A Phase 2 Open-Label Study to Evaluate Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)
Phase: PHASE2
Conditions: Very Low Risk, Low Risk, or Intermediate Risk MDS Per IPSS-R
Sponsor: Forma Therapeutics, Inc.

Cover Page for Protocol 
Sponsor name: 
Forma Therapeutics, a Novo Nordisk Company 
NCT number 
NCT05568225 
Sponsor trial ID: 
4202-ONC-203 
Official title of study: 
A Phase 2 Open-Label Study to Evaluate Etavopivat for the 
Treatment of Anemia in Patients with Myelodysplastic 
Syndromes (MDS) 
Document date*: 
31-Jul-2023
*Document date refers to the date on which the document was most recently updated.

Forma Therapeutics, Inc. 
Clinical Study Protocol 4202-ONC-203 
1 of 77 
Version 3.0; 31 July 2023 
CLINICAL TRIAL PROTOCOL 
Protocol No. 
4202-ONC-203 
Title: 
A Phase 2 Open-Label Study to Evaluate Etavopivat for the Treatment of 
Anemia in Patients with Myelodysplastic Syndromes (MDS) 
IND No.: 
160509 
Version: 
3.0 
Date: 
31 July 2023 
Prior Version(s): 
2.0 
Prior Date(s) 
15 June 2022 
1.0 
11 April 2022 (Not Implemented) 
Sponsor: 
Forma Therapeutics, Inc. 
300 North Beacon Street, Suite 501 
Watertown, MA 02472 
Telephone: 617-679-1970 
Medical Lead: 
Medical Monitoring 
Email: Fortitude_medicalmonitor@novonordisk.com 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
2 of 77 
Version 3.0; 31 July 2023 
INVESTIGATOR AGREEMENT PAGE  
Forma Therapeutics, Inc. 
Protocol 4202-ONC-203, Version 3.0 
31 July 2023 
By signing below I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary 
details for carrying out the study as described. I will conduct this study in accordance with 
the design and specific provision of this protocol and will make a reasonable effort to 
complete the study within the time designated. I will provide copies of this protocol and 
access to all information furnished by Forma Therapeutics to study personnel under my 
supervision. I will discuss this material with them to ensure they are fully informed about the 
study product and study procedures. I will let them know that this information is confidential 
and proprietary to Forma Therapeutics and that it may not be further disclosed to third 
parties. I understand that the study may be terminated, or enrollment suspended at any time 
by Forma Therapeutics, with or without cause, or by me if it becomes necessary to protect the 
best interests of the study subjects. 
I agree to conduct this study in full accordance with Food and Drug Administration 
Regulations, Institutional Review Board/Ethic Committee Regulations, Declaration of 
Helsinki and International Council for Harmonisation Guidelines for Good Clinical Practices, 
along with any applicable state and local regulations and any other institutional requirements. 
 
 
 
 
Principal Investigator 
 
Date 
Institution: 
 
Address 
 
 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
3 of 77 
Version 3.0; 31 July 2023 
SERIOUS ADVERSE EVENT REPORTING  
COMPLETE THE NOVO NORDISK SERIOUS ADVERSE EVENT (SAE) REPORT 
FORM AND SUBMIT TO NOVO NORDISK GLOBAL SAFETY WITHIN 24 HOURS 
OF KNOWLEDGE OF ANY SAE. IF THE SAE IS FATAL OR LIFE 
THREATENING, NOVO NORDISK MUST BE INFORMED IMMEDIATELY. 
 
EMAIL (encrypted), FAX, or upload to the 
CLINICAL WEBFORM the SAE REPORT 
FORM TO: 
GLOBAL MEDICAL MONITOR 
Fax: + 45 44427787 
Email: SOCLIN@NOVONORDISK.COM  
Webform: 
https://www.novonordisk.com/contact-
us/partners-safety-information-reporting-
hq.html 
 
Email: Fortitude_medicalmonitor@novonordisk.com 
For reporting of all SAEs, Investigators must email (encrypted), fax, or upload to the 
clinical webform all completed pages of the SAE report form within 24 hours of 
knowledge of the event to the following: 
Novo Nordisk Global Safety 
FAX: + 45 44427787 
EMAIL: SOCLIN@NOVONORDISK.COM  
CLINICAL WEBFORM: https://www.novonordisk.com/contact-us/partners-safety-
information-reporting-hq.html 
FOLLOW-UP INFORMATION TO SAEs MUST BE PROVIDED TO NOVO NORDISK 
GLOBAL SAFETY WITHIN 24 HOURS OF INVESTIGATOR KNOWLEDGE OF THE 
EVENT. 
ALL FORMS MUST BE DATED AND SIGNED 
In case of any questions, please reach out to: 
Fortitude_medicalmonitor@novonordisk.com 
 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
4 of 77 
Version 3.0; 31 July 2023 
TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT PAGE ....................................................................... 2 
SERIOUS ADVERSE EVENT REPORTING ................................................................ 3 
TABLE OF CONTENTS .................................................................................................. 4 
1.0 
PROTOCOL SUMMARY .................................................................................. 12 
1.1 
Synopsis ..................................................................................................... 12 
Novo Nordisk Safety Committee ............................................................... 16 
1.1.1 
Study Safety Review Committee .............................................. 16 
1.1.2 
Dose-limiting Toxicities Evaluation Period/Definition ............ 16 
1.2 
Schema ....................................................................................................... 18 
2.0 
INTRODUCTION................................................................................................ 24 
2.1 
Study Rationale .......................................................................................... 24 
2.2 
Background ................................................................................................ 24 
2.3 
Risk/Benefit Assessment ........................................................................... 25 
2.3.1 
Risk Assessment ....................................................................... 26 
2.3.2 
Benefit Assessment ................................................................... 27 
2.3.3 
Overall Benefit: Risk Conclusion ............................................. 28 
3.0 
STUDY OBJECTIVES AND ENDPOINTS ...................................................... 29 
3.1 
Primary Objective and Endpoints .............................................................. 29 
3.2 
Secondary Objectives and Endpoints......................................................... 29 
3.3 
Pharmacokinetic / Pharmacodynamic Objective and Endpoints ............... 30 
3.4 
Exploratory Objectives and Endpoints ...................................................... 30 
4.0 
STUDY DESIGN .................................................................................................. 31 
4.1 
Overall Design ........................................................................................... 31 
4.2 
Justification for Dose ................................................................................. 32 
4.3 
Treatment and Study Duration ................................................................... 32 
4.3.1 
Treatment Duration ................................................................... 32 
4.3.2 
End of Study Definition ............................................................ 33 
4.4 
Safety Committees Structure ..................................................................... 33 
4.4.1 
Novo Nordisk safety committee ............................................... 33 
4.4.2 
Study Safety Review Committee .............................................. 33 
4.5 
Dose-Limiting Toxicities Evaluation Period/Definition ............................ 33 
5.0 
STUDY POPULATION ...................................................................................... 35 
5.1 
Inclusion Criteria ....................................................................................... 35 
5.2 
Exclusion Criteria ...................................................................................... 36 
5.3 
Screen Failures ........................................................................................... 38 
6.0 
STUDY INTERVENTION, CONCOMITANT THERAPY, AND 
PRECAUTIONS .................................................................................................. 39 
6.1 
Clinical Trial Material................................................................................ 39 
6.2 
Preparation/ Handling/ Storage/ Accountability ........................................ 39 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
5 of 77 
Version 3.0; 31 July 2023 
6.3 
Study Drug Administration ........................................................................ 39 
6.4 
Study Intervention Compliance ................................................................. 40 
6.5 
Treatment of Overdose .............................................................................. 40 
6.6 
Missed Dose ............................................................................................... 40 
6.7 
Concomitant Therapy................................................................................. 40 
6.7.1 
Concomitant Medications ......................................................... 40 
6.8 
Precautions ................................................................................................. 41 
6.8.1 
Childbearing Potential ............................................................... 41 
6.8.1.1 
Contraception Guidelines................................................... 41 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/ WITHDRAWAL ......................................................... 43 
7.1 
Dose Modification / Discontinuation of Study Intervention...................... 43 
7.1.1 
Adverse Event Interruption/Stopping Criteria .......................... 43 
7.1.2 
Study Intervention Restart or Rechallenge after Stopping 
Criteria Met ............................................................................... 44 
7.2 
Treatment Discontinuation/ Withdrawal from the Study ........................... 44 
7.2.1 
Treatment Discontinuation ........................................................ 44 
7.2.2 
Study Withdrawal...................................................................... 45 
7.3 
Lost to Follow-up ....................................................................................... 45 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .............................................. 46 
8.1 
Baseline Characteristics ............................................................................. 46 
8.1.1 
Medical History ......................................................................... 46 
8.1.2 
MDS Disease History ................................................................ 46 
8.1.3 
Transfusion History ................................................................... 46 
8.1.4 
Medication History.................................................................... 46 
8.1.5 
Viral Serology / Antigen Testing .............................................. 46 
8.1.6 
Bone Marrow Aspirate .............................................................. 47 
8.2 
Efficacy Assessments................................................................................. 47 
8.2.1 
MDS Disease Assessment ......................................................... 47 
8.2.2 
Assessment of Transfusions ...................................................... 47 
8.2.2.1 
LTB/HTB Patient Transfusion Treatment Plan: ................ 47 
8.2.3 
Hemoglobin Response and Clinical Measures of Hemolysis ... 47 
8.2.4 
Iron Chelation Therapy and Iron Profile ................................... 47 
8.2.5 
Patient-Reported Outcomes ...................................................... 48 
8.2.6 
Bone Marrow Aspirate .............................................................. 48 
8.3 
Safety Assessments .................................................................................... 48 
8.3.1 
Clinical Laboratory Assessments .............................................. 48 
8.3.2 
Physical Examination ................................................................ 48 
8.3.3 
Hematology ............................................................................... 48 
8.3.4 
Hemoglobin Electrophoresis ..................................................... 48 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
6 of 77 
Version 3.0; 31 July 2023 
8.3.5 
Coagulation Parameters ............................................................ 48 
8.3.6 
Serum Chemistry ....................................................................... 49 
8.3.7 
Urinalysis .................................................................................. 49 
8.3.8 
12-Lead Electrocardiogram ....................................................... 49 
8.3.9 
Pregnancy .................................................................................. 49 
8.3.10 
Concomitant Medications and Procedures ................................ 49 
8.4 
Pharmacokinetic Sampling ........................................................................ 49 
8.5 
Pharmacodynamic Sampling ..................................................................... 50 
8.6 
Exploratory Laboratory Assessments ........................................................ 50 
8.7 
Adverse Events, Serious Adverse Events, and Other Safety Reporting .... 50 
8.7.1 
Definition of an Adverse Event................................................. 50 
8.7.2 
Serious Adverse Events............................................................. 50 
8.7.2.1 
Definition ........................................................................... 50 
8.7.2.2 
Events or Outcomes Not Qualifying as Serious Adverse 
Events ................................................................................ 51 
8.7.3 
Clinical Laboratory Assessments as Adverse Events ............... 51 
8.7.4 
Pregnancy or Drug Exposure during Pregnancy ....................... 52 
8.7.5 
Procedures for Recording and Reporting Adverse Events and 
Serious Adverse Events............................................................. 52 
8.7.6 
Grading the Severity of Adverse Events ................................... 52 
8.7.7 
Causal Relationship of Adverse Events to Investigational 
Medicinal Products.................................................................... 53 
8.7.8 
Outcome and Action Taken ...................................................... 53 
8.7.8.1 
Action Taken with Study Drug .......................................... 53 
8.7.8.2 
Outcome ............................................................................. 54 
8.7.9 
Follow-up of Adverse Events and Serious Adverse Events...... 54 
8.7.10 
Regulatory Aspects of Serious Adverse Event Reporting ........ 54 
8.7.10.1 
Investigator and Sponsor Responsibilities ......................... 54 
8.7.10.2 
Sponsor Reporting Timeline .............................................. 54 
8.7.11 
Special Situation Reports .......................................................... 54 
9.0 
STATISTICAL CONSIDERATIONS ............................................................... 56 
9.1 
Statistical Methods ..................................................................................... 56 
9.2 
Patient Populations for Analysis ................................................................ 56 
9.3 
Sample Size Considerations ....................................................................... 56 
9.4 
General Statistical Considerations ............................................................. 56 
9.4.1 
Multicenter Studies ................................................................... 56 
9.4.2 
Handling of Missing Data ......................................................... 57 
9.5 
Futility Assessment and Decision Rules .................................................... 57 
9.6 
Analysis of Efficacy ................................................................................... 57 
9.6.1 
Analysis of Primary Efficacy Endpoint .................................... 57 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
Clinical Study Protocol 4202-ONC-203 
 
7 of 77 
Version 3.0; 31 July 2023 
9.6.2
Analysis of Secondary Efficacy Endpoints ............................... 58
9.6.2.1
HI-E Criteria ≥ 8 weeks ..................................................... 58
9.6.2.2
HI-E criteria ≥ 16 weeks .................................................... 58
9.6.2.3
Additional Measures of Clinical Benefit ........................... 58
9.6.3
PK/PD and Exploratory Efficacy Analyses .............................. 59
9.6.3.1
Pharmacokinetic and/or Pharmacodynamic Modelling ..... 59
9.7 
Analysis of Study Population Endpoints ................................................... 59
9.7.1
Disposition and Reasons for Discontinuation ........................... 59
9.7.2
Demographics and Other Baseline Characteristics ................... 60
9.7.3
Study Drug Compliance ............................................................ 60
9.8 
Analysis of Safety Assessments................................................................. 60
9.8.1
Adverse Events.......................................................................... 60
9.8.2
Other Safety Assessments ......................................................... 60
10.0 
DATA MANAGEMENT AND RECORD KEEPING...................................... 62
10.1.1
Data Handling ........................................................................... 62
10.1.2
Computer Systems .................................................................... 62
10.1.3
Data Entry ................................................................................. 62
10.1.4
Medical Information Coding ..................................................... 62
10.1.5
Data Validation ......................................................................... 62
10.2
Record Keeping ......................................................................................... 62
11.0 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL ............ 63
11.1
Ethical Conduct of the Study ..................................................................... 63
11.2
Institutional Review Board/ Independent Ethics Committee..................... 63
11.3
Informed Consent....................................................................................... 63
11.4
Study Monitoring Requirements ................................................................ 63
11.5
Visits and Assessments in Emergency Situations ...................................... 64
11.6
Disclosure of Data...................................................................................... 64
11.7
Retention of Records.................................................................................. 64
11.8
Publication Policy ...................................................................................... 65
12.0 
REFERENCES ..................................................................................................... 66
13.0 
APPENDICES ...................................................................................................... 69
APPENDIX A:
RESPONSE CRITERIA FOR MDS ..................................... 69
APPENDIX B:
INTERNATIONAL PROGNOSTIC SCORING SYSTEM 
SCORE – REVISED ............................................................................................ 71
APPENDIX C:
DIAGNOSIS OF IDIOPATHIC/DE NOVO MDS 
ACCORDING TO WORLD HEALTH ORGANIZATION ............................ 73
APPENDIX D:
ECOG PERFORMANCE STATUS ...................................... 74
APPENDIX E:
CLINICAL LABORATORY ANALYTES .......................... 75
APPENDIX F:
EXAMPLES OF DRUGS THAT ARE STRONG 
INDUCERS OF CYP3A4/5 ................................................................................. 76
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
8 of 77 
Version 3.0; 31 July 2023 
APPENDIX G: 
SAMPLE TRANSFUSION PLAN: LTB AND HTB 
PATIENTS 
77 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
9 of 77 
Version 3.0; 31 July 2023 
LIST OF TABLES 
Table 1-1: 
Schedule of Events, Primary and Extension Treatment Periods.... 19 
Table 1-2  Schedule of Events – Optional Prolonged Treatment Period ........................... 22 
Table 6-1 
Acceptable contraceptive methods ................................................ 42 
Table 7-1  Suggested Dose Modifications for Treatment Related AEs ............................. 43 
 
