 12.1 of the protocol, the study plans to enroll and treat 50 subjects with 
RGI-2001.  “Control” subjects who would have been eligible for this trial will be obtained from the 
CIBMTR and used for a non-randomized comparator group (details in a separate SAP).   
2.4 
Study Population 
The study population consists of adult subjects aged 18 or older with specific hematologic 
malignancies (e.g., AML, ALL, MDS, MPD) and meeting specific inclusion/exclusion criteria 
(outlined in protocol, Sections 7.1 and 7.2). All subjects were assessed for suitability of alloHSCT 
based on institutional practice, using either a matched-related donor (MRD) or an unrelated donor 
(URD), and were enrolled after meeting the inclusion/exclusion criteria for this study. 
2.5 
Randomization/Blinding 
This is an open-label study and there is no randomization or blinding. 
2.6 
Treatment Administration 
All subjects were to receive 6 weekly doses of RGI-2001 100 μg/kg via IV administration over 30 
minutes. 
3.0 
ANALYSIS POPULATIONS  
As defined in the protocol the Safety Analysis Population will include all subjects with at least one 
infusion of study drug. Because this study is not randomized, this population is the same as the 
traditional intent-to-treat analysis population (ITT), excluding subjects that did not proceed with 
treatment.  This population will be used for both the efficacy and safety analyses. 
Per protocol “Subjects who do not complete the DLT window for reasons other than toxicity may 
be replaced”.  Since no subjects met this criterion, no replacement rules will be implemented in the 
analysis. 
4.0 
STATISTICAL METHODS OF ANALYSIS 
4.1 
Statistical Considerations 
Continuous variables will be summarized (based on the subjects with non-missing values) by the 
number of subjects (n), mean, standard deviation (SD), median, minimum value, and maximum 
value. Mean and median will be accurate to one more digit decimal point than the original data, and 
standard deviation will be accurate to two more-digit decimal points than the original data, and the 
decimal points of the maximum and minimum values will be the same as the original data. 
Categorical variables will be summarized (based on the subjects with non-missing values) by the 
frequency (count and percent) of subjects falling within the category. The denominator for all 


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percentages, unless otherwise specified, will be the number of subjects in the specified analysis 
population.  
Point estimates of time-to-event outcomes will be obtained using either Kaplan-Meier or cumulative 
incidence estimates, depending on whether endpoints have competing risks. Survival at a variety of 
specific endpoints will be presented in the tabled output, including Day 100 (i.e., primary endpoint 
for aGvHD) and Day 365 (i.e., EOS).  In addition (if applicable), the median length of survival (in 
days) will be presented.  Furthermore, listed data for all time-to-event outcomes will be provided. 
Regarding the time-to-event estimates, the time between begin and end dates for events and censors is 
important in the calculation.  If either of the dates are invalid, then the 1st will be assumed (for 
missing day) and/or January will be assumed (for missing month).  Assumptions will only be 
incorporated into the analysis if calculation of time does not result in a negative number of days. If 
negative, the subject will not be used in the analysis. If assumptions are needed, they will be 
flagged in the listings. 
Almost all data from the electronic case report form (eCRF) will be listed. For example, time 
(mm:hh) will be excluded from almost all listings except for the PK and PD listings.  From lab 
listings, the lab name and the original value for the dose in the units collected on the eCRF will be 
excluded and replaced with the value in SI units.  Also a few variables collected on the AE eCRF 
and other eCRFs will be excluded from the listings. 
Baseline will be defined as the last assessment completed prior to the administration of the study 
drug (Day 0, which corresponds with date of transplant).  
4.2 
Methods for Handling Dose Changes 
All subjects are scheduled to receive 6 weekly doses of RGI-2001 100 μg/kg via IV administration.  
Deviations from this schedule or dose will be included in the administration list, and will also be 
displayed in the summary table that is analyzed with continuous methods (e.g., displaying mean, 
minimum, and maximum). 
4.3 
Methods for Handling Missing Data 
No imputations will be made for missing data, except as described for the time-to-event analyses in 
Section 4.1 (above). 
4.4 
Interim Analysis 
There will be no interim analyses described within the scope of this SAP. 


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5.0 
STUDY SUMMARY 
5.1 
Subject Disposition 
Subject disposition will be summarized for all subjects by frequency counts and percentages of 
completed and discontinued status along with reason for discontinuation. This summary analysis 
will be based on all subjects in the clinical study database. Subject disposition for all subjects will 
be listed. Furthermore, a summary table for death will be reported. 
5.2 
Protocol Deviations 
A by-subject listing will be provided for all protocol deviations for all subjects. Major Protocol 
deviations will be summarized in a table. 
6.0 
EVALUATION OF DEMOGRAPHICS, BASELINE CHARACTERISTICS, AND 
PROPHYLACTIC TREATMENT 
All analyses in this section will be performed using the Safety Population. 
6.1 
Demographics 
Using the Safety Analysis Population, demographics (age, sex, race, and ethnicity) will be 
summarized using categorical and continuous methods, as appropriate. A by-subject listing will 
also be provided. 
6.2 
Baseline Characteristics 
A by-subject listing will be provided with height, weight, and BMI.  In addition, a summary table 
will be provided. 
6.3 
Disease Status Prior to HSCT 
A table will be provided to summarize: time since initial diagnosis, type of disease prior to HSCT, 
and other pre-enrollment disease characteristics collected on the Initial Disease Status and 
Evaluation Prior to HSCT eCRF. A by-subject listing will also be provided. 
6.4 
Graft Source and Donor Characteristics 
A table will be provided to summarize: donor/recipient sex matching, graft source, donor 
relationship to the subject, and donor/recipient CMV serostatus. A by-subject listing will also be 
provided. 
6.5 
Preparative Conditioning Regimen 
A summary table will be provided.  In addition, a by-subject listing will be provided with regimen, 
dose, route, start date, and other preparative information.  
6.6 
Concomitant Medications 
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Per protocol, concomitant medications are any prescription or over-the-counter preparations 
used from 2 days prior to the preparatory regimen before Day 0 through the end of the subject’s 
study participation. 
Medications will be coded using the World Health Organization (WHO) Drug Reference List 
version 1Q2019. These will be summarized via categorical methods by ATC class and preferred 
term, and all will be provided in a by-subject listing.  
In addition to the summary table for all concomitant medication, two subset tables will be 
presented.  The first will be a summary table to describe the concomitant medications given as 
aGvHD prophylaxis.  The second will be a summary table to describe the concomitant therapies 
given as treatment for GvHD with the first 100 days.  This second table will include a summary of 
the total dose received. Total Dose will be calculated as: Daily Dose (in mg units) * 
Adjusted_Duration (in days), where Daily Dose and Adjusted_Duration are defined per below 
using the start/stop/frequency/unit information recorded on the Concomitant Medication eCRF. 
