A Randomized Phase III Trial of Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With Either Orca-T, a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells, or Standard-of-Care Allogeneic Graft
Phase: PHASE3
Conditions: Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Mixed Phenotype Acute Leukemia, Undifferentiated Leukemia, Myelodysplastic Syndrome, Acute Leukemia, Therapy-Related Myelodysplastic Syndrome
Sponsor: Orca Biosystems, Inc.

Orca Bio 
3475 Edison Way, Suite C 
Menlo Park, CA 94025 
 ᜾
᜿
ᝀ
ᝁ info@orcabio.com  
www.orcabio.com 
 
 
 
Official Title of Study 
Precision-T (Phase III component) 
NCT Number 
NCT05316701 
Document Uploaded 
Precision-T Phase 3 Protocol Version 9.0, 09 May 2023 with 
Precision-T Phase 3 Statistical Analysis Plan, Version 4.0, 19 Sep 
2024 and Statistical Analysis Plan, Version 4.0 Memo, 13 Dec 
2024  
Date of Upload 
10 Jul 2025 
 
 
 
 

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PROTOCOL SIGNATURE PAGE 
Study Name: 
Precision-T (TRGFT-201) 
 
Protocol Title:  
A Phase Ib/Randomized Phase III Trial of Patients with Advanced 
Hematologic Malignancies Undergoing Allogeneic Hematopoietic 
Cell Transplantation with Either Orca-T, a T-cell-Depleted Graft with 
Additional Infusion of Conventional T cells and Regulatory T cells or 
Standard-of-Care Allogeneic Graft 
 
Sponsor: 
 
Orca Bio, Inc. 
 
Version/Date: 
Version 9.0, 09 May 2023 
 
 
 
 
Investigator Statement 
I have received and read the above-mentioned protocol and its attachments. I agree to 
conduct the described study in compliance with all stipulations of the protocol, regulations, 
and ICH E6 Guideline for Good Clinical Practice (GCP). I accept the responsibilities 
included herein in my role as Principal Investigator for the study and will ensure that all 
subinvestigators and study personnel comply with the provisions of this protocol.  
 
 
Principal Investigator 
Name:______________________________________________________ 
 
 
Principal Investigator 
Signature:___________________________________________________ 
 
 
Date:_______________________________________________________ 
 
 

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PROTOCOL AMENDMENT, VERSION 9.0: RATIONALE 
The following is an amendment to the Precision-T Protocol that has been modified to update 
the following: 
• Section 3.3.2: Stopping criteria were amended to align with stopping criteria provided to 
the Food and Drug Administration as part of an information request in January 2022. 
• Section 6.3.2: Language was added to clarify that FLT3, BCR-ABL, or IDH1/2 
inhibitors used for maintenance and declared by the investigator prior to randomization 
are acceptable. This does not represent a procedural change from previous protocol 
versions; rather, this simply clarifies the guidance in the protocol. 
 

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TABLE OF CONTENTS 
PRECISION-T CLINICAL STUDY PROTOCOL ...................................................................1 
PROTOCOL SIGNATURE PAGE ...........................................................................................2 
PROTOCOL AMENDMENT, VERSION 9.0: RATIONALE .................................................3 
TABLE OF CONTENTS ...........................................................................................................4 
LIST OF TABLES .....................................................................................................................8 
LIST OF FIGURES ...................................................................................................................8 
LIST OF ABBREVIATIONS ....................................................................................................9 
SYNOPSIS ...............................................................................................................................12 
1 
INTRODUCTION .................................................................................................17 
1.1 
Allogeneic Hematopoietic Cell Transplantation ..............................................17 
1.1.1 
T-Cell Depletion of Allografts .............................................................17 
1.2 
Role of Regulatory T Cells in AlloHCT ..........................................................18 
1.2.1 
Treg Preclinical Models of MAC-AlloHCT ..........................................18 
1.2.2 
Treg in AlloHCT: Retrospective Studies ...............................................18 
1.2.3 
Treg in AlloHCT: Prospective Studies ..................................................18 
1.2.4 
Treg and Tcon Addback in the Context of a T-Cell-Depleted MAC-
AlloHCT: Orca-T .................................................................................19 
1.3 
Precision-T Study Overview ............................................................................19 
1.3.1 
Dose Rationale .....................................................................................21 
1.3.2 
Patient Populations...............................................................................21 
1.3.3 
Risk/Benefit Statement ........................................................................22 
1.3.4 
Conditioning Regimen Options ...........................................................23 
2 
TRIAL OBJECTIVES AND ENDPOINTS ..........................................................24 
2.1 
Phase 3 Objectives ...........................................................................................24 
2.1.1 
Phase 3 Primary Objective ...................................................................24 
2.1.2 
Phase 3 Secondary Objectives .............................................................24 
2.1.3 
Phase 3 Exploratory Objectives ...........................................................24 
2.2 
Phase 1b Objectives .........................................................................................25 
2.2.1 
Phase 1b Primary Objectives ...............................................................25 
2.2.2 
Phase 1b Secondary Objectives ...........................................................25 
2.2.3 
Phase 1b Exploratory Objectives .........................................................25 
2.3 
Study Endpoints ...............................................................................................26 
2.3.1 
Phase 3 Primary Endpoint ....................................................................26 
2.3.2 
Phase 3 Secondary Endpoints ..............................................................26 
2.3.3 
Phase 3 Exploratory Endpoints ............................................................27 
2.3.4 
Phase 1b Primary Endpoints ................................................................28 
2.3.5 
Phase 1b Secondary Endpoints ............................................................28 

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2.3.6 
Phase 1b Exploratory Endpoints ..........................................................29 
3 
TRIAL STUDY DESIGN ......................................................................................30 
3.1 
Study Arms ......................................................................................................30 
3.2 
Review Committees .........................................................................................31 
3.2.1 
Data Monitoring Committee ................................................................31 
3.2.2 
Endpoint Adjudication Committee ......................................................31 
3.3 
Study Stopping Rules .......................................................................................31 
3.3.1 
Stopping Rules for Primary Graft Failure, Grade ≥3 aGVHD, 
and/or NRM: Precision-T Phase 1b Component .................................32 
3.3.2 
Additional Stopping Rules for Precision-T Phase 1b Component.......32 
3.4 
Medical Monitoring .........................................................................................33 
4 
STUDY POPULATIONS ......................................................................................35 
4.1 
Enrollment Procedure ......................................................................................35 
4.1.1 
Randomization .....................................................................................35 
4.2 
Donor Inclusion/Exclusion Criteria .................................................................36 
4.2.1 
Donor Inclusion Criteria ......................................................................36 
4.2.2 
Donor Exclusion Criteria (Phases 1b and 3) ........................................37 
4.3 
Recipient Inclusion/Exclusion Criteria ............................................................38 
4.3.1 
Global Recipient Inclusion Criteria (Applicable to both the Phase 
1b and Phase 3 Components of Precision-T) .......................................40 
4.3.2 
Phase 3-Specific Recipient Inclusion Criteria .....................................40 
4.3.3 
Phase 1b-Specific Recipient Inclusion Criteria ...................................41 
4.3.4 
Global Recipient Exclusion Criteria (Applicable to both the Phase 
1b and Phase 3 components of this study) ...........................................42 
5 
DONOR PROCEDURES AND GENERATION OF ORCA-T ............................44 
5.1 
Mobilization Therapy .......................................................................................44 
5.2 
Cell Collection .................................................................................................44 
5.2.1 
Donor Apheresis for Participants Assigned to Orca-T Arms ..............44 
5.2.2 
Donor Apheresis for Participants Assigned to the SoC Arm ...............44 
5.3 
Outcomes Following Processing (Orca-T Participants Only) .........................45 
6 
RECIPIENT TREATMENTS ................................................................................46 
6.1 
Investigational Product ....................................................................................46 
6.1.1 
Description, Packaging, and Labeling: Orca-T ....................................46 
6.1.2 
Dosing of Orca-T Drug Products .........................................................46 
6.1.3 
Dose Modifications ..............................................................................47 
6.2 
SoC Graft .........................................................................................................47 
6.3 
Concomitant Therapy.......................................................................................47 
6.3.1 
Required Therapies ..............................................................................47 
6.3.2 
Allowed Therapies ...............................................................................50 

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6.3.3 
Prohibited Therapies ............................................................................51 
7 
DISCONTINUATION/WITHDRAWAL CRITERIA ..........................................53 
7.1 
Withdrawal from the Study ..............................................................................53 
7.2 
Lost to Follow-Up ............................................................................................53 
8 
RECIPIENT STUDY ASSESSMENTS AND PROCEDURES ...........................55 
8.1 
Disease Evaluation ...........................................................................................55 
8.2 
AEs ...................................................................................................................56 
8.2.1 
Definitions............................................................................................56 
8.2.2 
Potential AEs .......................................................................................58 
8.2.3 
AE Severity ..........................................................................................58 
8.2.4 
Assessment of Causality ......................................................................59 
8.2.5 
Reporting and Recording of AEs .........................................................59 
8.2.6 
Follow-up of AEs and SAEs ................................................................60 
8.3 
AESIs ...............................................................................................................61 
8.3.1 
Posttransplant Lymphoproliferative Disorder ......................................61 
8.4 
GVHD ..............................................................................................................62 
8.4.1 
Assessment, Staging, and Grading of aGVHD ....................................62 
8.4.2 
Assessment, Staging, and Grading of cGVHD ....................................63 
8.4.3 
Responses to GVHD Treatment ...........................................................64 
8.5 
Study Modifications in Response to the COVID-19 Pandemic.......................64 
8.5.1 
General Guidelines ...............................................................................64 
8.5.2 
Prevention of COVID-19 After Transplant and Monitoring for 
COVID-19............................................................................................64 
8.6 
QOL Assessments ............................................................................................64 
8.6.1 
Instruments ...........................................................................................65 
9 
STATISTICAL CONSIDERATIONS...................................................................66 
9.1 
Sample Size and Power Calculation ................................................................66 
9.1.1 
Phase 3: Sample Size ...........................................................................66 
9.1.2 
Phase 1b Sample Size: Protocol Versions 1 Through 5 .......................66 
9.1.3 
Phase 1b Sample Size: Protocol Version 6 and Subsequent 
Versions ...............................................................................................66 
9.1.4 
Phase 1b: Justification for Additional Stopping Rules as Described 
in Section 4.3 .......................................................................................67 
9.2 
Endpoints .........................................................................................................68 
9.3 
Analysis Populations ........................................................................................68 
9.3.1 
Donor Populations ...............................................................................68 
9.3.2 
Phase 3: Recipient Populations ............................................................69 
9.3.3 
Phase 1b: Recipient Populations ..........................................................70 
9.4 
Statistical Analyses ..........................................................................................70 

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9.4.1 
Disposition of the Study Subjects ........................................................70 
9.4.2 
Demographic and Baseline Characteristics .........................................70 
9.4.3 
Exposure to Study Treatment...............................................................70 
9.4.4 
Analysis of Safety and Efficacy ...........................................................71 
9.4.5 
QOL .....................................................................................................73 
9.4.6 
Analysis of Pharmacodynamics ...........................................................74 
9.4.7 
Interim Analyses ..................................................................................75 
10 
REFERENCES ......................................................................................................77 
11 
APPENDICES .......................................................................................................86 
11.1 
Schedules of Activities (SoA) ..........................................................................86 
11.1.1 
Donor SoA: Donating for Participants Assigned to Orca-T Arms ......86 
11.1.2 
Donor SoA: Donating for Participants Assigned to the SoC Control 
Arm ......................................................................................................87 
11.1.3 
Recipient Schedule of Activities ..........................................................89 
11.2 
Quality Control and Assurance ........................................................................94 
11.3 
Study Governance Considerations ...................................................................94 
11.3.1 
Ethics Committee Approval .................................................................94 
11.3.2 
Ethical Conduct of the Study ...............................................................95 
11.3.3 
Financial Disclosure .............................................................................95 
11.3.4 
Subject Information and Consent.........................................................95 
11.3.5 
Subject Confidentiality ........................................................................96 
11.3.6 
Study Monitoring .................................................................................96 
11.3.7 
Study Records and Case Report Forms ...............................................97 
11.3.8 
Source Data and Source Documents ....................................................98 
11.3.9 
Use of Computerized Systems .............................................................99 
11.3.10 
Retention of Data .................................................................................99 
11.3.11 
Monitoring Committees .......................................................................99 
11.3.12 
Protocol Violations/Deviations ............................................................99 
11.3.13 
Study Termination .............................................................................100 
11.3.14 
Publication and Disclosure Policy .....................................................100 
11.4 
International Expert Panel Recommendations: Indications for AlloHSCT 
for Myelodysplastic Syndrome ......................................................................101 
11.5 
GVHD ............................................................................................................101 
11.5.1 
aGVHD ..............................................................................................101 
11.5.2 
cGVHD ..............................................................................................102 
11.6 
Revised International Prognostic Scoring System (IPSS-R) for 
Myelodysplastic Syndromes ..........................................................................106 
11.6.1 
Therapy-Related MDS .......................................................................107 
11.7 
DRI Risk Score Assessment ..........................................................................107 

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11.8 
Performance Status Criteria ...........................................................................111 
11.9 
HCT–CI..........................................................................................................111 
11.10 
Clinical Laboratory Studies ...........................................................................113 
11.11 
Definition of Woman of Childbearing Potential (WOCBP) ..........................115 
11.12 
Screening Questions for Creutzfeldt-Jakob Disease (CJD)/Variant CJD 
(vCJD) ............................................................................................................116 
11.13 
Definitions of CR, CRi, and Relapse .............................................................117 
11.13.1 
Definition of CR and CRi (Acute Leukemias) ..................................117 
11.13.2 
Definition of Relapse for AML and MPAL .......................................118 
11.13.3 
Definition of Relapse for ALL ...........................................................118 
11.13.4 
Response Criteria for Myelodysplatic Syndrome ..............................118 
11.14 
Response Criteria for BPDCN .......................................................................118 
11.15 
Definition of Relapse for CML ......................................................................118 
11.16 
Precision-T aGVHD Assessment and Reporting Guidelines .........................118 
11.17 
Precision-T cGVHD Assessment and Reporting Guidelines .........................135 
 
LIST OF TABLES 
Table 3-1 
Graft Failure Stopping Criteria ..................................................................32 
Table 3-2 
GVHD Criteria ...........................................................................................32 
Table 3-3 
Stopping Rule for Manufacturing Failure ..................................................33 
Table 3-4 
Stopping Rule for Nonrelapse-Related Death by Day +100 ......................33 
Table 3-5 
Stopping Rule for Grade 4 or 5 Infections by Day +100 ...........................33 
Table 6-1 
Myeloablative Conditioning Regimens .....................................................48 
Table 6-2 
Phase 1b-Specific, TMLI-Based Conditioning Regimen ..........................48 
Table 11-1 
Response Criteria for Acute GVHD ........................................................102 
Table 11-2 
aGVHD Steroid Response Terminology .................................................102 
Table 11-3 
Signs and Symptoms of Chronic GVHD* ...............................................104 
Table 11-4 
Response Determination for Chronic GVHD ..........................................105 
Table 11-5 
cGVHD Steroid Response Terminology .................................................106 
Table 11-6 
IPSS-R Prognostic Score Values .............................................................106 
Table 11-7 
IPSS-R Prognostic Risk Categories/Scores .............................................107 
Table 11-8 
Definitions and Scoring of Comorbidities Included in the HCT-CI ........112 
Table 11-9 
Protocol-Required Safety Laboratory Assessments .................................113 
Table 11-10 
Countries Considered to be at Risk for Transmission of vCJD ...............116 
 
LIST OF FIGURES 
Figure 4-1 
Recipient Eligibility Flowchart ..................................................................39 
Figure 11-1 
MDS AlloHCT Eligibility Flowchart ......................................................101 
Figure 11-2 
DRI AML Scoring Flow Chart ................................................................108 
Figure 11-3 
DRI MDS Scoring Flow Chart ................................................................109 
Figure 11-4 
DRI ALL Scoring Flow Chart .................................................................110 

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LIST OF ABBREVIATIONS 
AE 
adverse event 
AESI 
adverse event of special interest 
alloHCT 
allogeneic hematopoietic cell transplantation 
ALT 
alanine transaminase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AST 
aspartate transaminase 
ASTCT 
American Society for Transplantation and Cellular Therapy 
ATG 
antithymocyte globulin 
BF 
busulfan/fludarabine 
BFT 
busulfan/fludarabine/thiotepa 
BM 
bone marrow 
BPDCN 
blastic plasmacytoid dendritic cell neoplasm 
BSA 
body surface area 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CIBMTR 
Center for International Blood and Marrow Transplant Research 
CGFS 
chronic graft-versus-host-free survival 
CML 
chronic myeloid leukemia 
CMV 
cytomegalovirus 
CR 
complete remission 
CRF 
case report form 
CRi 
complete remission with incomplete hematologic recovery 
CRO 
contract research organization 
CRS 
cytokine release syndrome 
CT 
computed tomography 
CTL 
cytotoxic T lymphocyte 
CTCAE 
Common Terminology Criteria for Adverse Events 
Cy 
cyclophosphamide 
DIPSS 
Dynamic International Prognostic Scoring System 
DLCO 
diffusing capacity of the lung for carbon monoxide 
DLI 
donor lymphocyte infusion 
EBMT 
European Society for Blood and Marrow Transplantation 
EBV 
Epstein-Barr virus 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EF 
ejection fraction 
eGFR 
estimated glomerular filtration rate 
FEV1 
forced expiratory volume in the first second 
FSH 
follicle-stimulating hormone 
G-CSF  
granulocyte colony-stimulating factor 

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GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GRFS 
GVHD-free and relapse-free survival 
GVHD 
graft-versus-host disease 
HBsAg  
hepatitis B surface antigen  
HBV 
hepatitis B virus 
HCG 
human chorionic gonadotropin  
HCT 
hematopoietic cell transplantation  
HCT-CI 
Hematopoietic Cell Transplantation-Specific Comorbidity Index 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen  
HRT 
hormone replacement therapy 
HSPC 
hematopoietic stem and progenitor cell  
HSV 
herpes simplex virus 
HTLV 
human T-lymphotropic virus  
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IPSS 
International Prognostic Scoring System 
IPSS-R  
Revised International Prognostic Scoring System 
IRB  
institutional review board 
IRR 
infusion-related reaction 
ITT 
intention to treat 
IV 
intravenous(ly) 
LTFU 
long-term follow-up 
LVEF 
left ventricular ejection fraction 
MAC 
myeloablative conditioning 
MAGIC 
Mount Sinai Acute GVHD International Consortium 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intention to treat 
MRD 
minimal residual disease 
MSD 
matched sibling donor 
MUD 
matched unrelated donor 
MUGA 
multigated acquisition 
NAT 
nucleic acid test(ing) 
NIH 
National Institutes of Health 
NK 
natural killer (cell) 
NMDP 
National Marrow Donor Program 
NR 
no response 
NRM 
nonrelapse mortality 
OMRS 
Oral Mucosa Rating Scale 

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OS 
overall survival 
PBSC  
peripheral blood stem cell 
PET 
positron emission tomography 
PFT 
pulmonary function test 
PO 
oral(ly) 
PR 
partial response 
PRO 
patient-reported outcome 
P-ROM 
photographic range of motion 
PT 
prothrombin time 
PTLD 
posttransplant(ation) lymphoproliferative disorder 
PTT 
partial thromboplastin time 
RBC 
red blood cell 
SAE 
serious adverse event 
SoA 
schedule of activities 
SoC 
standard of care 
SUSAR 
suspected unexpected serious adverse reaction 
TBI 
total body irradiation 
TCD 
T-cell depletion 
TEAE 
treatment-emergent adverse event 
Tcon  
conventional T cell 
Treg 
regulatory T cell 
ULN 
upper limit of normal 
VGPR 
very good partial response 
VZV 
Varicella zoster virus 
WBC 
white blood cell 
WHO 
World Health Organization 
WNV 
West Nile virus 
WOCBP 
woman or women of childbearing potential  
 

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SYNOPSIS 
Orca Bio, Inc. 
Study Name: Precision-T  
(formerly TRGFT-201) 
Investigational Product: Orca-T 
Phase of Development: 1b/3 
Protocol Title: 
A Phase Ib/Randomized Phase III Trial of Patients with Advanced Hematologic 
Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation with Either 
Orca-T, a T-cell-Depleted Graft with Additional Infusion of Conventional T cells and 
Regulatory T cells or Standard-of-Care Allogeneic Graft 
Study Design: 
This study includes Phase 3 and Phase 1b components. All participants in both components 
will undergo myeloablative conditioning (MAC) prior to allogeneic hematopoietic stem 
cell transplantation (alloHCT). Allografts are derived from granulocyte colony-stimulating 
factor (G-CSF)-mobilized peripheral blood, and donors are human leukocyte antigen 
(HLA)-matched (8/8) related or unrelated donors. 
Phase 3: The Phase 3 is a randomized, open-label, multicenter study component of the 
Precision-T Study that will compare the outcomes between participants aged 18 to 
65 years receiving Orca-T followed by single-agent tacrolimus or standard-of-care (SoC) 
control allograft derived from mobilized peripheral blood followed by graft-versus-host 
disease (GVHD) prophylaxis with tacrolimus and methotrexate. Participants with acute 
leukemia (myeloid, lymphoid, or mixed phenotype) in complete remission or high-risk 
myelodysplastic syndrome are eligible for the Phase 3 study. Participants enrolled onto the 
Phase 3 component will be randomized in a 1:1 ratio to either the Orca-T or SoC arm.  
Phase 1b: The Phase 1b is a single-arm, multicenter study component of the Precision-T 
Study that aims to further characterize the safety and efficacy of Orca-T in participants 
aged 18 to 75 years with active (ie, not in complete response) leukemia and/or are disease 
risk index very high (Armand 2014), blastic plasmacytoid dendritic cell neoplasm 
(BPDCN), chronic myeloid leukemia (CML) with a history of blast crisis or accelerated 
phase, or participants who would be eligible for the Phase 3 component of Precision-T but 
have mild impairments of either renal and/or hepatic function as defined by an estimated 
glomerular filtration rate (eGFR) of 50 to <60 mL/min and/or a total bilirubin of >upper 
limit of normal (ULN) to ≤2x ULN. All participants enrolled onto the Precision-T Study 
prior to institution of Version 6 of the protocol were not subject to randomization and will 
therefore be analyzed as part of the Phase 1b population, regardless of whether they would 
have subsequently been eligible for the Phase 3 component. 

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Phase 3 Objectives: 
Primary:  
The primary objective of the Phase 3 component of Precision-T is to compare rates of 
survival free of moderate to severe chronic GVHD (cGVHD) (CGFS) between participants 
undergoing alloHCT with either Orca-T followed by single-agent tacrolimus or a control 
consisting of SoC unmanipulated allograft followed by tacrolimus plus methotrexate.  
Secondary: 
• To compare the rates of GVHD-free and relapse-free survival (GRFS) between 
participants undergoing alloHCT with either Orca-T or SoC 
• To compare the rates of moderate-to-severe cGVHD between participants 
undergoing alloHCT with either Orca-T or SoC 
• To compare the rates of relapse-free survival between participants undergoing 
alloHCT with either Orca-T or SoC 
 
Phase 1b Objectives: 
Primary: 
The primary objective of the Phase 1b component of Precision-T is to characterize the 
safety of administration of Orca-T followed by tacrolimus in participants undergoing 
alloHCT from HLA-matched donors (related or unrelated) who are not otherwise eligible 
for the Phase 3 component of Precision-T. 
Secondary: 
• To determine the 1-year overall survival, nonrelapse mortality, and GRFS in 
participants undergoing alloHCT with Orca-T 
• To measure the incidence and severity of acute GVHD (aGVHD) and cGVHD in 
participants undergoing alloHCT with Orca-T 
• To measure the incidence of serious infections in participants undergoing alloHCT 
with Orca-T 
• To measure the incidence and timing of engraftment in participants undergoing 
alloHCT with Orca-T 
 
The Phase 1b objectives also apply to all participants enrolled onto Precision-T prior to 
institution of Version 6 of the protocol who were not subject to randomization and will 
therefore be analyzed as part of the Phase 1b population. 
Study Sites: Multicenter in the continental United States 

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Study Populations:   
Phase 3 Study Population (Recipients) 
Adults aged 18 to 65 years who are eligible for alloHCT with 1 of the following diagnoses:  
• Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia in complete 
remission (CR) or in complete remission with incomplete hematologic recovery (CRi)  
• Myelodysplastic syndrome (MDS) with ≤10% blasts in the bone marrow who are 
eligible for transplant per 2017 International Expert Panel recommendations 
(de Witte 2017) 
and who meet all of the following criteria:  
• Are Disease Risk Index (DRI) risk category intermediate or high 
• Have an HLA-identical related or unrelated donor 
• Are planned to undergo a MAC-alloHCT with 1 of the conditioning regimens 
described in section 6.3.1.1 
 
Phase 1b Study Population (Recipients) 
Adults who are eligible for alloHCT with 1 of the following diagnoses:  
• Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia who are not 
in CR or CRi (active disease) and/or MDS with >10% to <20% bone marrow blast 
burden (ages 18 to 75 years) 
• Acute leukemia in CR/CRi or MDS that is DRI intermediate to high risk (ages 66 to 
75 years) 
• BPDCN (ages 18 to 65 years) 
• Participants aged 18 to 65 who would be eligible for the Phase 3 component of 
Precision-T except for mild impairments of renal and/or hepatic function as defined by 
an eGFR of 50 to <60 mL/min and/or a total bilirubin of >ULN to ≤2 x ULN and 
diagnosed with either of the following: 
• Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia that is in 
CR/CRi and DRI intermediate to high risk 
• MDS that is DRI intermediate to high risk 
 
 

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SoC consists of an unmanipulated allograft derived from the peripheral blood of a 
G-CSF-mobilized, matched donor. 
GVHD Prophylaxis 
Based on treatment arm assignment, recipients will receive GVHD prophylaxis as follows: 
Orca-T: single-agent tacrolimus starting on the day after Tcon infusion (typically day +3) 
SoC: dual-agent prophylaxis consisting of tacrolimus plus methotrexate starting on day −3 
Study Duration:  
Approximately 40 months for the main study (per individual subject: 1 month, screening 
and MAC; 3 days, Orca-T administration 
 or SoC allograft 
administration [day 0]; 2 years follow-up), followed by long-term survival and disease 
status follow-up 
Primary Endpoints: 
Phase 3: CGFS. An event for this time-to-event outcome is defined as death by any cause 
or moderate-to-severe cGVHD as defined by National Institutes of Health consensus 
criteria. 
Phase 1b:  
• Incidence of primary graft failure 
• Incidence, severity, and timing of grade 3 or 4 aGVHD 
 

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Participants enrolled onto the Phase 3 component of Precision-T will be randomized 1:1 to 
receive either Orca-T or SoC. Randomization will be stratified by the following: 
• Donor type (HLA-matched related versus HLA-matched unrelated) 
• DRI risk category (intermediate risk or high risk) 
 
The Phase 1b component of Precision-T is designed to further characterize the safety and 
tolerability of Orca-T and to perform an initial assessment of the efficacy of Orca-T in 
participants ineligible for the randomized Phase 3 component of Precision-T. These include 
participants with 1 of the following characteristics: 
• Active acute leukemia (ie, participants with acute leukemia who are not in either a 
complete remission [CR] or a CR with incomplete hematologic recovery [CRi]) 
(Armand 2014) 
• Diagnosed with BPDCN 
• Participants who have mildly impaired renal and/or hepatic function (defined as estimate 
glomerular filtration rate [eGFR] of 50 to 59 mL/min or total bilirubin >upper limit of 
normal [ULN]) but would otherwise be eligible for the Phase 3 component of Precision-T 
• Diagnosed with acute leukemia in remission (CR/CRi) that is DRI intermediate-to-high 
risk or MDS and aged 66 to 75 years 
• Diagnosed with DRI low-risk acute myeloid leukemia (AML) or chronic myeloid 
leukemia (CML), specifically: 
o CML in chronic phase with a prior history of accelerated phase or blast crisis, or 
resistant to or intolerant of more than 1 first and/or second-generation tyrosine 
kinase inhibitors  
o AML with inv(16) without accompanying complex cytogenetics. Such 
participants are considered DRI low risk and are therefore not eligible for the 
Phase 3 component of Precision-T. However, these participants may be 
candidates for alloHCT if they have certain high-risk features such as a history of 
relapse. 
• Phase 1b legacy component: All participants consented onto Precision-T prior to 
institution of Version 6 of the protocol at a given participating center were not subject to 
randomization and will therefore be enrolled onto the Phase 1b and analyzed as part of 
the Phase 1b population, regardless of whether they would have subsequently been 
eligible for the Phase 3 component. 
 