LIST OF FIGURES 
Figure 1: 
PKR Activation as a Strategy to Reduce the Anemia Associated 
with Myelodysplastic Syndrome.................................................... 25 
Figure 2: 
Healthy Volunteers PK/PD Simulations Identifies Potential Phase 2 
Dose Selections .............................................................................. 27 
Figure 3: 
Schema ........................................................................................... 31 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
10 of 77 
Version 3.0; 31 July 2023 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
2,3-DPG 
2,3-diphosphoglycerate 
AE 
adverse event 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ATC 
Anatomical Therapeutic Chemical 
ATP 
adenosine triphosphate 
AUC 
area under the plasma concentration-time curve 
BMA 
bone marrow aspirate 
BMB 
bone marrow biopsy 
BMI 
body mass index 
CFR 
Code of Federal Regulations 
COVID-19 
coronavirus disease 2019 
CRA 
clinical research associate 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DLT 
dose-limiting toxicities 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EOT 
end of treatment 
ESA 
erythropoiesis-stimulating agents 
FDA 
Food and Drug Administration 
FIH 
First-in-Human 
GCP 
Good Clinical Practice 
HepBsAg 
hepatitis B surface antigen 
HepBcAb 
hepatitis B core antibody 
Hb 
Hemoglobin 
HCV 
hepatitis C virus 
HI-E 
Hematologic improvement–erythroid 
HIV 
human immunodeficiency virus 
HTB 
High transfusion burden 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IPSS-R 
International Prognostic Scoring System-Revised 
IRB 
Institutional Review Board 
IUD 
intrauterine device 
IWG 
International Working Group 
LDH 
lactate dehydrogenase 
MAD 
multiple ascending dose 
LTB 
low transfusion burden 
MedDRA 
Medical Dictionary for Regulatory Activities 
MDS 
myelodysplastic syndromes 
NCI 
National Cancer Institute 
NTD 
non-transfusion dependent  
O2 
Oxygen 
P50 
partial pressure of O2 at which Hb O2 saturation of 50% is achieved 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
PKR 
pyruvate kinase-red blood cell 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
11 of 77 
Version 3.0; 31 July 2023 
PT 
preferred term 
QD 
once daily 
QoL 
Quality of Life 
QTcF 
QT interval corrected using Fridericia's correction formula 
QUALMS 
The Quality of Life in Myelodysplasia Scale  
RBC 
red blood cells 
RBC-TI 
RBC transfusion independence 
ROS 
reactive oxygen species 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCD 
sickle cell disease 
SOC 
system organ class 
SOP 
standard operating procedure 
SRC 
Safety Review Committee 
TD 
transfusion dependent 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse events 
TIBC 
Total Iron Binding Capacity 
t-MDS 
therapy-associated MDS 
ULN 
upper limit of normal 
WBC 
white blood cell 
WHO 
World Health Organization 
WHODrug 
World Health Organization Drug Dictionary 
 
 
 
 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
12 of 77 
Version 3.0; 31 July 2023 
1.0 
PROTOCOL SUMMARY  
1.1 
Synopsis  
Title: A Phase 2 Open-Label Study to Evaluate Etavopivat for the Treatment of Anemia in 
Patients with Myelodysplastic Syndromes (MDS) 
Rationale: 
Etavopivat (FT-4202) is a potent, selective, orally bioavailable, small-molecule activator of 
pyruvate kinase -red blood cell (PKR) being developed by Forma Therapeutics, Inc and is 
intended for use as a treatment for the anemia of MDS, inherited hemolytic anemias, and 
other refractory anemias. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 To assess hematologic improvement based 
on an erythroid response (HI-E) for ≥ 8 
weeks duration in patients with MDS 
within  
24 weeks of etavopivat treatment 
The HI-E for ≥ 8 weeks within 24 weeks of 
etavopivat. This endpoint will be based on the 
combined incidence of: 
o 
Non-transfusion dependent (NTD) patients: 
≥ 1.5 g/dL increase in hemoglobin (Hb) from 
baseline maintained ≥ 8 consecutive weeks and 
no transfusion of RBC units for anemia over a 
continuous 8-week treatment period   
o 
Low transfusion burden (LTB) patients: 
absence of any transfusion for ≥ 8 consecutive 
weeks 
o 
High transfusion burden (HTB) patients: 
reduction by ≥ 50% of red blood cell (RBC) 
units for ≥ 8 consecutive weeks 
Secondary 
 To assess HI-E for ≥ 8 weeks duration in 
this population of patients within 16 and 48 
weeks of etavopivat treatment 
 The HI-E for ≥ 8 weeks within 16 and 48 weeks of 
etavopivat 
This endpoint will be based on the combined 
incidence of: 
o 
NTD patients: ≥ 1.5 g/dL increase in Hb from 
baseline maintained ≥ 8 consecutive weeks and 
no transfusion of RBC units for anemia over a 
continuous 8-week treatment period 
o 
LTB patients: absence of any transfusion for 
≥ 8 consecutive weeks 
o 
HTB patients: reduction by ≥ 50% of RBC 
units for ≥ 8 consecutive weeks  
 To assess HI-E for ≥ 16 weeks duration in 
this population of patients within 24 and 48 
weeks of etavopivat treatment 
 The HI-E for ≥ 16 weeks within 24 and 48 weeks of 
etavopivat 
This endpoint will be based on the combined 
incidence of: 
o 
NTD patients: ≥ 1.5 g/dL increase in Hb from 
baseline maintained ≥ 16 consecutive weeks 
and no transfusion of RBC units for anemia 
over a continuous 8-week treatment period 
o 
LTB patients: absence of any transfusion for 
≥ 16 consecutive weeks 
o 
HTB patients: reduction by ≥ 50% of RBC 
units for ≥ 16 consecutive weeks 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
13 of 77 
Version 3.0; 31 July 2023 
 
 
 
 
Secondary, continued 
 To assess the safety and tolerability of 
etavopivat in patients with MDS 
 Incidence of adverse events (AEs), serious adverse 
events (SAEs), and AEs related to etavopivat 
 Number of premature discontinuations, dose 
interruptions, and dose reductions 
 To assess additional measures 
demonstrating potential clinical benefit 
 Overall response rate (2006 International Working 
Group [IWG] Criteria) (see Appendix A) 
 Duration of response (2006 IWG Criteria) 
 Reduction in RBC transfusions and rate of RBC 
transfusion independence ≥ 8 weeks in patients with 
LTB or HTB at study entry. 
 Increase in neutrophils and/or platelets counts 
 Decrease in ferritin and transferrin saturation (TSAT) 
 Decrease in iron chelation therapy 
 Overall survival 
Pharmacokinetic / Pharmacodynamic 
 To assess the pharmacokinetic (PK) and 
pharmacodynamic (PD) properties of 
etavopivat in patients with MDS 
 Etavopivat plasma PK parameters (including but not 
limited to): maximum observed plasma concentration, 
time to maximum observed plasma concentration, 
area under the plasma concentration-time curve from 
time zero until the last quantifiable time point (AUC0-
last), from time zero to infinity (AUC0-inf), for a dosing 
interval (AUCtau/AUC0-24). 
 RBC 2,3-diphosphoglycerate (2,3-DPG) and 
adenosine triphosphate (ATP) levels over time 
Exploratory 
 To examine safety trends in patients with 
MDS receiving etavopivat 
 Assessment of vital signs, clinical laboratory findings, 
and physical examination findings 
 To assess changes in quality-of-life in 
patients with MDS taking etavopivat 
 Change from baseline in Patient-Reported Outcome 
Measurement Information System (PROMIS) Fatigue 
Scale at Weeks 16, 24, and 48 
 Change from baseline in The Quality of Life in 
Myelodysplasia Scale (QUALMS) patient-reported 
outcome assessment at Weeks 16, 24, and 48 
 To characterize the biological effects of 
etavopivat treatment in patients with MDS 
 Cell colony analysis of bone marrow progenitors 
 Cytomorphology (blast, M/E, and ringed sideroblast 
determination) and cytogenetics of bone marrow 
 Markers of ineffective erythropoiesis and iron 
metabolism 
 Cancer-associated mutations and/or genetic 
alterations in responding and non-responding patients  
 Flow cytometry analysis of terminal erythroid 
differentiation (EU Only) 
Overall Design:  
This study is a multicenter, open-label, Phase 2 study in adult patients with very low, low 
risk, or intermediate risk MDS per the International Prognostic Scoring System-Revised 
(IPSS-R) classification (see Appendix B).  
The study will enroll up to 45 patients with MDS who will be evaluated for HI-E response 
composite derived from the MDS IWG 2018 criteria (modified by Platzbecker et al. 2019) 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
14 of 77 
Version 3.0; 31 July 2023 
(see Appendix A). HI-E response assessment will be based on the individual patient’s 
transfusion history in the 16 weeks prior to enrollment: 
 NTD patients (received ≤ 2 RBC units for anemia within the prior 16 weeks): Hb 
increase of ≥ 1.5 g/dL over a continuous 8-week treatment period and no 
transfusion of RBC units for anemia over a continuous 8-week treatment period 
o Approximately 15 patients meeting the criteria for NTD may be enrolled in 
this study 
 LTB patients (received 3 to 7 RBC units within the prior 16 weeks): No transfusion 
of RBC units for anemia over a continuous 8-week treatment period 
o Approximately 15 patients meeting the criteria for LTB may be enrolled in 
this study 
 HTB patients (received ≥ 8 RBC units in the prior 16 weeks): ≥ 50% reduction in 
RBC units transfused over a continuous 8-week period. 
o Approximately 15 patients meeting the criteria for HTB may be enrolled in 
this study 
Patients will be enrolled into a 48-week treatment period, including a 24-week Primary 
Treatment period and a 24-week Extension Treatment period. Patients demonstrating 
clinical benefit at the end of the 48-week treatment period may continue treatment. The 
dose of etavopivat is 400 mg once daily (QD) administered continuously; the selection of 
the starting dose is based on results from a Phase 1 study in patients with sickle cell disease 
(SCD) who were not receiving chronic RBC transfusions. 
After the 6th patient completes a minimum of 4-weeks of daily etavopivat treatment, a 
safety review meeting will be held to confirm that the safety, exposure, and 
pharmacological response (PK/PD profile) are consistent with prior experience of 
etavopivat dosing in healthy volunteers and patients with sickle cell disease or thalassemia.  
A futility assessment will be triggered when 15 patients across all strata or 8 patients in a 
single stratum reach 24 weeks of treatment, whichever occurs first. If both criteria are met 
at the same time, the overall futility assessment will be performed.  
The futility criterion is defined as follows: 
 All strata (n=15): ≤ 3 responses meeting HI-E criteria, sustained from Week 16 to 
Week 24.  
 Single stratum (n=8): 0 (zero) responses. 
If either the overall, or single stratum, futility criterion is met, enrollment may discontinue 
due to futility. Further enrollment may be considered if it is restricted to specific subsets of 
patients based on prior transfusion history. If neither criterion is met, enrollment will 
continue until a total of 45 response-evaluable patients are available at Week 24. 
Enrollment will not pause during assessment periods unless futility analysis suggests 
clinical need to pause. 
At final analysis, the study will evaluate the rate of MDS IWG 2018 criteria responses in 
the pooled, open-label etavopivat-treated patients versus a null-assumed rate of 20%.  
Treatment Duration: Duration of study treatment will be up to 48 weeks, including 24 
weeks in the Primary Treatment period and 24 weeks in the Extension Treatment period. 
Patients who demonstrate clinical benefit at 48 weeks of treatment, based on their MDS 
response assessment, may continue treatment until the patient experiences unacceptable 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
15 of 77 
Version 3.0; 31 July 2023 
toxicities, disease progression, withdraws consent, or meets any other discontinuation 
criteria (Section 7.2.1). 
Study Duration: Duration of study for an individual patient is approximately 58 weeks 
and includes a Screening Period (up to 6 weeks before study treatment), the 24-week 
Primary Treatment period, the 24-week Extension Treatment period, and Safety Follow-up 
visit occurring 28 days (+ 7 days) after last dose of study drug. The study duration will be 
greater than 58 weeks in patients who continue study treatment beyond the planned 48-
week treatment period due to clinical benefit.  
Number of Participants 
Approximately 45 patients will be enrolled.  
Key Inclusion Criteria 
Type of Participant and Disease Characteristics 
1. Documented diagnosis of idiopathic/de novo MDS according to World Health 
Organization (WHO) classification (see Appendix C) that meets the IPSS-R 
classification (see Appendix B) of very low, low, or intermediate risk disease, and: 
 < 5% blasts and no Auer rods in bone marrow based on local pathology 
review 
 < Intermediate risk cytogenetic abnormalities per IPSS-R (see Appendix B) 
2. Anemia defined as:  
 
NTD: Subjects with mean Hb concentration < 10.0 g/dL of 2 measurements 
(1 performed within 3 days prior to W1D1 and the other performed 7 to 28 
days prior to W1D1, not influenced by RBC transfusion within 7 days of 
measurement) and < 3 RBC transfusions for anemia in the prior 16 weeks 
before W1D1 of etavopivat dosing 
OR  
 Transfusion Dependent: Subjects having received ≥ 3 units of RBCs for the 
treatment of anemia within 16 weeks prior to W1D1 
3. Serum erythropoietin level > 200 U/L, OR, if ≤ 200 U/L, subject is non-responsive, 
refractory, or intolerant to erythropoiesis-stimulating agents, or erythropoiesis-
stimulating agents are contraindicated or unavailable. 
4. Eastern Cooperative Oncology Group performance status of ≤ 2 
(see Appendix D) 
5. Subject is non-responsive, refractory, or intolerant to luspatercept, or luspatercept is 
contraindicated or not indicated. 
6. No alternative treatment options are available and/or appropriate for the subject, at 
the discretion of the investigator. 
7. Patient is willing and able to adhere to the study visit schedule and other protocol 
requirements 
Key Exclusion Criteria 
MDS History 
1. MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
16 of 77 
Version 3.0; 31 July 2023 
2. Therapy-associated MDS (eg. t-MDS) that is known to have arisen as the result of 
chemical injury or treatment with chemotherapy and/or radiation for other diseases 
3. Known history of acute myeloid leukemia (AML) 
4. Any diagnosis of myelodysplastic/myeloproliferative neoplasms 
Medical Conditions 
5. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, 
or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding 
6. Absolute neutrophil count < 500/µL (0.5 × 109/L) 
7. Platelet count < 50,000/µL (50 × 109/L) without transfusion within 14 days  
8. Hepatic dysfunction characterized by any one of the following: 
 Alanine aminotransferase (ALT) > 3.0 × upper limit of normal (ULN) 
 Total bilirubin > 2.0 × ULN (in the absence of cholestasis) 
 History and/or evidence of cirrhosis 
 
Novo Nordisk Safety Committee  
Novo Nordisk will perform ongoing safety surveillance. Safety surveillance activities 
encompass the regular periodic safety data review from clinical trials, literature 
surveillance and safety information derived from other sources.  
If new safety signals are identified, these will be evaluated by the etavopivat internal safety 
committee. 
The safety committee is cross-functional and the only Novo Nordisk body responsible for 
providing integrated assessments of safety data and endorsing appropriate actions in case 
of a safety signal. 
Subsequently, safety information is communicated and reported to health authorities, 
ethics committees and investigators, as relevant and in accordance with regulatory 
requirements. 
1.1.1 
Study Safety Review Committee  
A safety review via Study SRC, consisting of, at a minimum, members of the clinical study 
team (including Medical Lead), pharmacovigilance, and Principal Investigators 
participating from at least 2 study sites, will occur within 4 weeks of the following: 
After the 6th patient completes a minimum of 4-weeks of daily etavopivat treatment, to 
confirm that the safety and PK/PD profile of 400 mg QD etavopivat continues to support 
enrollment and dosing of etavopivat. (See Section 4.4) 
 
1.1.2 
Dose-limiting Toxicities Evaluation Period/Definition  
Dose-limiting toxicities (DLTs) will be evaluated during the first 28 days of treatment 
using NCI-CTCAE v5.0.  
DLTs are determined by the Investigator and include any of the following AEs that are 
considered related to etavopivat (ie, all AEs of the specified grades except those that are 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
17 of 77 
Version 3.0; 31 July 2023 
clearly and incontrovertibly due to underlying malignancy or extraneous causes, eg, 
intercurrent illness or concomitant medication): 
 Non-Hematologic Toxicity  
o ≥ Grade 3 toxicity with the following exceptions: (1) nausea, vomiting, diarrhea 
lasting < 72 hours (with optimal medical management and other supportive care); 
(2) fatigue lasting < 1 week  
o Clinically relevant (requiring treatment or with potential clinical sequelae) 
≥ Grade 3 non-hematologic laboratory finding. This includes: 
- 
≥ Grade 3 electrolyte abnormality that lasts > 72 hours despite adequate 
management, unless the patient has clinical symptoms, in which case all 
Grade ≥ 3 electrolyte abnormality regardless of duration should count as a 
DLT.  
- 
Note: Grade ≥ 3 amylase or lipase elevation NOT associated with symptoms 
or clinical manifestations of pancreatitis does not need to be counted as a 
DLT  
o Hy’s law as defined by aspartate aminotransferase or alanine aminotransferase 
(ALT) > 3 × ULN and total bilirubin > 2 × ULN with alkaline phosphatase < 2 × 
ULN in the absence of a clear alternative explanation  
o Inability to tolerate/receive a minimum of 75% of etavopivat scheduled doses 
during first 28 days of treatment due to an AE of any grade that is considered 
related to etavopivat, unrelated to underlying malignancy or intercurrent illness, 
and unrelated to a concomitant medication 
 Any death not clearly due to the underlying disease or extraneous causes 
 Hematologic Toxicity  
o Grade 4 thrombocytopenia for > 7 days 
o Grade 3 thrombocytopenia with bleeding 
o Grade 4 neutropenia lasting for > 7 days 
o Febrile neutropenia / neutropenic fever 
 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
 
18 of 77 
Version 3.0; 31 July 2023 
1.2 
Schema  
 
VV-CLIN-180184 3.0
.