Daily Dose 
First calculate, Dose_mg: 
•
If “Dose Unit” (on eCRF) = mg then Dose_mg = “Dose” (from eCRF)
•
If the “Dose Unit” (on eCRF) not mg then calculate the dose for conversion to
mg
Next calculate, Daily_Dose: 
•
If “Frequency” (on eCRF) = daily then Daily_Dose = Dose_mg
•
If “Frequency” (on eCRF) = twice daily then Daily_Dose = Dose_mg*2
•
If “Frequency” (on eCRF) = every other day then Daily_Dose = Dose_mg*0.5
•
If “Frequency” (on eCRF) is specified differently than the examples above, use
similar logic to adjust in order to obtain the “Daily_Dose”.
Adjusted_Duration 
(days) 
First a Day100 variable: 
•
Day100 = Date of first treatment with RGI-2001 (ie, Start Date [Day 0]) plus
100
Next calculate, Adjusted_Duration: 
•
If Stop Date is provided and Stop Date ≤ Day100 then Duration = Stop Date
minus Start Date plus 1.
•
If Stop Date is provided and Stop Date > Day100 then Duration = Date_100
minus Start Date plus 1.
•
If Stop Date is not provided then Duration = Day100 minus Start Date plus 1.
7.0 
TREATMENT EXPOSURE 
Exposure to RGI-2001 will be summarized by the number of doses administered and the duration 
of exposure. The duration of exposure will be derived as the difference between the first 
administration date and the last administration date.  
Actual dose intensity (µg/kg/day) and the dose intensity (%) relative to the planned dose will be 
determined and summarized.  
A by-subject listings will also be provided. 
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8.0 
EVALUATION OF EFFICACY PARAMETERS 
All efficacy analyses will be performed on the Safety Analysis Population. As noted above, 
outcomes will ultimately be compared to data obtained from the CIBMTR and details of this 
comparison are contained in a separate SAP that is specific to this goal. Methods for estimation of 
efficacy parameters are provided below without mention of the methods that will be used for 
comparing efficacy parameters to the CIBMTR data. 
Binary outcomes will be summarized with proportions, continuous outcomes with means and 
medians, and time-to-event outcomes with Kaplan-Meier estimates or cumulative incidence 
estimates for endpoints with competing risks. 
Definitions of occurrence and timing of outcomes are described below. 
8.1 
 Acute GVHD 
For the primary and secondary endpoints as well as certain exploratory endpoints, Keystone criteria 
will be used for the determination of the severity of aGVHD. For outcomes at a defined time 
points, the event time will be defined as the time from the “start date” of first RGI-2001 infusion 
(i.e., transplant date/Day 0) to the first date aGvHD is diagnosed with Keystone criteria Grades II-
IV.  The first date of aGVHD will be identified using the following eCRFs: 
•
Initial report: aGvHD_d eCRFs with Question 10 = II-IV (i.e., Keystone Grades)
•
Maximum report: aGvHDmax eCRFs with Question 1 = II-IV (i.e., Keystone Grades)
The first diagnosis date across the eCRFs meeting the above criteria will be used to define the 
“event time” for this analysis.  Censoring: Subjects who are alive without these events will be 
censored at the date of completion of the last aGvHD assessment, with follow-up truncated at 180 
days.  Subjects who die without aGVHD will be treated as competing-risk events.  The occurrence 
of aGVHD as a function of time will be calculated using cumulative-incidence estimates. 
As an exploratory outcome, MAGIC criteria will be used for the determination of the severity of 
aGVHD.  Event time will be defined as the time from the “start date” of first RGI-2001 infusion to 
the first date aGvHD is diagnosed with MAGIC criteria Grades II-IV The first date will be 
identified using the following eCRFs: 
•
Initial report: aGvHD_d eCRFs with Question 8 = II-IV (i.e., MAGIC Grades)
•
Maximum report: aGvHDmax eCRFs with any of the following three categories:
o
Grade II: Stage 3 skin and/or stage 1 liver and/or stage 1 upper GI and/or stage 1
lower GI (questions 3,4,5, and 6 on the eCRF)
o
Grade III: Stage 2-3 liver and/or stage 2-3 lower GI, with stage 0-3 skin and/or
stage 0-1 upper GI
o
Grade IV: Stage 4 skin, liver, or lower GI involvement, with stage 0-1 upper GI


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The first diagnosis date across the eCRFs meeting the above criteria will be used to define the 
“event time” for this analysis. Censoring and competing-risk considerations will be the same as 
with the Keystone criteria (above). The occurrence of aGVHD as a function of time will be 
calculated using cumulative-incidence estimates. 
Similar to above, the analysis will be repeated for Keystone and Magic separately using only 
Grades III and IV. 
8.2 
Chronic GvHD 
Chronic GvHD (cGvHD) will be summarized visually as a function of time up to one year as a 
cumulative incidence estimates as well as by-visit frequency analysis. 
Severity ratings according to 2014 NIH Criteria will be used.  Event time will be defined as the 
time from the “start date” of first RGI-2001 infusion (i.e., transplant date) to the first date cGvHD 
is diagnosed with moderate or severe cGvHD (if multiple cGvHD_d eCRFs exist with 
moderate/severe ratings, the first diagnosis date across the eCRFs will be used for this event).  
Censoring: Subjects who are alive without these events will be censored at the date of completion 
of the last cGvHD assessment, with follow-up truncated at one year (365 days).  Subjects who die 
or relapse without cGVHD will be treated as competing-risk events at the time of death. The 
occurrence of cGVHD as a function of time will be calculated using cumulative-incidence 
estimates. 
Similar to above, the analysis will be repeated for using all severities (not just moderate and 
severe). 
8.3 
Overall Survival 
Overall survival (OS) probabilities will be calculated using Kaplan-Meier methodology.  Overall 
survival will be defined as the time from the “start date” of first RGI-2001 infusion to the date of 
death due to any cause.  Death date will be obtained from Discontinuation eCRF.  Censoring: 
Subjects who are known to have not died are censored at the date last known to be alive (usually 
EOS visit date), with follow-up truncated at one year (365 days).  There are no competing risk 
events.  Kaplan-Meier estimates of this endpoint as a function of time will be provide for visual 
purposes. 