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• Incidence of serious infections through day +365 
• Incidence and timing of neutrophil engraftment 
• Incidence and timing of platelet engraftment 
• Secondary graft failure 
 
 
 
 
 
  
 
 
 

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3.2 
Review Committees 
3.2.1 
Data Monitoring Committee 
An independent DMC will be established to regularly review safety data. The DMC will be 
composed of a minimum of 3 members who do not have any conflict of interests with the 
trial sponsor, including 2 clinicians and a biostatistician. The full membership, mandate, and 
processes of the DMC will be detailed in a separate DMC charter. The DMC will also be 
responsible for performing an interim analysis of efficacy data as described in section 9.4.7. 
3.2.2 
Endpoint Adjudication Committee 
An independent endpoint adjudication committee (EAC) will perform a blinded 
determination as to whether the criteria for aGVHD and/or cGVHD have been met for each 
participant, and the EAC will then grade aGVHD and cGVHD according to MAGIC grading 
criteria and 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus 
Working Group criteria, respectively (see sections 11.5.1 and 11.5.2). The EAC will be 
composed of a minimum of 3 experts in GVHD assessment. The full membership, mandate, 
and processes of the EAC will be detailed in the EAC Charter. 
3.3 
Study Stopping Rules 
This section defines stopping rules following the observation of specified safety events 
potentially associated with Orca-T. 
For the Phase 1b component of Precision-T, analyses for safety will be performed on a 
continuous rolling basis by the sponsor. 
For the Phase 3 component of Precision-T, the DMC will meet at least quarterly to review 
accumulated safety data obtained from both the Phase 3 and Phase 1b components. DMC 
oversight of trial safety data is described in further detail in the Precision-T DMC Charter. 
The DMC may recommend stopping a component of the study based on their assessment of 
safety data. 
Upon any activation of a stopping rule, enrollment onto that cohort (eg, the Phase 1b cohort 
for participants age 66 to 75 years) within the study will be paused, the DMC will convene to 
review all available data to date, and the DMC may recommend to the sponsor 1 of the 
following: 
• Termination of a component of the study 
• Amendment of the study protocol to modify the diagnoses allowed for enrollment, dose 
regimen(s) of Orca-T, GVHD prophylaxis, conditioning regimen(s), and/or other 
provision(s) to be determined by the DMC, such as modification to the Orca-T 
manufacturing procedure. No participants would be accrued into the study component in 
question until the study protocol is amended accordingly. 
Section 9.1.3 describes the statistical justification for these stopping criteria. 

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• A sponsor medical monitor will continue to provide primary oversight for participant 
enrollment on the Phase 1b component. 
• A medical monitor not affiliated with the sponsor, but rather employed by a contract 
research organization (CRO), will provide primary oversight for participants randomized 
on the Phase 3 component. 
 
For questions or concerns regarding Precision-T, queries should initially be directed to the 
CRO medical monitor. The CRO medical monitor may further direct questions to the sponsor 
medical monitor in limited circumstances due to participant safety concerns.  

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4 
STUDY POPULATIONS 
4.1 
Enrollment Procedure 
Potential donors and recipients will be approached for the study after the decision to proceed 
with transplantation is made and a suitable HLA-matched donor is identified. 
Donors and recipients may be enrolled (Phase 1b component) or randomized (Phase 3 
component) only after evaluation by the investigators at the respective sites and approval by 
the medical monitor (sponsor medical monitor for Phase 1b and CRO medical monitor for 
Phase 3). For both recipients and donors, the results of all relevant screening tests and 
procedures must be submitted to the sponsor or designee, including results of the most recent 
bone marrow biopsy/aspirate, safety laboratories, and infectious disease markers. All 
personal identifiable information should be redacted from these documents before 
submission. 
Donor study procedures, including informed consent, may be overseen at the investigator’s 
site (eg, related donors who reside near the investigator’s site) or via the National Marrow 
Donor Program (NMDP) (eg, unrelated donors and related donors who do not reside near the 
investigator’s site). 
Enrollment (Phase 1b component) or randomization (Phase 3 component) must occur prior to 
the transfer of apheresis products to Orca Bio’s manufacturing facility.  
For the Phase 3 component, investigators must declare the planned conditioning regimen for 
each participant prior to randomization. Investigators may choose different regimens that are 
contingent upon eventual treatment-arm assignment (eg, BFT if assigned to the Orca-T arm 
and TBI/Cy if assigned to SoC), but this choice should be stated prior to randomization and 
must not be altered after randomization. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as a protocol waiver or exemption, is not permitted. 
4.1.1 
Randomization 
Once the participant is deemed eligible and has given written informed consent, participants 
eligible for the Phase 3 component of Precision-T will be randomized to a treatment arm 
(Orca-T or SoC). All eligibility criteria must be confirmed prior to randomization.  
Randomization will be stratified by the following:  
• Donor type (sibling vs. unrelated)  
• DRI category (intermediate risk or high risk) 
 

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4.2 
Donor Inclusion/Exclusion Criteria 
4.2.1 
Donor Inclusion Criteria  
For both the Phase 1b and Phase 3 components of Precision-T, donors must meet all of the 
following criteria: 
1. Age ≥16 and ≤75 years at time of enrollment 
2. Matched to the participant as follows: 
Either of the following: 
a. Matched related donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1, all 
typed using DNA-based high-resolution methods 
b. Matched unrelated donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1, all 
typed using DNA-based high-resolution methods 
3. Willing to donate PBSC for up to 2 consecutive days 
4. Able to donate within North America or Hawaii  
5. Meets federal eligibility criteria for donors of viable, leukocyte-rich cells or tissues as 
defined by 21 CFR § 1271 2018 and all relevant FDA Guidance for Industry 
(Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and 
Tissue-Based Products, 2007; Use of Donor Screening Tests to Test Donors of 
Human Cells, Tissues and Cellular and Tissue-Based Products for Infection with 
Treponema pallidum [Syphilis], 2015; Use of Nucleic Acid Tests to Reduce the Risk 
of Transmission of Hepatitis B Virus from Donors of Human Cells, Tissues, and 
Cellular and Tissue-Based Products, 2016; Use of Nucleic Acid Tests to Reduce the 
Risk of Transmission of West Nile Virus from Living Donors of Human Cells, 
Tissues, and Cellular and Tissue-Based Products [HCT/Ps], 2016; Donor Screening 
Recommendations to Reduce the Risk of Transmission of Zika Virus by Human 
Cells, Tissues, and Cellular and Tissue-Based Products, 2018). 
6. Donors not meeting federal eligibility as described in criterion #5, may nonetheless 
be included if either of the following apply per 21 CFR § 1271.65 2018: 
a. The donor is a first-degree or second-degree blood relative of the recipient 
b. Urgent medical need, meaning no comparable human cell product is available and 
the recipient is likely to suffer death or serious morbidity without the human cell 
product, as attested by the investigator. 
7. Meets all other criteria for donation as specified by standard NMDP guidelines 
(NMDP donors) or institutional standards (non-NMDP donors). 
8. Female donors of child-bearing potential must have a negative serum or urine beta 
human chorionic gonadotropin (HCG) test at screening and within 1 to 5 days prior to 
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9. Capable of undergoing leukapheresis, have adequate venous access, and are willing to 
undergo insertion of a central catheter should leukapheresis via peripheral vein be 
inadequate 
10. Be agreeable to an additional donation of peripheral blood mononuclear cells (or bone 
marrow harvest) in the event of graft failure or mobilization failure 
 
4.2.2 
Donor Exclusion Criteria (Phases 1b and 3) 
For both the Phase 1b and Phase 3 components of Precision-T, donors meeting any of the 
following exclusion criteria will not be eligible: 
1. Evidence of active infection 
2. Seropositive for human immunodeficiency virus (HIV)-1 or -2 or human 
T-lymphotropic virus (HTLV)-1 or -2 
3. Positive for anti-hepatitis C (HCV) antibody or HCV nucleic acid testing (NAT) 
4. Positive serologic or PCR test results indicating acute or chronic hepatitis B virus 
(HBV) infection 
a. Donors whose HBV infection status cannot be determined conclusively by 
serologic test results (www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf) must 
be negative for HBV by PCR to be eligible for study participation 
5. Potential for Zika virus infection as defined as any of the following: 
a. Medical diagnosis of Zika virus infection in the past 6 months 
b. Residence in, or travel to, an area with active Zika virus transmission within the 
past 6 months. 
c. Unprotected sex within the past 6 months with a person who is known to have 
either of the risk factors listed above (donor exclusion criterion 5.a or 5.b) 
Donors determined to be ineligible based on the results of Zika virus screening may 
be determined to be eligible if: 
d. The donor has no signs or symptoms consistent with active Zika virus infection  
and 
e. Either of the following is true: 
i) The donor is a first-degree or second-degree blood relative of the 
recipient 
ii) Urgent medical need, meaning no comparable human cell product is 
available and the recipient is likely to suffer death or serious morbidity 
without the human cell product, as attested by the investigator. 
6. Women who are pregnant or breastfeeding 
 

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4.3 
Recipient Inclusion/Exclusion Criteria 
Recipients are eligible for either the Phase 1b or Phase 3 component depending on age and 
disease characteristics (Figure 4-1). Participants eligible for the Phase 3 may not be enrolled 
on the Phase 1b. 

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Figure 4-1 
Recipient Eligibility Flowchart 
 
Abbreviations: BPDCN, blastic plasmacytoid dentritic cell neoplasm; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; 
DRI, Disease Risk Index; eGFR, estimated glomerular filtration rate; MA-alloHCT, myeloablative allogeneic hematopoietic cell transplant; MDS, 
myelodysplastic syndrome; ULN, upper limit of normal. 
 

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4.3.1 
Global Recipient Inclusion Criteria (Applicable to both the Phase 1b and 
Phase 3 Components of Precision-T) 
Recipients in either the Phase 3 or Phase 1b components of this study must meet all of the 
following criteria: 
1. Planned to undergo MAC-alloHCT including 1 of the MAC regimens listed in 
section 6.3.1.1 
2.  Matched to a related or unrelated donor as follows: 
Either 1 of the following: 
a. Matched sibling donor who is an 8/8 match for HLA-A, -B, -C, and DRB1, all 
typed using DNA-based high-resolution methods, or 
b. Matched unrelated donor who is a 8/8 match at HLA-A, -B, -C, and DRB1, all 
typed using DNA-based high resolution methods 
3. Cardiac ejection fraction at rest ≥45% or shortening fraction of ≥27% by echocardiogram 
or radionuclide scan (multigated acquisition [MUGA]) 
4. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) 
≥50% 
5. Negative serum or urine beta-HCG test in females of childbearing potential (WOCBP) 
(see appendix 11.11)  
6. Alanine transaminase (ALT)/aspartate transaminase (AST) <3 times ULN 
 
4.3.2 
Phase 3-Specific Recipient Inclusion Criteria 
Recipients randomized to the Phase 3 component of this study must meet all of the following 
Phase 3-specific criteria: 
1.  Aged ≥18 and ≤65 years (ie, from age 18 to <66 years old) at the time of enrollment 
2.  Diagnosed with 1 of the following histopathologically confirmed diseases: 
a. Acute myeloid, lymphoid or mixed phenotype/undifferentiated leukemia in CR or 
CRi, with or without the presence of known minimal residual disease. CR/CRi is 
defined in appendix 11.13.1.1, and this assessment should be based on pathologic 
analysis of the screening bone marrow biopsy. 
b. MDS that is either of the following: 
• Indicated for alloHCT per the 2017 International Expert Panel recommendations 
(de Witte 2017) (see section 11.4) 
• Diagnosed with therapy-related/secondary MDS as defined by the World Health 
Organization (WHO) classification of myeloid malignancies (WHO 2017) 
(section 11.6.1) 

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For MDS, enrollment is limited to participants with ≤10% blast burden in the 
bone marrow based on a bone marrow biopsy performed during screening. 
Participants with >10% to <20% bone marrow blast burden may be considered for 
the Phase 1b active disease/DRI very high risk. 
3. DRI overall risk categorization of intermediate or high per Armand et al. (2014) 
4. Total bilirubin ≤ULN (participants with Gilbert’s syndrome may be included where 
hemolysis has been excluded and with approval of the medical monitor) 
5. eGFR ≥60 mL/minute  
 
Note: Upon activation of Version 6 of the Precision-T protocol at each participating 
transplant center, participants who are eligible for the Phase 3 may not be enrolled onto the 
Phase 1b component of Precision-T. Participants consented to earlier versions of the protocol 
(ie, prior to implementation of Version 6) may continue on the study component for which 
they were initially consented. 
4.3.3 
Phase 1b-Specific Recipient Inclusion Criteria 
1. Participants must be diagnosed with the following histopathologically confirmed diseases 
to be eligible for the Phase 1b component of the study. Allowable age ranges are listed 
within the specific disease categories below. Eligible cohorts include the following 
diagnoses: 
a. Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia (AML, 
ALL, or MPAL) that is not in morphologic CR/CRi and participants with MDS with 
>10% to <20% bone marrow blast burden (active leukemia cohort, participants aged 
18 to 75 years) 
b. AML, ALL, MPAL, or MDS that is in morphologic CR/CRi and intermediate to high 
risk per the DRI in participants aged 66 to 75 years at the time of enrollment. 
Participants with MDS must be indicated for alloHCT per 2017 International Expert 
Panel recommendations (de Witte 2017) and/or have therapy-related/secondary MDS 
as defined by the WHO classification of myeloid malignancies (WHO 2017) 
(section 11.6.1) 
c. BPDCN (participants aged 18 to 65 years) (see the 2016 revision to the World Health 
Organization classification of myeloid neoplasms and acute leukemia [Daniel 2016]) 
d. Participants aged 18 to 65 years who have mild impairments of renal and/or hepatic 
function as defined by an eGFR of 50 to <60 mL/min and/or a total bilirubin of 
>ULN to ≤2x ULN and diagnosed with either of the following: 
• Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia that 
is in CR/CRi and DRI intermediate to high risk 
• MDS that is DRI intermediate to high risk 

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e. DRI low risk leukemia, including the following: 
• CML in chronic phase with a history of blast crisis or accelerated phase (with 
chronic phase, blast crisis, and accelerated phase as defined by WHO 2017) 
and/or participants with chronic-phase CML that is resistant to or intolerant of 
more than 1 first and/or second-generation tyrosine kinase inhibitors (participants 
aged 18 to 65 years).  
Participants with CML in blast crisis or accelerated phase that has not been 
controlled to the point of reverting to chronic phase may be considered for 
enrollment into the active leukemia cohort (cohort “A” above), and 
• AML with inv(16) and without complex cytogenetics with high-risk disease 
features (eg, molecular markers, relapsed disease currently in CR2 and beyond, 
clonal evolution, etc.) (participants aged 18 to 65 years). 
2. eGFR ≥50 mL/minute  
3. Total bilirubin ≤2x ULN (participants with Gilbert’s syndrome may be included where 
hemolysis has been excluded and with approval of the medical monitor)  
 
4.3.4 
Global Recipient Exclusion Criteria (Applicable to both the Phase 1b and 
Phase 3 components of this study) 
Recipients meeting any of the following exclusion criteria will not be eligible: 
1. Prior alloHCT 
2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical 
corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are 
allowed. 
3. Planned DLI 
4. Planned pharmaceutical in vivo or ex vivo TCD, eg, posttransplant Cy, peritransplant 
antithymocyte globulin (ATG), or alemtuzumab. For participants who have previously 
been exposed to a TCD agent, a 5-half-life washout of the agent must occur prior to 
planned day 0 (day 0 is defined as the day of infusion of the Treg and HSPC drug products 
of Orca-T for participants assigned to an Orca-T arm or day of allograft infusion for 
participants assigned to the SoC arm). 
5. Recipient positive antidonor HLA antibodies against a mismatched allele in the selected 
donor determined by either of the following: 
• Positive crossmatch test of any titer (by complement-dependent cytotoxicity or 
flow cytometric testing) to any of the following HLA loci (if mismatched): 
HLA-A, -B, -C, –DRB1, -DQB1, -DQA1, -DPB1, or -DPA1 
• Presence of antidonor HLA antibody to any of the following HLA loci 
(if mismatched): HLA-A, -B, -C, –DRB1, -DQB1, -DQA1, -DPB1, or -DPA1, 
with mean fluorescence intensity (MFI) >1000 by solid phase immunoassay 

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6. Karnofsky performance score <70% (appendix 11.8) 
7. HCT-Specific Comorbidity Index (HCT-CI) >4 (appendix 11.9) 
8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy 
and with progression or no clinical improvement) at time of enrollment. Per American 
Society for Transplantation and Cellular Therapy (ASTCT) guidelines, a negative 
SARS-CoV-2 test is not required prior to alloHCT given prolonged viral shedding. 
However, alloHCT should be deferred in participants with signs or symptoms consistent 
with active COVID-19 infection (Dioverti 2022). 
9. Seropositive for HIV-1 or -2, HTLV-1 or -2, hepatitis B surface antigen (HBsAg), or 
hepatitis C antibody 
10. Known allergy or hypersensitivity to, or intolerance of, tacrolimus; section 6.3.1.1.1) 
11. Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal, or 
Streptomyces avidinii proteins 
12. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment 
13. Concurrent malignancies within 1 year, except nonmelanoma skin cancers that have been 
curatively resected 
14. Psychosocial circumstances that preclude the participant being able to go through 
transplant or participate responsibly in follow-up care 
15. Women who are pregnant or breastfeeding 
16. WOCBP or men who have sexual contact with WOCBP who are unwilling to use 
effective forms of birth control or abstinence for 1 year after transplantation. A WOCBP 
is defined in section 11.11. 
17. Any serious medical condition or abnormality in clinical laboratory tests that, in the 
investigator’s or medical monitor’s judgment, precludes the recipient’s safe participation 
in and completion of the study, or which could affect compliance with the protocol or 
interpretation of results. 
 

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Table 6-1 
Myeloablative Conditioning Regimens 
TBI/Cy 
 
TBI (1200–1420 cGy) 
 
Cy (100-120 mg/kg) 
TBI/Etoposide 
 
TBI (1200–1320 cGy) 
 
etoposide (60 mg/kg) 
BFT 
 
busulfan1 (9.6 mg/kg IV) 
 
fludarabine (160 mg/m2) 
 
thiotepa (10 mg/kg) 
Abbreviations: BFT, busulfan/fludarabine/thiotepa; Cy, cyclophosphamide; IV, intravenous(ly); TBI, total body 
irradiation. 
1 
Alternatively, busulfan may be dosed to maintain an average daily AUC of 4,800–6,000 µM-min 
(19.7 – 24.6 mg*H/L) per institutional practice. (Note: total doses are listed) 
 
Doses of conditioning agents and schedule of administration may vary slightly based on 
institutional practices. Modifications to the conditioning regimen doses must be approved by 
the medical monitor prior to initiating the treatment. Nonmyeloablative doses and/or 
regimens are not permitted.  
For the Phase 3 component, investigators must declare the planned conditioning regimen for 
each participant prior to randomization. Investigators may choose different regimens 
dependent on eventual treatment-arm assignment, but this choice must be stated prior to 
randomization and not altered after randomization. 
6.3.1.1.1 
Phase 1b-Specific Myeloablative Conditioning Regimens 
Participants enrolled onto the Phase 1b component of the Precision-T Study must receive 1 of 
the myeloablative regimens listed in Table 6-1 or the following total marrow and lymphoid 
irradiation (TMLI)-based regimen (Jensen 2018) (Table 6-2): 
Table 6-2 
Phase 1b-Specific, TMLI-Based Conditioning Regimen 
TMLI/Fludarabine/Melphalan 
 
TMLI (1200–2000 cGy) 
 
Fludarabine (125 mg/m2) 
 
Melphalan (140mg/m2) 
Abbreviations: TMLI, total marrow and lymphoid irradiation. 
 
Doses of conditioning agents and schedule of administration may vary slightly based on 
institutional practices. Nonmyeloablative doses and/or regimens are not permitted. The 
TMLI/fludarabine/melphalan regimen is allowed only for participants in Phase 1b; 
participants enrolled onto the Phase 3 component of Precision-T must receive 1 of the 
conditioning regimens listed in Table 6-1. 

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6.3.1.2 
GVHD Prophylaxis 
6.3.1.2.1 
GVHD Prophylaxis: Orca-T Arms 
All Orca-T recipients will receive GVHD prophylaxis consisting of single-agent tacrolimus. 
GVHD prophylaxis should begin on the day following Tcon infusion (typically day +3), 
starting no fewer than 12 hours after the start of the Tcon infusion. 
Tacrolimus should be initiated at 0.03 mg/kg/day IV, with a target trough blood level of 5 to 
10 ng/mL. If a trough level of <5 ng/mL is noted prior to the start of tapering of GVHD 
prophylaxis (see section 6.3.1.2.3), tacrolimus dosing must be increased to target the 
recommended trough level unless clinically contraindicated due to toxicity. Oral (PO) 
administration is permissible when the participant is able to tolerate food; tacrolimus dosing 
may be initiated via PO route if tolerated. 
6.3.1.2.2 
GVHD Prophylaxis: SoC Arm 
GVHD prophylaxis for the SoC arm will consist of tacrolimus plus methotrexate.  
Tacrolimus plus methotrexate: 
• Tacrolimus: Tacrolimus should be initiated at 0.03 mg/kg/day IV on day -3, with a target 
trough blood level of 5 to 10 ng/mL. If a trough level of <5 ng/mL is noted prior to the 
start of tapering of GVHD prophylaxis (see section 6.3.1.2.3), tacrolimus dosing should 
be increased to target the recommended trough level unless clinically contraindicated due 
to toxicity. PO administration is permissible when the participant is able to tolerate food; 
tacrolimus dosing may be initiated via PO route if tolerated. 
• Methotrexate: Methotrexate should be administered at the doses of 15 mg/m2 IV bolus on 
day +1, and 10 mg/m2 IV bolus on days +3, +6, and +11 after hematopoietic stem cell 
infusion. The day +1 dose of methotrexate should be given at least 24 hours after the 
hematopoietic stem cell infusion ends. Dose reduction of MTX due to worsening 
creatinine clearance after initiation of the conditioning regimen, high serum levels, or 
development of oral mucositis is allowed according to institutional practices. Leucovorin 
rescue is allowed according to institutional practices. 
 