 
 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
19 of 77 
Version 3.0; 31 July 2023 
Table 1-1: 
Schedule of Events, Primary and Extension Treatment Periods  
Assessments 
Screen 
Primary treatment period 
Extension treatment period 
Safety 
follow-
up visit 
Study Day/Week(s): 
D-42  
to -1 
W1D1 
b 
W2 
D1 
W4 
D1 
W6 
D1 
W8 
D1 
W10 
D1 
W12 
D1 
W14 
D1 
W16 
D1 
W20 
D1 
W22 
D1 
W24 
D1 
W26 
D1 
W28 
D1 
W30 
D1 
W32 
D1 
W34 
D1 
W36 
D1 
W38 
D1 
W40 
D1 
W42 
D1 
W44 
D1 
W46 
D1 
W48 
D1 
W52 
D1 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 D) 
Informed Consent (a) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Inclusion/Exclusion 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prior ESA/Luspatercept 
Therapies 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prior RBC and Platelet 
Transfusions 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Examination  
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Physical Examination (symptom 
directed) 
  
  
X 
X 
  
X 
  
X 
  
X 
X 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
  
X 
Height  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Weight and BMI 
X 
X 
X 
X 
  
X 
  
X 
  
X 
X 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
Vital Signs (including temp) d 
X 
X 
X 
X 
  
X 
  
X 
  
X 
X 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
ECOG PS 
X 
X 
  
X 
  
X 
  
X 
  
X 
X 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
ECG e 
X 
X 
X 
X 
  
X 
  
  
  
X 
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
Adverse Events f 
X 
Recorded Throughout 
 
Concomitant Medications 
X 
Recorded Throughout 
 
Hematology g 
X 
X 
X 
X 
X h 
X 
X h 
X 
X h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hb Electrophoresis 
X 
 
  
  
  
  
  
  
  
 
  
  
 
  
  
  
  
  
  
  
  
  
  
  
Serum Chemistry g 
X 
X 
X 
X 
  
X 
  
X 
  
X 
X 
  
X 
  
  
  
X 
  
  
  
 X 
  
  
  
X 
X 
Serum Iron Profile g 
X 
X 
  
X 
  
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
X 
X 
Iron/TIBC (TSAT) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis i 
X 
  
  
X 
  
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
X 
X 
Coagulation parameters g 
X 
  
  
X 
  
  
  
  
  
X 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
X 
X 
Serum Pregnancy Test j 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Serum Erythropoietin 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Serum Virology g 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
VV-CLIN-180184 3.0
.

 
 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
20 of 77 
Version 3.0; 31 July 2023 
Assessments 
Screen 
Primary treatment period 
Extension treatment period 
Safety 
follow-
up visit 
Study Day/Week(s): 
D-42  
to -1 
W1D1 
b 
W2 
D1 
W4 
D1 
W6 
D1 
W8 
D1 
W10 
D1 
W12 
D1 
W14 
D1 
W16 
D1 
W20 
D1 
W22 
D1 
W24 
D1 
W26 
D1 
W28 
D1 
W30 
D1 
W32 
D1 
W34 
D1 
W36 
D1 
W38 
D1 
W40 
D1 
W42 
D1 
W44 
D1 
W46 
D1 
W48 
D1 
W52 
D1 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 
D) 
(±3 D) 
Transfusion Data Collection and 
Assessment 
  
Assess and record on ongoing basis until end of treatment visit or 8 weeks after last dose of etavopivat, whichever comes first. Clinical staff should confirm if any transfusions 
were received by the patient (including any at outside local institutions in between study visits). 
  
PROMIS Fatigue Scale    
X 
X 
  
X 
  
X 
  
X 
  
X 
X 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
The QUALMS 
X 
X 
  
X 
  
X 
  
X 
  
X 
X 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
MDS Baseline Assessment 
(IPSS-R) k 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
MDS Response Assessment l 
  
  
  
  
  
  
  
  
  
X 
  
  
X m 
  
  
  
  
  
  
  
  
  
  
  
X 
X 
Exploratory Studies n 
X 
X 
  
X 
  
  
  
  
  
X 
X 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
PD Sampling o 
  
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
X 
PK Sampling p 
  
X 
X 
X 
  
  
  
  
  
  
  
  
 X 
  
  
  
  
  
  
  
  
  
  
  
X 
Study Drug Administration 
  
X   
Daily throughout treatment period 
  
Survival q 
 
 
Q 3 months after End of Trial visit 
 
Abbreviations: BMI = body mass index; D = day; ECOG PS = Eastern Cooperative Oncology Group performance status; ECG = electrocardiogram; ESA = Erythropoiesis-
stimulating agent; Hb = hemoglobin; ICF = informed consent form; IPSS-R = International Prognostic Scoring System-Revised; MDS = myelodysplastic syndromes; PK/PD 
= pharmacokinetics/pharmacodynamics; PROMIS = Patient-Reported Outcomes Measurement Information System; RBC = red blood cell; The QUALMS = The Quality of 
Life in Myelodysplasia Scale; W = week. 
 
Note: Study visits after W1D1 must be conducted within ± 3 days of the scheduled visit. For the purposes of assessments and analyses in this study, 4 weeks = 1 month. 
 
a. 
Informed consent must be obtained before any study-specific procedures are performed. The date of informed consent and W1D1 of study treatment may be a maximum 
of 56 days apart. The screening period (up to 42 days prior to W1D1 of treatment) starts only after informed consent is obtained AND a study-specific procedure is 
performed. 
b. W1D1 assessments should be performed prior to study drug administration and may be performed up to 3 days prior (Day -3 to Day -1).  
c. 
Patients who prematurely discontinue the study during the Primary or Extension Treatment Periods should complete the End of Treatment visit (W48D1) and a Safety 
Follow-up visit approximately 28 days after last dose of etavopivat (see Table 1-2).  
d. Recommend vital signs (blood pressure [BP] and heart rate [HR]) to be measured after a patient has rested for at least 5 minutes in the supine or recumbent position. A 
repeated measurement of HR and BP can be taken within 5 minutes if the first reading is outside the normal range and deemed clinically significant. 
e. 
Electrocardiograms (ECGs) (12-lead) should be recorded in triplicate. See Section 8.3.8 for detailed instructions on performing the ECGs. 
f. 
Adverse events are reported as described in Section 8.7.5. 
g. Assessments of iron profile (ferritin, transferrin (TIBC) and iron level) will be performed locally and will include the tests listed in Appendix E (as applicable). 
VV-CLIN-180184 3.0
.

 
 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
21 of 77 
Version 3.0; 31 July 2023 
h. Hematology assessments listed in Appendix E, may be performed as outpatient/non-study center. 
i. 
Urinalysis will be performed locally and will include assessment for color and appearance and dipstick analysis for the tests listed in Appendix E. 
j. 
Serum pregnancy test will be performed locally at Screening, and a urine pregnancy test may be performed if there is any suspicion of pregnancy during the study, for all 
female patients of child-bearing potential (see Section 6.8.1). If a urine pregnancy test is positive, the result must be confirmed with a serum pregnancy test. 
k. 
MDS baseline assessment during Screening to confirm IPSS-R category and study entry criteria requires bone marrow aspirate (BMA) samples for cytomorphology and 
cytogenetics and peripheral blood analysis. If a screening BMA cannot be obtained, bone marrow biopsy (BMB) may need to be performed. Local analysis will be used 
for study entry criteria review and treatment initiation. BMA screening samples (and where indicated, with results from local analysis) will be sent to central laboratories 
for confirmation of study entry criteria (see Section 8.1.6).  
l. 
MDS response assessment includes BMA for cytomorphology and cytogenetics, and assessment of hematologic improvement.  
m. Hematologic improvement assessment only to be performed at the W24D1 visit as no BMA samples for cytomorphology or cytogenetics at W24D1 are required (unless 
clinically indicated).  
n. Serum for exploratory studies will be collected during Screening, pre-dose at W1D1, W4D1, W16D1, W20D1, W24D1, W32D1, W40D1, and W48D1. Fresh BMA 
samples, BMA smears, and peripheral blood smears for exploratory studies will be collected at Screening, W16D1, and W48D1.  
o. PD samples will be collected pre-dose on W1D1, W2D1, W4D1, W48D1 and W52D1. 
p. PK samples will be collected as follows: 
1. W1D1 and W4D1: Pre-dose (within 1 hour prior to dose), 1 hour (±5 minutes), 2 hours (±15 minutes), 4 hours (±30 minutes), and 6 hours (±30 minutes) post-
dose 
2. W2D1 and W48D1: Pre-dose (within 1 hour prior to dose), 1 hour (±5 minutes), and 2 hours (±15 minutes) post-dose 
Note: If the scheduled time for a PK/PD sample coincides with a safety ECG, the safety ECG should be performed prior to the PK/PD sample collection. 
q. After a patient discontinues study treatment and has completed their last study treatment visit, the study site may contact the patient approximately every 3 months to 
collect survival data. 
 
  
 
VV-CLIN-180184 3.0
.

 
 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
22 of 77 
Version 3.0; 31 July 2023 
Table 1-2  Schedule of Events – Optional Prolonged Treatment Period  
Optional Prolonged treatment perioda 
Assessments 
Timeframe 
Physical Examination (symptom directed) 
Q 2 Months (±2 weeks) 
Weight and BMI 
Q 2 Months (±2 weeks) 
ECOG PS 
Q 2 Months (±2 weeks) 
Vital Signs (including temp) b 
Q 2 Months (±2 weeks) 
ECG c 
Q 2 Months (±2 weeks) 
Adverse Events d 
Recorded Throughout 
Concomitant Medications 
Recorded Throughout 
Hematology e 
Q 1 Month (±1 week) 
Serum Chemistry e 
Q 2 Months (±2 weeks) 
Serum Iron Profile e 
Q 6 Months (±4 weeks) 
Urinalysis f 
Q 6 Months (±4 weeks) 
Coagulation parameters e 
Q 6 Months (±4 weeks) 
Urine Pregnancy Test g 
Q 2 Months (±2 weeks) 
Transfusion Data Collection and Assessment h 
Ongoing 
PROMIS Fatigue Scale 
Q 6 Months (±4 weeks) 
The QUALMS  
Q 6 Months (±4 weeks) 
BMA 
Q 12 Months (±4 weeks), and or 
earlier if clinically indicated 
Hematologic Improvement 
Q 6 Months (±4 weeks) 
Exploratory studies 
Q 6 Months (±4 weeks) 
Study Drug Administration 
Daily during treatment period 
Survival j 
Q 3 months (±4 weeks) 
Abbreviations: BMI = body mass index; D = day; ECOG PS = Eastern Cooperative Oncology Group performance 
status; ECG = electrocardiogram; Hb = hemoglobin; HR = heart rate; MDS = myelodysplastic syndromes; 
PD = pharmacodynamics; PK = pharmacokinetics; PROMIS = Patient-Reported Outcomes Measurement Information 
System; Q = every; RBC = red blood cell; The QUALMS = The Quality of Life in Myelodysplasia Scale; Wks = 
weeks. 
 
Note: Study visits must be conducted within ± 2 weeks for Q 2 months assessments and ±1 month for the yearly BMA 
assessment. For the purposes of assessments and analyses in this study, 4 weeks = 1 month. 
 
a. 
Patients who demonstrate clinical benefit at 48 weeks of treatment, based on their MDS Response Assessment, 
may continue treatment until the patient experiences unacceptable toxicities, disease progression, withdraws 
consent, or meets any other discontinuation criteria (Section 7.2.1). 
VV-CLIN-180184 3.0
.