8.4 
Disease-Free Survival (DFS) 
DFS rates (synonymous with Relapse-Free Survival [RFS]) will be calculated using Kaplan-Meier 
methodology.  For each subject, DFS will be calculated as time from the “start date” of first RGI-
2001 infusion to relapse, disease progression, or death from any cause, whichever occurs first.  
Censoring: Subjects who do not experience any DFS events will be censored on the last evaluation 
of relapse/progression (using the Disease Status Follow-up eCRF), with follow-up not extending 
beyond one year.  There are no competing risk events.  Kaplan-Meier estimates of this endpoint as 
a function of time will be provide for visual purposes. 


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Date of first relapse will be obtained using the Disease Status Follow-up eCRF where Question 7 
“Disease Status” = “1st relapse” or “Relapse from complete remission”. This eCRF contains three 
dates: Question 1 Date of Bone Marrow Aspirate, Question 2 Date of Bone Marrow Biopsy, and 
Visit Date.  If multiple dates are provided, the first will be used to define the Date of First Relapse. 
Date of first progression will be obtained using the Disease Status Follow-up eCRF where 
Question 7 “Disease Status” = “Progression from hematologic improvement”.  Similar to relapse, 
the first of the three dates will be used to define the Date of First Progression. 
8.5 
Non-Relapse Mortality (NRM) 
Non-relapse mortality (NRM) rates will be calculated using a cumulative incidence estimate for 
visual purposes.  NRM will be defined as the occurrence of death without prior relapse, with 
relapse a competing risk for NRM.  For each subject, time to death will be calculated as described 
in the above OS section and time to relapse will be calculated as described in the DFS section.  
Event and censoring assignments will proceed as follows: 
•
Subjects with no relapse and no death will be censored at the last time known to be alive.
•
Subjects with no relapse who die will be counted as events.
•
Subjects with relapse will be considered a competing risk at the time of first relapse.
•
Follow-up will not extend beyond one year.
8.6 
Acute GVHD-Free Survival (GFS) 
Failure for the composite endpoint Grades II-IV aGvHD-free survival at Day 180 is the occurrence 
of Grades II-IV aGvHD by Day 180 or death. The time of failure, if both components occur, is the 
earliest of the two failures; if only one component occurs time of failure is the day of that failure. 
Grades III-IV aGvHD-free survival at Day 180 will also be calculated. For each of these, aGvHD 
will be graded according to Keystone criteria. Kaplan-Meier estimates of each will be provided for 
visual purposes, and in addition to the point estimates at Day 180, point estimates at one year will 
also be provided. Censoring is performed as described in the Acute GVHD and Overall Survival 
sections above. There are no competing risk events. 
8.7 
GvHD-Free, Relapse-Free Survival (GRFS) 
GRFS rates will be calculated using Kaplan-Meier methodology.  For each subject, GRFS will be 
calculated as time from first infusion of RGI-2001 to date of Grade III-IV aGVHD (defined 
below), moderate-to-severe cGVHD requiring systemic immune suppression (defined below), 
disease relapse or progression (defined above), or death by any cause (using Discontinuation 
eCRF), whichever occurs first. Censoring: Subjects who do not experience any of these events will 


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be censored on the last evaluation of relapse/progression (3 dates from last Disease Status eCRF), 
with follow-up truncated at one year (365 days). There are no competing risk events. 
Date of first Grade III-IV aGvHD will be obtained using Keystone Grading and the diagnosis date 
recorded on the aGvHD_d eCRF. 
Date of first use of systemic therapy for cGvHD will be defined using the Concomitant Medication 
eCRF as described in “Time to First Use of Systemic Therapy for GvHD” section below.   
8.8 
Time to First Use of Systemic Therapy for GvHD 
Date of first use of systemic therapy will be defined using the Concomitant Medication eCRF.  A 
subset of the Concomitant Medication eCRFs will be used to identify the first start date for the 
medication; this subset is defined in the TLF attachment on the applicable table.  This time analysis 
will be tabulated using continuous methods (mean/median/etc), and number of patients with at least 
one of these medications will be calculated using a simple proportion of the safety population.  
9.0 
EVALUATION OF SAFETY PARAMETERS 
All safety analyses will be performed using the Safety Analysis population. 
9.1 
Adverse Events 
Per protocol, an adverse event is defined as “any untoward medical occurrence in a subject or 
clinical investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment” (examples delineated in the protocol 
Section 10.1).  
Severity is defined from 1(mild) through 5(fatal), as described in protocol Section 10.2.2. 
An AE is considered as treatment emergent (TEAE) if it appears on or after the first dose date of 
RGI-2001, or was already present and worsened after the first dose date, up to 30 days after the last 
RGI-2001 dose date.  Any medical condition that is present at the time that the subject is screened 
will be considered as baseline and not be reported as an AE (instead as medical history). However, 
if the subject’s condition deteriorates at any time during the study, it will be recorded as an AE. 
Almost all AEs collected on the eCRFs will be considered TEAEs, no onset dates will be imputed.  
If an onset date is missing/invalid, then only included in listing and not included in summary table.  
If AE onset date is >30 days after the last RGI-2001 dose date, then it will not be considered a 
TEAE and therefore not included in the summary tables (only included in the listings). 
A summary table of TEAEs with a count and percent of subjects in various TEAE categories will 
be provided (for example: one or more TEAEs, study-medication related TEAEs, serious TEAEs, 
discontinued due to TEAEs). 
Verbatim adverse events will be mapped to preferred term (PT) and system organ class (SOC) 
using MedDRA V22.0.  All TEAEs will be summarized with frequency counts and percentages by 


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MedDRA SOC and PT.  A subject with multiple occurrences of an AE will be counted only once 
in the AE SOC-PT category in summary tables.  
Incidences of TEAEs by SOC and PT will be summarized by counts and percentages and provided 
for: (1) overall for all TEAEs and (2) various subsets (for example, Serious TEAEs, Related 
TEAEs, Grade 3 or 4 TEAEs, etc.). 
In addition, incidences of TEAEs by PT (not SOC) will be summarized by counts and percentages 
and provided for: (1) overall for all TEAEs and (2) various subsets.  For these PT-specific 
summary tables, the following hematologic preferred terms will be grouped and summarized under 
a common term: thrombocytopenia (i.e., thrombocytopenia and platelet count decreased), 
leukopenia (i.e., leukopenia and white blood cell count decreased), neutropenia (i.e., neutropenia 
and neutrophil count decreased), anemia (i.e., anemia and red blood cell count decreased), and 
lymphopenia (i.e., lymphopenia and lymphocyte decreased).  