6.3.1.2.3 
Tapering of GVHD Prophylaxis 
Tacrolimus taper can be initiated at a minimum of 90 days after HCT if there is no evidence 
of active GVHD, with a suggested taper to the prophylaxis regimen of approximately 20% of 
the dose per month. Initiating a GVHD prophylaxis taper prior to day +90 may only occur 
with medical monitor approval and in the setting of intolerance/toxicity of tacrolimus 
(ie, early taper is not allowed for lack of GVHD alone). 
For recipients who develop grade ≥2 aGVHD or cGVHD prior to day +90, treatment of 
GVHD should take precedence. For instance, completion of a corticosteroid taper should be 
considered before tapering of tacrolimus. 

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6.3.1.2.4 
Modifications to GVHD Prophylaxis Regimen 
With the exception of dose modifications, all modifications to the GVHD prophylaxis 
regimens must be discussed with the medical monitor, sponsor and/or designee, including in 
cases of intolerance. The reason(s) for modification will be recorded in the case report form 
(CRF). 
6.3.1.2.5 
Initial Treatment of aGVHD 
If a participant enrolled on the Phase 1b or either arm of the Phase 3 component of 
Precision-T develops aGVHD, the following treatment approach should be followed for 
first-line treatment of aGVHD (adapted from ASTCT guidelines for treatment of aGVHD) 
(Martin 2012): 
 
a.  Skin disease only (grade 1) – The recommended treatment is topical steroids. 
b.  Skin disease only (grade 2 or 3) – The recommended treatment is 1 mg/kg/day 
methylprednisolone or equivalently dosed prednisone. 
c.  Grade 2 upper gastrointestinal (GI) only–- The recommended treatment is 
1 mg/kg/day methylprednisolone or equivalently dosed prednisone.  
d. Any grade lower GI aGVHD, hepatic aGVHD, or stage 3 skin aGVHD–- The 
recommended treatment is methylprednisolone 2 mg/kg/day or equivalently dosed 
prednisone. 
 
Participants who are refractory or resistant to, dependent upon, or intolerant of 
corticosteroids, per BMT−NIH−CIBMTR Task Force definition (appendices 11.5.1.3 and 
11.5.2.2) (Schoemans  2018), may be considered for second-line therapy according to local 
institutional standards. 
6.3.1.2.6 
Antimicrobial Prophylaxis 
All cytomegalovirus (CMV)-seropositive recipients should receive letermovir prophylaxis 
beginning between day 0 and day +28; therapy should continue through day +100. 
Letermovir may be omitted for CMV-seropositive recipients only if contraindicated (eg, 
known hypersensitivity to letermovir) with medical monitor approval. Otherwise, all 
participants will receive prophylaxis against bacterial, fungal, and viral infections during the 
peritransplant period according to institutional practices, and any treatment should be 
recorded in the CRF. 
6.3.2 
Allowed Therapies 
Standard supportive care for HCT-related toxicity is permitted, including growth factors, IV 
immunoglobulin and blood product transfusions per local institutional standards. Cellular 
blood products (except for the HCT graft products themselves) should be irradiated in 
accordance with standard institutional guidelines. Other standard supportive care for 
symptom control or procedure-related toxicities is allowed, such as analgesics, antiemetics, 

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electrolyte replacement, and hydration. Other prescribed medications for nonneoplastic 
conditions are allowed, as well as vitamins and nutritional supplements. 
FLT3 inhibitors, BCR-ABL inhibitors, and IDH1/2 inhibitors may be used after transplant to 
prevent relapse per institutional practice. Intention to use these relapse-prevention therapies 
should be declared by the investigator prior to randomization for participants enrolled on the 
Precision-T Phase 3 component. 
Concomitant prednisone (or equivalent) may be used at a dose of ≤10 mg/day. The use of 
high-dose corticosteroid treatment to manage GVHD (section 8.4.1), hypersensitivity 
reactions, or other noncancer-related symptoms including use as premedication for known 
hypersensitivity reactions (eg, hypersensitivity to contrast for scans) and use as an antiemetic 
is allowed. Physiologic doses of corticosteroids for management of adrenal insufficiency are 
also allowed. 
Active infections may be treated in accordance with standard institutional guidelines. 
Viral-specific cytotoxic T lymphocyte (CTL) (donor- or third party-derived) may be 
administered for infections not responding to standard therapy, upon discussion with the 
medical monitor, sponsor, and/or designee. 
For participants enrolled onto the Phase 3 component of Precision-T, the use of other 
investigational agents is not allowed for either the donor or recipient. As noted above, FLT3, 
BCR-ABL, or IDH1/2 inhibitors used for the prevention of relapse are not prohibited, 
provided that their intended use is declared by the investigator prior to randomization. 
For participants enrolled onto the Phase 1b component of Precision-T, investigational agents 
may be considered upon approval of the medical monitor, sponsor, and/or designee after 
review of the research protocol and other supporting documents (eg, currently approved 
Investigator’s Brochure). Coenrollment on other studies that do not involve other 
investigational agents (eg, observational studies) may be allowed with medical monitor 
approval. 
Treatment of posttransplantation lymphoproliferative disorder (PTLD) (section 8.3.1) should 
be discussed with the medical monitor, sponsor, and/or designee. 
6.3.3 
Prohibited Therapies 
Subjects may not receive other investigational therapies (except for participants enrolled onto 
the Phase 1b component of Precision-T, as allowed by the medical monitor per section 6.3.2), 
immunosuppressive medications, radiotherapy, chimeric antigen receptor-T (CAR-T) cells, 
or other systemic antineoplastic therapy during the study except as explicitly allowed per 
protocol (see section 6.3.2).  
ATG is not allowed for GVHD prophylaxis on either Orca-T or SoC arms. 

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6.3.3.1 
DLI 
Preplanned DLIs are not permitted. Unplanned DLIs may not be administered without prior 
consultation with the medical monitor. Viral-specific CTL (donor derived or third party) may 
be given for treatment of infections not responding to standard therapy (eg, CMV, 
Epstein-Barr virus [EBV], adenovirus) with medical monitor approval. 

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7 
DISCONTINUATION/WITHDRAWAL CRITERIA 
7.1 
Withdrawal from the Study 
A subject may be discontinued and/or withdrawn from the study at any time for any of the 
following reasons: 
• AE(s) that, in the judgment of the participant, may be intolerable to continue therapy or, 
by judgment of the investigator, may cause severe or permanent harm or that rule out 
continuation in the study protocol. 
• Withdrawal of consent 
• Investigator decision: The investigator has the right to terminate the participation of any 
participant at any time if she or he deems it in the participants best interest. Reasons for 
study discontinuation might be 1 of the following: 
o Pregnancy 
o Unrelated medical illness or complication 
o Relevant noncompliance with the protocol, including nonreceipt of an HCT 
o Administrative reasons 
• Lost to follow-up (see details below, section 7.2) 
• Death 
• Initiation of a new anticancer therapy including chemotherapy, radiotherapy, or other 
cellular therapy for relapse. DLI for indications other than relapse is not allowed. 
However, if a participant does receive a DLI for a nonrelapse indication (a deviation), 
they should nonetheless continue to be followed per protocol.  
• Participants who are otherwise withdrawn from study may be followed as described in 
section 8, unless the subject withdraws their consent for long-term follow-up (LTFU).  
 
The sponsor or designee must be notified of all subject withdrawals. The reason(s) for 
withdrawal must be documented in the subject’s medical records and CRF. All data 
otherwise required at the end of the study must be obtained. 
7.2 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly does not return for 
scheduled visits and cannot be contacted by the study site. 

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The following actions must be taken if a participant does not return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible, counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study. 
• Before a participant is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, by 3 telephone calls 
and, if necessary, a certified letter sent to the participant’s last known mailing address or 
local equivalent methods). These contact attempts should be documented in the 
participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 

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8 
RECIPIENT STUDY ASSESSMENTS AND PROCEDURES 
Scheduled activities for recipients are shown in section 11.1.3. 
Only subjects who meet all inclusion and exclusion criteria will be enrolled in this study. 
Demographics include age, gender, and race. 
Medical history includes a thorough review of significant past medical history, current 
conditions, any treatment for prior malignancies and response to prior treatment, and any 
concomitant therapies. 
Disease history should include tumor type, stage, grade and grading system, sites of 
metastases, and mutational status/cytogenetics. 
Prior therapies includes all prior treatments for the primary disease, including dates, 
responses, and durations of responses. 
Participants withdrawn from the study due to initiation of new therapy for relapsed disease 
will be followed for GVHD, survival, and serious AEs (SAEs) considered related to the study 
product. 
During LTFU, participants will be followed for survival and disease status, which may be 
collected via telephone calls, participant medical records, and/or clinic visits. This includes 
survival for participants who have progressive disease or relapse while on study. Where 
available, dates of disease recurrence or progression, the next anticancer therapy 
administered, dates, and responses will be recorded. If the recipient withdraws from the 
study, the site’s staff may use a public information source (eg, county records) to obtain 
information about survival status only. 
8.1 
Disease Evaluation 
Disease evaluations (ie, evaluation of the recipient’s underlying malignancy) should be 
performed at the timepoints described in the Precision-T Recipient Schedule of Assessments 
(appendix 11.1.3). For participants with a history of leukemia or MDS, assessments should 
include at least a bone marrow aspirate/biopsy, including a sample for central assessment of 
MRD. The aspirate and biopsy should be evaluated locally for relapse. Other tests may be 
obtained as clinically indicated, such as cytogenetics or imaging. All data, including images 
and results of local MRD testing, scheduled or unscheduled, will be made available to the 
sponsor for possible independent adjudication. 

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8.2 
AEs 
8.2.1 
Definitions 
8.2.1.1 
AE 
An AE is any untoward medical occurrence associated with the use of Orca—T (Orca-T arm) 
or the unmanipulated allograft infusion (SoC arm), whether or not considered related to 
Orca-T or the SoC infusion. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), a symptom, or disease temporally associated 
with the use of Orca-T or SoC, whether or not considered related to Orca-T or SoC. 
All protocol-related AEs must be collected as outlined in section 8.2.5. 
The following information should be considered when determining whether or not to record a 
test result, medical condition, or other incident on the AE CRF: 
• From the time of signing the informed consent form (ICF), all Aes should be recorded.  
• All medical conditions present or ongoing prior to signing the ICF should be recorded. 
• All Aes (regardless of relationship to study drug) should be recorded from the date of 
informed consent through the end of the safety reporting period (section 8.2.5.1). 
Complications that occur in association with any procedure (eg, biopsy) should be 
recorded as Aes with assessed severity whether or not the procedure was protocol 
mandated. 
• Changes in medical conditions and Aes, including changes in severity, frequency, or 
character, during the safety reporting period should be recorded. 
 
8.2.1.1.1 
Examples of Events Meeting the AE Definition 
1. Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram [ECG], radiological scans, vital signs 
measurements), including those that worsen from baseline or are considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not related to 
progression of underlying disease). 
2. Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
3. New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study. 
4. Signs, symptoms, or the clinical sequelae of a medication error of the study product. 
5. Signs, symptoms, or the clinical sequelae of a suspected abuse or misuse of the study 
product. 
6. Pregnancy in a female participant or female partner of a male participant. 

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7. Transmission of an infectious agent through the study product. 
8. Lack of efficacy or failure of expected pharmacological action per se should not be 
reported as an AE or SAE. Such instances will otherwise be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from lack 
of efficacy may be reported as an AE or SAE if they fulfill the definition of an AE or 
SAE. 
 
8.2.1.2 
SAE 
An SAE or serious adverse reaction is any untoward medical occurrence that, at any dose, 
constitutes 1 of the following: 
• Results in death 
• Is life threatening 
NOTE: The term “life-threatening” in the definition of “serious” refers to an event in 
which the participant was at risk of death at the time of the event; it does not refer to an 
event which hypothetically might have caused death if it were more severe. CTCAE 
grade 4 events are not automatically defined as life threatening for SAE determination. 
For example, a grade 4 increase in ALT may or may not be deemed as life threatening by 
the investigator and/or sponsor. 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
NOTE: Per International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) SAE definition, hospitalization itself is not an AE 
but is an outcome of the event. Thus, hospitalization in the absence of an AE is not 
regarded as an AE and is not subject to expedited reporting. The following are examples 
of hospitalization that are not considered to be AEs: 
o Protocol-specified admission (eg, for procedure required by study protocol) 
o Admission for treatment of target disease of the study, or for a pre-existing 
condition (unless it is a worsening or increase in frequency of hospital admissions 
as judged by the clinical investigator) 
o Diagnostic admission (eg, for a work-up of an existing condition such as 
persistent pretreatment laboratory abnormality) 
o Administrative admission (eg, for annual physical) 
o Social admission (eg, placement for lack of place to sleep)  
o Elective admission (eg, for elective surgery) 
• Results in persistent or significant disability/incapacity 
NOTE: This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, or 

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accidental trauma (ie, sprained ankle) that may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
• Is a congenital anomaly/birth defect 
• Did not meet any of the above criteria, but, based upon appropriate medical judgment, 
could have jeopardized the subject and might have required medical or surgical 
intervention to prevent 1 of the outcomes listed above. 
 
8.2.2 
Potential AEs 
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious and those considered related to the study treatment or study procedures. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
8.2.3 
AE Severity 
aGVHD and cGVHD should be rated according to MAGIC and NIH consensus criteria as 
described in section 11.5. Otherwise, the investigator will rate severity of each AE according 
to the CTCAE Version 5.0. The highest grade throughout the course of an event should be 
reported. A new event should not be entered if the grade of an existing event changes. For all 
reported SAEs that increase in severity, the supplemental electronic CRFs (eCRFs) also need 
to be updated to reflect change in severity. 
When CTCAE Version 5.0 criteria cannot be used, the AE should be graded as defined 
below: 
• Grade 1: The AE is transient and easily tolerated by the subject (mild). 
• Grade 2: The AE causes the subject discomfort and interrupts the subject’s usual 
activities (moderate). 
• Grade 3 or 4: The AE causes considerable interference with the subject’s usual activities 
and may be incapacitating or life threatening (severe). 
• Grade 5: The AE resulted in death of the subject (severe). 
An event is defined as serious when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 

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8.2.4 
Assessment of Causality 
The investigator will use the following definitions to assess the relationship of the AE to the 
use of study drug: 
• Not Related: A clinical event, including laboratory test abnormality, with a temporal 
relationship to study product in which a causal relationship is improbable and/or in which 
other drugs, chemicals, underlying disease or other causes provide plausible explanations. 
• Related: A clinical event, including laboratory test abnormality, where the relationship to 
study product is definite, probable, possible and/or cannot be ruled out when considering 
other drugs, chemicals, underlying diseases, or other possible causes. 
 
The investigator should consider the following in assessing causality: 
• Alternative causes, such as underlying disease, concomitant therapy, and other risk 
factors as well as the temporal relationship of the event to study treatment administration 
will be considered and investigated. 
• The investigator will also consult the Investigator’s Brochure (IB) in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important 
that the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to the electronic data capture system for the study. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
• The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. 
 
8.2.5 
Reporting and Recording of AEs 
8.2.5.1 
Safety Reporting Period 
The safety reporting period for all AEs and SAEs is from the time of signing of the ICF 
through day +730 (with day 0 defined as the day the recipient receives the Orca-T HSPC 
drug product [if assigned to Orca-T] or allograft infusion [if assigned to SoC]). Each SAE 
must be followed until the SAE returns to baseline (resolves or recovers to baseline), the 
SAE stabilizes (resolves or recovers with sequelae), the SAE is considered not recovered or 
not resolved by the investigator, or the subject dies (the SAE may be ongoing at the time of 
death). SAE outcome may not be possible to collect when a subject withdraws consent. 

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All nonserious AEs will be followed through the safety reporting period. 
8.2.5.2 
AE Reporting: Phase 1b 
In the event of an SAE, whether associated with study drug or not, the investigator will notify 
the Precision-T sponsor within 24 hours of the site being made aware of the SAE. All SAEs 
must be reported using the SAE report form. Detailed instructions on how to complete this 
form are described in the Precision-T SAE/AESI Report Form Completion Guidelines. 
Suspected unexpected serious adverse reactions (SUSAR) for the study drug will be reported 
in accordance with 21 Code of Federal Regulations (CFR) 312.32. 
8.2.5.3 
AE Reporting: Phase 3 
For the Phase 3 component of Precision-T, all SAEs should be reported to the sponsor within 
24 hours of the site being made aware of the SAE. All SAEs must be reported using the SAE 
report form. Detailed instructions on how to complete this form are described in the 
Precision-T SAE/AESI Report Form Completion Guidelines. SUSARs for the study drug 
will be reported in accordance with 21 CFR 312.32. 
8.2.5.4 
AE and SAE Recording 
1. When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
2. All AEs will be recorded in source documents based on the reporting guidelines outlined 
herein, with sufficient detail to allow for grading per CTCAE Version 5, and reported 
with all relevant information on the appropriate eCRF page. 
3. It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the sponsor and/or designated CRO in lieu of completion of the appropriate 
CRF page. 
4. There may be instances when copies of medical records for certain cases are requested by 
the sponsor and/or CRO, designee, or regulatory authority. In this case, all participant 
identifiers, with the exception of the participant number, will be redacted on the copies of 
the medical records before submission to the sponsor or designee. 
5. The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
 
8.2.6 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and any nonserious AEs of special 
interest (section 8.3), will be followed until resolution, stabilization, the event is otherwise 
explained, or the participant is lost to follow-up (as defined in section 7.2). 

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8.3 
AESIs 
AESIs for both the Phase 1b and Phase 3 components of Precision-T are as follows: 
• PTLD 
• Any primary or secondary graft failure event 
• Any grade veno-occulsive disorder/sinusoidal obstruction syndrome  
• Any grade thrombotic microangiopathy (TMA) 
• Any grade ≥2 infection 
 
For all AESIs, the overall specific diagnosis (eg, PTLD), not an individual sign and/or 
symptom, should be reported as described in the Precision-T SAE/AESI Report Form 
Completion Guidelines. If the AESI in question meets criteria for seriousness per 
section 8.2.1.2., the event is an SAE and should be reported as described in section 8.2.5. 
AESIs should be reported within 5 business days of the site being made aware of the AESI. 
All data relevant to diagnosis, staging, grading, treatment, and outcomes of AESIs must be 
made available to the sponsor for later independent review or adjudication. This includes all 
source documents such as medical notes, laboratory and imaging studies, biopsies, 
pathology, and consultant reports.  
8.3.1 
Posttransplant Lymphoproliferative Disorder  
PTLD is defined as a lymphoma that occurs after HCT or solid organ transplantation. It is a 
known complication of HCT and may be generally diagnosed and treated according to local 
institutional standards. Suggested approaches to the diagnosis of PTLD are as follows: 
• Participants suspected of PTLD (eg, fever of unknown origin >39°C with 
lymphadenopathy and/or hepatosplenomegaly) should undergo appropriate imaging 
studies (eg, computed tomography [CT] and/or positron emission tomography [PET] 
scanning of at least the chest and abdomen) and testing for EBV viremia. Biopsies should 
be sought and include studies of routine morphology, immunophenotyping, and EBV (eg, 
EBER in situ hybridization) testing. 
• The diagnosis of PTLD requires a biopsy consistent with the 2017 WHO classification of 
PTLD (nondestructive [plasmacytic hyperplasia, infectious-mononucleosis–like and 
florid follicular hyperplasia], polymorphic, monomorphic, or Hodgkin-lymphoma-like), 
along with lymphoma-type-appropriate staging procedures such as CT with or without 
18F-fluorodeoxyglucose PET (Swerdlow 2016, Swerdlow 2017, Dierickx 2018). 
Treatment of PTLD, such as reduction of immunosuppression, rituximab, chemotherapy 
radiation, cellular therapy and/or antivirals, should be discussed with the medical monitor, 
sponsor, or designee. 

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8.4 
GVHD 
aGVHD and cGVHD are components of the primary and key secondary endpoints of the 
Phase 3 component of Precision-T. The following instructions for assessment, staging, and 
grading of GVHD will apply to participants enrolled on the Precision-T Phase 3 and Phase 
1b components. 
8.4.1 
Assessment, Staging, and Grading of aGVHD 
aGVHD will be staged and graded per MAGIC standardization criteria (Harris 2016). Please 
see the guidelines for the assessment of aGVHD and for documentation of signs, symptoms, 
and testing associated with aGVHD assessment in section 11.15. 
The time of onset of acute grades 2 to 4 and 3 or 4 aGVHD will be recorded, as well as the 
maximum grade achieved. Responsiveness to treatment should also be assessed according to 
section 11.5.1.2. The aGVHD endpoint will be evaluated through day +365. 
An assessment for aGVHD should be performed at all visits indicated by the Recipient SoA 
(appendix 11.1.2) and at any unscheduled visit through day +365. These assessments should 
be recorded in the dedicated aGVHD eCRF. 
Treatment of aGVHD should be implemented per section 6.3.1.2.5. 
8.4.1.1 
Documentation of aGVHD 
As noted in section 3.2.2, an EAC will independently grade and assess aGVHD. To facilitate 
review, if a participant develops grade ≥2 aGVHD, sites should perform the following tasks 
at a) initial diagnosis of aGVHD and b) any future study visit in which signs or symptoms of 
aGVHD worsen: 
• A careful history and physical should be performed, taking care to record all signs and 
symptoms that are possibly or probably related to aGVHD. 
• Visible manifestations of aGVHD (eg, rash) should be described in detail. This should 
include descriptions of skin findings, body areas involved, and a percentage of body 
surface area involved. 
• Daily diarrhea volumes should be measured and reported. 
• Symptoms such as abdominal pain or nausea should be described in detail, and longevity 
of symptoms should be reported. 
• Pathology reports from any biopsies performed to assess for aGVHD (eg, colonoscopy 
with biopsy) should be provided to the sponsor. 
 
Guidelines for the assessment of aGVHD and for documentation of signs, symptoms, and 
testing associated with aGVHD assessment are listed in section 11.4. 

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8.4.2 
Assessment, Staging, and Grading of cGVHD 
cGVHD will be diagnosed, staged, and graded per the International NIH Chronic GVHD 
Diagnosis and Staging Consensus Working Group criteria (Jagasia 2015) appendix 11.5.1.3). 
Nine organs will be scored on a 0 to 3 scale to reflect degree of cGVHD involvement. Liver 
and pulmonary function test results and use of systemic therapy for treatment of cGVHD will 
also be recorded. These data will allow calculation of the NIH global severity scores of mild, 
moderate, and severe cGVHD. Assessment of development of cGVHD will occur up to 2 
years after HCT. For participants who develop cGVHD, responsiveness to treatment should 
be assessed according to appendix 11.5.2.2. 
An assessment for cGVHD should be performed at all visits indicated by the Recipient SoA 
(appendix 11.1.3) and at any unscheduled visit through day +730. These assessments should 
be recorded in the dedicated cGVHD eCRF. 
Guidelines for the assessment of cGVHD and for documentation of signs, symptoms, and 
testing associated with cGVHD assessment are listed in appendix 11.16. 
8.4.2.1 
Documentation of cGVHD 
cGVHD should be assessed and graded as described in Jagasia 2015 (see also 
appendix 11.5.2). Nine organ systems will be scored as part of this assessment. As noted in 
section 3.2.2, an EAC will independently grade and assess cGVHD. To facilitate review, if a 
participant develops any grade cGVHD, sites should perform the following tasks at a) initial 
diagnosis of cGVHD and b) at any future study visit in which signs or symptoms of cGVHD 
worsen (ie, organ scoring and/or grade of cGVHD is increased): 
• A careful history and physical should be performed, taking care to record all signs and 
symptoms that are possibly or probably related to cGVHD. 
• Visible manifestations of cGVHD (eg, lichen planus-like features, sclerotic features) 
should be described in detail. This should include descriptions of findings, body areas 
involved, and a percentage of body surface area involved. Examination should include 
skin, mouth, eyes, genitalia, etc. 
• Limitations in the range of motion of joints should be documented according to the 
scoring system in section 11.17. 
• Pathology reports from any biopsies performed to assess for cGVHD should be provided 
to the sponsor. 
• Consultation notes from specialists assessing for the presence of cGVHD (eg, 
ophthalmology assessments) should be provided to the sponsor. 
 
Guidelines for the assessment of cGVHD and for documentation of signs, symptoms, and 
testing associated with cGVHD assessment are listed in section 11.17. 

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8.4.3 
Responses to GVHD Treatment 
Responses to all therapies will be recorded according to appendix 11.5.1.2 for cGVHD and 
by the International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group 
criteria for chronic GVHD (appendix 11.5.2.2) (Lee 2015). 
8.5 
Study Modifications in Response to the COVID-19 Pandemic 
8.5.1 
General Guidelines 
Sites participating in Precision-T should review current ASTCT guidelines for prevention, 
diagnosis, and management of COVID-19 in donors and recipients (Waghmare 2020). Sites 
should additionally make any site-specific COVID-19 guidelines and procedures available to 
the sponsor for review upon request. 
8.5.2 
Prevention of COVID-19 After Transplant and Monitoring for COVID-19 
Recipients of alloHCT have compromised immune systems and may be at particularly high 
risk for poor outcomes related to COVID-19 (Dholaria 2020). 
• Sites should review current ASTCT guidelines and local institutional procedures to 
minimize the study participants’ (both donors and recipients) risk of exposure to 
SARS-CoV-2 (Waghmare 2020). 
• When deemed clinically appropriate by the investigator, protocol-specified follow-up 
clinic visits should be modified to minimize the participant’s risk of exposure to 
SARS-CoV-2. This may include conversion of in-person visits to alternative visits (eg, 
phone contacts or video visits). 
 