 
 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
  
23 of 77 
Version 3.0; 31 July 2023 
b. 
Vital signs should be measured after a patient has rested for at least 5 minutes in the supine or recumbent 
position. A repeated measurement of HR and BP should be taken within 5 minutes if the first reading is outside 
the normal range and deemed clinically significant. 
c. 
ECG (12-lead) should be recorded in triplicate after a patient has rested for at least 5 minutes in the supine 
position, with the three ECGs collected within about a five-minute window. If the scheduled time for a safety 
ECG coincides with a blood collection, the safety ECG should be performed prior to the blood collection. The 
same timing for obtaining safety ECGs (ie, prior to blood collection) should be used for all safety ECG 
measurements. If the ECG cannot be performed prior to blood collection, the ECG should be done after a 
sufficient rest period of at least 15 minutes to minimize interference with ECG measurements. 
d. 
Adverse events are reported as described in Section 8.7.5. 
e. 
Assessments will be performed locally and will include the tests listed in Appendix E (as applicable). 
f. 
Urinalysis will be performed locally and will include assessment for color and appearance and dipstick analysis 
for the tests listed in Appendix E. Microscopic analysis performed as clinically indicated. 
g. 
Serum pregnancy test will be performed locally during Screening, and a urine pregnancy test may be performed 
if there is any suspicion of pregnancy during the study, for all female patients of childbearing potential.  
h. 
Assess and record on ongoing basis until the end of treatment visit or 8 weeks after last dose of etavopivat, 
whichever comes first. Clinical staff should confirm if any transfusions were received by the patient (including 
any at outside local institutions in between study visits). 
i. 
PD samples will be collected at the end of treatment visit. 
Note: If the scheduled time for a PK sample coincides with a safety ECG, the safety ECG should be performed 
prior to the PK sample collection. 
j. 
After a patient discontinues study treatment and has completed their last study treatment visit, the study site will 
contact the patient approximately every 3 months to collect survival data. 
 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
24 of 77 
Version 3.0; 31 July 2023 
2.0 
INTRODUCTION  
2.1 
Study Rationale  
Etavopivat (FT-4202) is a potent, selective, orally bioavailable, small-molecule activator of 
pyruvate kinase-red blood cell (PKR) being developed by Forma Therapeutics, Inc. and is intended 
for use as a treatment for the anemia of myelodysplastic syndromes (MDS), inherited hemolytic 
anemias, and other refractory anemias.  
In patients with very low risk, low risk, or intermediate risk MDS, the clinical hypothesis is that 
PKR activation will increase hemoglobin levels and/or reduce transfusion burden. 
2.2 
Background  
Myelodysplastic syndromes are a heterogeneous group of clonal disorders of hematopoietic stem 
cells characterized by ineffective hematopoiesis that manifests as anemia, neutropenia and/or 
thrombocytopenia of variable severity. These often result in red blood cell (RBC)-transfusion 
dependent anemia, increased risk of infection, and/or hemorrhage, as well as the potential to 
progress to acute myeloid leukemia (AML) (Fenaux et al. 2013; Ades et al. 2014). Patients with 
MDS can be categorized into 1 of 5 risk groups according to the International Prognostic Scoring 
System-Revised (IPSS-R) (ie, very low, low, intermediate, high, and very high) based on bone 
marrow cytogenetics, bone marrow blast percentage and peripheral blood cytopenias (Greenberg et 
al. 2012). From this risk classification, a population of patients with anemia as the predominant 
cytopenia can be identified with a lower rate of AML progression and longer survival. Anemia 
within this population can range in severity from mild (asymptomatic) to severe, requiring regular 
RBC transfusion support. Of the approximately 80-90% of patients with MDS who develop anemia, 
40% become transfusion dependent (Zeidan et al. 2013). 
Lower hemoglobin (Hb) levels and RBC transfusion dependence are associated with poor 
cardiovascular outcomes and increased mortality in patients with MDS (Platzbecker et al. 2019; 
Zeidan et al. 2013). Long-term RBC transfusion dependence also has significant clinical impact 
including iron overload and its associated complications and potentially negative impact on health-
related quality of life (Fenaux et al. 2019). A therapeutic option that would raise hemoglobin levels 
and/or achieve transfusion independence or reduced transfusion burden in patients with MDS for a 
sustained period of time is an important unmet medical need. 
Pyruvate kinase-red blood cell is a key enzyme in glycolysis and production of adenosine 
triphosphate (ATP) (Zanella et al. 2005). Adenosine triphosphate has been shown to support overall 
RBC membrane integrity and stress resilience (Betz et al. 2009). Increased ATP may thus decrease 
hemolysis and extend RBC lifespan. ATP also supports elimination of reactive oxygen species 
(ROS) which damage RBCs and impairs their functionality, and reduces vascular adhesion 
associated with membrane injuries (Banerjee et al. 2004). This increase in ATP based on direct 
effects of PKR activation is accompanied by a decrease in 2,3-diphosphoglycerate (2,3-DPG), a 
metabolic intermediate that regulates the affinity of hemoglobin for oxygen. Decreased 2,3-DPG 
results in increased affinity of hemoglobin for oxygen (Macdonald 1977; Kalfa et al. 2019; Estepp 
et al. 2020). Increased oxygen affinity may reduce the premature release of oxygen reducing the 
generation of ROS within the RBC. 
PKR is expressed early in the hematopoietic stem cell differentiation into the erythroid progenitor 
lineage, leading to the observation that metabolic abnormalities or stress early in erythroid 
progenitor development may alter the differentiation of erythroid progenitors into mature RBCs 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
25 of 77 
Version 3.0; 31 July 2023 
(Kim et al. 2005). Studies in murine models of PKR deficiency and β-thalassemia have linked the 
role of glucose metabolism to apoptosis (Mathias et al. 2000; Lang et al. 2002; Aizawa et al. 2005). 
The addition of a PKR-activator improves the anemia and the ineffective erythropoiesis observed in 
the bone marrow of β-thalassemic mice, suggesting the pathogenesis of the anemia of β-thalassemia 
is not only due to hemolysis but also ineffective erythropoiesis (Matte et al. 2021). These 
observations have been demonstrated clinically where a PKR activator has improved the anemia of 
patients with pyruvate-kinase deficiency and thalassemia (Grace et al. 2019; Kuo et al. 2021). 
In patients with MDS, the clinical hypothesis is that the ineffective erythropoiesis associated with 
MDS may be in part due to insufficient glycolysis/glucose metabolism leading to increased 
erythroid lineage apoptosis. The addition of etavopivat may improve the energy status (ATP) and 
decrease apoptotic signaling, leading to improved RBC differentiation/development and decreased 
anemia (increased Hb). Moreover, increased ATP levels in the mature RBC may improve the health 
of the RBC, prolonging survival of both the autologous RBC and the donor RBC in MDS patients 
receiving RBC transfusions for anemia resulting in a decrease in the transfusion requirements 
(Figure 1). 
Figure 1: 
PKR Activation as a Strategy to Reduce the Anemia Associated with 
Myelodysplastic Syndrome  
 
2,3-DPG = 2,3-diphosphoglycerate; ATP = adenosine triphosphate; Hb = hemoglobin; PKR = pyruvate kinase-red blood 
cell; RBC = red blood cell. 
2.3 
Risk/Benefit Assessment  
Etavopivat is a potent, selective, orally bioavailable PKR activator with a wide therapeutic margin 
relative to preclinical toxicity. Clinical studies in healthy volunteers and patients with SCD 
continues to support an acceptable safety profile for continuous dosing in patients with hemolytic 
anemias. Exposures that are well tolerated, result in maximum pharmacodynamic (PD) effects of 
increased ATP with a concomitant reduction in 2,3-DPG that have translated into improved RBC in 
RBC health and function in healthy and SCD RBCs (Forsyth et al. 2022; Schroeder et al. 2022). 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
26 of 77 
Version 3.0; 31 July 2023 
Ongoing studies in patients with SCD continue to support these initial findings and are supportive 
for expanding these studies into MDS. More detailed information about the known and expected 
benefits and risks and reasonably expected adverse events (AEs) of etavopivat may be found in the 
Investigator’s Brochure. 
2.3.1 
Risk Assessment  
A First-in-Human (FIH) clinical study (Protocol 4202-HVS-101) entitled “A Randomized, Placebo-
controlled, Double Blind, Single Ascending and Multiple Ascending Dose Study to Assess the 
Safety, Pharmacokinetics and Pharmacodynamics of FT-4202 in Adult Healthy Volunteers and 
Sickle Cell Disease Patients” is currently on-going. As of 22-November-2021, a total of 90 healthy 
subjects had been enrolled in the study, including 32 subjects in the single ascending dose (SAD) 
cohorts, 48 subjects in the multiple ascending dose (MAD) cohorts, and 10 subjects in the food 
effect cohort. In addition, 42 patients with SCD had been enrolled into the SCD cohorts, including 7 
patients in the SAD cohort, 10 patients in the SCD MAD-1 cohort (etavopivat [300 mg] or placebo 
once daily [QD] × 14 days), 10 patients in the SCD MAD-2 cohort (etavopivat [600 mg] or placebo 
QD × 14 days), and 15 patients in the 12-week open-label cohort (etavopivat [400 mg]). 
For the healthy subject cohorts, the most common treatment-emergent adverse event (TEAE) was 
headache, which was reported in 10 (27.8%) subjects receiving 2-weeks of etavopivat and 
2 (16.7%) subjects receiving 2-weeks of placebo. For headache TEAEs, there was no apparent 
relationship between daily etavopivat exposure and incidence. No treatment-emergent serious 
adverse events (TESAEs) were reported and there were no TEAEs that led to dose 
reduction/interruption or discontinuation of study drug. 
For the SCD cohorts, as of 22-November-2021, 3 TEAEs (arthralgia, headache, and palpitations) 
were reported in 2 (40%) patients who received a single dose (700 mg) of etavopivat and 3 TEAEs 
(back pain, myalgia, and pruritus) were reported in 2 (100%) patients receiving placebo. For 
patients with SCD receiving 2-weeks of etavopivat, the TEAEs reported in > 1 patient were sickle 
cell anemia with crisis (n=6 [37.5%]), headache (n=4 [25.0%]), nausea (n=3 [18.8%]), and vomiting 
(n=2 [12.5%]). No TESAEs were reported for the SCD SAD cohort; 1 (12.5%) patient in the MAD-
2 cohort was reported with a TESAE of unrelated Grade 3 sickle cell anemia with crisis. There were 
no TEAEs that led to dose reduction/interruption or discontinuation of study drug for the SCD SAD 
or MAD cohorts.  
In adult and adolescent patients with SCD (n=15) receiving 400 mg etavopivat QD for 12 weeks in 
the open-label portion of Study 4202-HVS-101, etavopivat was well tolerated (Brown et al. 2021b). 
In the 12-week cohort, the TEAEs reported in > 1 patient were sickle cell anemia with crisis 
(n=7 [46.7%]), headache (n=4 [26.7%]), and dizziness, nausea, and upper respiratory tract infection 
(n=2 [13.3%] for each). TESAEs were reported in 5 (33.3%) patients in the 12-week open-label 
cohort (2 patients with events of unrelated Grade 3 sickle cell anemia with crisis and single-patient 
events of acute chest syndrome [unrelated Grade 3], corona virus infection [unrelated Grade 3], 
deep vein thrombosis [DVT; possibly related Grade 3], non-cardiac chest pain [unrelated Grade 3], 
and syncope [unrelated Grade 3]). The DVT event led to discontinuation of study drug. 
These preliminary human data are supported by nonclinical toxicity studies in rats and monkeys 
with up to 9 months of etavopivat dosing (see the Investigator’s Brochure for additional details). 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
27 of 77 
Version 3.0; 31 July 2023 
2.3.2 
Benefit Assessment  
In the FIH clinical study 4202-HVS-101, etavopivat exposure resulted in sustained reductions in 
2,3-DPG levels and sustained increases in ATP levels in the RBCs of healthy subjects. 
Additionally, increased Hb oxygen affinity (decreased P50 [partial pressure of oxygen (O2) at which 
Hb O2 saturation of 50% is achieved]) was observed at all doses, correlating with the observed 
reductions in 2,3-DPG (Kalfa et al. 2019). Based on a dose-exposure-response analysis performed 
utilizing the pharmacokinetic (PK)/ PD results from the healthy volunteer studies, maximal PKR 
activation is anticipated at a dose ≥ 400 mg QD (maximum and sustained ATP and 2,3-DPG effects 
are predicted at dose levels ≥ 150 mg daily and ≥ 400 mg daily, respectively, Figure 2).  
Figure 2: 
Healthy Volunteers PK/PD Simulations Identifies Potential Phase 2 Dose 
Selections  
  
ATP = adenosine triphosphate; 2,3-DPG = 2,3-diphosphoglycerate; PD = pharmacodynamic; PK = pharmacokinetic 
QD = once daily. 
In the FIH clinical study 4202-HVS-101, a single dose of 700 mg of etavopivat has been evaluated 
in patients with SCD (n=7 [Estepp et al. 2020]). Etavopivat demonstrated similar PK in both 
healthy volunteers and patients with SCD. In the sickle RBC’s, 24 hours after 700 mg of etavopivat, 
ATP blood concentrations increased by 30% and 2,3-DPG blood concentrations decreased by 26%. 
Increased O2 affinity (decreased P50) with a decreased point of sickling and an improved sickle 
RBC deformability were observed in all etavopivat-treated patients. Improved sickle RBC 
membrane function, as demonstrated by Lorrca® Osmoscan was also noted. Improved hematologic 
parameters (~0.9 mg/dL Hb increase compared to placebo controls) were also observed.  
Doses of 300 mg and 600 mg etavopivat QD for 14 days were evaluated in patients with SCD, with 
overlapping PD activity and biologic effects observed across doses (Brown et al. 2020; Brown et al. 
2021a; Brown et al. 2021b). Notably, despite the increased exposure observed with etavopivat 600 
mg QD vs. 300 mg QD, PD responses (decreased 2,3-DPG and increased ATP) were comparable 
across the two 14-day SCD cohorts confirming prior studies in healthy RBCs predicting that 
etavopivat doses ≥ 400 mg QD would provide maximum PD activity (Brown et al. 2021a; Brown et 
al. 2021b).  
In adult and adolescent patients with SCD receiving 400 mg etavopivat QD for 12 weeks in the 
open-label portion of Study 4202-HVS-101, Hb increases > 1 g/dL were observed in 11/15 (73%) 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
28 of 77 
Version 3.0; 31 July 2023 
patients with a mean (range) response of 1.5 (0.75-2.35) g/dL (Brown et al. 2021b). Notably, these 
Hb responses were sustained throughout the 12-week treatment period. Similar to results for the 2-
week cohorts, significant and sustained decreases in absolute reticulocytes, indirect bilirubin, and 
lactate dehydrogenase (LDH) were noted by 2 weeks, with sustained responses throughout the 
12-week treatment period. Importantly, improved sickle RBC functions associated with metabolic 
health, adhesion, and vaso-occlusion were observed after 2 weeks of etavopivat treatment, with 
evidence that these improvements in RBC functional health may persist for several weeks after 
treatment discontinuation. 
Based on these initial findings, the dose level of 400 mg QD selected for evaluation in patients with 
very low, low, or intermediate-risk-MDS. 
2.3.3 
Overall Benefit: Risk Conclusion  
In Study 4202-HVS-101, reductions in 2,3-DPG and increases in ATP levels in RBCs of healthy 
volunteers and patients with SCD confirm PKR activation by etavopivat. Increased Hb O2 affinity 
in RBCs from healthy volunteers and patients with SCD demonstrates proof of mechanism 
consistent with observations from preclinical studies. Additionally, increased Hb levels along with 
marked reduction of absolute reticulocytes, indirect bilirubin and LDH in SCD patients receiving 
400 mg etavopivat daily provide proof of concept that a PKR activator can improve the anemia 
associated with SCD. These data, together with the available safety data from Study 4202-HVS-101 
(see the Investigator’s Brochure for additional details), support further clinical development of 
etavopivat and suggest that patients with MDS enrolled in this study have the potential to benefit 
from treatment with etavopivat. 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
29 of 77 
Version 3.0; 31 July 2023 
3.0 
STUDY OBJECTIVES AND ENDPOINTS  
3.1 
Primary Objective and Endpoints  
Objective 
Endpoints 
 To assess hematologic improvement 
based on an erythroid response (HI-E) 
for ≥ 8 weeks duration in patients with 
MDS within 24 weeks of etavopivat 
treatment 
 
The HI-E for ≥ 8 weeks within 24 weeks of etavopivat 
This endpoint will be based on the combined incidence of: 
o 
Non-transfusion dependent (NTD) patients: ≥ 1.5 g/dL 
increase in Hb from baseline maintained ≥ 8 consecutive 
weeks and no transfusion of RBC units for anemia over a 
continuous 8-week treatment period 
o 
Low transfusion burden (LTB) patients: absence of any 
transfusion for ≥ 8 consecutive weeks 
o 
High transfusion burden (HTB) patients: reduction by 
≥ 50% of red blood cell (RBC) units for ≥ 8 consecutive 
weeks 
3.2 
Secondary Objectives and Endpoints  
Objectives 
Endpoints 
 To assess for HI-E for ≥ 8 weeks 
duration in this population of patients 
within 16 and 48 weeks of etavopivat 
treatment 
 The HI-E for ≥ 8 weeks within 16 and 48 weeks of etavopivat 
This endpoint will be based on the combined incidence of: 
o 
NTD patients: ≥ 1.5 g/dL increase in Hb from baseline 
maintained ≥ 8 consecutive weeks and no transfusion of 
RBC units for anemia over a continuous 8-week treatment 
period 
o 
LTB patients: absence of any transfusion for 
≥ 8 consecutive weeks 
o 
HTB patients: reduction by ≥ 50% of RBC units for 
≥ 8 consecutive weeks  
 To assess HI-E for ≥ 16 weeks duration 
in this population of patients within 24 
and 48 weeks of etavopivat treatment 
 The HI-E for ≥ 16 weeks within 24 and 48 weeks of etavopivat 
This endpoint will be based on the combined incidence of: 
o 
NTD patients: ≥ 1.5 g/dL increase in Hb from baseline 
maintained ≥ 16 consecutive weeks and no transfusion of 
RBC units for anemia over a continuous 8-week treatment 
period 
o 
LTB patients: absence of any transfusion for 
≥ 16 consecutive weeks 
o 
HTB patients: reduction by ≥ 50% of RBC units for 
≥ 16 consecutive weeks 
 To assess the safety and tolerability of 
etavopivat in patients with MDS 
 Incidence of AEs, serious adverse events (SAEs), and AEs related 
to etavopivat 
 Number of premature discontinuations, dose interruptions, and dose 
reductions 
 To assess additional measures 
demonstrating potential clinical benefit 
 Overall response rate (2006 International Working Group [IWG] 
Criteria) (see Appendix A) 
 Duration of response (2006 IWG Criteria) 
 Reduction in RBC transfusions and rate of RBC transfusion 
independence ≥ 8 weeks in patients with LTB or HTB at study 
entry 
 Increase in neutrophils and/or platelets counts 
 Decrease in ferritin and transferrin saturation (TSAT)  
 Decrease in iron chelation therapy 
 Overall survival 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
30 of 77 
Version 3.0; 31 July 2023 
3.3 
Pharmacokinetic / Pharmacodynamic Objective and Endpoints  
Objective 
Endpoints 
 To assess the PK and PD properties of 
etavopivat in patients with MDS 
 
Etavopivat plasma PK parameters (including but not limited to): 
maximum observed plasma concentration, time to maximum 
observed plasma concentration, area under the plasma 
concentration-time curve from time zero until the last quantifiable 
time point (AUC0-last), from time zero to infinity (AUC0-inf), for a 
dosing interval (AUCtau/AUC0-24). 
 