All AEs will be provided in a by-subject listing, as well as individual AE listings for various 
subsets (e.g., serious, leading to study discontinuation, etc.).  
The by-subject listings will include the duration of each event. Duration will be calculated as the 
stop date of the event minus the start date, unless the event is determined ongoing at exit.  Duration 
will not be calculated for events with invalid start/stop dates, where invalid is defined as a non-
calendar date (e.g., 32-dec-2021, 15-hex-2020). 
9.2 
Infections 
Incidence of any TEAE infection will be provided, as well as a frequency distribution to describe 
the type of infection (e.g., bacterial/viral/fungal). These will also be provided in a by-subject 
listing. 
9.3 
Myeloid and Platelet Engraftment 
Per protocol, “Myeloid engraftment will be defined as the first of 3 consecutive days when the 
absolute neutrophil counts (ANC) exceeds 0.5 x 109/L and platelet engraftment will be defined as 
the first of 3 consecutive days when the platelet count exceeds 20 x 109/L without transfusion 
support.”. 
The time to ANC engraftment will be calculated based on the date recorded in the CRF by the sites 
(calculated as: Date of ANC Recovery minus Initial RGI-2001 Infusion date).  Engraftment times 
(using the first date for each subject) will be summarized using continuous methods among those 
who engraft, and the median time to ANC engraftment will be estimated as the time that the 
cumulative incidence estimate of the probability of engraftment reaches or exceeds 0.5 x109/L. 
Similar tabulated analyses will be presented for time of platelet recovery/engraftment. 


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9.4 
Vital Signs 
Vital signs including systolic and diastolic blood pressure (BP), body temperature, heart rate, and 
respiratory rate were to be obtained within 15 minutes prior to RGI-2001 infusion and were to be 
repeated within 30 minutes after the infusion.  These will be summarized in a table and provided in 
a by-subject listing. 
9.5 
Karnofsky Performance Status 
The Karnofsky Performance Status (scale ranging from 0-100) is collected at screening and at 
various timepoints throughout the Treatment and Follow-Up Periods, as indicated in the schedule 
of events in the protocol. This score will be summarized at baseline and Day 60, with change from 
baseline to Day 60. The analysis will be performed using continuous methods. All data, including 
other timepoints besides Day 60 will be provided in a by-subject listing. 
9.6 
Evaluation of Laboratory Parameters 
Chemistry, hematology, urinalysis, coagulation and other laboratory parameters will be collected at 
screening and various timepoints throughout the treatment and follow-up periods, as indicated in 
the schedule of events in the protocol.   
Local laboratories were used for all laboratory assessments. Laboratory testing, results, and normal 
ranges were provided by local laboratories.  Out-of-range values (i.e., “low”, “normal”, or “high”) 
will be derived by the Sponsor’s database using the normal ranges provided by the individual local 
laboratories. Descriptive statistics by visit for laboratory parameters will be provided including 
change from baseline; these summaries will be based on SI units since each local laboratories may 
record values using different units.  
In addition, for selected parameters, shift tables from baseline and figures of the values over time 
will be provided.  For these selected parameters, if applicable, grading will be assigned using 
CTCAE version 5.0 guidelines (Appendix A) and summary tables will be provided. 
9.7 
Evaluation of Donor/Host Chimerism 
Chimerism (method, cell source, number of donor cells and percent donor cells) will be presented 
in a by-subject listing. 
9.8 
Evaluation of Other Safety Parameters 
Physical Exam and Urine Pregnancy Test were to be performed or measured at the scheduled time-
points as indicated in the schedule of events in the protocol. A by-subject listing will be provided 
for each of them. 


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Pharmacokinetic, pharmacodynamics and biomarker endpoints (as described in Protocol Sections 
9.3.2-9.3.4) will be analyzed outside the scope of this SAP; separate reports will be created, as 
needed. 
10.0 CONVENTIONS FOR CALCULATIONS AND TABULATIONS 
Table 10.0 Conventions for Calculations and Tabulations 
CONVENTION 
DESCRIPTION 
Age calculation 
Age is derived within the database; it will not be calculated in 
SAS (Statistical Analysis Software).  It is calculated as an 
integer in years as the difference between the subject’s date of 
informed consent and the date of birth.  
Baseline 
Baseline is defined as the last assessment completed prior to the 
administration of the study drug on Day 0, (which also 
corresponds to date of transplant), unless specified otherwise. 
Study Day 
Date of visit or evaluation – date of first administration of RGI-
2001.  Per protocol, the first dose will be administered on 
Day 0. 
Percentage calculation 
Percentages are calculated as 100 x (numerator/denominator). 
Rounding is not necessary because rounding is handled by the 
display format. Denominator is the total number of subjects in a 
column group unless otherwise specified.  
AE counting: general 
summary 
In summary displays, AEs are counted only once per subject 
within a category (e.g., overall and preferred term).  
AE counting: summary by 
assessment 
When AEs are summarized within levels of another AE 
assessment (e.g., causality or severity), AEs are counted once 
per subject at the worst level of the assessment (e.g., least 
complementary relationship or greatest severity).  
Change from Baseline 
Current visit value – baseline visit value 
Percent Change from 
Baseline 
100 x ((current visit value – baseline visit value) / baseline visit 
value) 
11.0 SPECIFICATIONS FOR ANALYSIS DISPLAYS 
All headers, titles, footnotes, and footers specified in the table and listing shells will be displayed in 
the produced output. Notes to the programmer will not be included in the produced output. Any 
minor deviation will not necessitate a revision to the Statistical Analysis Plan (SAP) nor will it be 
considered a deviation from planned analyses. Only major differences in the analysis methods or 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 15 
data handling will necessitate such documentation. The shells of tables and listings will be 
provided in a separate document from this SAP. 
11.1 Format 
All analysis displays will be created by using statistical and summarization procedures in SAS®, 
Version 9.4 or later, using a line size of 132 and a page size of 50. All margins of all tables and 
listings will be a minimum of 0.8 inch. 
All displays are intended to be printed in landscape layout unless otherwise specified. 
At the top of each table/listing, a number followed by the title will be presented. After the title line, 
a sub-title or population information may be presented. Horizontal lines will appear before and 
after the column heading of the table/listing. Footnotes will be under the main body of the table or 
listing display.  
The sponsor’s name, protocol number, status of the output (i.e., draft or final), SAS program name, 
and the date and time of creation will be on the output. The page number will appear on the upper 
right corner of each output (Page X of Y).  
Also included will be the source of the data (SDTM module for Listings, and Listing number for 
Tables). 