8.6 
QOL Assessments 
The value of patient-reported outcomes (PROs) is increasingly recognized in HCT, as studies 
regarding the relationship between PROs and HCT complications are emerging. Baseline 
PROs are associated with healthcare utilization after HCT and risk of aGVHD in alloHCT 
recipients (Johnson 2021). These findings underscore the potential utility of 
pretransplantation PROs as important prognostic factors for HCT. 
QOL is individualized, highly subjective, and may change over time. For patients diagnosed 
with hematological malignancies, QOL domains are initially impaired at diagnosis, yet 
improve within 6 months (Alibhai 2009). With HCT being a potentially curative therapy for 
hematologic malignancies, early studies have focused on HCT outcomes. As a result of 
advances in symptom management and cellular therapies, patients are living longer. This is 
exemplified by the longitudinal evaluations and identifying not only the impact of 
posttransplant complications but also the impact such treatment modalities have on QOL. 

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8.6.1 
Instruments 
At timepoints specified in the Recipient SoA (appendix 11.1.3), questionnaires will be 
administered to all participants enrolled on Precision-T. 
To gain an understanding of global QOL, longitudinal assessments will be conducted 
utilizing the EQ-5D. To identify changes in overall health status in the context of HCT, QOL 
will be measured by the Functional Assessment of Cancer Therapy - Bone Marrow 
Transplant (FACT-BMT).  
8.6.1.1 
EQ-5D-5L 
The EQ-5D is a well-known, reliable, and valid standardized measure of health status 
developed by the EuroQol Group in 1990 to provide a simple, generic measure of health for 
clinical and economic appraisal. The EQ-5D is a descriptive measure that consists of 
2 sections: a short questionnaire and a visual analog scale (VAS). The questionnaire covers 
five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression. Each dimension requires a response to a health state, which requires a 
response to 1 of 5 levels (5L): no problems, slight problems, moderate problems, severe 
problems, and extreme problems. Respondents also self-rate their perceived health status on 
vertical VAS, ranging from 0 (the worst possible health status) to 100 (the best possible 
health status) (Herdman 2011).  
8.6.1.2 
FACT-BMT  
The FACT-BMT provides a comprehensive overview regarding the multidimensional 
construct of QOL (Cella 1993; Kopp 2000). It is a reliable and valid instrument that measures 
5 dimensions of QOL in HCT recipients. FACT-BMT is comprised of the FACT-General 
(FACT-G) instrument which includes 27 items (Cella 1993) and the Bone Marrow 
Transplantation Subscale (BMTS), which is a 23- item instrument (McQuellon 1997). The 
FACT-G assesses QOL domains: physical (7 items), social (7 items, including sexual 
satisfaction), emotional (6 items), and functional (7 items, including work, sleep, and leisure 
activities) (Cella 1993). The transplant-specific segment assesses physical well-being, social/ 
family well-being, emotional well-being, functional well-being, and additional concerns 
(McQuellon 1997). 
The FACT-BMT takes approximately 10 to 15 minutes to complete. Participants respond to 
questions using a 5-point Likert-type response scale ranging from 0 to 4 (0 = not at all; 1 = a 
little bit; 2 = somewhat; 3 = quite a bit; and 4 = very much). Higher scores indicate a better 
QOL.  

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9 
STATISTICAL CONSIDERATIONS 
9.1 
Sample Size and Power Calculation 
9.1.1 
Phase 3: Sample Size 
Assume the effect of the experimental regimen for bone marrow transplant (BMT), against a 
standard of care, is assessed using a time-to-event Cox regression analysis, where the 
primary endpoint is CGFS. To achieve 90% power with a true HR = 0.40 and 1-sided alpha 
of 0.025, the required number of events needed is 56 events (see Fleming and Harrington 
[Fleming 1991] p. 395 and Al-Khalidi et al, [Al-Khalidi 2011] Equation 5.) This true HR of 
0.40 corresponds approximately to 12-month event-free CGFS rates of 55% versus 79% 
(equal to event rates at 12 months equal to 45% of participants for SoC vs 21% of 
participants for Orca-T).  
The number of participants required to achieve 56 events based on the above assumptions is 
165 participants.  
In order to account for 5% loss to follow-up in both treatment arms, 174 participants will be 
randomized. 
9.1.2 
Phase 1b Sample Size: Protocol Versions 1 Through 5 
Prior to Version 6 of the Precision-T Protocol, the sample size of the study as a whole was 
based on the presence of 3 arms; Arms I, II, and III (28 participants in each arm) were set 
primarily to ensure adequate power to rule out excessive primary graft failure in any of the 
arms (analyzed separately). For reference purposes, the justification for the sample size in 
Versions 1 through 5 of the protocol is retained below in italics: 
The same stopping rules and sample size calculations were used for all three arms. Historical control 
data (Olsson 2015) indicate primary graft failure occurred in approximately 2.5% of PBSC-based 
transplants with matched related or unrelated donors. They further report odds ratios for PGF for 
patients with AML/ALL with active disease vs. AML/ALL in CR (Arm II vs Arm I, OR = 1.54) and MDS 
vs. AML/ALL (Arm III vs Arm I, OR=1.38), which would correspond to only slightly increased PGF 
incidence of 3.9% and 3.5%. Therefore, we set a maximum acceptable PGF rate of 5% for each of the 
three arms, and propose the same stopping rule in each arm where enrollment will cease if 4 or more 
graft failures are observed among n=28 evaluable patients. If the true graft failure rate is as expected 
(≤ 5%), there is a ≤ 4.9% chance of observing 4 or more graft failures in n = 28 patients (type I error). 
If the true graft failure rate is 15% higher than expected, then there is an 84% chance of observing 4 
or more graft failures in n = 28 patients (power).  
All calculations were based on exact binomial distributions.  
Starting with Protocol Version 6, the sample size of the remaining Phase 1b component of 
Precision-T will be based on the methodology described in section 9.1.3. 
9.1.3 
Phase 1b Sample Size: Protocol Version 6 and Subsequent Versions 
In Version 6 and subsequent versions of the Precision-T Protocol, Arms I, II, and III are 
eliminated from the Phase 1b component of the study, as noted in section 3.1. Participants 

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infection rate is 20%. If the true failure rate is 20%, the stopping rule will be triggered on 
average after approximately 17 participants are evaluable for this endpoint. 
In addition, the stopping criteria for grade ≥3 aGVHD (section 3.3.1, Table 3-2) reflect a 
maximum acceptable rate of 15% for these events occurring by day +100. This stopping rule 
has an 11% chance of being triggered if the true toxicity rate is 15%, and an 85% chance of 
being triggered if the true toxicity rate is 35%. If the true toxicity rate is 35%, the stopping 
rule will be triggered on average after approximately 14 participants are evaluable for the 
safety endpoint. 
The stopping criteria for manufacturing failure (section 3.3.2, Table 3-3) reflect a maximum 
acceptable rate of 4% of these events occurring. This stopping rule has a 9.5% chance of 
being triggered if the failure rate is 4%, and an 80% chance of being triggered if the true 
failure rate is 16%. If the true failure rate is 16%, the stopping rule will be triggered on 
average after approximately 16 participants are evaluable for this endpoint.  
The stopping criteria for grade 5 toxicity that is at least probably related to Orca-T by 
day +100 (section 3.3.2, Table 3-4) reflect a maximum acceptable rate of 8% of these events 
occurring. This stopping rule has a 9.2% chance of being triggered if the failure rate is 8%, 
and an 81% chance of being triggered if the true failure rate is 24%. If the true failure rate is 
24%, the stopping rule will be triggered on average after approximately 16 participants are 
evaluable for this endpoint. 
The stopping criteria for grade 4 or 5 infections occurring through day +100 (section 3.3.2, 
Table 3-5) reflect a maximum acceptable rate of 30% of these events occurring. This 
stopping rule has a 10% chance of being triggered if the infection rate is 30%, and an 87% 
chance of being triggered if the true infection rate is 55%. If the true failure rate is 55%, the 
stopping rule will be triggered on average after approximately 17 participants are evaluable 
for this endpoint. 
9.2 
Endpoints 
Endpoints are described in section 2.3 above. Primary and secondary endpoints are defined in 
this study for recipients only. 
9.3 
Analysis Populations 
9.3.1 
Donor Populations 
• Donor set: all donor subjects who complete at least 1 screening procedure 
• Donor intention-to-treat (ITT) analysis set: all donor subjects who complete mobilization 
and initiate apheresis 
 

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For recipients, frequency distributions of the received doses of the components of Orca-T 
will be presented by arm, using the recipient full analysis set. 
9.4.4 
Analysis of Safety and Efficacy 
For Phase 3, efficacy will be analyzed using the ITT analysis set (a sensitivity analysis will 
utilize the mITT analysis set). For Phase 1b, efficacy will be analyzed using the full analysis 
set. For both phases, safety will be analyzed using the safety analysis set. 
9.4.4.1 
Analysis of Primary Endpoint 
For Phase 3, the final analysis will occur when 56 CGFS events are observed. Nearly all of 
the experimental 1-sided 0.025 false positive error rate will be spent at the time of the final 
analysis of the primary endpoint, as the O’Brien-Fleming boundary used for the interim 
analyses preserved the (1-sided) 0.005 false positive error rate (see SAP). To be specific, at 
least 0.0250 – 0.0006 = 0.0244 of the (1-sided) false positive error remains for the final 
analysis. Hence, the 2-sided p-value that will be used at the final analysis is 0.049. Statistical 
significance will be achieved at the final analysis with an estimated HR = 0.573, 
corresponding to estimated 12-month event-free rates of 55% versus 71%. 
The primary efficacy hypothesis will be tested using a Cox’s Proportional Hazard model 
stratified by the randomization strata to calculate the hazard ratio and the associated 90% CI.  
Kaplan-Meier survival estimates (product-limit estimates) will be presented by treatment 
group together with a summary of associated statistics for survival time with associated 
2-sided 90% CIs.  
In particular, the survival rate at 6, 12, 18, and 24 months will be estimated with 
corresponding 2-sided 90% CIs. The CIs for the median will be calculated according to 
Brookmeyer and Crowley (1982), and the CIs for the survival function estimates at the time 
points defined above will be derived using the log-log transformation according to 
Kalbfleisch and Prentice (2002). The estimate of the standard error will be computed using 
Greenwood’s formula. 
The primary Phase 3 efficacy analysis will be based on the ITT population, with participants 
who are lost to follow-up or do not experience CGFS censored at their last on-study visit 
date. Participants who relapse after randomization and prior to receiving study treatment will 
be censored at their date of relapse. 
Sensitivity analyses of the primary Phase 3 endpoint will be performed as described in the 
SAP. 
The Phase 1b primary endpoint of incidence and timing of primary graft failure will be 
analyzed by presenting the percentage of participants with primary graft failure through 
day +28 along with the associated 90% Clopper-Pearson exact binomial confidence interval. 
Timing will be analyzed by computing median time to primary graft failure along with 25th 
and 75th percentiles based on a Kaplan-Meier analysis. 

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The primary Phase 1b endpoint of incidence and severity of grade ≥3 aGVHD by day +100 
will be analyzed by presenting a frequency analysis of this endpoint along with the associated 
90% Clopper-Pearson exact binomial confidence interval. Frequencies by severity may also 
be presented. 
9.4.4.2 
Analysis of Secondary Endpoints 
For Phase 1b: Neutrophil engraftment through day +28, platelet engraftment through 
day +50, secondary graft failure through day +100, aGVHD through day +180, 
steroid-refractory aGVHD though day +180, cGVHD through day +730, PTLD through 
day +730, disease relapse through day +730, and NRM will be summarized using the 
cumulative incidence method, treating death (or, for NRM, disease relapse/progression) as a 
competing risk. Maximum stages, grades and/or severity scores for aGVHD and cGVHD will 
also be summarized as frequencies and percentages. GVHD progression-free survival will be 
analyzed using Kaplan-Meier method, with quartiles and associated 90% confidence 
intervals presented. 
Overall survival will be estimated using the Kaplan-Meier method, with quartile estimates 
and associated 90% confidence intervals presented.  
For Phase 3: Analysis of moderate-to-severe cGVHD through day +730 will utilize the 
cumulative incidence method, with death included as a competing event. Medians and 
quartiles will be generated along with associated 90% confidence intervals. 
Analysis of GRFS through day +365 will be based on a Cox Proportional model as described 
above for the primary efficacy endpoint. 
Analysis of relapse-free survival through day +730 will be based on a Cox Proportional 
model as described above for the Phase 3 primary efficacy endpoint. 
Analysis of the Phase 3 secondary endpoints at the interim and final analyses will proceed 
using a hierarchial testing procedure as described in the SAP. If the trial is not stopped at the 
time of the interim analysis, the p-values used in the final analysis of the secondary 
endpoint(s) will be the p-value used for the final analysis of the primary endpoint, 
specifically a 1-sided 0.0244 p-value if the endpoint was not tested at the time of the interim 
analysis using the gatekeeping procedure. If the secondary endpoint was tested at the time of 
the interim analysis, the p-value used for the final analysis will be adjusted as described in 
the SAP. 
Safety analyses for both phases will involve examination of the incidence, severity, and type 
of TEAEs reported, changes in vital signs and laboratory test results from baseline (the 
assessment prior to first dose) to specified time points throughout the study, and concomitant 
therapy use. Safety analyses are described in further detail below. 

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9.4.4.3 
TEAEs 
TEAEs reported during the study will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). The incidence of TEAEs will be summarized by arm, dose, and the 
following: 
• System organ class (SOC) and preferred term 
• SOC, preferred term, and severity 
 
These summaries will be presented for the following subsets: 
• All AEs 
• SAEs 
• AESIs 
• AEs leading to treatment discontinuation 
 
For tables reporting AEs by severity, if a subject has multiple occurrences of an AE with the 
same SOC and preferred term, the most severe event will be presented. 
9.4.4.4 
Clinical Laboratory Evaluation 
Laboratory parameters will be summarized by arm and dose at each visit. Each summary will 
include the values of the laboratory parameters and their change from baseline. Shift tables 
from baseline will be presented for laboratory values in the chemistry and hematology 
panels. Parameters will be classified according to the laboratory reference normal ranges. A 
listing will be provided for values out of the normal range as well as clinically significant 
abnormal laboratory values. 
9.4.4.5 
Vital Signs 
Vital signs, including pulse, blood pressure, temperature, height, and body weight will be 
summarized by time point. For each assessment of vital signs, change and percent change in 
vital signs from baseline will be summarized by disease and cohort. 
9.4.4.6 
Karnofsky Performance Status 
Karnofsky performance status will be summarized for each visit by arm and dose. Shifts 
from baseline to the best and worst post-baseline score may be tabulated. 
9.4.5 
QOL 
With the implementation of Version 6 of the Precision-T protocol, QOL will be assessed for 
all participants enrolled on Precision-T. 

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9.4.7 
Interim Analyses 
An interim analysis will be performed for the primary and secondary efficacy endpoints in 
Phase 3 only. The O’Brien-Fleming boundary for definitive evidence of benefit will be used, 
protecting an experimental 1-sided 0.025 false-positive error rate. 
A single interim analysis is planned for when 37 primary endpoint events are observed. This 
represents 2/3 of the expected 56 primary efficacy events at the time of the final analysis. 
Based on 2/3 of the expected total number of events, a 1-sided alpha = 0.0006 will be utilized 
for the interim analysis of the primary efficacy endpoint.  
At the time of the interim analysis, testing of the primary and secondary endpoints will utilize 
a gate-keeping algorithm with the endpoints tested in the following order:  
(1) CGFS (primary efficacy endpoint)  
(2) GVHD and relapse-free survival through day +365 
(3) Moderate-to-severe cGVHD  
(4) Relapse-free survival through day +730 
The 1-sided nominal p-value that will be used for the interim analysis of the primary 
endpoint will be 0.0006. At L = 36 events, this boundary would be crossed with an estimated 
HR = 0.326, corresponding approximately to estimated 12-month event-free CGFS rates of 
55% (SoC) versus 82% (Orca-T). 
A hierarchal testing strategy will be used for the interim analysis with the above 4 endpoints 
tested in order. Specifically, if the interim analysis of the primary endpoint of CGFS rejects 
the null hypothesis of no treatment effect, the secondary efficacy endpoints will be tested 
first for GRFS, then for moderate-to-severe cGVHD, and finally for RFS. Testing of GRFS 
will be performed only if the null hypothesis for the primary endpoint is rejected. Testing of 
moderate-to-severe cGVHD will be performed only if the null hypotheses for the primary 
endpoint and for GRFS are rejected. Testing of RFS will be performed only if the null 
hypotheses for the primary endpoint, GRFS, and moderate-to-severe cGVHD are rejected. 
The p-values used in the testing of each of the secondary endpoints will be computed based 
on the observed information fraction for that endpoint at the time of the interim analysis. 
If the treatment effect for the primary efficacy endpoint is significant, no further testing of 
this endpoint (at the time of the final analysis) will occur, although descriptive statistics may 
be presented at that time. Similarly, if (after using the hierarchal testing strategy) the 
estimated treatment difference for any of the secondary efficacy endpoints is significant at 
the time of the interim analysis, no further testing of that endpoint will occur at the time of 
the final analysis, although descriptive statistics may be generated at that time. Only 
endpoints that are not significant at the time of the interim analysis will be tested at the time 
of the final analysis. 

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In addition to the above interim analysis, a sample size re-estimation procedure will be used 
when 2/3 of the 174 participants (115 participants) have been enrolled and followed for at 
least 3 months. Details on this analysis are found in the SAP. 

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11.2 
Quality Control and Assurance 
Quality assurance and quality control systems will be implemented and maintained with 
Standard Operating Procedures by the sponsor or designee, as appropriate, to ensure that this 
clinical study is conducted and data are generated, documented (recorded) and reported in 
compliance with the protocol, ICH E6 Good Clinical Practice (GCP): Consolidated Guidance, 
the Declaration of Helsinki, and the applicable regulatory requirements. 
This study will be monitored by the sponsor in accordance with GCP and may be audited or 
reviewed by independent Quality Assurance personnel, Independent Ethics Committee (IEC), 
and/or regulatory authorities. This implies that monitors and auditors/inspectors will have the 
right to inspect the study sites at any time during and/or after completion of the study and will 
have direct access to data/source documents, including the subject’s file, study specific 
correspondence, and ICF. By participating in this study, investigators agree to this requirement. 
Measures will be undertaken to protect the confidentiality of records that could identify subjects, 
respecting the privacy and confidentiality rules in accordance with applicable regulatory 
requirements. 
11.3 
Study Governance Considerations 
11.3.1 
Ethics Committee Approval 
At a minimum, the following documents must be reviewed and approved by Ethics Committees 
(ECs) (including institutional review boards [IRBs] and IECs), as required by local laws and EC 
requirements, before subjects are screened for entry into the study: 
• Study protocol and amendment(s) 
• Written ICF(s) and consent form updates 
• Subject recruitment procedures (eg, advertisements) 
• Written information to be provided to subjects 
• IB and available safety information. Note: ECs do not generally approve IBs. 
• Information about payments and compensation available to subjects, if applicable 
 
The EC approval must be in writing, clearly identifying the study (by protocol date and/or 
version) and the documents reviewed, including informed consent and date of the review. The 
investigator has the responsibility to provide the sponsor with the written EC approval prior to 
initiating any study-related procedures. The investigator also has the responsibility to inform the 
EC of serious and unexpected AEs and protocol deviations and provide the EC with a synopsis 
of the study report upon study completion according to the EC’s policy. 
The NMDP IRB will be responsible for the review and continuing oversight of protocol 
procedures that relate only to NMDP unrelated donors. The IRB used by the Principal 

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Investigator’s institution will be responsible for the review and continuing oversight of protocol 
procedures that relate to any study subjects other than NMDP unrelated donors. 
11.3.2 
Ethical Conduct of the Study 
This study is to be conducted in accordance with the protocol, sponsor’s standard operating 
procedures, ICH E6 GCP, the Declaration of Helsinki and all other applicable regulatory 
requirements. Investigators must immediately notify the sponsor or designee (if applicable) of 
serious breaches in GCP that have occurred at their study site, which are likely to effect to a 
significant degree (a) the safety or physical or mental integrity of the subjects of the study or (b) 
the scientific value of the study. 
11.3.3 
Financial Disclosure 
Information on financial disclosure will be collected for all studies. 
11.3.4 
Subject Information and Consent 
Note: all references to “subject” in this section refer to the study subject (recipient or donor as 
applicable) or his/her legally acceptable representative. 
A conference will be held with the participant, and family if available, to discuss this study and 
alternative treatments available for the treatment of the underlying disease. The conference will 
be conducted by the Principal Investigator or other designated physician. Potential risks 
associated with the study treatments should be discussed as objectively as possible. 
Prior to participation in any study-specific procedures, each subject must sign and date an 
EC -approved written ICF in a language the subject can understand. 
The sponsor will provide a template of the consent form to each center. Each center will 
customize the template according to their local requirements and submit it for review by their 
local EC. 
The language in the written information about the study should be as non-technical as practical 
and should be understandable to the subject. Before informed consent is obtained, the 
investigator should provide the subject ample time and opportunity to inquire about the study and 
to decide whether or not to participate. 
All questions about the study should be answered to the satisfaction of the subject. The written 
ICF should be signed and personally dated by the subject and by the person who conducted the 
informed consent discussion, with any additional signatures obtained as required by applicable 
local regulations and EC requirements. Each subject will be informed that participation is 
voluntary and that he/she can withdraw from the study at any time. All subjects will receive a 
copy of their signed and dated ICF. 

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11.3.5 
Subject Confidentiality 
In order to permit easy identification of the individual subject during and after the study, the 
investigator is responsible for keeping an updated log that contains subject (donor and recipient) 
identification information. This document will be reviewed by the site monitor for completeness. 
However, in order to ensure the subject’s confidentiality, the document will be maintained at the 
site and no copy will be made. 
The processing of personal data in pursuit of this study will be limited to those data that are 
reasonably necessary to investigate the utility of the study medications used in this study. These 
data will be processed with adequate precautions to ensure confidentiality according to local 
laws. 
The sponsor ensures that the personal data are as follows: 
• Collected for a specified and legitimate purpose. 
• Processed fairly and lawfully. 
• Accurate and up to date. 
 
Explicit consent for the processing of personal data will be obtained prospectively from the 
participating subject. 
The sponsor, whose responsibilities require access to personal data, agrees to keep the identity of 
study subjects confidential. This confidentiality will be maintained in accordance with national 
and local requirements. Confidentiality will be maintained by masking individual names and 
other personal identifiers. With the exception of date of birth and other treatment related dates, 
which are necessary to confirm eligibility, monitor safety, and measure outcomes, no personal 
identifiers will be collected by the sponsor. 
11.3.6 
Study Monitoring 
The sponsor or designee will monitor this clinical study through monitoring visits and remote 
data checks to check the adequacy of site staff and facilities, and to ensure adherence to the 
protocol, study procedures, and applicable regulations. The site monitor will also assess proper 
CRF completion and source document retention. The investigator and study site staff are 
expected to provide adequate space for monitoring visits and to allocate sufficient time to permit 
adequate review of the study’s progress. The investigator will permit study-related monitoring, 
audits, EC review and regulatory inspection(s), providing direct access to source data/documents 
and study-related facilities (eg, pharmacy, diagnostic laboratories). 
As noted in section 3.3.2, primary medical monitoring duties for the Phase 3 trial will be 
performed by a non-sponsor medical monitor. 

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11.3.7 
Study Records and Case Report Forms 
11.3.7.1 
Study Records 
The investigator and affiliated institution shall maintain the study documents and records as 
specified in “Essential Documents for the Conduct of a Clinical Trial” (ICH E6 section 8), and as 
required by the applicable regulatory requirement(s). This includes, but is not limited to the 
protocol, CRFs, AE reports, subject source data (original records or certified copies), 
correspondence with health authorities and EC, consent forms, investigator’s curriculum vitae, 
delegation log, monitor visit logs, laboratory reference ranges and laboratory certification or 
quality control procedures and laboratory director curriculum vitae. Subject source data must be 
maintained as original records or a certified copy (ie, copy of original information that has been 
verified, as indicated by a dated signature, as an exact copy having all of the same attributes and 
information as the original). The investigator and affiliated institution should take measures to 
prevent accidental or premature destruction of documents. 
Study sites may utilize site-owned electronic medical record systems and/or other computer 
systems to generate, collect and store subject source data, provided that those systems are 
adherent to 21CFR part 11 requirements and other regulations pertaining to electronic systems. 
When such systems will be used for the study, their use and supporting infrastructure (eg, 
access/security, written procedures, technical support, and training as applicable) will be 
identified and documented in site assessment or site visit reports by the sponsor or designee. If 
electronic medical records are maintained (eSource data), the method of verification must be 
agreed upon between the investigational staff and the sponsor. 
11.3.7.2 
CRF 
Where referenced in this protocol, CRFs refer to electronic CRFs, as defined for the study. A 
CRF must be completed for each subject who has given informed consent. In the case of a screen 
failure, at a minimum the following data will be entered into the CRF: consent date, 
demography, and reason for screen failure. All entries into the CRF are ultimately the 
responsibility of the investigator. 
The CRF must be completed at the time of, or shortly after the subject's visit, with the exception 
of results of tests performed outside the investigator's office, so that they always reflect the latest 
observations of the subjects participating in the study. If certain information is Not Done, Not 
Available or Not Applicable, the investigator must record this according to the CRF completion 
instructions. 
Source documents must be made available to the site monitor. Remote monitoring will evaluate 
CRFs for completeness and consistency. The CRF entries will be compared with the source 
documents to ensure that there are no discrepancies. A subset of all study data will require onsite 
source data verification as specified in the Site Monitoring Plan. All CRF entries, corrections and 
alterations are to be made by the responsible investigator or his/her designee. The site monitor 
may query the data but cannot edit CRF entries recorded by the site designee. 