RBC 2,3-DPG and ATP levels over time 
3.4 
Exploratory Objectives and Endpoints  
Objectives 
Endpoints 
 To examine safety trends in patients 
with MDS receiving etavopivat 
 
Assessment of vital signs, clinical laboratory findings, and 
physical examination findings 
 To assess changes in quality-of-life in 
patients with MDS taking etavopivat 
 
Change from baseline in Patient-Reported Outcome Measurement 
Information System (PROMIS) Fatigue Scale at Weeks 16, 24, 
and 48 
 
Change from baseline in The Quality of Life in Myelodysplasia 
Scale (QUALMS) patient-reported outcome assessment at 
Weeks 16, 24, and 48 
 To characterize the biological effects of 
etavopivat treatment in patients with 
MDS 
 
Cell colony analysis of bone marrow progenitors 
 
Cytomorphology (blast, M/E, and ringed sideroblast 
determination) and cytogenetics of bone marrow 
 
Markers of ineffective erythropoiesis and iron metabolism 
 
Cancer-associated mutations and/or genetic alterations in 
responding and non-responding patients  
 
Flow cytometry analysis of terminal erythroid differentiation (EU 
Only) 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
31 of 77 
Version 3.0; 31 July 2023 
4.0 
STUDY DESIGN  
4.1 
Overall Design  
This study is a multicenter, open-label Phase 2 study in adult patients with very low, low risk or 
intermediate risk MDS per the IPSS-R classification (see Appendix B). The study will enroll 
approximately 45 patients (see Figure 3).  
Figure 3: 
Schema  
 
Initially, 6 patients will be enrolled and dosed a minimum of 4-weeks with etavopivat 400 mg daily 
to confirm if safety, exposure, and pharmacological response (PK/PD profile) are consistent with 
prior experience of etavopivat dosing in healthy volunteers and patients with SCD or thalassemia. 
Approximately 45 MDS patients (inclusive of the initial 6 patients enrolled for safety/PK/PD 
confirmation) will be enrolled and evaluated for an erythroid response based on the revised MDS 
IWG 2018 criteria (see Appendix A). Response assessment will be based on the individual patient’s 
transfusion history in the 16 weeks prior to enrollment: 
 NTD patients (received ≤ 2 RBC units for anemia within the prior 16 weeks): Hb increase of 
≥ 1.5 g/dL over a continuous 8-week treatment period and no transfusion of RBC units for 
anemia over a continuous 8-week treatment period 
o Approximately 15 NTD patients may be enrolled in this study 
 LTB patients (received 3 to 7 RBC units within the prior 16 weeks): No transfusion of RBC 
units for anemia over a continuous 8-week treatment period 
o Approximately 15 LTB patients may be enrolled in this study 
 HTB patients (received ≥ 8 RBC units in the prior 16 weeks): ≥ 50% reduction in RBC units 
transfused over a continuous 8-week period. 
o Approximately 15 HTB patients may be enrolled in this study 
A futility assessment will be triggered when 15 patients across all strata or 8 patients in a single 
stratum reach 24 weeks of treatment, whichever occurs first. If both criteria are met at the same 
time, the overall futility assessment will be performed. 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
32 of 77 
Version 3.0; 31 July 2023 
The futility criterion is defined as follows: 
 All strata (n=15): ≤ 3 responses meeting HI-E criteria, sustained from Week 16 to Week 24 
 Single stratum (n=8): 0 (zero) responses 
 
If either the overall or single stratum futility criterion is met, enrollment may discontinue for futility 
or further enrollment restricted to specific subsets of patients based on prior transfusion history may 
be considered. If neither criterion is met, enrollment will continue until a total of 45 response-
evaluable patients are available at Week 24. 
Enrollment will not pause during assessment periods unless futility analysis suggests clinical need 
to pause. 
Patients will be enrolled into a 48-week treatment period, followed by a 28-day off-drug period. A 
safety follow-up visit occurs at the End of the Study (W52D1).  
Patients demonstrating clinical benefit at the end of the planned 48-week treatment period may be 
offered the opportunity to remain on treatment and enter the Optional Prolonged treatment period. 
Patients who enter the Optional Prolonged treatment period will follow the Schedule of Events 
outlined in Table 1-2. Patients who permanently discontinue treatment during the Optional 
Prolonged treatment period should attend a safety follow-up visit no sooner than 28 days after their 
last dose of etavopivat. 
Novo Nordisk will perform ongoing safety surveillance. Safety surveillance activities encompass 
the regular periodic safety data review from clinical trials, literature surveillance and safety 
information derived from other sources.  
If new safety signals are identified, these will be evaluated by the etavopivat internal safety 
committee. 
4.2 
Justification for Dose  
Dose selection for this study was based on an integrated evaluation of available etavopivat safety, 
PK, and PD data in healthy subjects and patients diagnosed with SCD following QD dosing for up 
to 84 consecutive days (see also Section 2.3.1 and Section 2.3.2). 
Evidence of pharmacological activity, consistent with the expected PD effects of PKR activation, 
was demonstrated following a single dose and repeated dosing of etavopivat in healthy subjects and 
patients with SCD. Based on a dose-exposure-response analysis, maximal PKR activation is 
anticipated at a dose ≥ 400 mg QD. Overlapping PD activity and biologic effects were observed at 
doses of 300 mg and 600 mg QD for 14 days in patients with SCD and no dose-limiting toxicities 
(DLTs) were reported. Taken together, dose selection of 400 mg QD enables further evaluation of 
the dose that is expected to safely offer benefit (see also Section 2.3.2). 
4.3 
Treatment and Study Duration  
4.3.1 
Treatment Duration  
Duration of study treatment will be 48 weeks, including 24 weeks in the Primary Treatment period, 
and 24 weeks in the Extension Treatment period. 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
33 of 77 
Version 3.0; 31 July 2023 
Duration of study for an individual patient may last up to 58 weeks and includes a Screening Period 
(up to 6 weeks before study treatment), the treatment period of the study for up to 48 weeks, and a 
Safety Follow-up visit at 28 days (+ 7 days) after last dose of study drug. Study duration in patients 
who continue etavopivat treatment due to clinical benefit will be > 58 weeks. 
4.3.2 
End of Study Definition  
The study will end when the last patient’s last visit of the extension treatment period occurs, 
approximately 52 weeks after the last patient is enrolled in the efficacy portion of the study. The 
study will stop when all patients who enter the optional prolonged treatment period complete a 
safety follow-up visit or discontinue study participation. 
For the purposes of the primary analysis, a patient is considered to have completed the study if 
he/she has completed 48 weeks of treatment, and either attended the safety follow-up visit at W52 
or entered the optional prolonged treatment period. 
4.4 
Safety Committees Structure  
4.4.1 
Novo Nordisk safety committee  
Novo Nordisk will perform ongoing safety surveillance. Safety surveillance activities encompass 
the regular periodic safety data review from clinical trials, literature surveillance and safety 
information derived from other sources.  
If new safety signals are identified, these will be evaluated by the etavopivat internal safety 
committee. 
The safety committee is cross-functional and the only Novo Nordisk body responsible for providing 
integrated assessments of safety data and endorsing appropriate actions in case of a safety signal. 
Subsequently, safety information is communicated and reported to health authorities, ethics 
committees and investigators, as relevant and in accordance with regulatory requirements. 
4.4.2 
Study Safety Review Committee  
A safety review via Study SRC, consisting of, at a minimum, members of the clinical study team 
(including Medical Lead), pharmacovigilance, and Principal Investigators participating from at least 
2 study sites, will occur within 4 weeks of the following: 
 After the 6th patient completes a minimum of 4-weeks of daily etavopivat treatment, to 
confirm that the safety and PK/PD profile of 400 mg QD etavopivat continues to support 
enrollment and dosing of etavopivat. 
4.5 
Dose-Limiting Toxicities Evaluation Period/Definition  
Dose-limiting toxicities (DLTs) will be evaluated during the first 28 days of treatment using NCI-
CTCAE v5.0.  
DLTs are determined by the Investigator and include any of the following AEs that are considered 
related to etavopivat (ie, all AEs of the specified grades except those that are clearly and 
incontrovertibly due to underlying malignancy or extraneous causes, eg, intercurrent illness or 
concomitant medication): 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
34 of 77 
Version 3.0; 31 July 2023 
 Non-Hematologic Toxicity  
o ≥ Grade 3 toxicity with the following exceptions: (1) nausea, vomiting, diarrhea lasting < 
72 hours (with optimal medical management and other supportive care); (2) fatigue lasting 
< 1 week  
o Clinically relevant (requiring treatment or with potential clinical sequelae) ≥ Grade 3 non-
hematologic laboratory finding. This includes: 
- 
≥ Grade 3 electrolyte abnormality that lasts > 72 hours despite adequate management, 
unless the patient has clinical symptoms, in which case all Grade ≥ 3 electrolyte 
abnormality regardless of duration should count as a DLT.  
- 
Note: Grade ≥ 3 amylase or lipase elevation NOT associated with symptoms or 
clinical manifestations of pancreatitis does not need to be counted as a DLT  
o Hy’s law as defined by aspartate aminotransferase or alanine aminotransferase (ALT) > 3 × 
ULN and total bilirubin > 2 × ULN with alkaline phosphatase < 2 × ULN in the absence of 
a clear alternative explanation  
o Inability to tolerate/receive a minimum of 75% of etavopivat scheduled doses during first 
28 days of treatment due to an AE of any grade that is considered related to etavopivat, 
unrelated to underlying malignancy or intercurrent illness, and unrelated to a concomitant 
medication 
 Any death not clearly due to the underlying disease or extraneous causes 
 Hematologic Toxicity  
o Grade 4 thrombocytopenia for > 7 days 
o Grade 3 thrombocytopenia with bleeding 
o Grade 4 neutropenia lasting for > 7 days 
o Febrile neutropenia / neutropenic fever 
 
 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
35 of 77 
Version 3.0; 31 July 2023 
5.0 
STUDY POPULATION  
This study will enroll approximately 45 total adult patients with MDS.  
The inclusion and exclusion criteria are detailed below; the Sponsor of this clinical investigation, 
Forma Therapeutics, Inc., does not grant waivers of inclusion or exclusion criteria. 
5.1 
Inclusion Criteria  
Participants are eligible to be included in the study only if all the following criteria apply: 
Informed Consent 
1. 
Patient has provided documented informed consent; the informed consent form (ICF) must 
be reviewed and signed by each patient prior to any study-related assessments/procedures 
being conducted. 
Age 
2. 
Age ≥ 18 years at time of first dose 
Sex and Contraceptive/Barrier Requirements 
3. 
Patients, if female and of childbearing potential, must agree to use acceptable methods of 
contraception and agree not to donate ova from study start to 90 days after the last dose of 
study drug, and who if male are willing to use acceptable methods of contraception and 
agree not to donate sperm, from study start to 90 days after the last dose of study drug. 
Disease Specific Requirements 
4. 
Documented diagnosis of idiopathic/de novo MDS according to 2016 WHO classification 
(see Appendix C) that meets IPSS-R classification (see Appendix B) of very low, low, or 
intermediate risk disease, and: 
 
< 5% blasts and no Auer rods in bone marrow based on local pathology review 
 
< Intermediate risk cytogenetic abnormalities per IPSS-R 
5. 
Anemia defined as:  
 
NTD: Subjects with mean Hb concentration < 10.0 g/dL on 2 measurements 
(1 performed within 3 days prior to W1D1 and the other performed 7 to 28 days 
prior to W1D1, not influenced by RBC transfusion within 7 days of measurement) 
and < 3 RBC transfusions for anemia in the prior 16 weeks before W1D1 of 
etavopivat dosing 
OR  
 
Transfusion Dependent: Subjects having received ≥ 3 units of RBCs for the 
treatment of anemia within 16 weeks prior to W1D1 
6. 
Serum erythropoietin level > 200 U/L, OR, if ≤ 200 U/L, subject is non-responsive, 
refractory, or intolerant to erythropoiesis-stimulating agents, or erythropoiesis-stimulating 
agents are contraindicated or unavailable. 
7. 
Eastern Cooperative Oncology Group performance status of ≤ 2 
(see Appendix D) 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
36 of 77 
Version 3.0; 31 July 2023 
8. 
Subject is non-responsive, refractory, or intolerant to luspatercept, or luspatercept is 
contraindicated or not indicated. 
9. 
No alternative treatment options are available and/or appropriate for the subject, at the 
discretion of the investigator. 
10. Patient is willing and able to adhere to the study visit schedule and other protocol 
requirements 
5.2 
Exclusion Criteria  
Patients are excluded from the study if they meet any of the following criteria 
MDS History 
1. 
MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality 
2. 
Therapy-associated MDS (eg. t-MDS) that is known to have arisen as the result of chemical 
injury or treatment with chemotherapy and/or radiation for other diseases 
3. 
Known history of AML 
4. 
Any diagnosis of myelodysplastic/myeloproliferative neoplasms 
Medical Conditions 
5. 
Female who is breast feeding or pregnant 
6. 
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or 
autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding 
7. 
Absolute neutrophil count < 500/µL (0.5 × 109/L) 
8. 
Platelet count < 50,000/µL (50 × 109/L) without transfusion within 14 days 
9. 
Hepatic dysfunction characterized by: 
 ALT > 3.0 × ULN 
 Total bilirubin > 2.0 × ULN (in the absence of cholestasis, and > 3.0 ULN in patients 
with a diagnosis of Gilbert syndrome) 
 History and/or evidence of cirrhosis 
10. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; 
calculated by the local laboratory < 30 mL/min/1.73 m2) or on chronic dialysis. 
11. Patients with clinically significant and active bacterial, fungal, parasitic, or viral infection. 
 Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic 
therapy should delay Screening and enrollment until active therapy has been 
completed and the infection resolved 
 Patients with acute viral infections without available therapies (e.g., coronavirus 
disease 2019 [COVID-19]) should delay Screening and enrollment until the acute 
infection has resolved. 
Note: Infection prophylaxis is allowed (see concomitant medication restrictions). 
12. Known human immunodeficiency virus (HIV) infection 
13. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis 
B core antibody [HepBcAb] positive) 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
37 of 77 
Version 3.0; 31 July 2023 
14. Active hepatitis C infection 
15. History of malignancy, other than MDS, requiring systemic chemotherapy and/or radiation 
beyond low-dose radiation of skin non-melanoma skin cancer. 
 Patients with malignancy considered surgically cured are eligible (eg, non-melanoma 
skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast) 
 Patients with incidental histologic findings of prostate cancer (T1a or T1b) are eligible  
16. History of unstable or deteriorating cardiac or pulmonary disease within 180 days prior to 
consent including but not limited to the following: 
 Unstable angina pectoris or myocardial infarction or elective coronary intervention 
 Heart disease, heart failure as classified by the New York Heart Association 
classification 3 or higher, or significant arrhythmia requiring treatment, 
 Pulmonary fibrosis or pulmonary hypertension which are clinically significant 
ie, ≥ Grade 3 National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0 (or higher)  
17. Uncontrolled hypertension, defined as repeated elevation of diastolic blood pressure ≥ 100 
mmHg despite adequate treatment 
18. Any condition affecting drug absorption, such as major surgery involving the stomach or 
small intestine (prior cholecystectomy is acceptable).  
Prior/Concomitant Therapy 
19. Prior treatment with azacitidine (injectable or oral) or decitabine (injectable or oral) 
20. Use of erythropoietin (ESA), other hematopoietic growth factor treatment or lenalidomide 
within 30 days of starting study treatment or anticipated need for such agents during the 
study. If patient has stage 3 or 4 chronic kidney disease (CKD) defined by 30 mL/min/1.73 
m2 ≤ eGFR <60 mL/min/1.73 m2 and has been on a stable ESA dose for ≥6 months and 
plans to continue on ESA at the same dose throughout the duration of the study, patient is 
eligible. 
 