Conventions for Tables 
Tables will be delivered to the sponsor in Microsoft Word, Times New Roman, 10-point font. If 
necessary for formatting, an alternate font type or size may be used. The conventions for the 
analysis displays are shown in Table 11.1.1.  
Table 11.1.1 Conventions for Tables 
CONVENTION 
DESCRIPTION 
Decimals for summary 
statistics 
General Rule: Relative to the number of decimals in the original 
data, 1 more decimal for the mean, median, and percentiles, 2 
more decimals for standard deviation (SD) will be displayed, 
and the same number for minimum, maximum, and/or range. 
The maximum number of decimals will be 4. Some lab 
parameters or other data may require judicious deviation from 
this rule. Wherever possible, data will be decimal aligned.  
Decimals and format for 
percentages 
Unless otherwise specified, frequency tabulations will be 
presented by number and percentage, with the percentage in 
parentheses following the number. Percentages will be displayed 
to 1 decimal. A count of zero will exclude any percentage 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023
    Page 16 
display. The ‘%’ will not follow the percentage value if ‘n (%)’ 
is displayed in the column header. 
Conventions for Listings 
Listings will be delivered to the sponsor in Microsoft Word, Courier New, 8-point font. If 
necessary for formatting, an alternate font type or size may be used. The conventions for the 
listings are shown in Table 11.1.2 and apply for each listing where relevant. 
Table 11.1.2 Conventions for Listings 
CONVENTION 
DESCRIPTION 
Population 
All enrolled subjects will be included unless otherwise specified. 
Subject Number 
Subject numbers will be displayed as site number – subject 
number (XX-XXX).  
Dates 
Date information in the listing will use the date9. format (i.e., 
01JAN2011) where possible. Otherwise, date formats will be 
displayed as recorded on the eCRF. 
Unknown 
‘U’ will represent ‘Unknown’ in date variables and categorical 
variables unless otherwise specified on the eCRF. 
Missing Values 
Missing values will be listed as represented in the clinical 
database (e.g., blanks, ‘NR’ for not reported). 
Variable Units 
In the listings, a unit associated with a variable will be presented 
within parentheses in the column label.  
Visit Description 
A visit column will be provided with the visit label and an 
adjacent column with the corresponding date of evaluation, if 
available. Screening will be the label for screening visits. 
Sort Order 
All listings will be sorted by subject number, followed by the 
visit date (if available), then by collection date (if available), 
then time (if available), or in the case of AEs and medications, 
start date followed by stop date.  


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 17 
11.2 Summary Tables to Be Provided 
Table 11.2 Summary Tables 
Table Number and Title 
Analysis 
Population 
Table 14.1.1: Subject Disposition (All Subjects) 
All 
Table 14.1.2: Deaths 
Safety Analysis 
Table 14.1.3: Subject Enrollment by Site 
Safety Analysis 
Table 14.1.4: Major Protocol Deviations 
Safety Analysis 
Table 14.1.5: Demographics 
Safety Analysis 
Table 14.1.6: Study Disease Characteristics 
Safety Analysis 
Table 14.1.7: Donor Characteristics (Safety Population) 
Safety Analysis 
Table 14.1.8: Conditioning Regimen (Safety Population) 
Safety Analysis 
Table 14.1.9: RGI-2001 Treatment Exposure (Safety Population) 
Safety Analysis 
Table 14.1.10: Concomitant Medications (Safety Population) 
Safety Analysis 
Table 14.1.11: Concomitant Medications Given as Acute GvHD Prophylaxis 
(Safety Population) 
Safety Analysis 
Table 14.1.12: Systemic Steroids and Other Therapies Given for Treatment of 
GvHD (Safety Population) 
Safety Analysis 
Table 14.2.2.1: Acute GVHD Incidence (Safety Population) 
Safety Analysis 
Table 14.2.2.2: Chronic GVHD Incidence (Safety Population) 
Safety Analysis 
Table 14.2.2.3: Acute GVHD by Organ by Stage by Keystone Criteria - 
Incidence (Safety Population) 
Safety Analysis 
Table 14.2.2.4: Acute GVHD by Organ by Stage by MAGIC Criteria - 
Incidence (Safety Population) 
Safety Analysis 
Table 14.2.2.5: Acute GvHD-Free Survival (GFS) using Keystone Criteria 
(Safety Analysis Population) 
Safety Analysis 
Table 14.2.2.6: Non-Relapse Mortality (NRM) (Safety Analysis Population) 
Safety Analysis 
Table 14.2.2.7: GvHD-Free, Relapse-Free survival (GRFS) (Safety Analysis 
Population) 
Safety Analysis 
Table 14.2.2.8: Overall Survival (OS) (Safety Analysis Population) 
Safety Analysis 
Table 14.2.2.9: Relapse-Free survival (RFS) (Safety Analysis Population) 
Safety Analysis 
Table 14.2.2.10: Time to Myeloid Engraftment (Safety Analysis Population) 
Safety Analysis 
Table 14.2.2.11: Time to Platelet Engraftment Criteria (Safety Analysis 
Population) 
Safety Analysis 
Table 14.2.3: Karnofsky Performance Status – Observed and Change from 
Baseline (Safety Population) 
Safety Analysis 
Table 14.3.1.1: Summary of Treatment-Emergent Adverse Events (Safety 
Population) 
Safety Analysis 
Table 14.3.1.2: Treatment-Emergent Adverse Events - Incidence by SOC and 
Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.3: Serious TEAEs – Incidence by SOC and Preferred Term 
(Safety Population) 
Safety Analysis 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 18 
Table Number and Title 
Analysis 
Population 
Table 14.3.1.4: Related TEAEs – Incidence by SOC and Preferred Term 
(Safety Population) 
Safety Analysis 
Table 14.3.1.5: Serious and Related TEAEs – Incidence by SOC and 
Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.6: Grade 3 or 4 TEAEs – Incidence by SOC and Preferred Term 
(Safety Population) 
Safety Analysis 
Table 14.3.1.7: Grade 3 or 4 TEAEs and Related – Incidence by SOC and 
Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.8: Grade 5 TEAEs – Incidence by SOC and Preferred Term 
(Safety Population) 
Safety Analysis 
Table 14.3.1.9: Grade 5 TEAEs and Related – Incidence by SOC and 
Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.10: TEAEs occurring in ≥20% of Subjects– Incidence by SOC 
and Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.11: TEAEs – Incidence by SOC and Preferred Term, and Worst 
Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.12: Grade 3 or 4 TEAEs – Incidence by SOC, Preferred Term, 
and Worst Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.13: Grade 3 or 4 TEAEs and Related – Incidence by SOC, 
Preferred Term, and Worst Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.14: TEAEs occurring in ≥20% of Subjects– Incidence by SOC, 
Preferred Term, and Worst Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.15: TEAEs Leading to RGI-2001 Dose Interruption or 
Reduction – Incidence by SOC, Preferred Term, and Worst Grade (Safety 
Population) 
Safety Analysis 
Table 14.3.1.16: TEAEs Leading to Discontinuation of RGI-2001 – Incidence 
by SOC, Preferred Term, and Worst Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.17: TEAEs Leading to Discontinuation from the Study – 
Incidence by SOC, Preferred Term, and Worst Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.18: TEAEs with Dose-Limiting Toxicity – Incidence by SOC, 
Preferred Term, and Worst Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.19: Infection TEAEs – Incidence by SOC, Preferred Term, and 
Worst Grade (Safety Population) 
Safety Analysis 
Table 14.3.1.20: TEAEs – Incidence by Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.21: Related TEAEs – Incidence by Preferred Term (Safety 
Population) 
Safety Analysis 
Table 14.3.1.22: Serious TEAEs – Incidence by Preferred Term (Safety 
Population) 
Safety Analysis 
Table 14.3.1.23: Grade 3 or 4 TEAEs – Incidence by Preferred Term (Safety 
Population) 
Safety Analysis 
Table 14.3.1.24: Grade 3 or 4 TEAEs and Related – Incidence by Preferred 
Term (Safety Population) 
Safety Analysis 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 19 
Table Number and Title 
Analysis 
Population 
Table 14.3.1.25: Grade 5 TEAEs – Incidence by Preferred Term (Safety 
Population) 
Safety Analysis 
Table 14.3.1.26: Grade 5 TEAEs and Related – Incidence by Preferred Term 
(Safety Population) 
Safety Analysis 
Table 14.3.1.27: TEAEs occurring in ≥20% of Subjects– Incidence by 
Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.28: TEAEs Leading to RGI-2001 Dose Interruption or 
Reduction – Incidence by Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.29: TEAEs Leading to Discontinuation of RGI-2001 – Incidence 
by Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.30: TEAEs Leading to Discontinuation from the Study – 
Incidence by Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.31: TEAEs with Dose-Limiting Toxicity – Incidence by 
Preferred Term (Safety Population) 
Safety Analysis 
Table 14.3.1.32: Treatment-Emergent Infections by Type (Safety Population) 
Safety Analysis 
Table 14.3.5.1: Serum Chemistry Laboratory Values – Observed and Change 
from Baseline (Safety Population) 
Safety Analysis 
Table 14.3.5.2: Hematology Laboratory Values – Observed and Change from 
Baseline (Safety Population) 
Safety Analysis 
Table 14.3.5.3: Coagulation Laboratory Values – Observed and Change from 
Baseline (Safety Population) 
Safety Analysis 
Table 14.3.5.4: Urinalysis Laboratory Values – Observed and Change from 
Baseline (Safety Population) 
Safety Analysis 
Table 14.3.5.5: ECG Parameter Values – Observed and Change from 
Baseline (Safety Population) 
Safety Analysis 
Table 14.3.5.6: Vital Sign Values – Observed and Change from Baseline 
(Safety Population) 
Safety Analysis 
Table 14.3.5.7: Hematology Laboratory Values Worsening from Baseline 
Grade 0-2 to Grade 3-4 During the Treatment-Emergent Period (Safety 
Population) 
Safety Analysis 
Table 14.3.5.8: Serum Chemistry Laboratory Values Worsening from 
Baseline Grade 0-2 to Grade 3-4 During the Treatment-Emergent Period 
(Safety Population) 
Safety Analysis 
Table 14.3.5.9: Shifts in Hematology Laboratory from Baseline During the 
Treatment-Emergent Period (Safety Population) 
Safety Analysis 
Table 14.3.5.10: Shifts in Serum Chemistry Laboratory from Baseline During 
the Treatment-Emergent Period (Safety Population) 
Safety Analysis 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 20 
11.3 Listings to Be Provided 
Listings are numbered considering the ICH guidance. 
Table 11.3 Listings 