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A copy of each subject’s CRF will be maintained by the investigator. A copy of the subject’s 
CRFs can be provided to the investigator at the end of the trial or at other times as requested. The 
investigator must sign that the CRFs provided are accurate prior to final data lock for that subject 
and prior to site closure. 
In addition to the clinical data management systems/databases, other systems may be used to 
collect and analyze study data. For example: 
• Laboratory Information Systems or proprietary systems will be used by the processing 
laboratory for storing and/or analyzing manufacturing data collected throughout the study. 
• Statistical software will be used for the statistical analysis of the study data, as outlined in the 
Statistical Analysis Plan. 
 
11.3.8 
Source Data and Source Documents 
The nature and location of all source documents will be identified to ensure that all sources of 
original data required to complete the CRF are known to the company and investigational staff. 
These source documents are to be accessible for verification by the site monitor. 
Source documents are required for all data entered into the CRF, including but not limited to: 
• Subject identification (name, date of birth, sex). As noted previously, subjects will be 
identified by a study ID and the link between the participant’s name and study ID will be 
kept confidential. 
• Documentation that a subject meets eligibility criteria, ie, medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria). 
• Documentation that protocol-specific procedures were performed, including handling and 
administration of the study drug. 
• Record of all AEs (including those not required to be recorded in the CRF per the safety 
reporting section of this protocol) and associated AE characteristics (including start and stop 
dates, investigator assessment of severity and relationship to the study medication). Prior and 
concomitant therapy (including start and stop dates and indication for use). 
• Date of study completion and reason for early discontinuation, if applicable. 
 
The author of an entry in the source documents should be identifiable as well as the date of the 
entry. Direct access to source documentation (medical records) must be allowed for the purpose 
of verifying that the data recorded in the CRF are consistent with the original source data. The 
investigator will provide certified copies of the subject’s medical records in the event that site’s 
policy does not permit direct access to the electronic medical records. 

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11.3.9 
Use of Computerized Systems 
An Electronic Data Capture system to capture protocol-required subject data will be used. Sites 
will enter data from source documents onto electronic CRFs for each study visit using a 
web-based interface. Study monitors and data management personnel will use this system to 
review data and generate queries and reports as needed. 
Information on the above system will be provided to the investigator, site personnel, and other 
personnel as appropriate. Measures will be taken to ensure data security and accuracy, including 
but not limited to user training, granting of user accounts and privileges to trained and authorized 
personnel in a role-based manner, username/password/electronic signature requirements 
enforcement, programmed and manual edit checks as outlined in data validation specifications, 
computer generated audit trails, centralized data management, and routine study monitoring. The 
systems used will be compliant with United States 21 Code of Federal Regulations Part 11 and 
Annex 11 on Computerized Systems (annex to the Guide to Good Manufacturing Practice for 
Medicinal Products) in the European Union and Canada, and the data collected will be archived 
(at minimum) for the period specified by applicable regulatory requirements. 
11.3.10 
Retention of Data 
The sponsor will inform the investigator in writing when it is acceptable to dispose of any study 
records. To enable evaluation and/or audits from regulatory authorities or the sponsor, the 
investigator agrees to keep records, including the identity of all study subjects (eg, subject 
identification code list and all source documents), all original signed ICFs, copies of all CRFs, 
original laboratory reports, detailed records of study medication disposition and all essential 
documents for the conduct of a clinical study. To comply with international regulations, the 
records should be retained by the investigator for at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region, or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. However, the investigator 
may need to retain these documents for a longer period if required by the local regulatory 
requirements or by an agreement with the sponsor. 
11.3.11 
Monitoring Committees 
Monitoring committees for this study are described in section 3.2. Further details regarding the 
DMC and the EAC can be found in their respective charters. 
11.3.12 
Protocol Violations/Deviations 
Unless there is a safety concern, there should be no deviations or violations of the study protocol. 
In the event of a safety concern, the investigator or designee must document and explain the 
reason for any deviation from the approved protocol. The investigator may implement a 
deviation from, or a change to, the protocol to eliminate an immediate hazard to study subjects 
without prior EC approval. Immediately after the implemented deviation or change, the 
investigator must submit a report explaining the reasons for the protocol violation or deviation to 
the EC and the sponsor. The sponsor is responsible for notifying the regulatory authorities, if 
required. 

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11.3.13 
Study Termination 
The sponsor reserves the right to close any investigational site(s) or terminate the study at any 
time for any reason. Reasons for the closure of a study site or termination of a study by the 
sponsor may include (but are not limited to) the following: 
• Successful completion of the study at the investigational site. 
• The required number of subjects for the study has been recruited. 
• Failure of the investigator to comply with the protocol, GCP guidelines or local 
requirements. 
• Safety concerns. 
• Inadequate recruitment of subjects by the investigator. 
 
11.3.14 
Publication and Disclosure Policy 
The data and results of the study will be owned solely by the sponsor and shall be confidential 
information of the sponsor, subject to the investigator's publication rights outlined in the 
agreement between the investigator/institution and the sponsor regarding the conduct of the 
clinical study (the “Clinical Study Agreement”). It is understood by the investigator that the 
sponsor may use the information developed in this clinical study in connection with the 
development of its compounds and therefore, may disclose it as required to other clinical 
investigators or regulatory agencies. To allow for the use of the information derived from this 
clinical study, the investigator understands that he/she has an obligation to provide and disclose 
test results and all data developed during this study to the sponsor. 
Any publication or presentation of the results of this clinical study by the investigator may only 
be made in strict compliance with the provisions of the Clinical Study Agreement. The 
investigator should understand that it is not the sponsor’s intention to prevent publication of the 
data generated in the clinical study. However, the sponsor reserves the right to control the form 
and timing of such publication for commercial reasons. 

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11.4 
International Expert Panel Recommendations: Indications for AlloHSCT for 
Myelodysplastic Syndrome 
The following is adapted from De Witte et al (de Witte 2017). 
Figure 11-1 
MDS AlloHCT Eligibility Flowchart 
 
11.5 
GVHD 
11.5.1 
aGVHD 
11.5.1.1 
aGVHD Clinical Grading and Staging 
All staging and grading of aGHVD will be performed according to the MAGIC Standardization 
(Harris 2016). 
Guidelines for the assessment of aGVHD and for documentation of signs, symptoms, and testing 
associated with aGVHD assessment are listed in appendix 11.15. 

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11.5.1.2 
Acute GVHD Response Evaluation 
Responses to treatment (eg, corticosteroids) will be assessed as shown in Table 11-1 
(MacMillan 2010). 
Table 11-1 
Response Criteria for Acute GVHD 
Complete response 
(CR) 
Complete resolution of acute GVHD symptoms in all organs, without secondary 
GVHD therapy 
Partial response 
(PR) 
Improvement in GVHD stage in all initial GVHD target organs without 
complete resolution and without worsening in any other GVHD target organs, 
without secondary GVHD therapy 
Very good partial 
response (VGPR) 
Improvement in GVHD in all initial GVHD target organs, with maximum Stage 
I involvement in one or more organs (except upper gastrointestinal tract), 
without secondary GVHD therapy 
No response (NR) 
Same grade of GVHD or progression of GVHD in any organ or death, or the 
addition of secondary GVHD therapy 
Progression 
Worsening GVHD in at least 1 organ with or without amelioration in any organ 
 
11.5.1.3 
aGVHD Steroid Response 
Corticosteroid refractoriness, resistance, dependence and intolerance will be defined as per the 
EBMT-NIH-CIBMTR Task Force Position Statement (Schoemans 2018), outlined in Table 11-2. 
Table 11-2 
aGVHD Steroid Response Terminology 
Terminology 
Criteria 
Refractoriness 
or Resistance 
 
Progression of acute GVHD within 3−5 days of therapy onset with 
≥2 mg/kg/day of prednisone; OR 
 
Failure to improve within 5−7 days of treatment initiation; OR 
 
Incomplete response after more than 28 days of immunosuppressive treatment 
including steroids 
Dependence 
 
Inability to taper prednisone below 2 mg/kg/day, OR 
 
A recurrence of acute GVHD activity during steroid taper 
Intolerance 
 
Emergence of unacceptable toxicity due to the use of corticosteroids 
Adapted from Schoemans 2018. 
 
11.5.2 
cGVHD 
11.5.2.1 
cGVHD Diagnosis 
The diagnosis of cGVHD will be based on 2014 International NIH Chronic GVHD Diagnosis 
and Staging Consensus Working Group criteria and requires at least one diagnostic manifestation 
of chronic GVHD or at least one distinctive manifestation plus a pertinent biopsy, laboratory or 
other tests (eg, pulmonary function tests (PFTs), Schirmer’s test), evaluation by a specialist 

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(ophthalmologist, gynecologist) or radiographic imaging showing cGVHD in the same or 
another organ (Table 11-3) (Jagasia 2015). Biopsy or other testing is encouraged and often 
valuable to confirm the presence of cGVHD, but it is not always feasible and is not mandatory if 
the participant has at least 1 of the diagnostic findings of cGVHD. 
Guidelines for the assessment of cGVHD and for documentation of signs, symptoms, and testing 
associated with cGVHD assessment are listed in section 11.17. 

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Table 11-3 
Signs and Symptoms of Chronic GVHD* 
Organ or 
Site 
Diagnostic (Sufficient to Establish 
the Diagnosis of cGVHD) 
Distinctive1 (Seen in cGVHD, but Insufficient 
Alone to Establish a Diagnosis) 
Skin 
Poikiloderma 
Lichen planus-like features 
Sclerotic features 
Morphea-like features 
Lichen sclerosus-like features 
Depigmentation 
Papulosquamous lesions 
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 
Mouth 
Lichen planus-like changes 
Xerostomia 
Mucoceles 
Mucosal atrophy 
Ulcers 
Pseudomembranes 
Eyes 
 
New onset dry, gritty, or painful eyes 
Cicatricial conjunctivitis 
Keratoconjunctivitis sicca 
Confluent areas of punctate keratopathy 
Genitalia 
Lichen planus-like features 
Lichen sclerosis-like features 
Erosions 
Fissures 
Females 
Vaginal scarring or clitoral/labial 
agglutination 
Ulcers 
Males 
Phimosis or urethral/meatus scarring 
or stenosis 
 
GI Tract 
Esophageal web 
Strictures or stenosis in the upper to 
mid third of the esophagus 
 
Lung 
Bronchiolitis obliterans diagnosed 
with lung biopsy 
Bronchiolitis obliterans syndrome2 
Air trapping and bronchiectasis on chest CT 
Muscles, 
fascia, joints 
Joint stiffness or contractures 
secondary to fasciitis or sclerosis 
Myositis or polymyositis3 
Abbreviations: cGVHD, chronic graft-versus-host disease; GI, gastrointestinal. 
1 
In all cases, infection, drug effect, malignancy, or other causes must be excluded. 
2 
Bronchiolitis obliterans syndrome can be diagnostic for lung cGVHD only if distinctive sign or symptom is 
present in another organ. 
3 
Diagnosis of cGVHD requires biopsy. 
*Adapted from Jagasia 2015. 

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11.5.2.2 
cGVHD Response Evaluation 
cGVHD responses to therapy will be based upon 2014 International NIH Chronic GVHD 
Diagnosis and Staging Consensus Working Group clinician assessments (Table 11-4) 
(Lee 2015).  
Table 11-4 
Response Determination for Chronic GVHD 
Organ 
Complete Response 
Partial Response 
Progression 
Skin 
NIH Skin Score 0 after 
previous involvement 
Decrease in NIH Skin 
Score by 1 or more points 
Increase in NIH Skin Score by 1 
or more points, except 0 to 1 
Eyes 
NIH Eye Score 0 after 
previous involvement 
Decrease in NIH Eye Score 
by 1 or more points 
Increase in NIH Eye Score by 1 
or more points, except 0 to 1 
Mouth 
NIH Modiﬁed OMRS 0 after 
previous involvement 
Decrease in NIH Modiﬁed 
OMRS of 2 or more points 
Increase in NIH Modiﬁed 
OMRS of 2 or more points 
Esophagus NIH Esophagus Score 0 after 
previous involvement 
Decrease in NIH 
Esophagus Score by 1 or 
more points 
Increase in NIH Esophagus 
Score by 1 or more points, 
except 0 to 1 
Upper GI 
NIH Upper GI Score 0 after 
previous involvement 
Decrease in NIH Upper GI 
Score by 1 or more points 
Increase in NIH Upper GI Score 
by 1 or more points, except 0 to 
1 
Lower GI 
NIH Lower GI Score 0 after 
previous involvement 
Decrease in NIH Lower GI 
Score by 1 or more points 
Increase in NIH Lower GI Score 
by 1 or more points, except 
from 0 to 1 
Liver 
Normal ALT, alkaline 
phosphatase, and Total 
bilirubin after previous 
elevation of 1 or more 
Decrease by 50% 
Increase by 2 x ULN 
Lungs 
-Normal %FEV1 after 
previous involvement 
-If PFTs not available, NIH 
Lung Symptom Score 0 
after previous involvement 
-Increase by 10% predicted 
absolute value of %FEV1 
-If PFTs not available, 
decrease in NIH Lung 
Symptom Score by 1 or 
more points 
-Decrease by 10% predicted 
absolute value of %FEV1 
-If PFTs not available, increase 
in NIH Lung Symptom Score 
by 1 or more points, except 0 to 
1 
Joints and 
fascia 
Both NIH Joint and Fascia 
Score 0 and P-ROM score 
25 after previous 
involvement by at least 
1 measure 
Decrease in NIH Joint and 
Fascia Score by 1 or more 
points or increase in 
P-ROM score by 1 point 
for any site 
Increase in NIH Joint and Fascia 
Score by 1 or more points or 
decrease in P-ROM score by 
1 point for any site 
Global 
Clinician overall severity 
score 0 
Clinician overall severity 
score decreases by 2 or 
more points on a 0 – 10 
scale 
Clinician overall severity score 
increases by 2 or more points on 
a 0 – 10 scale 
ALT, alanine transaminase; FEV1, forced expiratory volume in the first second; GI, gastrointestinal; NIH, National 
Institutes of Health; OMRS, Oral Mucosa Rating Scale; PFTs, pulmonary function tests; P-ROM, photographic 
range of motion; ULN, upper limit of normal. 
Adapted from Lee 2015. 
 

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11.5.2.3 
cGVHD Steroid Response 
Corticosteroid refractoriness, resistance, dependence, and intolerance will be defined as per the 
EBMT-NIH-CIBMTR Task Force Position Statement (Schoemans 2018), outlined in Table 11-5. 
Table 11-5 
cGVHD Steroid Response Terminology 
Terminology 
Criteria 
Refractoriness 
or Resistance 
• 
Chronic GVHD progression while on prednisone at ≥1 mg/kg/day for 1−2 weeks, 
OR 
• 
Stable GVHD disease while on ≥0.5 mg/kg/day (or 1 mg/kg every other day) of 
prednisone for 1−2 months 
Dependence 
• 
Inability to taper prednisone below 0.25 mg/kg/day (or >0.5 mg/kg every other 
day) in at least 2 unsuccessful attempts separated by at least 8 weeks 
Intolerance 
• 
Emergence of unacceptable toxicity due to the use of corticosteroids 
Adapted from Schoemans 2018. 
 
11.6 
Revised International Prognostic Scoring System (IPSS-R) for 
Myelodysplastic Syndromes 
The Revised International Prognostic Scoring System (IPSS-R) involves the combination of the 
scores of 5 main features (Table 11-6) to determine a risk category (Table 11-7) 
(Greenberg 2012). 
Table 11-6 
IPSS-R Prognostic Score Values 
Prognostic Variable 
0 
0.5 
1 
1.5 
2 
3 
4 
Cytogenetics* 
Very good 
— 
Good 
— 
Intermediate 
Poor 
Very poor 
BM blast, % 
≤2 
— 
>2% to <5% 
— 
5% to 10% 
>10% 
— 
Hemoglobin 
≥10 
— 
8 to <10 
<8 
— 
— 
— 
Platelets 
≥100 
50 to <100 
<50 
— 
— 
— 
— 
ANC 
≥0.8 
<0.8 
— 
— 
— 
— 
— 
Abbreviations: ANC, absolute neutrophil count; BM, bone marrow; IPSS-R, Revised International Prognostic 
Scoring System. 
* Cytogenetic categories: 
Very good: -Y, del(11q) 
Good: normal, del(5q), del(12p), del(20q), double including del(5q) 
Intermediate: del(7q), +8, +19, i(17q), any other single or double independent clones 
Poor: −7, inv(3)/t(3q)/del(3q), double including −7/del(7q), complex with 3 abnormalities 
Very poor: complex with >3 abnormalities 
From Greenberg 2012. 
 

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Table 11-7 
IPSS-R Prognostic Risk Categories/Scores 
Risk Category 
Risk Score 
Very low 
≤1.5 
Low 
>1.5–3 
Intermediate 
>3.4–4.5 
High 
>4.5–6 
Very High 
>6 
From Greenberg 2012. 
 
11.6.1 
Therapy-Related MDS 
Independent of IPSS-R scoring, therapy-related MDS requires the following disease features to 
be present: 
• History of prior treatment with cytotoxic chemotherapy or radiation therapy. 
• Morphologic evidence of significant dysplasia (ie, ≥10 % of erythroid precursors, 
granulocytes, or megakaryocytes) on the peripheral blood smear or bone marrow 
examination, in the absence of other causes of dysplasia. In the absence of morphologic 
evidence of dysplasia, a presumptive diagnosis of MDS can be made in participants with 
otherwise unexplained refractory cytopenias together with certain genetic abnormalities 
characteristic of therapy-related MDS. 
• Blast count in bone marrow is ≤20 percent. 
11.7 
DRI Risk Score Assessment  
DRI risk score flow charts were adapted from the following references:  
DRI scoring for AML, ALL and MDS. MDS definitions (high and low risk disease): 
(Armand 2014) 
AML cytogenetics: (Armand 2012b) 
MDS cytogenetics and stage (early and advanced): (Armand 2010) 
For patients with mixed phenotype acute leukemia/acute leukemia of ambiguous lineage, the 
DRI Risk Score should be calculated using the flowchart for AML if the leukemic blasts express 
a preponderance of myeloid markers or the flowchart for ALL if the leukemic blasts express a 
preponderance of lymphoid markers.

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Figure 11-2 
DRI AML Scoring Flow Chart 
 
Adapted from Armand 2014 and Armand 2012a 

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Figure 11-3 
DRI MDS Scoring Flow Chart 
 
Adapted from Armand 2014 and Armand 2012a 

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Figure 11-4 
DRI ALL Scoring Flow Chart 
 
Adapted from Armand 2014 
 

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11.8 
Performance Status Criteria 
Karnofsky Status 
Karnofsky 
Grade 
ECOG 
Grade 
ECOG Status 
Normal, no complaints 
100 
0 
Fully active, able to carry on all pre-disease 
performance without restriction 
Able to carry on normal 
activities. Minor signs or 
symptoms of disease 
90 
1 
Restricted in physically strenuous activity but 
ambulatory and able to carry out work of a 
light or sedentary nature, eg, light housework, 
office work 
Normal activity with effort 
80 
1 
Restricted in physically strenuous activity but 
ambulatory and able to carry out work of a 
light or sedentary nature, eg, light housework, 
office work 
Care for self. Unable to carry 
on normal activity or to do 
active work 
70 
2 
Ambulatory and capable of all selfcare but 
unable to carry out any work activities. Up 
and about more than 50% of waking hours 
Requires occasional 
assistance, but able to care for 
most of his needs 
60 
2 
Ambulatory and capable of all selfcare but 
unable to carry out any work activities. Up 
and about more than 50% of waking hours 
Requires considerable 
assistance and frequent 
medical care 
50 
3 
Capable of only limited selfcare, confined to 
bed or chair more than 50% of waking hours 
Disabled. Requires special 
care and assistance 
40 
3 
Capable of only limited selfcare, confined to 
bed or chair more than 50% of waking hours 
Severely disabled. 
Hospitalization indicated 
though death nonimminent 
30 
4 
Completely disabled. Cannot carry on any 
selfcare. Totally confined to bed or chair 
Very sick. Hospitalization 
necessary. Active supportive 
treatment necessary 
20 
4 
Completely disabled. Cannot carry on any 
selfcare. Totally confined to bed or chair 
Moribund 
10 
4 
Completely disabled. Cannot carry on any 
selfcare. Totally confined to bed or chair 
Dead 
0 
5 
Dead 
From Oken 1982. 
 
11.9 
HCT–CI 
The HCT–CI is calculated as the sum of the weighted scores for comorbidities present in the 
subject, as shown in Table 11-8. 

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Table 11-8 
Definitions and Scoring of Comorbidities Included in the HCT-CI 
Comorbidity 
Definition 
Weighted 
Score 
Arrhythmia 
Atrial fibrillation or flutter, sick sinus syndrome, or ventricular 
arrhythmias 
1 
Cardiac 
Coronary artery disease1, congestive heart failure, myocardial 
infarction, or EF ≤ 50% 
1 
Inflammatory 
bowel disease 
Crohn’s disease or ulcerative colitis 
1 
Diabetes 
Requiring treatment with insulin or oral hypoglycemics but not diet 
alone 
1 
Cerebrovascular 
disease 
Transient ischemic attack or cerebrovascular accident 
1 
Psychiatric 
disturbance† 
Depression or anxiety requiring psychiatric consult or treatment 
1 
Hepatic, mild 
Chronic hepatitis, bilirubin >ULN to 1.5 x ULN, or AST/ALT >ULN 
to 2.5 x ULN 
1 
Obesity 
Participants with a body mass index >35 kg/m2 
1 
Infection 
Requiring continuation of antimicrobial treatment after day 0 
1 
Rheumatologic 
Systemic lupus erythematosus, rheumatoid arthritis, polymyositis, 
mixed connective tissue disease, or polymyalgia rheumatica 
2 
Peptic ulcer 
Requiring treatment 
2 
Moderate/severe 
renal 
Serum creatinine >2 mg/dL, on dialysis, or prior renal transplantation 
2 
Moderate 
pulmonary 
DLCO and/or FEV1 66%-80% or dyspnea on slight activity 
2 
Prior solid 
tumor2 
Treated at any time point in the patient’s past history, excluding 
nonmelanoma skin cancer 
3 
Heart valve 
disease 
Except mitral valve prolapse 
3 
Severe 
pulmonary 
DLCO and/or FEV1 ≤65% or dyspnea at rest or requiring oxygen 
3 
Moderate/severe 
hepatic 
Liver cirrhosis, bilirubin >1.5 x ULN, or AST/ALT >2.5 x ULN 
3 
Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; DLCO, diffusing capacity of the lung for 
carbon monoxide; EF, ejection fraction; forced expiratory volume in the first second; HCT-CI, Hematopoietic Stem 
Cell Transplant-Specific Comorbidity Index; ULN, upper limit of normal. 
1 
One or more vessel-coronary artery stenosis requiring medical treatment, stent, or bypass graft. 
2 
Recent analysis (Shouval et al. 2022), has indicated that prior diagnosis of a solid tumor is not an 
independent predictor of non-relapse mortality. Therefore, if a participant has a history of a solid 
tumor that was treated with curative intent ≥ 5 years prior to planned day 0 with no evidence of 
recurrence of that tumor, the participant may be considered to have a score of zero for this category. 
Adapted from Sorror et al. 2005. 
 

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11.12 
Screening Questions for Creutzfeldt-Jakob Disease (CJD)/Variant CJD 
(vCJD) 
All donors should be screened for risk of CJD/vCJD transmission. However, donors determined 
to be ineligible, based on the results of required testing and/or screening, may nonetheless be 
included if either apply, as per 21 CFR § 1271.65 2018: 
• The donor is a first-degree or second-degree blood relative of the recipient 
• Urgent medical need, meaning no comparable human cell product is available and the 
recipient is likely to suffer death or serious morbidity without the human cell product, as 
attested by the investigator.  
If applicable, the investigator should discuss the risk of CJD/vCJD transmission with the 
Recipient. 
Table 11-10 
Countries Considered to be at Risk for Transmission of vCJD 
 
 
Screening questions: 
1. Since 1980, have you ever lived in or traveled to any country considered to be at risk for 
transmission of vCJD (variant Creutzfeldt-Jakob disease)? (refer to Table 11-9). If no, skip to 
question #2. If yes, please respond to the following: 
a. From 1980 through 1996, did you spend time that adds up to 3 months or more in the 
United Kingdom (England, Northern Ireland, Scotland, Wales, the Isle of Man, the 
Channel Islands, Gibraltar, or the Falkland Islands)? 
b. Since 1980, have you received a transfusion of blood or blood components while in the 
UK or France? 
c. Since 1980, have you spent time that adds up to 5 years or more (including time spent in 
the UK between 1980 and 1996) in any country considered to be at risk for transmission 
of vCJD (variant Creutzfeldt-Jakob Disease)? (refer to Table 11-9)  
2. From 1980 through 1996, were you a member of the U.S. military, a civilian military 
employee, or a dependent of either a member of the U.S. military or civilian military 
employee? 

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3. From 1980 through 1990, did you spend a total of 6 months or more associated with a 
military base in any of the following countries: United Kingdom, Belgium, Netherlands, or 
Germany? 
4. From 1980 through 1996, did you spend a total of 6 months or more associated with a 
military base in any of the following countries: Spain, Portugal, Turkey, Italy, or Greece? 
5. Have any of your blood relatives ever had Creutzfeldt-Jakob Disease? 
6. Have you ever received growth hormone made from human pituitary glands? 
7. Have you ever received a dura mater (brain covering) graft? 
 