21. Prior use of luspatercept: 
 NTD patients must not have received luspatercept within 30 days prior to W1D1 
treatment 
 Transfusion-dependent (TD) patients must not have received luspatercept within 80 
days prior to W1D1 treatment 
22. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 
(CYP)3A4/5 (see Appendix F) within 14 days of starting study treatment or anticipated need 
for such agents during the study. 
23. Prior allogeneic or autologous stem cell transplant or any organ transplant 
24. Initiation of a new chelation therapy within 90 days before the first dose of study treatment 
Prior/Concurrent Clinical Study Experience 
25. Participated in another clinical trial of an investigational agent (or medical device) within 
30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently 
participating in another trial of an investigational agent (or medical device). 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
38 of 77 
Version 3.0; 31 July 2023 
Other Exclusions 
26. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, 
may preclude safe participation, confound study interpretation, interfere with compliance, or 
preclude informed consent. 
5.3 
Screen Failures  
Screen failures are defined as patients who consent to participate in the clinical trial but are not 
eligible for participation according to inclusion/exclusion criteria. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure patients to meet 
requirements from regulatory authorities. Minimal information includes demography, screen failure 
details and eligibility criteria. 
If the patient has failed the inclusion criteria or fulfilled one of the exclusion criteria related to lab 
values or pathology analysis, only one re-sampling of the relevant parameter within 2 weeks is 
allowed if the result is expected to fall within the timeframe limit. However, in case of technical 
issues (e.g. haemolysed or lost samples), resampling is allowed for the affected parameters or 
pathology samples. If a timeframe longer than 2 weeks is required for analysis, the patient must be 
re-screened; all screening assessments must be repeated (including laboratory parameters) and the 
patient must be reconsented.  Screening bone marrow results may be used if the subject is 
reconsented within 90 days of the latest bone marrow procedure. 
If the patient has failed any other inclusion criterion, or fulfilled any other exclusion criterion, 
resampling/rescreening is not allowed. 
 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
39 of 77 
Version 3.0; 31 July 2023 
6.0 
STUDY INTERVENTION, CONCOMITANT THERAPY, AND PRECAUTIONS  
6.1 
Clinical Trial Material  
Intervention Name 
Etavopivat 
Type 
drug 
Dose Formulation 
tablet 
Unit Dose Strength 
200 mg 
Dosage Level 
two tablets daily 
Route of Administration 
oral 
Use 
experimental 
Sourcing 
Sponsor 
Appearance 
film coated, oval-shaped tablets 
Packaging and Labeling 
blister pack 
See the Study Pharmacy Manual for additional detail. 
6.2 
Preparation/ Handling/ Storage/ Accountability  
All study drugs will be transported, received, stored, and handled strictly in accordance with the 
container or product label, the instructions supplied to the research site and its designated 
pharmacy, the site’s standard operating procedures (SOPs), and applicable regulations. Appropriate 
storage temperature and transportation conditions will be maintained for the study drug from the 
point of manufacture up to delivery of the study drug. 
Upon receipt by the study site, the study drug will be promptly transferred to the appropriate 
environmentally controlled storage area. The research pharmacy staff will examine the shipment 
and temperature monitoring devices, if applicable, to verify that the study drugs were received in 
acceptable condition. Once inspected, the study drug will be stored in a secure area with access 
restricted to authorized research pharmacy staff, under physical conditions consistent with the 
investigational product’s specific requirements. 
The research site’s pharmacist or delegate is responsible for ensuring that all study drug received at 
the site is inventoried and accounted for throughout the study, according to applicable regulations 
and the site’s SOPs. All original containers, whether empty or containing study drug will be 
returned to the pharmacy. Study drug returned by study patients will be stored and disposed of 
according to the Sponsor’s instructions. Contents of the study drug containers will not be combined. 
Unused study drug and study drug returned by the patients will be available for verification by the 
Sponsor’s site monitor. See the Study Pharmacy Manual for additional detail, including reporting of 
Product Complaints. 
6.3 
Study Drug Administration  
Etavopivat may be taken with or without food. Each dose should be taken with a glass of water. 
Subjects should be instructed to take their daily dose at approximately the same time each day 
except for dosing on in-clinic visiting days. 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
40 of 77 
Version 3.0; 31 July 2023 
6.4 
Study Intervention Compliance  
Patients will be asked to return their unused study drug as well as their empty drug packets at each 
clinic visit. The study site will record the number of pills dispensed and the number returned at each 
visit, thereby assessing compliance. 
6.5 
Treatment of Overdose  
For this study, any dose of etavopivat greater than the intended dose will be considered an overdose 
(see also Section 8.7.11). There is no known antidote for etavopivat. Should an overdose occur, the 
patient should be treated with appropriate supportive care based on medical judgment.  
As described in Section 8.7.11, in the event of an overdose, the Investigator should: 
• Monitor the patient for any AE/SAE and laboratory abnormalities 
• Document the quantity of the excess dose as well as the duration of the overdose 
• Complete the Special Situations Report form and fax/email to Novo Nordisk Global Safety 
within 24 hours of knowledge of the event (as outlined in Section 8.7.11) 
6.6 
Missed Dose  
Subjects will be instructed that if they miss a dose by 12 or more hours after the scheduled dosing 
time, they should skip the dose and take the next dose of study drug as scheduled. 
6.7 
Concomitant Therapy  
6.7.1 
Concomitant Medications  
All medications taken by patients from Screening until the completion of the Safety Follow-up visit 
will be documented as concomitant medications. The reported medications will be reviewed and 
evaluated by the Investigator to determine if they affect a patient’s eligibility or continued 
participation in the study. 
 
Patients are required to avoid starting new non-prescription medicine within 14 days to first study 
dose and throughoput the study, unless discussed with the investigator. The use of St John’s wort 
should be avoided in this period. 
Strong inducers of CYP3A4/5 (see Appendix F) are prohibited during the study. 
With the exception of strong inducers of CYP3A4/5, concomitant prescribed medications are 
allowed for patients if prescribed by the Investigator to treat clinical events or exempted by the 
Medical Lead on a case-by-case basis because they would be unlikely to affect the study results or 
patient safety. 
Use of erythropoietin or thrombopoietin mimetics are prohibited during the study and within 
30 days prior to starting study treatment, with the exception of erythropoietin (ESA) in patients with 
diagnosed stage 3 or 4 CKD and who had been on a stable ESA dose for ≥6 months and plans to 
continue ESA at the same dose throughout the duration of the study. Hematopoietic growth factors 
for the treatment of transient neutropenia may be used when clinically indicated. 
Current use of luspatercept is prohibited during the study and within 30 to 80 days before starting 
study treatment (based on transfusion history). 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
41 of 77 
Version 3.0; 31 July 2023 
6.8 
Precautions  
Because etavopivat is an investigational agent in development, all possible side effects are not yet 
known. Please refer to the etavopivat Investigator’s Brochure for additional Warnings and 
Precautions. 
6.8.1 
Childbearing Potential  
Female patients of child-bearing potential must have a negative serum pregnancy test during the 
Screening period. Urine pregnancy testing may be performed locally if indicated during the study. If 
a urine pregnancy test is positive, the result must be confirmed with a serum pregnancy test. 
Female patients may not be pregnant, lactating, or breast-feeding or plan to become pregnant 
(including ova donation) within 90 days of last study drug administration.  
Female patients will be considered of childbearing potential after the onset of their first menstrual 
period. For all patients of childbearing potential, acceptable methods of contraception including 
abstinence, must be in use from the time of consent through the final study visit, and for 90 days 
after the last dose of study drug. Patients who are not sexually active during the Screening Period 
must agree to the contraceptive requirements if they become sexually active with a partner of the 
opposite sex during the study and for 90 days after the last dose of study drug.  
Adult female patients are deemed of non-childbearing potential if they are either surgically sterile 
(hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 
weeks (182 days) before the Screening visit) or are post-menopausal, defined as spontaneous 
amenorrhea for at least 2 years, with follicle-stimulating hormone in the post-menopausal range at 
the Screening visit. 
 
It should be noted, that based on nonclinical toxicity studies no effect on fertility and embryofetal 
development have been observed. Based on the non-clinical data, the safety committee endorsed the 
category for the Embryo-fetal risk assessment: Unlikely risk of human teratogenicity/fetotoxicity.  
 
6.8.1.1 
Contraception Guidelines  
Sexually active female patients of childbearing potential and sexually active male patients must use 
an acceptable method of contraception, as a minimum, during their participation in the study from 
the time of consent until 90 days after the last administration of study drug. If a patient prefers to 
use more highly effective forms of birth control, that is allowed. 
Acceptable methods of contraception under this protocol are listed below. Periodic abstinence 
(calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhoea method are not acceptable methods of contraception.  
Male patients 
Male patients who can father a child and are sexually active must agree to use at least an acceptable 
effective method of contraception, which includes:  
 Abstinence: abstinence can be used, when in line with the preferred and usual lifestyle of the 
patient.   
 Male condom 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
42 of 77 
Version 3.0; 31 July 2023 
 If a male patient confirms that his female partner(s) is not of childbearing potential (ie, post-
surgical sterilization, as defined above) or is using an acceptable method of contraception, 
this is acceptable as the only means of contraception. 
Examples of acceptable methods of contraception for male patients’ female partner(s) are listed in 
Table 6-1. 
Male patients with documented infertility or surgical sterilization (performed at least six months 
before the first dose of study drug) are exempt from the contraception requirement. Infertility may 
be documented through examination of a semen specimen or by demonstration of the absence of the 
vas deferens on ultrasound before the first dose of study drug (W1D1).   
Female patients 
Female patients of childbearing potential must agree to use an acceptable method of contraception, 
as a minimum, consistently and correctly, as described in Table 6-1. 
As a minimum, contraception should be maintained until 90 days after treatment discontinuation. 
Table 6-1 
Acceptable contraceptive methods  
CONTRACEPTIVESa ALLOWED DURING THE TRIAL INCLUDE: 
ACCEPTABLE METHODSb 
 Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action 
 Male or female condom with or without spermicidec 
 Cervical cap, diaphragm, or sponge with spermicide 
 A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double barrier methods). 
NOTES 
a. 
Contraceptive use by men or women should comply with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. Considered effective, but not highly effective – failure rate of ≥1% per year. Periodic abstinence (calendar, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhoea method (LAM) are not acceptable methods of contraception. 
c. 
Male condom and female condom should not be used together (due to risk of failure with friction). 
 
 
VV-CLIN-180184 3.0
.

Forma Therapeutics, Inc. 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
43 of 77 
Version 3.0; 31 July 2023 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/ WITHDRAWAL  
A patient may be discontinued at any time during the trial at the discretion of the investigator for 
safety, behavioural, compliance or administrative reasons. If a patient is prematurely discontinued 
from participation in the study prior to Week 48, the Investigator or designee must make every 
effort to perform the assessments scheduled for the EOT visit (W48D1) and schedule a Safety 
Follow-up visit 28 days after last study treatment. (see Table 1.2). 
The Investigator will document the reason(s) for study drug discontinuation on the electronic case 
report form (eCRF) and the patient’s source medical record. Patients who permanently discontinue 
the study treatment should be encouraged to continue participating in safety follow-up. Only 
patients who withdraw consent will be considered as withdrawn from the trial. Once a patient 
permanently discontinues study treatment, they may not be retreated. 
7.1 
Dose Modification / Discontinuation of Study Intervention  
7.1.1 
Adverse Event Interruption/Stopping Criteria  
Criteria for treatment interruption, dose reduction, and treatment discontinuation due to AEs will be 
assessed at the investigator’s discretion (see Section 8.7.6 and Section 8.7.7). Specific reporting 
criteria for liver enzyme abnormalities are provided in Section 8.7.2  
Table 7-1  Suggested Dose Modifications for Treatment Related AEs  
Severity 
Non-Hematologic  
Hematologic 
Grade 3 
Hold treatment until recovery to ≤ G1 or 
baseline, whichever is worseb, then resume at 
the next lower dose level (50% reduction). 
Contact Medical Monitoring if resumption of 
etavopivat at full dose is clinically indicated. 
Continue treatment at the same dose. If dose 
interruption is clinically indicated, resume dosing at 
same dose level after recovery to ≤ G2 or baseline, 
whichever is worse. 
Grade 4 
Permanently discontinue treatmentc 
Hold treatment until recovery to ≤ G2 or baseline, 
whichever is worse, then resume at the next lower 
dose level. 
Contact Medical Monitoring if resumption of 
etavopivat at full dose is clinically indicated. 
a. 
In the event of Grade 3 nausea, vomiting, diarrhea, or rash, the patient can continue at the same dose if the 
patient is responsive to treatment measures within 72 hr. 
b. 
A patient with a Grade 4 AE may resume treatment at the next lower dose level if the AE recovers to Grade 0-
1 or baseline and if in the opinion of the Investigator and Sponsor, the patient can be monitored for recurrence of AE. 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
44 of 77 
Version 3.0; 31 July 2023 
7.1.2 
Study Intervention Restart or Rechallenge after Stopping Criteria Met  
Patients who require treatment interruption > 28 days for a related AE will be withdrawn from the 
study.  
Patients who require a dose reduction after recovery from the AE causing a treatment interruption 
should be seen in clinic. At the Investigator’s discretion, restarting a patient’s study treatment at the 
modified dose prior to a clinic visit using the patient’s previous study treatment supply is allowed. 
However, the rationale and instructions for how the patient should modify their daily dose of study 
treatment should be documented. 
After a dose reduction, if treatment is tolerated at the reduced dose for ≥ 14 days, a dose increase to 
the original dose is allowed (i.e., rechallenge). Patients should be seen in clinic and receive a new 
supply of study treatment reflecting the modified dose. Rechallenge without a clinic visit is not 
allowed, unless discussed with the Medical Monitor. Recurrence of the same AE after a rechallenge 
should follow the dose interruption/modification steps outlined above. However, in these cases if 
the AE recurred within 4 weeks of the rechallenge, a subsequent dose increase is not allowed. 
A new Grade 3 or higher AE occurring while the patient is receiving a reduced dose should require 
treatment discontinuation. Discussion with the Global Medical Monitor is required before restarting 
treatment. 
Treatment discontinuation may be required if the AE causing the dose interruption and dose 
reduction re-occurs at Grade 2 or higher while the patient is receiving the reduced dose. Discussion 
with the Global Medical Monitor is required before restarting treatment. 
7.2 
Treatment Discontinuation/ Withdrawal from the Study  
7.2.1 
Treatment Discontinuation  
Treatment discontinuation is defined as any patient who permanently stops receiving study drug. A 
patient should be discontinued from study treatment if, in the opinion of the Investigator or 
Sponsor, it is medically necessary, or if it is the wish of the patient. 
Patients who prematurely discontinue study drug prior to 48 weeks of treatment will have an EOT 
(W48D1) visit performed at the time of discontinuation followed by the Safety Follow-up visit 
within 28 days. 
Patients must be discontinued from treatment for any of the following reasons: 
 An AE that requires permanent discontinuation of study treatment 
 Withdrawal of consent by the patient 
 Treatment interruption for > 28 days due to a related AE 
 Lack of efficacy 
 Disease progression 
 Pregnancy 
 Patient lost to follow-up 
 Investigator decision 
 Noncompliance to protocol 
 Termination of the study by the Sponsor 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
45 of 77 
Version 3.0; 31 July 2023 
AEs leading to the discontinuation of study drug will be followed for 28 days after administration 
of last dose of study drug or until resolution, resolution to baseline, or until the event is considered 
stable or chronic. 
7.2.2 
Study Withdrawal  
Patients may voluntarily withdraw from the study at any time for any reason without prejudice.  
Patients may withdraw or be withdrawn from the study for any of the following reasons: 
 Death 
 Lost to follow-up 
 Termination of study by Sponsor 
 Withdrawal of consent 
 