Listing Number and Title 
Analysis 
Population 
Listing 16.2.1 Study Completion 
All Subjects 
Listing 16.2.2 Protocol Deviations 
All Subjects 
Listing 16.2.3 Eligibility 
All Subjects 
Listing 16.2.4.1 Demographics 
All Subjects 
Listing 16.2.4.2 Height and Weight 
Safety 
Listing 16.2.4.3 Medical History 
Safety 
Listing 16.2.4.4 Initial Disease Status and Evaluation Prior to HSCT 
Safety 
Listing 16.2.4.5 Prior Therapies 
Safety 
Listing 16.2.4.6 HLA Typing and Donor Information 
Safety 
Listing 16.2.4.7 ECG 
Safety 
Listing 16.2.5.1 AlloHSCT Product Manipulation Methods 
Safety 
Listing 16.2.5.2 AlloHSCT Administration 
Safety 
Listing 16.2.5.3 Study Drug RGI-2001 IV infusion Administration 
Safety 
Listing 16.2.6.1 ANC and Platelet Recovery 
Safety 
Listing 16.2.7.1 Adverse Events 
Safety 
Listing 16.2.7.2 Serious Adverse Events 
Safety 
Listing 16.2.7.3 Dose-Limiting Toxicities 
Safety 
Listing 16.2.7.4 AEs Leading to Study Discontinuation 
Safety 
Listing 16.2.7.5 AEs Leading to Study Drug Interruption, Reduction, 
or Discontinuation 
Safety 
Listing 16.2.7.6 AEs Leading to Death 
Safety 
Listing 16.2.7.7 List of Serious Adverse Events (Part 2) 
Safety 
Listing 16.2.7.8 Infections 
Safety 
Listing 16.2.8.1 Laboratory Results – Serum Chemistry 
Safety 
Listing 16.2.8.2 Laboratory Results - Hematology 
Safety 
Listing 16.2.8.3 Laboratory Results - Coagulation 
Safety 
Listing 16.2.8.4 Laboratory Results - Urinalysis 
Safety 
Listing 16.2.8.5 Laboratory Results – Microscopic Urinalysis 
Safety 
Listing 16.2.8.6 Laboratory Results – Viral Tests 
Safety 
Listing 16.2.8.7 Serum Pregnancy Test 
Safety 
Listing 16.2.9 Preparative Regimen 
Safety 
Listing 16.2.10 PK Blood Draw 
Safety 
Listing 16.2.11 Blood samples for Immunophenotyping and 
Exploratory Studies 
Safety 
Listing 16.2.12 Molecular Diagnostics 
Safety 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 21 
Listing Number and Title 
Analysis 
Population 
Listing 16.2.13 Physical Exam 
Safety 
Listing 16.2.14 Assessments of aGvHD and cGvHD 
Safety 
Listing 16.2.15 Dates for aGVHD and cGVHD 
Safety 
Listing 16.2.16 aGvHD Assessments Keystone Criteria 
Safety 
Listing 16.2.17 aGvHD Assessments MAGIC Criteria 
Safety 
Listing 16.2.18 cGvHD Development and Maximum Grade since Last 
Report 
Safety 
Listing 16.2.19 Karnofsky Performance Status (KPS) 
Safety 
Listing 16.2.20 Chimerism 
Safety 
Listing 16.2.21 Disease Status (Part A) 
Safety 
Listing 16.2.22 Disease Status (Part B) 
Safety 
Listing 16.2.23 Concomitant Medications Given for GvHD 
Prophylaxis  
Safety 
Listing 16.2.24 Concomitant Medications – Other Than Those Given 
for GVHD Prophylaxis 
Safety 
Listing 16.2.25 Concomitant Procedures 
Safety 
Listing 16.2.26 Vital Signs 
Safety 
Listing 16.2.27 AlloHSCT Product Analysis 
Safety 
Listing 16.2.28 Lising for Time-to-Event Analyses 
Safety 
Listing 16.2.29 Acute GvHD via Keystone Criteria: Lising for Time-
to-Event Analyses 
Safety 
Listing 16.2.30 Acute GvHD via MAGIC Criteria: Lising for Time-to-
Event Analyses 
Safety 
Listing 16.2.31 Chronic GvHD: Lising for Time-to-Event Analyses 
Safety 
Listing 16.2.32 Dates for aGVHD and cGVHD 
Safety 
Listing 16.2.33 Dates for Outcomes 
Safety 
11.4 Figures to Be Provided 
Table 11.4 Figures 
Figure Number and Title 
Analysis 
Population 
Figure 1.1 Hemoglobin by Study Day Scatter Plot 
Safety 
Figure 1.2 Leukocytes by Study Day Scatter Plot 
Safety 
Figure 1.3 Lymphocytes by Study Day Scatter Plot 
Safety 
Figure 1.4 Neutrophils by Study Day Scatter Plot 
Safety 
Figure 1.5 Platelets by Study Day Scatter Plot 
Safety 
Figure 1.6 BUN by Study Day Scatter Plot 
Safety 
Figure 1.7 Creatine by Study Day Scatter Plot 
Safety 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 22 
Figure Number and Title 
Analysis 
Population 
Figure 1.8 AST by Study Day Scatter Plot 
Safety 
Figure 1.9 ALT by Study Day Scatter Plot 
Safety 
Figure 1.10 GGT by Study Day Scatter Plot 
Safety 
Figure 1.11 Albumin by Study Day Scatter Plot 
Safety 
Figure 1.12 Total Bilirubin by Study Day Scatter Plot 
Safety 
Figure 1.13 Direct Bilirubin by Study Day Scatter Plot 
Safety 
Figure 2.1 GvHD-free Survival (Keystone Grades II-IV) 
Safety 
Figure 2.2 GvHD-free Survival (Keystone Grades III-IV) 
Safety 
Figure 2.3 Overall Survival (OS) 
Safety 
Figure 2.4 Non-Relapse Mortality (NRM) 
Safety 
Figure 2.5 Relapse Free-Survival (RFS) 
Safety 
Figure 2.6 GvHD-free, relapse-free survival GRFS 
Safety 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 23 
Appendix A 
Assignment of CTCAE grades for Laboratory values using CTCAE Version 5.0: 
Parameter 
CTCAE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
ALT 
Alanine 
aminotransferase 
increased 
>ULN - 3.0 x
ULN if
baseline was
normal; 1.5 -
3.0 x baseline
if baseline
was abnormal
>3.0 - 5.0 x
ULN if
baseline was
normal; >3.0
- 5.0 x
baseline if
baseline was
abnormal
>5.0 - 20.0 x
ULN if
baseline was
normal; >5.0 -
20.0 x
baseline if
baseline was
abnormal
>20.0 x ULN
if baseline was
normal; >20.0
x baseline if
baseline was
abnormal
 - 
ALP 
Alkaline 
phosphatase 
increased 
>ULN - 2.5 x
ULN if
baseline was
normal; 2.0 -
2.5 x baseline
if baseline
was abnormal
>2.5 - 5.0 x