If Donors answer in the affirmative to any of the above questions, they are considered to be at 
risk of transmitting CJD/vCJD. This fact should be communicated to the Recipient site as a 
component of the donor screening packet. As noted, Donor blood products may still be used if 
there is urgent medical need, meaning no comparable human cell product is available and the 
recipient is likely to suffer death or serious morbidity without the human cell product, as attested 
by the investigator. 
11.13 
Definitions of CR, CRi, and Relapse 
11.13.1 
Definition of CR and CRi (Acute Leukemias) 
11.13.1.1 
Definition of CR for AML and MPAL 
For AML and MPAL, a CR is defined according to FDA draft guidance for industry ("Acute 
Myeloid Leukemia: Developing Drugs and Biological Products for Treatment (August 2020)" 
available at https://www.fda.gov/media/140821/download): 
1. Bone marrow blasts <5% by morphologic examination 
2. Absence of circulating blasts in the peripheral blood by morphologic examination 
3. No evidence extramedullary disease 
4. ANC >1.0 × 109/L (1,000/µL) 
5. Platelet count >100 × 109/L (100,000/µL) 
CRi is defined as meeting all CR criteria except for residual neutropenia (<1.0 × 109/L) and/or 
thrombocytopenia (<100 × 109/L). 
11.13.1.2 
Definition of CR for ALL 
For ALL, a CR is defined per the CIBMTR, https://www.cibmtr.org/manuals/fim/1/en/topic/all-
response-criteria, accessed 4 December 2021): 
1. <5% blasts in the bone marrow 
2. Normal maturation of all cellular components in the bone marrow 
3. No extramedullary disease (eg, central nervous system, soft tissue disease) 

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4. ANC >1,000/µL 
5. Platelets >100,000/µL 
6. Transfusion independence 
CRi is defined as meeting all CR criteria except for residual neutropenia (≤1.0 × 109/L) and/or 
thrombocytopenia (≤100 × 109/L). 
11.13.2 
Definition of Relapse for AML and MPAL 
The definition of relapse for AML and MPAL is based on the AML International Working 
Group recommendations (Döhner 2010), and is defined as the emergence of any of the following 
after prior achievement of a CR or CRi: 
• bone marrow blasts ≥5%; or  
• reappearance of blasts in the blood; or  
• development of extramedullary disease 
11.13.3 
Definition of Relapse for ALL 
The definition of relapse for ALL is based on the European Working Group for Adult ALL 
recommendations (Gökbuget 2017), and is defined as the emergence of any of the following 
after prior achievement of a CR or CRi: 
• bone marrow blasts ≥5%; or  
• development of extramedullary disease 
11.13.4 
Response Criteria for Myelodysplatic Syndrome 
Myelodysplastic syndrome responses should be graded according to the 2006 IWG guidelines 
(Cheson 2006). 
11.14 
Response Criteria for BPDCN 
BPDCN responses should be graded according to the methods described in Frankel et al. 
(Frankel 2014). 
11.15 
Definition of Relapse for CML 
Relapse after alloHCT will be defined as the emergence of BCR-ABL positivity and/or 
cytogenetic relapse that requires the institution of secondary therapy for CML. This includes the 
use of donor lymphocyte infusion, tyrosine kinase inhibitors (TKIs), or chemotherapy in 
response to molecular and/or cytogenetic progression. The date of relapse will be the date in 
which the molecular and/or cytogenetic progression was identified. The use of TKIs targeting 
BCR-ABL prophylactically to prevent relapse is not considered a relapse-defining event. 
11.16 
Precision-T aGVHD Assessment and Reporting Guidelines 
The aGVHD Assessment Worksheet begins on the following page. 

Subject Study ID Code: __________________ Date: _______________ Study Visit Day (Days After Transplant): ___________ 
Precision-T | aGVHD Worksheet v2.0 | 27Jan2023  
 
Page 1 
 
 
PRECISION-T 
Acute GVHD Target Organ Abnormality Assessment 
Worksheet 
 
Subject Study ID Code:__________________________________________ 
 
 
Date (dd-MON-year): ___________________________________________ 
 
 
Assessor: ______________________________________________________ 
(aGVHD should be assessed by the principal investigator or subinvestigators) 
 
Please indicate Study Visit Day (days after transplant) and visit type (in-person, etc.) by checking the 
appropriate box below: 
 
 
Days After 
Transplant 
+14 
+21 
+28 
+35 
+42 
+49 
+56 
+100 
+180 
+365 
Unscheduled 
Visit 
In-person 
assessment 
(strongly 
preferred) 
 
 
 
 
 
 
 
 
 
 
(Please indicate 
days after 
transplant) 
Remote/tele-
visit assessment: 
 
 
 
 
 
 
 
 
 
 
 
Missed visit 
retrospective 
assessment: 
 
 
 
 
 
 
 
 
 
 
 

Subject Study ID Code: __________________ Date: _______________ Study Visit Day (Days After Transplant): ___________ 
Precision-T | aGVHD Worksheet v2.0 | 27Jan2023  
 
Page 2 
Acute GVHD Assessment Timepoints 
Evaluation for acute GVHD via a target organ assessment must occur at the protocol mandated 
assessment schedule, as well as at any visit between scheduled assessments (ie, unscheduled 
visits) where abnormalities in target organs are identified, from day +14 through day +365. An 
aGVHD assessment form is not required for unscheduled visits that occur within 7 days of 
another documented visit unless the participant has new or evolving signs or symptoms of 
possible acute GVHD.  
 
Hospitalizations outside of the scheduled assessments are considered unscheduled visits, and an 
aGVHD assessment should be performed upon admission and weekly thereafter for the duration 
of hospitalization. 
 
Assessment must include completion of the “aGVHD Target Organ Abnormality Assessment 
Worksheet” by a GVHD provider. The worksheet must be completed as a part of the visit and 
should not rely on extracting data from the EMR to complete. 
 
 
All abnormalities in GVHD target organs must be recorded, even if explained by a non-GVHD 
cause. These should also be reported as adverse events. 
 
Endpoint Adjudication Data 
GVHD assessments will be reviewed by the study Endpoint Adjudication Committee. Please 
additionally provide a copy of the clinic visit note, redacted of any protected health information, 
for any aGVHD assessment visit where GVHD is considered a potential diagnosis, or 
abnormalities are identified in any acute GVHD target organ. Pathology reports and radiology 
reports of studies performed to evaluate for the presence of GVHD must also be provided. 
Missed aGVHD Assessment 
Every effort should be made to evaluate participants on mandated visit days and during 
applicable unscheduled visits. However, if a subject is seen at the Transplant center at a 
protocol mandated visit between day +14 and day +365 and a GVHD assessor does not 
complete an assessment worksheet at the time of the visit, the PI or a subinvestigator must 
review the medical record from the visit and complete this form based on the data available. 
Missed assessments with retrospective evaluation for GVHD should be indicated as such above 
(page 1). 
Remote Visits 
In the event a remote visit is required due to the Covid-19 pandemic, the assessment must still be 
performed. Every effort should be made to conduct a video assessment of the target aGVHD 
organs. 
Diagnosis of aGVHD 
As noted above, a clinic note should be provided for any aGVHD assessment time point where 
GVHD is considered a potential diagnosis, or abnormalities are identified in any acute GVHD 
target organ. If aGVHD is diagnosed on a given visit, the clinic note should document all 
pertinent signs and symptoms. 

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11.17 
Precision-T cGVHD Assessment and Reporting Guidelines 
The cGVHD Assessment Worksheet begins on the following page. 

Subject Study ID Code: __________________ Date: _______________ Study Visit Day (Days After Transplant): ___________ 
Precision-T | cGVHD Worksheet v1.0 | 06 Oct2022  
 
Page 1 
 
PRECISION-T 
Chronic GVHD Assessment Worksheet 
 
Subject Study ID Code: _________________________________________ 
 
Date (dd-MON-year): ___________________________________________ 
 
Assessor: _____________________________________________________ 
(cGVHD should be assessed by the principal investigator or subinvestigators) 
 
Please indicate Study Visit Day (days after transplant) and visit type (in-person, etc) by checking the 
appropriate box below: 
 
 
Days After Transplant 
+56 
+100 
+180 
+270 
+365 
+545 
+730 
Unscheduled visit 
In-person assessment 
(strongly preferred) 
 
 
 
 
 
 
 
(Please indicate 
days post-
transplant):  
Remote/tele-visit 
assessment: 
 
 
 
 
 
 
 
 
Missed visit 
retrospective 
assessment: 
 
 
 
 
 
 
 
 
 
 

Subject Study ID Code: __________________ Date: _______________ Study Visit Day (Days After Transplant): ___________ 
Precision-T | cGVHD Worksheet v1.0 | 06 Oct2022  
 
Page 3 
above and at all unscheduled visits from day +56 through day +730. 
 
 
 

Subject Study ID Code: __________________ Date: _______________ Study Visit Day (Days After Transplant): ___________ 
Precision-T | cGVHD Worksheet v1.0 | 06 Oct2022  
 
Page 9 
Other indicators, clinical features or complications related to chronic GVHD (check all that apply and 
assign a score to severity (0-3) based on functional impact where applicable none – 0, mild – 1, moderate – 
2, severe – 3):  
 □ Ascites (serositis): _____ 
□ Pericardial effusion: _____ 
□ Pleural effusion(s): _____ 
□ Nephrotic syndrome: _____ 
□ Myasthenia gravis: _____ 
□ Peripheral Neuropathy: ____ 
□ Polymyositis: _____ 
□ Weight loss >5% without GI 
symptoms: _____ 
 
□ Eosinophilia >500/μl: _____ 
□ Platelets <100,00/μl: _____ 
□ Others (specify): _____ 
 
Has a biopsy to assess for the presence of GVHD been obtained since the last cGVHD assessment? 
 □ NO 
□ YES: If yes, please provide a PHI-redacted copy of the pathology report(s) and indicate sites biopsied: 
 
□ Skin 
□ Mouth 
□ GI tract 
□ Liver 
□ Lungs 
□ Genital tract 
□ Other (specify): _________________ 
 
NIH Global/Overall Severity of Chronic GVHD Grading 
 
Mild chronic GVHD:  
• 
1 or 2 Organs involved with no more than score 1 plus Lung score of 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 of 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 2 scores 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. 
• 
If 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). 
 
Overall GVHD 
Severity 
(Opinion of evaluator) 
□ No GVHD 
□ Mild 
□ Moderate 
□ Severe 
 

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STATISTICAL ANALYSIS PLAN 
 
 
19 September 2024 
 
Sponsor: Orca Bio, Inc. 
 
Protocol Name: Precision-T 
A Phase Ib /Randomized Phase III Trial of Patients with Advanced Hematologic Malignancies 
undergoing Allogeneic Hematopoietic Cell Transplantation with Either Orca-T, a T-cell-
Depleted Graft with Additional Infusion of Conventional T cells and Regulatory T cells, or 
Standard-of-Care Allogeneic Graft 
 
 
Phase 3 Only 

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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN .............................................................................................. 1 
TABLE OF CONTENTS ............................................................................................................... 2 
LIST OF TABLES ......................................................................................................................... 5 
LIST OF FIGURES ....................................................................................................................... 6 
TABLE OF ABBREVIATIONS ................................................................................................... 7 
1 
INTRODUCTION ............................................................................................................. 8 
2 
STUDY OBJECTIVES ...................................................................................................... 9 
2.1 
Primary Objective ........................................................................................................... 9 
2.2 
Secondary Objectives ...................................................................................................... 9 
2.3 
Exploratory Objectives ................................................................................................... 9 
3 
STUDY OVERVIEW ...................................................................................................... 11 
3.1 
Study Design ................................................................................................................. 11 
3.1.1 
Endpoint Adjudication Committee ............................................................................ 12 
3.2 
Sample Size ................................................................................................................... 12 
4 
STUDY ENDPOINTS AND COVARIATES ................................................................. 13 
4.1 
Study Endpoints/Estimands .......................................................................................... 13 
4.1.1 
Primary Endpoints and Primary Estimand ................................................................. 13 
4.1.2 
Secondary Endpoints and Primary Estimand ............................................................. 14 
4.1.2.1 
Secondary Endpoint 2: Time to Moderate or Severe cGVHD ............................... 14 
4.1.2.2 
Secondary Endpoint 3: OS ...................................................................................... 15 
4.1.2.3 
Secondary Endpoint 3: GRFS up to 2 Year ............................................................ 15 
4.1.3 
Exploratory Endpoints ............................................................................................... 16 
4.1.3.1 
NRM ....................................................................................................................... 16 
4.1.3.2 
RFS ......................................................................................................................... 17 
4.1.3.3 
Death up to Day +100 and Death up to Day +180 .................................................. 17 
4.1.3.4 
Incidence and Timing of Grade 2 Through 4 aGVHD and Grade 3 or 4 
aGVHD ................................................................................................................... 17 
4.1.3.5 
Incidence and Timing of Neutrophil Engraftment .................................................. 19 
4.1.3.6 
Incidence and Timing of Platelet Engraftment ....................................................... 19 
4.1.3.7 
Incidence and Severity of Grade ≥3 Infection and Grade ≥4 Infection .................. 19 
4.1.3.8 
Incidence and Severity (All Grades) of aGVHD and cGVHD ............................... 21 
4.1.3.9 
Incidence of Steroid-Refractory aGVHD and Steroid-Refractory cGVHD ........... 21 

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4.1.3.10 
Incidence of Grade ≥3 and Grade ≥4 Mucositis ..................................................... 21 
4.1.3.11 
TPN up to Day +100 ............................................................................................... 21 
4.1.3.12 
Duration of Initial Hospitalization due to AlloHCT and Incidence and 
Duration of Rehospitalization due to AE ................................................................ 21 
4.1.3.13 
ISFS......................................................................................................................... 21 
4.1.3.14 
Immune Reconstitution ........................................................................................... 21 
4.1.3.15 
QoL Endpoints ........................................................................................................ 22 
4.2 
Planned Covariates........................................................................................................ 22 
5 
HYPOTHESES AND/OR ESTIMATIONS .................................................................... 23 
6 
DEFINITIONS ................................................................................................................. 24 
6.1 
General Study-Related Definitions ............................................................................... 24 
6.1.1 
Participant, Donor, and Recipient .............................................................................. 24 
6.1.2 
Baseline ...................................................................................................................... 24 
6.1.3 
Duration (including time-to-event efficacy endpoints) .............................................. 24 
6.1.4 
Study Day................................................................................................................... 24 
6.1.5 
Time-Related Unit Conversion .................................................................................. 24 
6.1.6 
Data Cutoff Date ........................................................................................................ 24 
6.1.7 
Visit Window for Analyses at 1 Year and 2 Years .................................................... 25 
6.2 
Estimand-Related Definitions ....................................................................................... 25 
6.2.1 
Intercurrent Events ..................................................................................................... 25 
6.2.2 
Policies Used to Handle Intercurrent Events ............................................................. 26 
6.2.3 
Disease Relapse and Disease Relapse Date ............................................................... 26 
6.3 
Safety-Related Definitions ............................................................................................ 27 
6.3.1 
Treatment-Emergent Period ....................................................................................... 27 
6.3.2 
AESIs ......................................................................................................................... 27 
6.3.3 
Identified and Potential Risks .................................................................................... 27 
7 
ANALYSIS SETS ........................................................................................................... 29 
7.1 
Donor Analysis Set ....................................................................................................... 29 
7.2 
Recipient Analysis Sets................................................................................................. 29 
7.3 
Subgroup Analyses ....................................................................................................... 29 
8 
INTERIM ANALYSIS .................................................................................................... 31 
9 
DATA SCREENING AND ACCEPTANCE .................................................................. 33 
9.1 
General Principles ......................................................................................................... 33 

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9.2 
Data Handling and Electronic Transfer of Data ........................................................... 33 
9.3 
Handling of Incomplete Dates ...................................................................................... 33 
9.3.1 
Imputation of Partially Missing Dates of AEs and Concomitant Medications .......... 33 
9.3.1.1 
Missing Day Only for Start Date ............................................................................ 33 
9.3.1.2 
Missing Day Only for Stop Date ............................................................................ 33 
9.3.2 
Imputation of Partially Missing Dates of Other Datasets .......................................... 33 
9.4 
Outliers .......................................................................................................................... 34 
9.5 
Distributional Characteristics........................................................................................ 34 
9.6 
Validation of Statistical Analyses ................................................................................. 34 
10 
STATISTICAL METHODS OF ANALYSIS ................................................................. 35 
10.1 
General Principles ......................................................................................................... 35 
10.2 
Participant Accountability ............................................................................................ 35 
10.3 
Important Protocol Deviations ...................................................................................... 35 
10.4 
Demographic and Baseline Characteristics .................................................................. 35 
10.5 
Efficacy Analysis .......................................................................................................... 36 
10.5.1 
EAC Output ............................................................................................................... 37 
10.5.2 
Intercurrent Event and Missing Visits for Estimands ................................................ 38 
10.5.2.1 
Intercurrent Event ................................................................................................... 38 
10.5.2.2 
Missing Assessments .............................................................................................. 38 
10.5.3 
Analysis of Primary Efficacy Endpoint ..................................................................... 38 
10.5.4 
Analysis of Secondary Efficacy Endpoints ................................................................ 39 
10.5.5 
Analysis of Exploratory Efficacy Endpoints ............................................................. 39 
10.5.6 
Analysis of Health-Related QoL Endpoints .............................................................. 40 
10.5.6.1 
FACT-BMT and EQ-5D-5L ................................................................................... 40 
10.5.6.2 
Modified 7-Day Lee cGVHD Symptom Scale ....................................................... 42 
10.5.7 
Biomarker Analysis ................................................................................................... 42 
10.6 
Safety Analyses ............................................................................................................. 42 
10.6.1 
Adverse Events .......................................................................................................... 42 
10.6.1.1 
General Contents of TEAE Analyses ..................................................................... 42 
10.6.2 
Hospitalization ........................................................................................................... 44 
10.6.3 
Laboratory Test Results ............................................................................................. 44 
10.6.4 
Vital Signs .................................................................................................................. 45 
10.6.5 
Karnofsky Performance Score ................................................................................... 45 

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10.6.6 
Chimerism .................................................................................................................. 45 
10.6.7 
Exposure to Investigational Product .......................................................................... 45 
10.6.8 
Exposure to Concomitant Medication/Procedure/Surgery ........................................ 46 
10.6.8.1 
Conditioning Regimen ............................................................................................ 46 
10.6.8.2 
GVHD Prophylaxis ................................................................................................. 47 
10.6.8.3 
GVHD Treatment .................................................................................................... 47 
10.6.8.4 
Exposure Response Analysis .................................................................................. 47 
11 
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES ......................................... 49 
12 
REFERENCES ................................................................................................................ 50 
13 
APPENDICES ................................................................................................................. 52 
13.1 
Groups of AEs and Medications ................................................................................... 52 
13.2 
Sensitivity Analysis/Supplementary Analysis .............................................................. 54 
13.3 
Summary of Changes .................................................................................................... 59 
13.3.1 
Version 2.0 vs Version 1.0 ......................................................................................... 59 
13.3.2 
Version 3.0 vs Version 2.0 ......................................................................................... 60 
13.3.3 
Version 4.0 vs Version 3.0 ......................................................................................... 63 
 
LIST OF TABLES 
Table 1 
Primary Estimand for cGFS ................................................................................. 13 
Table 2 
Primary Estimand for Time to Moderate or Severe cGVHD .............................. 14 
Table 3 
Primary Estimand for OS ..................................................................................... 15 
Table 4 
Primary Estimand for GRFS ................................................................................ 15 
Table 5 
Primary Estimand for NRM ................................................................................. 16 
Table 6 
Primary Estimand for RFS ................................................................................... 17 
Table 7 
Primary Estimand for Time to First Onset of Grade 2 through 4 aGVHD .......... 18 
Table 8 
Primary Estimand for Time to First Onset of Grade 3 or 4 aGVHD ................... 18 
Table 9 
Primary Estimand for Time to First Onset of Grade ≥3 Infection ....................... 20 
Table 10 
Primary Estimand for Time to First Onset of Grade ≥4 Infection ....................... 20 
Table 11 
Treatment-Emergent Period ................................................................................. 27 
Table 12 
Orca-T Components (HSPC, Treg, and Tcon) Dosing Variables ........................... 46 
Table 13 
Planned Exposure-Response Analyses ................................................................ 47 
Table 14 
MedDRA PT Grouping Strategy for IRR ............................................................ 52 

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Table 15 
MedDRA PT Grouping Strategy for Infections ................................................... 52 
Table 16 
Tyrosine Kinase Inhibitors for Prevention of Relapse ......................................... 53 
Table 17 
Sensitivity and Supplementary Analysis for cGFS .............................................. 54 
Table 18 
Sensitivity and Supplementary Analysis for Time to Moderate or Severe 
cGVHD ................................................................................................................ 55 
Table 19 
Sensitivity and Supplementary Analysis for GRFS ............................................. 55 
Table 20 
Sensitivity and Supplementary Analysis for OS .................................................. 55 
Table 21 
Estimand for Sensitivity Analysis for cGFS Including All Assessments 
Regardless of Missingness ................................................................................... 56 
Table 22 
Estimand for Sensitivity Analysis for cGFS: Intercurrent Events 1 and 2 .......... 56 
Table 23 
Estimand for Sensitivity Analysis for Time to Moderate or Severe cGVHD 
Including All Assessments Regardless of Missingness ....................................... 58 
 
LIST OF FIGURES 
Figure 1 
Planned Interim and Primary Analyses of Primary and Secondary 
Endpoints ............................................................................................................. 32 

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TABLE OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
aGVHD 
acute graft-versus-host disease 
alloHCT 
allogeneic hematopoietic cell transplantation 
ATC 
anatomical therapeutic chemical 
cGVHD 
chronic graft-versus-host disease 
CSR 
clinical study report 
eCRF 
electronic case report form 
EDC 
electronic data capture 
GRFS 
graft-versus-host disease-free and relapse-free survival 
GVHD 
graft-versus-host disease 
HSPC 
hematopoietic stem and progenitor cell 
IPD 
important protocol deviation 
IRR 
infusion-related reaction 
ISFS 
immunosuppression-free survival 
IWRS 
interactive web response system 
MCID 
minimal clinical important difference  
NA 
not applicable 
NRM 
nonrelapse mortality 
OS 
overall survival 
PTLD 
posttransplantation lymphoproliferative disorder 
QoL 
quality of life 
RFS 
relapse-free survival 
SOS 
sinusoidal obstruction syndrome 
TEAE 
treatment-emergent adverse event 
TMA 
thrombotic microangiopathy 
VOD 
veno-occlusive disease 

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3.1.1 
Endpoint Adjudication Committee  
An independent endpoint adjudication committee (EAC) will perform a blinded determination as 
to whether the criteria for aGVHD and/or cGVHD have been met for each participant, and the 
EAC will then grade aGVHD and cGVHD according to Mount Sinai Acute GVHD International 
Consortium (MAGIC) grading criteria and International National Institutes of Health (NIH) 
Chronic GVHD Diagnosis and Staging Consensus Working Group criteria, respectively (see 
sections 11.5.1 and 11.5.2 of the Precision-T Protocol). The EAC will be composed of a 
minimum of 3 experts in GVHD assessment. The full membership, mandate, and processes of 
the EAC will be detailed in the EAC Charter. Primary estimands of primary and secondary 
endpoints with aGVHD or cGVHD components will be based on the assessments from the EAC.  
3.2 
Sample Size 
The primary endpoint of cGFS per EAC is used to evaluate the effect of the experimental 
regimen for hematopoietic cell transplantation (HCT) against a standard of care. To achieve 90% 
power with a true hazard ratio (HR) = 0.40 and 1-sided alpha of .025, the required number of 
events needed is 56 (see Fleming and Harrington 1991, p. 395 and Al-Khalidi et al. 2011, 
Equation 5). This true HR of 0.40 corresponds approximately to 12-month event-free cGFS rates 
of 79% versus 55% for Orca-T and SoC, respectively (event rates at 12 months equal to 21% of 
participants for Orca-T versus 45% of participants for SoC). 
The number of participants required to achieve 56 events based on the above assumptions is 165. 
To account for 5% loss to follow-up in both treatment arms, 174 participants will be randomized. 

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4 
STUDY ENDPOINTS AND COVARIATES 
4.1 
Study Endpoints/Estimands 
4.1.1 
Primary Endpoints and Primary Estimand 
cGFS is defined as the time from the date of HCT (ie, day 0) to the date of death from any cause 
or the first onset of moderate or severe cGVHD (graded per NIH consensus criteria), whichever 
is earlier, within 2 years after day 0.  
Table 1 
Primary Estimand for cGFS 
Treatments 
Population 
Variable (Endpoint) 
Population Level Summary 
Orca-T versus SoC 
as randomized 
ITT analysis set 
cGFS per EAC 
P value from stratified log-rank test 
stratified by the randomization 
stratification factors; 
hazard ratio from stratified Cox model 
stratified by the randomization 
stratification factors 
General Censoring Rules 
Participants who received HCT (either SoC or Orca-T) and are alive and free from moderate or severe cGVHD 
will be censored at the last documented absence of moderate or severe cGVHD. 
Participants who received HCT (either SoC or Orca-T) but have no cGVHD assessment after day 0 will be 
censored at day 0 except that a death within 56 + 3a days after day 0 will be counted as an event since no cGVHD 
assessment is scheduled prior to the visit of day +56. 
Participants who do not receive HCT (either SoC or Orca-T) will be censored at randomization with a 
hypothetical day 0 added at randomization.  
Handling of Intercurrent Events 
ALL intercurrent events (treatment policy): Intercurrent events are considered irrelevant, and all available data 
will be included for the derivation of cGFS. 
Handling of Missing Assessments 
The rules described below is only apply to participants who received HCT (either SoC or Orca-T)  
• 
A participant will be censored at last cGVHD assessment prior to the first missing cGVHD assessment if no 
cGFS event (moderate or severe cGVHD, or death) has occurred up to the data cutoff date 
• 
A participant will be considered to have an event at one day after the last cGVHD assessment prior to the 
first cGVHD missing assessment if the first onset of cGFS event  (moderate or severe cGVHD, or death) is 
after the first cGVHD missing assessment 
Note:  
• 
The evaluation of missing cGVHD assessments discussed above for cGFS per the EAC will be based on 
whether a scheduled cGVHD survey was performed by investigators and nominal visit names (day +56, day 
+100, etc.) reported by investigators will be used. 
• 
The date of the last cGVHD assessment prior to the first missing cGVHD assessment discussed above is 
defined as below: 
- 
In general, it is defined as the date of the last cGVHD survey (scheduled or unscheduled) performed by 
investigator prior to the first missing scheduled cGVHD survey.  
- 
However, if no moderate or severe cGVHD is reported by EAC and the first missing scheduled cGVHD 
survey occurs between the date of last absence of moderate and severe cGVHD per EAC and the death 
date, it is defined as the date of last absence of moderate and severe cGVHD per EAC. 
• 
If an unscheduled assessment is conducted within 1 month of a missed scheduled assessment, the missed 
scheduled assessment will not be counted as missing. 