7.3 
Lost to Follow-up  
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a patient fails to return to the clinic for a required study visit: 
 The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the patient wishes to and/or should continue in the 
study. 
 Before a patient is deemed lost to follow-up, the Investigator or designee must make every 
reasonable effort to regain contact with the patient with a minimum of 3 telephone contact 
attempts and if these fail, follow-up with a certified letter to the patient’s last known mailing 
address These contact attempts should be documented in the patient’s medical record. 
 Should the patient continue to be unreachable, he/she will be considered to have withdrawn 
from the study. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
46 of 77 
Version 3.0; 31 July 2023 
8.0 
STUDY ASSESSMENTS AND PROCEDURES  
All study assessments will be performed at the visits and time points outlined in the Schedule of 
Events (Table 1-1, and Table 1-2). 
8.1 
Baseline Characteristics  
8.1.1 
Medical History  
Medical histories will be obtained and will include demographic data; histories of acute, chronic, 
and infectious disease; surgical histories; and any reported conditions affecting major body systems. 
Any history of earlier chemotherapy or radiation therapy must be recorded. 
All findings on medical history will be evaluated by the Investigator for clinical significance and 
patient’s eligibility for trial participation. 
8.1.2 
MDS Disease History  
Diagnosis of MDS with prior diagnostic cytogenetic and cytomorphologic evaluations, prior IPSS-
R scores, and any prior therapies will be obtained.  
8.1.3 
Transfusion History  
RBC transfusion history will be collected during Screening and will include up to a minimum of 16 
weeks prior to initiation of study treatment on W1D1 (e.g., an RBC transfusion occurring prior to 
etavopivat dosing on W1D1 should be collected as part of the patient’s transfusion history).  
All transfusions, RBC and platelet transfusions received by the patients will be recorded in the 
source documentation and eCRF in a dedicated page, and not as medication history.  
Sites who prescribe transfusions and have the transfusion records only in volumes should use for 
conversion of volume to units based on the following criteria, in order to obtain number of units 
within the last 16 weeks to assess the eligibility: one unit in this protocol refers to a quantity of 
packed RBCs approximately 200-350 mL. (i) Sites who use transfusion bags within this range, or 
≥ 350 mL, the conversion in units should be done by dividing the volume transfused to the patient 
by 350 mL, (ii) sites who use transfusion bags < 200 mL, the conversion in units should be done by 
dividing the volume transfused to the patient by 200 mL. 
8.1.4 
Medication History  
All medications (prescription and non-prescription, herbal medications/natural health products, 
cannabinoids, and investigational drugs) taken by the patients during the 30 days prior to Screening 
will be recorded in the source documentation and eCRF as medication history. Additionally, non-
prescription medications should be avoided for 7 days prior to W1D1, and 14 days for St. John’s 
wort as outlined in Section 6.7.1. 
8.1.5 
Viral Serology / Antigen Testing  
Viral serology / antigen testing will be performed during Screening and will include: HIV, 
HepBsAg, HepBcAb, and Hepatitis C virus (HCV) by polymerase chain reaction. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
47 of 77 
Version 3.0; 31 July 2023 
8.1.6 
Bone Marrow Aspirate  
A bone marrow aspirate (BMA) will be performed during the Screening period to confirm 
eligibility and IPSS-R score, including cytogenetics, and cytomorphology. Local analysis will be 
used for study entry criteria and treatment initiation, and redacted result reports shared with sponsor 
for eligibility confirmation. BMA screening samples (and where indicated, with results from local 
analysis) will be sent to central laboratories for confirmation of study entry criteria and for 
exploratory studies. If the IPSS-R score cannot be verified, or it is determined the patient had ≥ 5% 
blasts at study entry, the patient may be taken off treatment.  
8.2 
Efficacy Assessments  
8.2.1 
MDS Disease Assessment  
The MDS Disease Assessment will be performed as described in Table 1-1 and Table 1-2. The 
disease assessment will use response criteria per Cheson et al. 2006 (Appendix A) and will include 
assessment of hematologic improvement (HI-E criteria, modified based on Platzbecker et al. 2019).  
An assessment of hematologic improvement response only may be made when a bone marrow 
aspirate is not performed (for example Week 24 Day 1 of treatment).   
8.2.2 
Assessment of Transfusions  
RBC, and platelet, transfusions will be recorded on an ongoing basis throughout the study as 
indicated in Table 1-1 and Table 1-2. For any RBC, and platelet, transfusions received during the 
study, collect Hb and platelet values prior to transfusion, the number of units transfused, and the 
dates of transfusion. If available, the Hb/hematocrit of the transfused unit should also be collected.  
8.2.2.1 
LTB/HTB Patient Transfusion Treatment Plan:  
Each patient will have an individualized transfusion treatment plan in place prior to study treatment 
(see Appendix G). This treatment plan assumes a pre-transfusion Hb value is collected within 
7 days of a scheduled transfusion. The decision on the RBC transfusion schedule and amount of 
RBC units to transfuse will be based on the following parameters: 
 
1) A baseline pre-transfusion Hb threshold determined by the mean of all documented pre-
transfusion Hb values during the 16 weeks prior to start of study treatment. 
2) During treatment, if the pre-transfusion Hb level is increased by ≥ 1 g/dL compared to the 
pre-transfusion Hb threshold for that patient, transfusion may be delayed by a minimum of 7 
days and/or the number of units transfused may be reduced by 1 or more RBC units. 
8.2.3 
Hemoglobin Response and Clinical Measures of Hemolysis  
Hemoglobin response and measures of hemolysis (reticulocytes, unconjugated bilirubin, and LDH) 
will be assessed.  
8.2.4 
Iron Chelation Therapy and Iron Profile  
Iron chelation therapy will be recorded at Screening and on an ongoing basis throughout the study. 
Iron profile, consisting of ferritin, iron and transferrin levels, will be measured during Screening, on 
W1D1 and throughout the study. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
48 of 77 
Version 3.0; 31 July 2023 
8.2.5 
Patient-Reported Outcomes  
Patient-reported outcomes (PROs) will be evaluated using the PROMIS fatigue scale and the 
QUALMS assessment.  
The PROMIS is a patient-reported health outcome measurement system which can be used to 
evaluate quality of life in both children and adults. The PROMIS Fatigue 7a short form will be 
administered during scheduled clinic visits. The QUALMS is a validated MDS specific scale 
developed through input from MDS patients, their caregivers and providers.  
The PROMIS and The QUALMS assessments will be performed throughout the study, as indicated 
in Table 1-1 and Table 1-2. 
8.2.6 
Bone Marrow Aspirate  
A BMA, for response assessments and research, will be obtained as indicated in Table 1-1 and 
Table 1-2.  
8.3 
Safety Assessments  
8.3.1 
Clinical Laboratory Assessments  
A list of testing to be performed on the blood and urine samples is provided in (Appendix E). All 
laboratory safety data will be reviewed by the Investigator or designee for clinical significance as 
defined by an applicable list of normal values on file (i.e., local or central, as applicable).  
Additional laboratory samples may be taken at the discretion of the Investigator or designee (e.g., if 
the results of any tests fall outside reference ranges or if clinical symptoms necessitate testing to 
ensure patient safety). 
8.3.2 
Physical Examination  
Full and symptom-directed physical examinations will be performed according to the schedule in 
Table 1-1, and Table 1-2. Full physical examinations, assessing the patient’s overall health and 
physical condition, will consist of the following body systems: eyes, ears, nose, throat, lymph 
nodes, dermatologic, cardiovascular, respiratory, gastrointestinal, musculoskeletal, and nervous 
systems. 
8.3.3 
Hematology  
Hematology assessments will be performed according to the schedule in Table 1-1 and Table 1-2. A 
list of hematology tests to be performed is provided (Appendix E).  
8.3.4 
Hemoglobin Electrophoresis  
A hemoglobin electrophoresis will be performed locally according to the schedule in Table 1-1. 
8.3.5 
Coagulation Parameters  
Coagulation parameters assessments will be performed according to the schedule in Table 1-1 and 
Table 1-2. A list of coagulation parameters tests to be performed is provided (Appendix E). 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
49 of 77 
Version 3.0; 31 July 2023 
8.3.6 
Serum Chemistry  
Chemistry assessments will be performed according to the schedule in Table 1-1 and Table 1-2. A 
list of serum chemistry tests to be performed is provided (Appendix E).  
8.3.7 
Urinalysis  
Urinalysis will include assessment of color, appearance, and by urine dipstick according to the 
schedule in Table 1-1 and Table 1-2. Microscopic analysis (RBCs, white blood cells [WBCs], 
microalbumin, bacteria and casts) may be performed as clinically indicated. A list of the tests to be 
performed is provided (Appendix E). 
8.3.8 
12-Lead Electrocardiogram  
12-Lead ECGs will be performed according to the schedule in Table 1-1 and Table 1-2. 
Electrocardiograms (ECGs) (12-lead) should be recorded in triplicate after a patient has rested for at 
least 5 minutes in the supine position. All Triplicate ECGs will be taken one minute apart or with 
the three ECGs collected within about a five-minute window. 
If the scheduled time for a safety ECG coincides with a blood collection, the safety ECG should be 
performed prior to the blood collection. The same timing for obtaining safety ECGs (ie, prior to 
blood collection) should be used for all safety ECG measurements. If the ECG cannot be performed 
prior to blood collection, the ECG should be done after a sufficient rest period of at least 15 minutes 
to minimize interference with ECG measurements. 
8.3.9 
Pregnancy  
A serum pregnancy test for the presence of β-human chorionic gonadotropin (β-HCG) will be 
performed during Screening for all female participants of childbearing potential. 
During active study participation, pregnancy tests will be urine pregnancy tests and will be 
performed locally if indicated. 
If a urine pregnancy test is positive, study treatment must be held until the results are confirmed 
with a serum pregnancy test, and permanently discontinued if confirmed positive. Results of all 
pregnancy tests will be reported and must be negative prior to study continuation and/or dosing (see 
also Section 8.7.4). 
8.3.10 
Concomitant Medications and Procedures  
All medications received by the patient while in the study as described in Section 6.7.1, or any 
procedures that the patient has undergone will be recorded according the Schedule of Events 
(Table 1-1, Table 1-2). 
8.4 
Pharmacokinetic Sampling  
Venous blood samples will be collected to characterize the PK of etavopivat. Samples will be 
collected, processed, and shipped according to a lab manual provided by the Sponsor and/or 
bioanalytical laboratory. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
50 of 77 
Version 3.0; 31 July 2023 
8.5 
Pharmacodynamic Sampling  
Pharmacodynamic analysis will include measurement of 2,3-DPG and ATP and will be conducted 
as indicated in Table 1-1 and Table 1-2. 
8.6 
Exploratory Laboratory Assessments  
Exploratory laboratory samples will be collected according to the Schedule of Events (Table 1-1 
and Table 1-2).  
Samples obtained will include BMA to evaluate bone marrow progenitors by cell colony assays and 
terminal erythroid differentiation by flow cytometric analysis. BMA and peripheral blood will be 
obtained for cancer-associated mutations and/or genetic alterations.  
Serum will be obtained to evaluate markers of ineffective erythropoiesis and iron metabolism, 
including but not limited to erythropoietin, soluble transferrin receptor, iron, total iron binding 
capacity (including transferrin saturation), erythroferrone, and hepcidin.  
Refer to the study laboratory manual for additional details on processing, storage, and shipment of 
exploratory laboratory samples where indicated.  
8.7 
Adverse Events, Serious Adverse Events, and Other Safety Reporting  
8.7.1 
Definition of an Adverse Event  
An AE is defined as any untoward medical occurrence in a patient administered a medicinal product 
that does not necessarily have a causal relationship with this treatment.  
An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an investigational product, 
whether or not the AE is related to the investigational medicinal product.  
This includes an exacerbation of pre-existing conditions or events, intercurrent illnesses, drug 
interaction, or the significant worsening of the indication under investigation that is not recorded 
elsewhere on the eCRF under specific efficacy assessments.  
Anticipated fluctuations of pre-existing conditions that do not represent a clinically significant 
exacerbation or worsening are not considered AEs. 
It is the responsibility of the Investigator to document all AEs that occur during the study (from 
time of the first dose of study drug through 28 days after the last dose of study drug). AEs should be 
elicited by asking the patient a non-leading question (eg, “Have you experienced any new or 
changed symptoms since we last asked/since your last visit?”). The existence of an AE may be 
concluded from a spontaneous report of the patient; from the physical examination; or from special 
tests such as the ECG, laboratory assessments, or other study-specified procedure (source of AE).  
8.7.2 
Serious Adverse Events  
8.7.2.1 
Definition  
An SAE is any untoward medical occurrence that occurs at any dose that: 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
51 of 77 
Version 3.0; 31 July 2023 
 Results in death. Any event resulting in death during the reporting period [from time of the 
first dose of study drug through 28 days after last dose of study drug] must be treated as an 
SAE and reported as such.  
 Is life-threatening (patient is at immediate risk of death from the event as it occurred) NOTE: 
this is different than life-threatening severity criteria.  
 Requires in-patient hospitalization (formal admission to a hospital for medical reasons) or 
prolongation of existing hospitalization. NOTE: visits to Emergency Rooms, Urgent Care, 
Accident/Emergency Units, or visits resulting in brief care under, ‘Observation Status’, do 
not meet the criteria of in-patient hospitalization. 
 Results in persistent or significant disability/incapacity 
 Results in a congenital anomaly/birth defect 
 Important medical events that may not result in death, are not life-threatening, or do not 
require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition.  
The following must be reported as an SAE using the important medical event criterion if no other 
seriousness criteria are applicable: 
 Suspicion of transmission of infectious agents via IMP 
 Risk of liver injury defined as alanine aminotransferase (ALT) or aspartate aminotransferase 
(AST) > 3x ULN and total bilirubin > 2x ULN where no alternative aetiology exists (Hy’s 
law) 
 