ULN if
baseline was
normal; >2.5
- 5.0 x
baseline if
baseline was
abnormal
>5.0 - 20.0 x
ULN if
baseline was
normal; >5.0 -
20.0 x
baseline if
baseline was
abnormal
>20.0 x ULN
if baseline was
normal; >20.0
x baseline if
baseline was
abnormal
 - 
AST 
Aspartate 
aminotransferase 
increased 
>ULN - 3.0 x
ULN if
baseline was
normal; 1.5 -
3.0 x baseline
if baseline
was abnormal
>3.0 - 5.0 x
ULN if
baseline was
normal; >3.0
- 5.0 x
baseline if
baseline was
abnormal
>5.0 - 20.0 x
ULN if
baseline was
normal; >5.0 -
20.0 x
baseline if
baseline was
abnormal
>20.0 x ULN
if baseline was
normal; >20.0
x baseline if
baseline was
abnormal
 - 
Total 
Bilirubin 
Blood bilirubin 
increased 
>ULN - 1.5 x
ULN if
baseline was
normal; > 1.0
- 1.5 x
baseline if
baseline was
abnormal
>1.5 - 3.0 x
ULN if
baseline was
normal; >1.5
- 3.0 x
baseline if
baseline was
abnormal
>3.0 - 10.0 x
ULN if
baseline was
normal; >3.0 -
10.0 x
baseline if
baseline was
abnormal
>10.0 x ULN
if baseline was
normal; >10.0
x baseline if
baseline was
abnormal
 - 
Direct 
Bilirubin 
Blood bilirubin 
increased 
>ULN - 1.5 x
ULN if
baseline was
normal; > 1.0
- 1.5 x
baseline if
>1.5 - 3.0 x
ULN if
baseline was
normal; >1.5
- 3.0 x
baseline if
>3.0 - 10.0 x
ULN if
baseline was
normal; >3.0 -
10.0 x
baseline if
>10.0 x ULN
if baseline was
normal; >10.0
x baseline if
baseline was
abnormal
-


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REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 24 
Parameter 
CTCAE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
baseline was 
abnormal 
baseline was 
abnormal 
baseline was 
abnormal 
BUN 
Blood Urea 
Nitrogen Increased 
23 – 26 
27 – 31 
> 31
- 
- 
Cholesterol 
Cholesterol high 
>ULN - 300
mg/dL;
>ULN - 7.75
mmol/L
>300 - 400
mg/dL; >7.75
- 10.34
mmol/L
>400 - 500
mg/dL;
>10.34 - 12.92
mmol/L
>500 mg/dL;
>12.92
mmol/L
 - 
Creatine 
Phosphokinas
e (CPK) 
CPK increased 
>ULN - 2.5 x
ULN
>2.5 x ULN -
5 x ULN
>5 x ULN -
10 x ULN
>10 x ULN
 - 
Creatinine 
Creatinine 
increased 
>ULN - 1.5 x
ULN
>1.5 - 3.0 x
baseline; >1.5
- 3.0 x ULN
>3.0 x
baseline; >3.0
- 6.0 x ULN
>6.0 x ULN
 - 
Fibrinogen 
Fibrinogen 
decreased 
<1.0 - 0.75 x 
LLN; if 
abnormal, 
<25% 
decrease 
from baseline 
<0.75 - 0.5 x 
LLN; if 
abnormal, 25 
- <50%
decrease
from baseline
<0.5 - 0.25 x 
LLN; if 
abnormal, 50 - 
<75% 
decrease from 
baseline 
<0.25 x LLN; 
if abnormal, 
75% decrease 
from baseline; 
absolute value 
<50 mg/dL 
 - 
Hemoglobin 
Hemoglobin 
increased 
Increase in 
>0 - 2 g/dL
Increase in 
>2 - 4 g/dL
Increase in >4 
g/dL 
 - 
- 
Hemoglobin 
Anemia 
Hemoglobin 
(Hgb) <LLN 
- 10.0 g/dL;
<LLN - 6.2
mmol/L;
<LLN - 100
g/L
Hgb <10.0 - 
8.0 g/dL; 
<6.2 - 4.9 
mmol/L; 
<100 - 80g/L 
Hgb <8.0 
g/dL; <4.9 
mmol/L; <80 
g/L; 
 - 
- 
Lymphocyte 
Lymphocyte count 
decreased 
<LLN - 
800/mm3; 
<LLN - 0.8 x 
10e9/L 
<800 - 
500/mm3; 
<0.8 - 0.5 x 
10e9 /L 
<500 - 
200/mm3; 
<0.5 - 0.2 x 
10e9 /L 
<200/mm3; 
<0.2 x 10e9 /L 
 - 
Lymphocyte 
Lymphocyte count 
increased 
 - 
>4000/mm3 -
20,000/mm3
>20,000/mm3
-
- 


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023 
    Page 25 
Parameter 
CTCAE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Neutrophil 
Neutrophil count 
decreased 
<LLN - 
1500/mm3; 
<LLN - 1.5 x 
10e9 /L 
<1500 - 
1000/mm3; 
<1.5 - 1.0 x 
10e9 /L 
<1000 - 
500/mm3; 
<1.0 - 0.5 x 
10e9 /L 
<500/mm3; 
<0.5 x 10e9 /L 
 - 
Platelet 
Platelet count 
decreased 
<LLN - 
75,000/mm3; 
<LLN - 75.0 
x 10e9 /L 
<75,000 - 
50,000/mm3; 
<75.0 - 50.0 
x 10e9 /L 
<50,000 - 
25,000/mm3; 
<50.0 - 25.0 x 
10e9 /L 
<25,000/mm3; 
<25.0 x 10e9 
/L 
 - 
Leukocytes 
White blood cell 
decreased 
<LLN - 
3000/mm3; 
<LLN - 3.0 x 
10e9 /L 
<3000 - 
2000/mm3; 
<3.0 - 2.0 x 
10e9 /L 
<2000 - 
1000/mm3; 
<2.0 - 1.0 x 
10e9 /L 
<1000/mm3; 
<1.0 x 10e9 /L 
 - 
Leukocytes 
Leukocytosis 
- 
- 
>100,000/mm
3
- 
- 
Mag-nesium 
Hyper-
magnesemia 
>ULN - 3.0
mg/dL;
>ULN - 1.23
mmol/L
 - 
>3.0 - 8.0
mg/dL; >1.23
- 3.30 mmol/L
>8.0 mg/dL;
>3.30 mmol/L;
Triglycerides 
Hyper-
triglyceridemia 
150 mg/dL - 
300 mg/dL; 
1.71 mmol/L 
- 3.42
mmol/L
>300 mg/dL -
500 mg/dL;
>3.42
mmol/L - 5.7
mmol/L
>500 mg/dL -
1000 mg/dL;
>5.7 mmol/L -
11.4 mmol/L
>1000 mg/dL;
>11.4 mmol/L;
Albumin 
Hypo-
albuminemia 
<LLN - 3 
g/dL; <LLN - 
30 g/L 
<3 - 2 g/dL; 
<30 - 20 g/L 
<2 g/dL; <20 
g/L 
Blood 
Glucose 
Hypoglycemia 
<LLN - 55 
mg/dL; 
<LLN - 3.0 
mmol/L 
<55 - 40 
mg/dL; <3.0 - 
2.2 mmol/L 
<40 - 30 
mg/dL; <2.2 - 
1.7 mmol/L 
<30 mg/dL; 
<1.7 mmol/L; 
Mag-nesium 
Hypo-magnesemia 
<LLN - 1.2 
mg/dL; 
<LLN - 0.5 
mmol/L 
<1.2 - 0.9 
mg/dL; <0.5 - 
0.4 mmol/L 
<0.9 - 0.7 
mg/dL; <0.4 - 
0.3 mmol/L 
<0.7 mg/dL; 
<0.3 mmol/L; 
GGT 
GGT Increased 
>ULN - 2.5 x
ULN if
baseline was
normal; 2.0 -
2.5 x baseline
if baseline
was abnorma
>2.5 - 5.0 x
ULN if
baseline was
normal; >2.5
- 5.0 x
baseline if
>5.0 - 20.0 x
ULN if
baseline was
normal; >5.0 -
20.0 x
baseline if
>20.0 x ULN
if baseline was
normal; >20.0
x baseline if
baseline was
abnormal


Statistical Analysis Plan  
REGiMMUNE Corporation 
Protocol: RGI-2001-003 
FINAL 14JUL2023
    Page 26 
Parameter 
CTCAE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
baseline was 
abnormal 
baseline was 
abnormal