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Abbreviations: cGFS, chronic graft-versus-host disease-free survival; cGVHD, chronic graft-versus-host disease; 
EAC, endpoint adjudication committee; HCT, hematopoietic cell transplantation; ITT, intention to treat; 
SoC, standard of care. 
a  Day +56 is the first scheduled cGVHD assessment, with day 0 defined as Orca-T HSPC administration or SoC 
HCT date, and a 3-day window is allowed for the visit. 
4.1.2 
Secondary Endpoints and Primary Estimand 
4.1.2.1 
Secondary Endpoint 2: Time to Moderate or Severe cGVHD 
Time to moderate or severe cGVHD is defined as the time from HCT to the first onset of 
moderate or severe cGVHD within 2 years after day 0. Death within 2 years after day 0 without 
prior moderate or severe cGVHD is considered a competing event.  
Table 2 
Primary Estimand for Time to Moderate or Severe cGVHD 
Treatments 
Population 
Variable (Endpoint) 
Population Level Summary 
Orca-T versus SoC 
as randomized 
ITT analysis set 
Time to first onset of 
moderate or severe 
cGVHD per EAC 
with death as a 
competing event 
P value from stratified Gray's (Gray 1988) 
stratified by randomization stratification factors 
to assess the equality of cumulative incidence 
functions between treatment groups; 
HR with 95% CI from the stratified 
subdistribution proportional hazards model  
(Fine and Gray 1999; Zhou et al. 2011) 
stratified by randomization stratification factors 
General Censoring Rules 
Participants who received HCT (either SoC or Orca-T), and are still alive, and have not experienced moderate or 
severe cGVHD will be censored at the last documented absence of moderate or severe cGVHD.  
Participants who received HCT (either SoC or Orca-T) but have no cGVHD assessment after day 0 will be 
censored at day 0 except that a death within 56 + 3a days after day 0 will be counted as a competing event since 
no cGVHD survey is scheduled prior to the visit of day +56. 
Participants who do not receive HCT (either SoC or Orca-T) will be censored at randomization with a 
hypothetical day 0 added at randomization.  
Handling of Intercurrent Events 
ALL intercurrent events (treatment policy): Intercurrent events are considered irrelevant, and all available data 
will be included for the derivation of time to moderate or severe cGVHD 
Handling of Missing Assessments 
The rules described below is only apply to participants who received HCT (either SoC or Orca-T)  
• 
A participant will be censored at last cGVHD assessment prior to the first missing cGVHD assessment if 
neither event (moderate or severe cGVHD) or competing event (death) occurs up to the data cutoff date 
• 
A participant will be considered to have an event at one day after the last cGVHD assessment prior to the 
first cGVHD missing assessment if the first onset of moderate or severe cGVHD is after the first cGVHD 
missing assessment 
• 
A participant will be considered to have a competing event at one day after the last cGVHD assessment prior 
to the first cGVHD missing assessment if no moderate or severe cGVHD occurs prior to the death and the 
death is after the first cGVHD missing assessment.  
Note:  
• 
The evaluation of missing cGVHD assessments discussed above for cGFS per the EAC will be based on 
whether a scheduled cGVHD survey was performed by investigators and nominal visit names (day +56, day 
+100, etc.) reported by investigators will be used. 

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• 
The date of the last cGVHD assessment prior to the first missing cGVHD assessment discussed above is 
defined as below: 
- 
In general, it is defined as the date of the last cGVHD survey (scheduled or unscheduled) performed by 
investigator prior to the first missing scheduled cGVHD survey.  
- 
However, if no moderate or severe cGVHD is reported by EAC and the first missing scheduled cGVHD 
survey occurs between the date of last absence of moderate and severe cGVHD per EAC and the death 
date, it is defined as the date of last absence of moderate and severe cGVHD per EAC. 
• 
If an unscheduled assessment is conducted within 1 month of a missed scheduled assessment, the missed 
scheduled assessment will not be counted as missing. 
Abbreviations: cGVHD, chronic graft-versus-host disease; CI, confidence interval; EAC, endpoint adjudication 
committee; HCT, hematopoietic cell transplantation; HR, hazard ratio; ITT, intention to treat; SoC, standard of 
care. 
a  Day +56 is the second scheduled cGVHD assessment, with day 0 defined as Orca-T HSPC administration or SoC 
HCT date, and a 3-day window is allowed for the visit. 
4.1.2.2 
Secondary Endpoint 3: OS 
OS is defined as the time from randomization to death from any cause. 
Table 3 
Primary Estimand for OS 
Treatments 
Population 
Variable (Endpoint) 
Population Level Summary 
Orca-T versus SoC 
as randomized 
ITT analysis set 
OS 
P value from stratified log-rank test stratified 
by the randomization stratification factors; 
hazard ratio from stratified Cox model 
stratified by the randomization stratification 
factors 
General Censoring Rules 
Participants who are alive will be censored at the date last known to be alive.  
Handling of Intercurrent Events 
ALL intercurrent events (treatment policy): Intercurrent events are considered irrelevant, and all available data 
will be included for the derivation of OS. 
Handling of Missing Assessments 
Missing assessments will be disregarded, and all available data will be used for the derivation of OS. 
Abbreviations: ITT, intention to treat; OS, overall survival; SoC, standard of care. 
4.1.2.3 
Secondary Endpoint 3: GRFS up to 2 Year 
GRFS is defined as the time from HCT to death from any cause, relapse, the first onset of grade 
3 or 4 aGVHD (graded per MAGIC criteria), or the first onset of moderate or severe cGVHD 
(graded per NIH consensus criteria), whichever is earliest, within 2 years from day 0.  
Table 4 
Primary Estimand for GRFS 
Treatments 
Population 
Variable (Endpoint) 
Population Level Summary 
Orca-T versus SoC 
as randomized 
ITT analysis set 
GRFS per EAC 
P value from stratified log-rank test 
stratified by the randomization 
stratification factors; 
hazard ratio from stratified Cox model 
stratified by the randomization 
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5 
HYPOTHESES AND/OR ESTIMATIONS 
The following hypotheses will be tested using the gatekeeping strategy in the order listed below: 
1. Primary hypothesis: The null hypothesis is that there is no difference between treatment 
groups with respect to cGFS per EAC versus the alternative hypothesis that the treatment 
groups differ. The null hypothesis will be rejected if the P value from a 2-sided stratified 
log-rank test stratified by randomization stratification factors is less than the threshold 
determined by the alpha spending function specified in section 10.5 at the given analysis 
(interim or primary analysis).  
2. Secondary hypothesis 1: The null hypothesis is that there is no difference between 
treatment groups with respect to time to moderate or severe cGVHD per EAC versus the 
alternative hypothesis that the treatment groups differ. The null hypothesis will be 
rejected if the P value from a 2-sided stratified Gray's test (Gray 1988) stratified by the 
randomization stratification factors is less than the threshold determined by the alpha 
spending function specified in section 10.5 at a given analysis (interim or primary 
analysis).  
3. Secondary hypothesis 2: The null hypothesis is that there is no difference between 
treatment groups with respect to OS versus the alternative hypothesis that the treatment 
groups differ. The null hypothesis will be rejected if the P value from a 2-sided stratified 
log-rank test stratified by randomization stratification factors is less than the threshold 
determined by the alpha spending function specified in section 10.5 at a given analysis 
(interim or primary analysis).  
4. Secondary hypothesis 3: The null hypothesis is that there is no difference between 
treatment groups with respect to GRFS per EAC up to 2 year after alloHCT versus the 
alternative hypothesis that the treatment groups differ. The null hypothesis will be 
rejected if the P value derived from a 2-sided stratified log-rank test stratified by 
randomization stratification factors is less than the threshold determined by the alpha 
spending function specified in section 10.5 at a given analysis (interim or primary 
analysis).  

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6 
DEFINITIONS 
6.1 
General Study-Related Definitions 
6.1.1 
Participant, Donor, and Recipient 
Participant refers specifically to an individual who was randomized in this study to receive 
Orca-T or SoC HCT. Donor refers specifically to an individual who donated blood that was 
intended to be used in the HCT. Recipient is also used to refer to an individual who was 
randomized to receive HCT (ie, participant) as needed to clearly distinguish those individuals 
from donors. 
6.1.2 
Baseline 
The reference date for time-to-event endpoints is specified in their corresponding definitions.  
For analyzing safety data and demographic and baseline disease characteristics, baseline is 
defined as the last assessment taken prior to the day of the conditioning regimen. 
6.1.3 
Duration (including time-to-event efficacy endpoints)  
The duration between 2 dates (eg, start date and end date) will be calculated as follows unless 
otherwise specified: 
(end date  – start date + 1) (in days) 
6.1.4 
Study Day 
The date of SoC HCT or Orca-T HSPC infusion is defined as day 0. Study day will be defined 
using the date of SoC HCT or Orca-T HSPC infusion (day 0) as a reference and will be defined 
as follows: 
date of interest – date of Orca-T HSPC infusion/SoC HCT 
6.1.5 
Time-Related Unit Conversion 
To calculate years/months/weeks from days, the following formulas will be used: 
years = number of days ÷ 365.25 
months = number of days ÷ 30.4375 (ie, 365.25/12) 
weeks = number of days ÷ 7 
Values based on the above computations will be rounded to tenths. 
6.1.6 
Data Cutoff Date 
For the interim and primary analysis triggered by the number of cGFS events per EAC (37 or 
56 events, respectively), the cutoff date is the date of the last assessment related to an 
EAC-confirmed 37th or 56th event, respectively. Due to the EAC review process, there may be 
more than 37 or 56 adjudicated events prior to the cutoff date. For the interim analysis, exact 37 
events will be used, unless multiple events occur on the same day as the 37th event, in which 
case all events occurring on or before that date will be included. For both data reported in 
electronic data capture (EDC) system and EAC data, only the data up to the data cutoff date will 

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be used for the interim analysis. Specifically, if the moderate or severe cGVHD event onset date 
per EAC, or the last date when the EAC confirmed the absence of moderate or severe cGVHD, 
falls after the data cutoff date, it will be treated as an absence of moderate or severe cGVHD at 
the data cutoff date. The actual event date or the last confirmation date will not be used for the 
derivation of cGFS per EAC. For the primary analysis, all adjudicated events will be included. If 
more than 37 or 56 events are used for the analysis, the efficacy boundaries (P value critical 
value) will be adjusted correspondingly using the alpha spending function specified in section 
10.5. 
Comprehensive data cleaning for the interim and primary analysis will only be applied to data 
collected up to the data cutoff date defined above. A data snapshot will be extracted from the 
clinical database after the data cutoff date, but only the data collected up to the data cutoff date 
will be used to create the tables, figures, and listings for the CSR.  
Comprehensive data cleaning will be applied to all data collected prior to the final database lock.  
6.1.7 
Visit Window for Analyses at 1 Year and 2 Years  
For the estimands of primary, secondary, exploratory time to event endpoints, the phrase of 
“within 1 year after/from day 0” or “within 2 years after/from day 0” is used to limit the 
assessments and/or events included for the derivation of the endpoints.  
Specially for cGFS, time to moderate or severe cGVHD, GRFS, and time to grade 2 through 
grade 4 aGVHD or time to grade 3 or grade 4 aGVHD, where aGVHD and/or cGVHD and/or 
disease relapse are events, ‘within 1 year’ and ‘within 2 years’ are only used to limit the 
inclusion of death events for the time to event endpoint derivation, whether death is an event or 
competing event, while including all cGVHD assessments, aGVHD assessments and disease 
evaluation. This is because the last scheduled aGVHD assessment is planned at the day +365 
visit, so aGVHD assessments may occur beyond 1 year but are not expected to occur much later. 
Similarly, since the last scheduled cGVHD assessment and disease evaluation are planned at the 
day +730 visit, cGVHD assessments and disease relapse evaluation may occur after 2 years but 
are not expected to occur much later.  
For other time to endpoints where a given AE, other than aGVHD or cGVHD, is an event (eg, 
grade ≥3 infection), it is noted that no general AE is required to be reported after EOAP which is 
expected to occur at the 2-year mark but Orca-T related AEs are still required to be reported after 
it. To have a fair comparison between the two arms, ‘within 1 year’ and ‘within 2 years’ are used 
to limit the inclusion of both death events and the given AE. 
Considering the protocol’s visit window of ± 21 days for those two visits,  “within 1 year 
after/from day 0” is defined as “within 365 + 21 days after/from day 0’ and “within 2 years 
after/from day 0” is defined as “within 730 + 21 days after day 0”. The 21-day window ensures 
the relevant assessments and events used for the derivation fall within a similar time frame. 
6.2 
Estimand-Related Definitions 
6.2.1 
Intercurrent Events 
Although the treatment policy will be used for all intercurrent events for the primary estimands 
for the primary and secondary endpoints, the following intercurrent events will be identified and 
may be considered for sensitivity or supplementary analyses: 

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1. Use of donor lymphocyte infusion (DLI) for relapse, chimerism, or other reasons 
2. 2nd alloHCT or other cellular therapy (excluding DLI) 
3. Changes in GVHD prophylaxis for any reason, including early tapering of tacrolimus  
4. Received aGVHD treatment beyond first line (ie, aGVHD treatment beyond 
corticosteroids)  
5. Use of investigational treatment for aGVHD or cGVHD 
6. Use of rituximab for any reason including Epstein-Barr virus reactivation  
7. Use of ruxolitinib for prevention of disease recurrence 
8. Use of imatinib (or other BCR-ABL inhibitors) for prevention of disease recurrence  
9. Disease relapse 
Intercurrent events of manufacturing failure, harvest failure, and graft failure will be addressed 
by using the ITT analysis set (primary estimands) and per-protocol analysis set (estimands for 
supplementary analysis). 
6.2.2 
Policies Used to Handle Intercurrent Events  
Hypothetical policy strategy  
A scenario is envisaged in which the intercurrent event would not occur: the value of the variable 
to reflect the clinical question of interest is the value which the variable would have taken in the 
hypothetical scenario defined. For this study, by hypothetical policy strategy, relevant 
assessments/events after the intercurrent event will be excluded from the derivation of the 
corresponding time-to-event endpoint.  
Treatment policy strategy 
The occurrence of the intercurrent event is considered irrelevant in defining the treatment effect 
of interest: the value for the variable of interest is used regardless of whether the intercurrent 
event occurs. 
Treatment policy will be used for the primary estimands for all primary and secondary endpoints, 
while hypothetical policy may be used for certain intercurrent events for some 
sensitivity/supplementary analyses.  
6.2.3 
Disease Relapse and Disease Relapse Date 
In general, a participant will be considered to have experienced disease relapse if the disease 
evaluation eCRF indicates so. The disease relapse date reported in the disease evaluation eCRF 
will be used as the relapse date. If a participant has started a new anticancer therapy to treat 
MRD positivity in the absence of disease relapse as defined in the protocol recorded in the 
disease evaluation eCRF, this participant will be considered to have relapsed at the initialization 
of the new anticancer therapy. If MRD is negative after randomization or MRD was not tested, 
this participant will NOT be considered to have relapsed. Initiation of maintenance therapy pre-
specified in the eligibility form with or without MRD positivity will not be counted as a relapse. 
If more than 5 participants are considered to have disease relapse due to positive 
postrandomization MRD without disease relapse documented in the disease evaluation eCRF, a 
sensitivity analysis will be conducted by censoring those participants at their last disease 
assessment.  

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6.3 
Safety-Related Definitions 
6.3.1 
Treatment-Emergent Period 
All adverse events (AEs), serious AEs (SAEs), AEs of special interest (AESIs), aGVHD events, 
and cGVHD events with an onset during the TEAE period defined in Table 11 will be considered 
treatment emergent and included in the corresponding AE summary tables. All AEs reported by 
sites, regardless of whether they are treatment emergent or not, will be listed. A summary table 
will also be provided for AEs with an onset on or after the conditioning regimen but prior to 
day 0. 
Table 11 also defines the treatment emergent period for laboratory data, concomitant 
medications, vital signs, and physical examinations. Details on the corresponding analyses are 
provided in sections 10.6.3, 10.6.4, and 10.6.8. 
Table 11 
Treatment-Emergent Period 
TEAE Period 
Safety Data Category 
Day 0 to day +100 
all AEs, laboratory data, vital signs, physical examinationsa 
Day 0 to 1 year 
aGVHD events 
Day 0 to 2 years 
SAEs, AESIs, and cGVHD events, limited laboratory data: ANC, Hb, PLT, AST, ALT, 
Tbili, creatinine, and concomitant medications 
Abbreviations: AE, adverse event; AESI, adverse event of special interest; aGVHD, acute graft-versus-host disease; 
ANC, absolute neutrophil count; AST, aspartate transaminase, ALT, alanine transaminase, cGVHD, chronic 
graft-versus-host disease; Hb, hemoglobin; HCT, hematopoietic cell transplantation; PLT, platelets; SAE, 
serious adverse event, Tbili, total bilirubin. 
a  For physical exam, eCRF is designed to confirm whether a physical examination took place and the date of the 
exam; Clinical data from the physical examination will not be formally collected but clinically significant 
abnormal findings (i.e. adverse events) will be recorded. 
6.3.2 
AESIs 
Analyses of AESIs will be based on sites’ reporting of an AE belonging to 1 of the AESI 
categories listed below. AESIs for Orca-T are as follows:  
• Secondary malignancy, including posttransplantation lymphoproliferative disorder 
(PTLD) 
• Grade ≥3 infection 
• Graft failure (primary or secondary) 
• Thrombotic microangiopathy (TMA) 
• VOD/sinusoidal obstruction syndrome (SOS) 
6.3.3 
Identified and Potential Risks 
Identified and potential risks for Orca-T are listed below: 
• Identified risks 
− aGVHD 
− cGVHD 

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− Graft failure 
• Potential risks 
− Batch manufacturing failure 
− Infusion-related reaction (IRR) 
− Hypersensitivity 
− Grade ≥3 infection 
− TMA 
− VOD/SOS 
− Secondary malignancy, including PTLD 
For participants who received nonconforming Orca-T batches (ie, batch manufacturing failure), 
separate summaries of time to neutrophil engraftment, time to platelet engraftment, and the 
number of participants with primary or secondary graft failure will be provided. 
Except for batch manufacturing failure, AESIs and potential/identified risks are defined by a 
single preferred term (PT), system organ class (SOC), or SMQ. If there is not a relevant SMQ 
available or available SMQs do not align with the events typically seen in the transplant setting, 
customized MedDRA queries will be created based on medical review. 
Primary graft failure is defined as being alive without recovery of neutrophils (ie, without 
achieving an ANC ≥500/mm3 for 3 consecutive days) at day +28 without another identifiable 
cause such as relapsed/persistent disease. Secondary graft failure is defined as neutrophil 
engraftment followed by subsequent decline in ANC <500/mm3 unresponsive to growth factor 
therapy by day +100 without another identifiable cause such as relapsed/persistent disease. Graft 
failure includes both primary graft failure and secondary graft failure, which are reported as AEs. 
Analysis of IRRs and hypersensitivity require grouping of Medical Dictionary for Regulatory 
Activities preferred terms (PTs). IRR is defined as treatment-emergent AEs of any MedDRA PT 
listed in Table 14 with an onset within 24 hours after administration of any Orca-T or SoC 
infusion. Additional AEs may be added to Table 14 based on medical review of the accumulated 
data. The final set of AEs will be provided in the CSR.  
Hypersensitivity is defined as TEAEs identified within the SMQ of hypersensitivity and the 
SMQ of anaphylactic reaction with an onset within 24 hours of Orca-T or SoC infusion. The PTs 
retrieved from the 2 referenced SMQs will be medically reviewed and may be customized to 
ensure applicability to the TEAEs typically observed in the transplant setting. The final set of 
PTs for any modified SMQs of hypersensitivity and anaphylaxis will be provided in the 
summary of clinical safety. 
Infection includes all PTs under the SOC “infections and infestations.” For all infection events 
that are grade ≥3, customized MedDRA queries (Table 15) will be utilized that group events by 
type of organism (fungal, viral, bacterial, and other). The final PTs included to define each 
category will be included in the summary of clinical safety. 
Secondary malignancy, including PTLD, is defined as AEs included in the SMQ of malignancies 
that occurred following administration of Orca-T or SoC. 

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7 
ANALYSIS SETS 
7.1 
Donor Analysis Set 
The donor analysis set consists of all donors who complete mobilization and initiate apheresis. 
The donor analysis set will be used for all summary tables and listing for donors. 
7.2 
Recipient Analysis Sets 
The analysis sets for recipients are defined below: 
Analysis Set 
Description 
ITT analysis set 
All enrolled participants who are randomized to either Orca-T or SoC, regardless of 
whether they receive Orca-T/SoC or not. Participants will be analyzed according to their 
randomized treatment assignment.  
Per-protocol analysis set All participants in the ITT analysis set who meet all inclusion/exclusion criteria, receive 
their randomized treatment, and do not experience any important protocol deviations 
that may affect evaluation of the efficacy of the treatment. Important protocol deviations 
that may affect evaluation of the efficacy will be defined prior to the data snapshot for 
the interim analysis and may be updated for the primary analysis. 
Safety analysis set 
Participants in the ITT analysis set who have received either Orca-T or SoC from donors 
who are 8/8 match for HLA-A, -B, -C, and -DRB1, analyzed according to the treatment 
received. 
Abbreviations: ITT, intention to treat; SoC, standard of care. 
7.3 
Subgroup Analyses 
Subgroup analyses will be performed on the primary and secondary endpoints using the primary 
estimand for the subgroups defined below. Additionally, subgroup analyses will also be 
conducted on the primary and secondary endpoints derived based investigators’ assessment on 
aGVHD and/or cGVHD, as well as possibly on certain efficacy-related exploratory endpoints. 
Key safety tables, as discussed in section 10.6, may also be repeated for the same subgroups. The 
subgroups analyzed may include the following or others not listed here:  
•
Gender (male or female)
•
Gender match between donor and recipient (gender matched or gender mismatched)
•
Race (Caucasian or non-Caucasian)
•
Ethnicity (Hispanic/Latino or non-Hispanic/Latino)
•
DRI score (intermediate or high)
•
Donor status (MSD or MUD)
•
Underlying disease (AML, ALL, MPAL, or MDS)
•
HCT Comorbidity Index (HCT-CI) score (score ≤2 or score ≥3)
•
Conditioning regimen (total body irradiation [TBI]-based or BFT)
•
Receipt of DLI (yes or no)
•
FLT3, BCR‑ABL, or IDH1/2 inhibitors for prevention of relapse (yes or no)
•
Use of rituximab after HCT (yes or no)
•
Sites (Stanford or non-Stanford)
•
Relationship of CMV status at baseline between donor and recipient (positive/positive,
positive/negative, negative/positive, or negative/negative)

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• Relationship of ABO types between donor and recipient (A/A, A/AB, etc.) 
• Recipient age in years (≥55 or <55) 
• Donor age in years (above or below median) 
• MRD at baseline (participants with ALL or AML) (positive or negative) 
• Steroid responsive aGVHD treatment or steroid refractory aGVHD treatment or steroid 
dependent aGVHD treatment (participants who develop aGVHD with grade ≥ 2 only)   
 
In general, given a subgroup, if number of participants in either arm is less than 5, there is no 
need to repeat the efficacy tables for that subgroup. 

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Figure 1 
Planned Interim and Primary Analyses of Primary and Secondary Endpoints 
  
 

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9 
DATA SCREENING AND ACCEPTANCE 
9.1 
General Principles 
The objective of the data screening is to assess the quantity, quality, and statistical characteristics 
of the data relative to the requirements of the planned analyses. The database will be subject to 
edit checks outlined in the data management plan by Orca Bio Clinical Data Management 
(CDM). Any critical data issues will be communicated to CDM for resolution before the data 
snapshot for each of the planned analyses. 
9.2 
Data Handling and Electronic Transfer of Data 
Orca Bio CDM will provide all data to be used in the planned analyses. This study uses Zelta as 
EDC system. 
9.3 
Handling of Incomplete Dates 
9.3.1 
Imputation of Partially Missing Dates of AEs and Concomitant Medications 
The original dates reported by sites before any imputation will be used to determine whether an 
AE or a concomitant medication is treatment emergent or not. If an AE or concomitant 
medication cannot be determined to be treatment emergent or not due to a missing or partially 
missing start/end date, the AE or concomitant medication should be considered treatment 
emergent. 
For AEs and concomitant medication, start and stop dates with only the day missing may be 
imputed when the calculation of the duration of an AE or a concomitant medication is needed. If 
imputation of an incomplete stop date is required and both the start date and the stop date are 
incomplete, then the start date will be imputed first. 
9.3.1.1 
Missing Day Only for Start Date 
If the month and year of the incomplete start date are the same as the month and year of day 0, 
then day 0 will be assigned to the missing day. 
If either the year is before the year of day 0 or if both years are the same but the month is before 
the month of day 0, then the last day of the month will be assigned to the missing day. 
If either the year is after the year of day 0 or if both years are the same but the month is after the 
month of day 0, then the first day of the month will be assigned to the missing day. 
Concomitant procedure/surgery date is considered as start date and imputed using the same rule 
described above. 
9.3.1.2 
Missing Day Only for Stop Date 
If the stop date is the same year and month as the death date, the date of death will be assigned to 
the missing date; otherwise, the last day of the month will be assigned to the missing day.  
9.3.2 
Imputation of Partially Missing Dates of Other Datasets 
In addition to adverse event, concomitant medication, concomitant procedure/surgery, missing 
dates with only day missed from other datasets may be imputed if needed for the analysis, for 

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example, the last contact date in the Survival Status dataset. And in general, the date will be 
imputed the first day of the month unless such an imputation creates inconsistency within the 
dataset or cross different datasets.  
9.4 
Outliers 
Any suspected outliers will be investigated by the study team and will be included in the 
database unless they are determined to be the result of an error or if sufficient supporting 
evidence or explanation exists to justify their exclusion. Any outliers excluded from the analysis 
will be discussed in the CSR, including the reasons for exclusion and the impact of their 
exclusion on the study results. 
9.5 
Distributional Characteristics 
The statistical assumptions for analysis methods will be assessed. For example, the proportional 
hazards assumption will be visually checked by plotting log(-log(survival)) versus log(time) by 
treatment. If the assumptions for the distributional characteristics are not met, these will be 
described, and further analyses may be carried out using data transformations or alternative 
analysis methods. 
The use of transformations or alternative analysis methods will be justified in the CSR. 
9.6 
Validation of Statistical Analyses 
Tables, figures, and listings will be produced with validated programs. Programs will be 
developed and maintained and output will be verified in accordance with the sponsor’s relevant 
SOP(s). The production environment for statistical analyses consists of the SAS System 
version 9.4 or later. 

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10 
STATISTICAL METHODS OF ANALYSIS 
10.1 
General Principles 
Data will be pooled across sites for summary analyses unless specified otherwise.  
For both efficacy and safety analyses, summary tables will present the data by treatment. The 
overall summary of TEAEs will present data by conditioning regimen, treatment and separately 
by disease type, and treatment. 
The subgroup analyses described in section 7.3 will evaluate any potential differences in efficacy 
and safety between different disease types and/or conditioning regimens. 
For continuous variables, descriptive statistics will be presented, including the number of 
participants used in the calculation (n), mean, standard deviation (SD), median, and range 
(minimum and maximum). 
For categorical variables, summaries will reflect frequencies and percentages, with the 
denominator for percentages being the number of participants in the corresponding analysis set, 
unless specified otherwise.  
Listings will be provided and, if needed, sorted by site and participant number.  
10.2 
Participant Accountability 
The number and percentage of participants who were screened, randomized, received HCT 
(either Orca-T or SoC), were ongoing at the time of the data cutoff, ended active participation in 
the study (along with the reasons), and completed study will be summarized by treatment. The 
number and percentage of participants randomized will be tabulated by the stratification factors 
and by study site. Key study dates will be presented, including the first participant randomized, 
last participant randomized, and data cutoff date for analysis. 
10.3 
Important Protocol Deviations 
Important protocol deviations (IPDs) are defined as a subset of protocol deviations that might 
significantly affect the completeness, accuracy, and/or reliability of the study data or that might 
significantly affect a participant’s rights, safety, or well-being.  
IPD categories will be defined by the study team and updated during the IPD reviews throughout 
the study prior to database lock. These definitions of IPD categories, subcategory codes, and 
descriptions will be used for the study. 
The number and percentage of participants who experience each of the IPDs will be presented. A 
listing and a summary table by category of all IPDs will be provided. 
10.4 
Demographic and Baseline Characteristics 
Demographic (ie, age, age group [<55 or ≥55], sex, race, and ethnicity) and baseline disease 
characteristics will be summarized by treatment using descriptive statistics on the ITT analysis 
set. If multiple races have been reported for a participant, the participant will be categorized as 
multiple races. The baseline characteristics to be summarized include the following: 
• Primary disease 

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• Donor-recipient relationship: MUD or MSD 
• Karnofsky performance status score 
• HCT Comorbidity Index (HCT-CI) score (score ≤2 or score ≥3) 
• Disease status at transplantation (excluding MDS) 
• MRD at baseline (participants with AML or ALL only) (positive or negative) 
• IPSS-R prognostic score (MDS only) 
• DRI score (intermediate or high) 
• Relationship of CMV status between a recipient and the corresponding donor 
(negative/negative, negative/positive, positive/negative, or positive/positive) 
• Relationship of ABO types between donor and recipient (A/A, or, A/AB, etc.) 
• Gender match between donor and recipient (gender matched, or gender mismatched) 
10.5 
Efficacy Analysis 
The study will have an overall alpha of .05 with 2-sided testing.  
To preserve the overall significance level, statistical testing of the primary and secondary 
endpoints will follow a hierarchical structure.  
First, the primary endpoint of cGFS per EAC will be tested. The critical 2-sided P value for 
cGFS is .0116 for the interim analysis and .0464 for the primary analysis if the interim analysis 
is based on exactly 37 events out of the total of 56 events using the spending function described 
in section 8. If the primary endpoint is significant, secondary endpoints will be tested 
sequentially. For each of the secondary endpoints, if tested, a generalized Haybittle–Peto 
boundary will be used between the interim and primary analyses. That is, the critical value for 
the P value at each of the interim analyses will be 2-sided .0001, while the critical value at the 
primary analysis will still be 2-sided .05. 
If Orca-T demonstrates superiority to SoC with respect to cGFS per the EAC, the secondary 
endpoint of time to moderate or severe cGVHD per the EAC will be tested. If Orca-T 
demonstrates superiority to SoC with respect to time to moderate or severe cGVHD per the EAC, 
the secondary endpoint of OS will be tested. If Orca-T demonstrates superiority to SoC with 
respect to OS,GRFS per the EAC up to 2 years will be tested. 
The time of the occurrence of 56 cGFS events will be used to define the timing of interim or 
primary analysis for secondary endpoints as described in section 8, even if the primary efficacy 
endpoint cGFS has already been assessed as significant at the time of its interim analysis and will 
not be tested at the primary analysis. 
For time-to-event endpoints without competing risks, the presentation will be by treatment and 
include the number of participants who were censored and the number of participants who 
experienced the event of interest along with their respective percentages. The Kaplan-Meier 
method will be applied to estimate event-free probabilities at selected timepoints and quantiles 
for each treatment arm. Greenwood’s formula (Kalbfleish and Prentice 1980) for standard error 
will be used to calculate confidence intervals (CIs) for the estimated event-free probability. CIs 
for quartiles of each group will be estimated per Brookmeyer and Crowley (Brookmeyer and 
Crowley 1982) using a log-log transformation. The analysis will be complemented by the 
provision of Kaplan-Meier curves by treatment. The P value for the hypothesis test for the 
primary estimand will be calculated from a stratified log-rank test stratified by randomization 

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stratification factors. In addition, a stratified Cox model stratified by randomization stratification 
factors will be applied to provide the hazard ratio (HR) between the 2 arms for the primary 
estimand. For sensitivity analyses, an unstratified log-rank test and unstratified Cox model may 
be used. 
For time-to-event endpoints with a competing event, the presentation will be by treatment arm 
and include the number of participants who were censored, the number of participants who 
experienced the event of interest, and the number of participants who experienced a competing 
event, along with the corresponding percentages. Nonparametric estimation of the cumulative 
incidence rate by treatment accompanied by the corresponding 95% CI at selected timepoints, 
considering the presence of competing risk events, will be provided. Curves illustrating 
cumulative incidence along the time since randomization will also be provided. Gray’s test 
(Gray 1988) will be performed to assess the equality of cumulative incidence functions between 
treatment groups. The P value for the hypothesis test for the primary estimand will be calculated 
from the stratified Gray's test stratified by randomization stratification factors, and the stratified 
subdistribution proportional hazards model (Fine and Gray 1999; Zhou et al. 2011) stratified by 
randomization stratification factors will be used to calculate treatment HR with 95% CI. For 
sensitivity analyses, an unstratified Gray’s test (Gray 1988) and unstratified subdistribution 
proportional hazards model (Fine and Gray 1999) may be used. 
Reverse Kaplan-Meier method (Schemper and Smith, 1996) will be used to provide the median 
follow time for cGFS, OS, and GRFS. 
10.5.1 
EAC Output 
The EAC will review blinded patient profiles from the clinical database which may include 
aGVHD/cGVHD assessments; concomitant medication; posttransplantation anticancer therapy; 
GVHD prophylaxis; hospitalizations; AEs; relevant laboratory test results; ALT, AST, and 
bilirubin values; CMV viral loads; C diff test results; and PFT results, if performed. Additional 
source documents will also be provided directly from sites to the EAC as part of the standard 
dossier contents for cases/events requiring review (EAC Charter version 1.0, section 8).  
Instead of providing a by-visit assessment, the EAC will provide an overall GVHD profile to 
include the whole safety follow-up course, including but not limited to the following: 
• Whether or not a participant experienced aGVHD/cGVHD 
− If not, the last documented absence of aGVHD/cGVHD 
− If yes, the worst overall grade/severity and the date of either the onset of a GVHD 
event of interest or the last date when the participant is free of GVHD events of 
interest. GVHD events of interest are grade 3 or 4 aGVHD or moderate or severe 
cGVHD. 
The EAC output description above will be used to derive all the related endpoints per EAC. Note 
that the evaluation of missing cGVHD/aGVHD assessments will also be based on whether a 
scheduled cGVHD/aGVHD survey was performed by investigators and nominal visit names 
(day +56, day +100, etc.) reported by investigators will be used for efficacy endpoints per EAC 
since EAC does not provide by-visit assessments.  

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10.5.2 
Intercurrent Event and Missing Visits for Estimands 
10.5.2.1 
Intercurrent Event 
Treatment policy will be used for all intercurrent events defined in section 6.2 for the primary 
estimands for all the time-to-event endpoints.  
A summary of intercurrent events will be provided by treatment and may include the number and 
percentage of participants who experienced each of the intercurrent events. 
Sensitivity/supplementary analyses with hypothetical policies employed for intercurrent events 
will be performed. 
10.5.2.2 
Missing Assessments 
Primary estimands for cGFS and time to moderate or severe cGVHD will handle the data 
differently when there is a missing cGVHD assessment(s), and details are provided in Table 1 
and Table 2. If an unscheduled assessment is conducted within 1 month of a missed scheduled 
assessment, the missed scheduled assessment will not be counted as missing. 
All events of interest for the time to event endpoints (ie, moderate or severe cGVHD, grade 3 or 
4 aGVHD, and relapse) are severe events that are unlikely to be overlooked by investigators or 
other site personnel or to go unreported by participants. Therefore,  sensitivity analyses will be 
performed by including all events and/or assessments regardless of the extent of missing data. 
For cGFS and exploratory endpoints, missing assessments will be disregarded and all the 
assessments and/or events after the missing assessments will be included for the derivation of the 
endpoints as their primary estimands.  
Details are provided in the corresponding estimands. 
10.5.3 
Analysis of Primary Efficacy Endpoint 
A 2-sided stratified log-rank test stratified by the randomization factors will be used to compare 
cGFS per EAC between the Orca-T group the SoC group. In addition, the HR with a 95% CI will 
be estimated from a stratified Cox regression model stratified by the randomization factors. The 
KM summaries described in section 10.5 will be performed by treatment. The primary analysis 
will be performed on the ITT analysis set using the primary estimand described in Table 1.  
Sensitivity and supplementary analyses described in Table 17 will be performed. Those 
sensitivity and supplementary analyses differ from the primary estimand in 1 or more of the 
following aspects: 
• The per-protocol analysis set will be used instead of the ITT analysis set. 
• For GVHD related endpoints, assessments per investigator will be used versus 
assessments per EAC. To derive endpoints per investigator assessment for aGVHD 
and/or cGVHD, only the information from the aGVHD/cGVHD survey eCRF will be 
used, although additional information may be available in adverse event and 
aGVHD/cGVHD response eCRFs, since the aGVHD/cGVHD survey eCRF provides the 
most comprehensive evaluation.  
• Unstratified analyses will be used instead of stratified ones. 
• Hypothetical policy instead of treatment policy will be used to handle intercurrent events. 
• Different approaches will be used when there is a missing assessment. 

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Subgroup analyses will be performed to explore the consistency of the treatment effect for 
subgroups described in section 7.3. To examine the impact of stratification errors (if any), the 
primary analysis may be repeated using the values of the stratification values reported on the 
CRF rather than through Interactive Web Response System (IWRS) if discrepancy between those 
two is observed.  
10.5.4 
Analysis of Secondary Efficacy Endpoints 
As described in section 10.5, if the primary endpoint is significant, the secondary endpoints will 
use a fixed sequence algorithm with the endpoints tested in the following order, with a given 
endpoint tested only if all the previous endpoint tests were significant: 
1. cGFS per EAC 
2. Time to moderate-to-severe cGVHD per EAC 
3. OS 
4. GRFS per EAC up to 2 year 
The interim and primary analyses for each secondary endpoint, if tested, are planned as described 
in Figure 1. 
A generalized Haybittle–Peto boundary will be used between the interim and primary analyses 
for secondary endpoints. That is, the critical value for the P value at each of the interim analyses 
will be 2-sided .0001, while the primary analysis will maintain the 2-sided critical value of .05. 
For time to moderate-to-severe cGVHD per EAC, the primary estimand is provided in Table 2. 
The P value from the stratified Gray's test (Gray 1988) stratified by randomization stratification 
factors will be used to determine whether the hypothesis test is significant. The analysis 
approaches for time-to-event endpoints with a competing event described in section 10.5 will be 
used. Sensitivity and supplementary analyses similar to those for the primary endpoint and 
described in Table 18 will be performed. 
For OS, the primary estimand is provided in Table 3. The P value from the stratified log-rank 
test stratified by randomization stratification factors will be used to determine whether the 
hypothesis test is significant. KM analysis approaches and Cox models described in section 10.1 
will be used. Sensitivity and supplementary analyses described in Table 20 will be performed. 
For GRFS per EAC up to 2 year, the primary estimand is provided in Table 4. The P value from 
the stratified log-rank test stratified by randomization stratification factors will be used to 
determine whether the hypothesis test is significant. KM analysis approaches and Cox models 
described in section 10.5 will be used. Sensitivity and supplementary analyses described in 
Table 19 will be performed. 
10.5.5 
Analysis of Exploratory Efficacy Endpoints 
For each of exploratory endpoints, the corresponding analysis set is defined in section 4.1.3. 
For NRM, the primary estimand is provided in Table 5. The descriptive P value from the 
stratified Gray's test (Gray 1988) stratified by randomization stratification factors will be 
provided. The analysis approaches time to event endpoints with a competing event described in 
section 10.5 will be used. 

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For RFS, the primary estimand is provided in Table 6. The descriptive P value from the stratified 
log-rank test stratified by randomization stratification factors will be used to determine whether 
the hypothesis test is significant. KM analysis approaches and Cox models described in 
section 10.5 will be used. 
Death up to day +100 and death up to day +180 will be summarized.  
Time to grade 2 through 4 aGVHD, time to grade 3 or 4 aGVHD, time to grade ≥3 infection, and 
time to grade ≥4 infection with death as a competing event will be analyzed using approaches 
described in section 10.5 for time-to-event endpoints with a competing event. 
The summary of all grade aGVHD and cGVHD, steroid-refractory aGVHD and steroid-
refractory cGVHD, and grade ≥3 mucositis and grade ≥4 mucositis will be provided as part of 
the safety summary.  
For the incidence and timing of neutrophil engraftment, the number of participants who have 
achieved neutrophil engraftment either by day +28 and by day +100 will be provided by 
treatment. Summary statistics will also be provided including mean, SD, median, Q1, Q3, and 
range for days from day 0 to neutrophil engraftment. Similarly, the number of participants who 
have achieved platelet engraftment by day +50 and by day +100 will be provided with summary 
statistics. The same summary statistics will also be provided for days from day 0 to platelet 
engraftment. Additionally, the incidence of platelet transfusions will also be summarized. 
The number of participants who received TPN will be summarized by treatment received. 
The duration of initial hospitalization due to alloHCT starting from day 0 will be summarized by 
treatment received, together with the number of participants who are admitted to the ICU and the 
number of days in the ICU due to alloHCT. 
The number of participants who are rehospitalized due to AEs, cumulative duration of 
rehospitalization due to AEs, number of periods of rehospitalization due to AEs, and average 
duration of rehospitalization due to AEs will be summarized by treatment received. The same 
analysis will be performed for number of participants who are admitted to ICU due to AEs, 
cumulative days in the ICU due to AEs, number of times of admission to the ICU due to AEs, 
and average days in the ICU per time due to AEs. 
The number and percentage of participants who meet criteria for ISFS will be summarized by 
treatment received. 
The absolute number (per μL of peripheral blood) of T cells, NK cells, and B cells in recipients 
will be summarized by treatment received.  
The analysis of health-related QoL endpoints is described in section 10.5.6. 
10.5.6 
Analysis of Health-Related QoL Endpoints 
10.5.6.1 
FACT-BMT and EQ-5D-5L 
FACT-BMT and EQ-5D-5L will be used for this study, with assessments taken at screening, 
day +14, day +28, day +56, day +100, day +180, day +270, day +365, and day +730. 

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EQ-5D-5L  
The EQ-5D-5L is a widely used generic measure of health status consisting of 2 parts. The first 
part (the descriptive system) assesses health in 5 dimensions (mobility, self-care, usual activities, 
pain/discomfort, anxiety/depression), each of which has 5 levels of response (no problems, slight 
problems, moderate problems, severe problems, extreme problems/unable to). This part of the 
EQ-5D questionnaire provides a descriptive profile that can be used to generate a health state 
profile. The second part of the questionnaire consists of a visual analogue scale (VAS) on which 
the patient rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best 
imaginable health). 
The measurements from this instrument include EQ-5D-5L dimension responses, EQ VAS, and 
EQ-5D index. The EQ-5D index will be calculated using United States of America value sets 
(Pickard et al. 2019; Euro QoL 2022) 
FACT-BMT  
The FACT-BMT was designed to measure QoL in patients undergoing bone marrow 
transplantation. It combines the FACT-G, a widely used assessment primarily assessing physical 
well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), and 
functional well-being (FWB), with Bone Marrow Transplantation Subscale (BMTS) to measure 
BMT-specific concerns (McQuellon et al. 1997). The following scores will be derived from the 
questionnaire: 
• PWB score 
• SWB score 
• EWB score 
• FWB score 
• BMTS score 
• FACT-BMT trial outcome index (TOI) 
• FACT-G total score 
• FACT-BMT total score 
The assessment taken at screening will be the baseline assessment. For each score listed for 
FACT-BMT and EQ VAS and EQ-5D index, the analysis will be performed on the safety 
analysis set subjects who have valid baseline value and at least one postbaseline value. 
The scores listed for FACT-BMT and EQ VAS and EQ-5D index will be summarized 
descriptively at each visit for the observed value, change from baseline, and percent change from 
baseline. EQ-5D-5L dimension response will be summarized by presenting the number of 
participants and percentage for each level of response by visit. For FACT-BMT total score and 
EQ-5D index, the number and percentage of participants who have achieved minimal clinical 
important difference (MCID) will also be provided. MCID here refers to FACT BMT total score 
change from baseline ≥7 or EQ-5D index change from baseline ≥0.07 (McQuellon et al. 1997; 
Yost and Eton 2005; Pickard et al. 2007). 
For each of the scores listed for FACT-BMT, EQ VAS, and EQ-5D index, a mixed effects model 
for repeated measures (MMRM) will be performed to compare the between-treatment difference 
adjusting for correlations across multiple timepoints within a participant and controlling for the 
baseline value. Adjusted mean difference and 95% CIs will be presented to illustrate the effect of 

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number of participants whose postbaseline worst laboratory assessment has a higher grade than 
the baseline assessment, and the number of participants whose postbaseline worst grade is grade 
3 or 4, together with the percentage. Baseline is defined as the last assessment prior to the day of 
conditioning regimen. If the laboratory assessment is taken on the same day as the first day of the 
conditioning regimen, the laboratory assessment is considered to be after the conditioning 
regimen. The postbaseline refers to the assessments after unmanipulated SoC allograft or Orca-T 
HSPC transfusion. 
Only baseline and treatment emergent laboratory assessments will be included for the summary 
tables. The treatment emergent period for laboratory data is described in more detail in Table 11. 
A listing of the results with CTCAE grade for selected laboratory parameters will be provided. 
All the laboratory assessments for the selected parameters will be presented in the listings with 
treatment emergent records flagged.  
Laboratory test-related AEs defined by the SMQ of haemorrhage laboratory terms and the 
SMQof haematopoietic cytopenias will be summarized by SOC, PT, and worst grade 
(section 10.6.1.1). 
10.6.4 
Vital Signs 
Summary of statistics for temperature, supine systolic blood pressure (BP), supine diastolic BP, 
pulse, respiratory rate, and pulse oximetry will be provided for 30 minutes and 1 hour 
assessments following administration of Orca-T HSPC/Treg/Tcon infusion and SoC HCT 
infusion including baseline assessments. Summary of the number and percentage of participants 
who have the following outlier vital signs will also be provided: 
•
Temperature ≥38°C
•
Systolic blood pressure (SBP) <90 mmHg
The treatment emergent period for vital signs is described in more detail in Table 11. A listing of 
vital signs will also be provided with treatment emergent records flagged. 
10.6.5 
Karnofsky Performance Score 
Karnofsky performance score will be summarized for each visit by treatment. Shifts from 
baseline to the best and worst post-baseline score may be tabulated. 
10.6.6 
Chimerism 
The percentage of donor granulocytes, T cells, B cells, NK cells, and CD34+ cells will be 
summarized for recipients by treatment and visit. Additional analysis may include visual 
presentation of the data or summarization of data within a subgroup. 
10.6.7 
Exposure to Investigational Product 
For each of the Orca-T infusions (HSPC, Treg, and Tcon), summary statistics will be provided by 
treatment group for the following variables as outlined in  CD45+ cell dose/kg, viable cell 
dose/kg, total CD45+ cell dose (CD45+ cell dose/kg times participant’s weight), and viable cell 
dose (viable cell dose/kg times participant's weight) as shown in Table 12. 

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10.6.8.2 
GVHD Prophylaxis 
All GVHD prophylaxis medication received by participants from day 0 through 2 years (plus the 
visit window of 21 days) will be included in the summary. The pharmacokinetic profile of 
tacrolimus will be evaluated. 
10.6.8.3 
GVHD Treatment 
All GVHD treatment medications received by participants from day 0 through 2 years (plus the 
visit window of 21 days) will be included in the summary. Summary statistics (the number and 
percentage) for participants who are steroid responsive and who are steroid refractory will be 
provided. 
Concomitant surgery and procedures after HCT and within 2 years after HCT will also be 
summarized by treatment received, ATC classification (level 2), and PT (see Table 11). 
10.6.8.4 
Exposure Response Analysis 
An exploratory exposure-response analysis will be performed in the safety analysis set to 
evaluate the dose-response relationship for each of Orca-T's components. The exposure-related 
variables (independent variables) and output endpoints (dependent variables) for the analysis are 
listed in Table 13. Selection of these endpoints is based on the biological plausibility of an effect 
produced by each component of Orca-T, and only those participants whose drug product meets 
release specifications will be included in the respective analysis. 
Table 13 
Planned Exposure-Response Analyses 
Dose Specification 
Endpoint(s) 
HSPCs 
 
Total number of viable CD34+ cells 
neutrophil engraftmenta by day +28 (yes or no) 
Dose of viable CD34+ cells/kg 
neutrophil engraftmenta by day +28 (yes or no) 
Tregs 
 
Total number of viable Treg cells 
moderate or severe cGVHD (yes or no) at 1 year 
Dose of viable Treg cells/kg 
moderate or severe cGVHD (yes or no) at 1 year 
Tcons 
 
Total number of viable Tcon cells 
CD3 count over time 
Dose of viable Tcon cells/kg 
CD3 count over time 
Abbreviations: ANC, absolute neutrophil count; cGVHD, chronic graft-versus-host disease; HSPCs, hematopoietic 
stem and progenitor cells; Tcons, conventional T cells; Tregs, regulatory T cells 
a     Neutrophil engraftment is defined as achieving an ANC ≥500/mm3 for 3 consecutive days by day +28. The first 
of the 3 days is designated the day of engraftment. If ANC never drops below 500/mm3, day +1 is designated 
the day of engraftment. 
 
Unstratified and stratified Cochran-Mantel-Haenszel test with continuity correction will be 
conducted for the binary endpoints. The stratification will be the conditioning regimen (TBI vs 

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non-TBI). For CD3 count over time, longitudinal analysis models will be applied with 
appropriate covariates.  
Additional clinical outcome endpoints and statistical models may be explored for the exposure-
response analyses if needed. 

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12 
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Figure 1 
Planned Analyes for Primary and Secondary Endpoints