8.7.2.2 
Events or Outcomes Not Qualifying as Serious Adverse Events  
The following are not considered SAEs and therefore do not need to be reported as such: 
 Pre-planned procedures (planned prior to signing of ICF) or elective hospitalization such as 
social and/or convenience situations (e.g., hospitalization due to weather or travel issues) 
Overdose of either study drug or concomitant medication unless the event meets SAE criteria (e.g., 
hospitalization). However, the event should still be captured as described in Section 8.7.11. 
8.7.3 
Clinical Laboratory Assessments as Adverse Events  
It is the responsibility of the Investigator to assess the clinical significance of all abnormal values as 
defined by the applicable list of reference ranges from the laboratory (i.e., local or central, as 
applicable). In some cases, significant changes in lab values within the normal range will require 
similar judgment. 
An abnormal laboratory value that is not already associated with an AE is to be recorded as an AE 
only if any one of the following criteria is met: 
 An action on the study drug is made as a result of the abnormality 
 Intervention for management of the abnormality is required 
 At the discretion of the Investigator should the abnormality be deemed clinically significant 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
52 of 77 
Version 3.0; 31 July 2023 
8.7.4 
Pregnancy or Drug Exposure during Pregnancy  
If a patient becomes pregnant during the study the Investigator is to stop dosing with study drug 
immediately. A pregnancy is not considered to be an AE or SAE; however, it must be reported to 
the Sponsor using the Pregnancy Report Form within the same timelines as an SAE. This applies to 
a female patient or the female partner of a male patient. The pregnancy should be followed through 
to outcome, whenever possible. Once the outcome of the pregnancy is known, the Pregnancy 
Outcome Reporting Form should be completed and reported to the Sponsor. AEs or SAEs that 
occur during pregnancy will be assessed and processed according to the AE or SAE processes using 
the appropriate AE or SAE forms. Should the outcome of pregnancy meet SAE criteria (for 
example, spontaneous abortion, congenital anomaly, stillbirth, etc.), that should be reported as an 
SAE accordingly. 
8.7.5 
Procedures for Recording and Reporting Adverse Events and Serious Adverse 
Events  
Any AE or SAE that occurs from time of the first dose of study drug through 28 days after the last 
dose of study drug should be recorded on the AE eCRF. Only SAEs that occur from the time of 
consent until first dose of study drug that are considered to be related to a protocol-mandated 
procedure need to be reported as an SAE. All other AEs and SAEs from time of consent until first 
dose of study drug should be reported as medical history.  
In order to avoid vague, ambiguous, or colloquial expressions, the AE should be recorded in 
standard medical terminology rather than the patient’s own words. Whenever possible, the 
Investigator should combine signs and symptoms that constitute a single disease entity or syndrome 
into a final diagnosis, if appropriate. For example, fever, cough, and shortness of breath may be 
reported as pneumonia, if that is the final diagnosis. Each AE is to be evaluated for duration, 
severity, seriousness, and causal relationship to the investigational drug. The action taken and the 
outcome must also be recorded.  
Serious Adverse Events: SAEs that occur during Screening and are related to a protocol-mandated 
procedure or SAEs that occur from first dose to within 28 days after last dose of study drug, 
whether or not related to study drug, must be reported to Novo Nordisk Global Safety within 24 
hours of knowledge of the event (see Page 4). After the 28-day reporting window, only SAEs 
assessed as related to study drug need to be reported. All SAEs, regardless of relationship to study 
drug, must be reported using the Novo Nordisk SAE Report Form. It is important that the 
Investigator provides an assessment of relationship of the SAE to study treatment at the time of the 
initial report. The contact information for reporting of SAEs can be found on the Novo Nordisk 
SAE Report Form itself and is also provided on Page 4. 
8.7.6 
Grading the Severity of Adverse Events  
The severity of the AE will be graded according to the CTCAE grading scale (Grades 1-5), per 
CTCAE v5. Should criteria not be available for a specific event term, the definitions noted below 
may be used: 
 Grade 1 (Mild): event is usually transient and does not interfere with the patient’s daily 
activities 
 Grade 2 (Moderate): event introduces a low level of inconvenience or concern to the patient 
and may interfere with daily activities 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
53 of 77 
Version 3.0; 31 July 2023 
 Grade 3 (Severe): event interrupts the patient’s usual daily activities and hospitalization (or 
prolongation of hospitalization) may be required 
 Grade 4 (Life-threatening): event requires urgent intervention to prevent death NOTE: this is 
different than life-threatening serious criteria. 
 Grade 5 (Fatal): Event resulted in death 
8.7.7 
Causal Relationship of Adverse Events to Investigational Medicinal Products  
Medical judgment should be used to determine the cause of the AE considering all relevant factors 
such as, but not limited to, the underlying study indication, coexisting disease, concomitant 
medication, relevant history, pattern of the AE, temporal relationship to the study medication, 
dechallenge or rechallenge. It should be evaluated as to whether or not there is a reasonable 
possibility that the study drug caused the event. 
Not Related (includes events thought to be Unlikely Related) 
 An AE that is clearly due to extraneous causes (eg, concurrent disease, concomitant 
medications, disease under study, etc.) 
 It does not follow a reasonable temporal sequence from administration of study drug 
 It does not follow a known pattern of response to study drug 
 It does not reappear or worsen when study drug is restarted 
 An alternative explanation is likely even if not clearly identifiable 
Related (includes events thought to be Probably or Possibly Related) 
 An AE that is difficult to assign to alternative causes 
 It follows a strong or reasonable temporal sequence from administration of study drug 
 It could not be reasonably explained by the patient’s clinical state, concurrent disease, or 
other concomitant therapy administered to the patient 
 It follows a known response pattern to study drug 
 It is confirmed with a positive rechallenge or supporting laboratory data 
8.7.8 
Outcome and Action Taken  
The Investigator will record the action taken and outcome for each AE according to the following 
criteria: 
8.7.8.1 
Action Taken with Study Drug  
 None 
 Dose reduced 
 Study drug held/interrupted 
 Study drug permanently discontinued 
 Not applicable (patient not on study drug at the time of the event) 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
54 of 77 
Version 3.0; 31 July 2023 
8.7.8.2 
Outcome  
 Recovered/Resolved 
 Recovered/Resolved with sequelae 
 Not recovered/Not resolved 
 Death 
 Lost to follow-up/Unknown 
8.7.9 
Follow-up of Adverse Events and Serious Adverse Events  
All AEs and SAEs occurring during the study are to be followed up in accordance with good 
medical practice until resolution or stabilization, until the event returns to baseline status, is 
determined to be a chronic condition or until patient is lost to follow-up or dies.  
8.7.10 
Regulatory Aspects of Serious Adverse Event Reporting  
8.7.10.1 
Investigator and Sponsor Responsibilities  
All SAEs, regardless of relationship to study drug, must be reported to the Sponsor within 24 hours 
of knowledge of the event, according to the procedures below. It is important that the Investigator 
provide an assessment of relationship of the SAE to study treatment at the time of the initial report. 
The Novo Nordisk SAE Report Form must be used for reporting SAEs. The contact information for 
reporting of SAEs can be found on the Novo Nordisk SAE Report Form and Pregnancy Reporting 
Forms. 
The Sponsor or its designee is responsible for submitting reports of AEs associated with the use of 
the drug that are both serious and unexpected to the United States Food and Drug Administration 
(FDA), according to 21 Code of Federal Regulations (CFR) 312.32; to the European regulatory 
authorities according to the European Commission Clinical Trials Directive (2001/20/EC); and to 
other applicable regulatory authorities, according to national law and/or local regulations. 
All Investigators participating in ongoing clinical studies with the study medication will receive 
copies of these reports for prompt submission to their Institutional Review Board (IRB) or 
Independent Ethics Committee (IEC). In accordance with the European Commission Clinical Trials 
Directive (2001/20/EC), the Sponsor or its designee will notify the relevant ethics committees in 
concerned member states of applicable suspected unexpected serious adverse reactions as individual 
notifications or through periodic line listings. 
8.7.10.2 
Sponsor Reporting Timeline  
The Sponsor or its designee will submit all safety updates and periodic reports to the regulatory 
authorities as required by applicable regulatory requirements (ie, within 7 days for treatment related 
unexpected fatal or life-threatening events; within 15 days for all other treatment related unexpected 
serious events).  
8.7.11 
Special Situation Reports  
Special situation reports include reports of overdose, medication error, abuse or misuse.  
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
55 of 77 
Version 3.0; 31 July 2023 
1. Overdose: Refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively (accidentally or intentionally), which is above the maximum 
recommended dose according to the protocol. Clinical judgement should always be applied. In 
cases of a discrepancy in the drug accountability, overdose will be established only when it is 
clear that the patient has taken additional dose(s), or the Investigator has reason to suspect that 
the patient has taken additional dose(s).  
2. Misuse: Refers to situations where the medicinal product is intentionally and inappropriately 
used in a way that is not in accordance with the protocol instructions or local prescribing 
information and may be accompanied by harmful physical and/or psychological effects.  
3. Abuse: Is defined as persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects. 
4. Medication error: Is any unintentional error in the prescribing, dispensing, or administration 
of a medicinal product by a healthcare professional, patient, or consumer, respectively. The 
administration or consumption of the unassigned treatment and administration of an expired 
product are always reportable as medication errors, cases of patients missing doses of 
investigational product are not considered reportable as medication error. 
All special situation events as described above must be reported on the Special Situations Report 
form and faxed/emailed to Novo Nordisk Global Safety (contact information listed below) within 
24 hours of knowledge of the event. All AEs associated with these Special Situation events should 
be reported as AEs or SAEs (as applicable) as well as recorded on the AE eCRF and/or the Novo 
Nordisk SAE report form. Details of the symptoms and signs, clinical management, and outcome 
should be provided, when available. 
Novo Nordisk Global Safety 
Fax: + 45 44427787 
e-mail: SOCLIN@NOVONORDISK.COM  
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
56 of 77 
Version 3.0; 31 July 2023 
9.0 
STATISTICAL CONSIDERATIONS  
9.1 
Statistical Methods  
Complete details of the statistical analyses to be performed will be documented in a statistical 
analysis plan (SAP). This document will include details of analysis populations, summary 
strategies, analytic approaches, and any amendments to the proposed analyses listed here. Any 
changes in analyses from those planned in the SAP will be detailed in the final study report. 
9.2 
Patient Populations for Analysis  
 Full Analysis Set (FAS): All patients who signed the informed consent and received at least 
1 dose of etavopivat. 
 Interim Assessment Set: The first 15 patients overall or first 8 patients per transfusion 
history stratum in the FAS who completed the Week 24 Response visit and have a baseline 
record of the primary endpoint. 
 Efficacy Evaluable Set: All patients in the FAS who have completed the Week 24 Response 
visit and who have a baseline record of the primary endpoint. 
 Per-Protocol Set (PPS): All patients in the Full Analysis Set who did not have any major 
protocol violations impacting the efficacy outcomes. 
 Safety Set: All patients who received at least one dose of etavopivat.  
 Pharmacokinetic Set: All Safety Set patients who have at least one evaluable concentration 
for etavopivat at a scheduled PK time point after the start of dosing. For patients with 
protocol violations or events with potential to affect the PK concentrations, a decision 
regarding inclusion in the analysis will be made on a case-by-case basis.  
9.3 
Sample Size Considerations  
An overall sample size of N=45 will provide 87.3% power to detect an increase in the response rate 
for the HI-E criteria. Specifically, the assumed response rates are 40% for the etavopivat 
intervention and 20% otherwise (null-hypothesis comparator). One-sided testing, a significance 
level of 0.025, and the exact binomial distribution are used for the calculations.   
9.4 
General Statistical Considerations  
Continuous variables will be summarized descriptively via number of patients, mean, standard 
deviation, minimum, median, and maximum. Categorical variables will be summarized as the 
number and percent of patients in each category. Data summaries will be performed using the 
nominal visit unless otherwise specified.  
Unless otherwise specified, all testing will be 2-sided at the 0.05 level of significance.  
All data collected on study in the eCRF will be included in data listings. 
9.4.1 
Multicenter Studies  
Data collected will be analyzed as a whole. Exploratory analyses by individual study sites may be 
conducted as warranted. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
57 of 77 
Version 3.0; 31 July 2023 
9.4.2 
Handling of Missing Data  
For patient reported outcome data, missing data imputation will be based on published instrument 
specific methods. 
Full details of how missing data will be handled will be described in the SAP. 
9.5 
Futility Assessment and Decision Rules  
A futility assessment threshold has been selected for this study once 15 patients overall or 8 patients 
in a single transfusion stratum have evaluable responses on the HI-E criteria at Week 24, whichever 
occurs first. If the overall futility assessment is performed and ≤ 3 responses are observed, 
enrollment may discontinue for futility. If there are 4 or more responses at 24-weeks observed, 
enrollment will continue until a total of approximately 45 response evaluable patients are available 
at Week 24. If the stratum-specific futility assessment is performed and no responses are observed, 
further enrollment may be restricted to specific subsets of patients based on prior transfusion 
history.   
Enrollment will not pause during assessment periods unless futility analysis suggests clinical need 
to pause. 
Assuming the pooled response rate of 40% is met, the probability of incorrectly declaring futility 
with 15 evaluable patients is 0.0905. This is calculated using the binomial cumulative distribution 
function with parameters n=15, p=0.4, x=3. 
The single stratum futility assessment allows for the possibility that response rates in a single 
stratum may be lower than 40%, but the pooled response rate after incorporating the other strata 
could still reach 40%. The per-stratum futility threshold is intended to terminate enrollment in a 
stratum where the true response rate can be expected to be <25%. Under a binomial distribution 
with parameters n=8 and p=0.25, the probability of observing x=0 successes is 0.10011. 
9.6 
Analysis of Efficacy  
The primary analysis of Efficacy will be performed using the Efficacy Evaluable Set. Sensitivity 
will be performed using the PPS. 
9.6.1 
Analysis of Primary Efficacy Endpoint  
The primary endpoint is the pooled incidence of the HI-E criteria of ≥ 8 weeks duration (across 
strata), and it will be summarized with frequencies and proportions. Specifically, the primary 
endpoint is assessed following 24 weeks of etavopivat treatment. During those 24 weeks, if there 
had been an 8-week interval (or longer) where one of the below 3 conditions was 
maintained/persistently held, then the incidence of the primary endpoint is fulfilled: 
 NTD patients: ≥ 1.5 g/dL increase in Hb from baseline  
 LTB patients: absence of any transfusion 
 HTB patients: reduction by ≥ 50% of RBC units 
Analysis of the pooled incidence will test the hypothesis: 
H0: 0.2 ≤ P1 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
58 of 77 
Version 3.0; 31 July 2023 
H1: 0.2 > P1 
Where P0 = 0.20 is the assumed null proportion and P1 is the observed proportion for etavopivat 
treated patients. This will be tested using a one-sided binomial exact test at the significance level of 
0.025 for accuracy. 
Tabular summaries will also include the exploratory incidence and test for each of the separate 
strata.  
9.6.2 
Analysis of Secondary Efficacy Endpoints  
The analysis of all secondary endpoints will be based on the Efficacy Evaluable Set.  Sensitivity of 
the primary analysis will be performed using the PPS.   
9.6.2.1 
HI-E Criteria ≥ 8 weeks  
The HI-E criteria of ≥ 8 weeks will also be evaluated following 16 and 48 weeks of treatment. The 
summary and analysis at Weeks 16 and 48 will follow the same methodology as the primary 
endpoint. 
9.6.2.2 
HI-E criteria ≥ 16 weeks  
The incidence of HI-E responses lasting 16 weeks or longer within 24 and 48 weeks of etavopivat 
treatment, will be evaluated using the following 3 conditions: 
 NTD: ≥ 1.5 g/dL increase from baseline maintained for at least 16 consecutive weeks 
 LTB: no transfusion for at least 16 weeks 
 HTB: reduction by ≥ 50% in RBC units for at least 16 consecutive weeks. 
Responses will be summarized and analyzed with the same methodology as the primary endpoint. 
9.6.2.3 
Additional Measures of Clinical Benefit  
Additional measures of potential clinical benefit will be summarized with descriptive statistics. 
These consist of the following: 
 Overall Response Rate (2006 IWG Criteria) 
 Duration of response (2006 IWG Criteria) 
 Increase in neutrophils and/or platelets 
 Decrease in ferritin and decrease in iron chelation therapy 
 Overall survival 
 Reduction in RBC transfusions and rate of RBC transfusion independence (RBC-TI) in patients 
with LTB or HTB at study entry 
 
The Overall Response Rate (ORR) and duration of response are based on the 2006 IWG Criteria 
(Cheson et al. 2006) as assessed at each scheduled assessment. ORR will be summarized with 
descriptive statistics by disease strata and overall. Duration of response will be summarized with 
quantiles based on product limit estimates (ie, Kaplan-Meier). Duration of response is defined as 
the time from date of first known incidence of a 2006 IWG criteria response to the most recent date 
that the 2006 IWG criteria is not met following the initial response. If the subject has met IWG 
criteria throughout the period following the initial response, the subject will be censored at the latest 
date of end of study, loss to follow-up, or death. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
59 of 77 
Version 3.0; 31 July 2023 
 
Overall survival is defined as the time from first dose to date of death. If the subject was alive at last 
contact, the end date will be censored at the latest of either end of study, loss to follow-up, or study 
discontinuation. Overall survival will be summarized with quantiles based on product limit 
estimates, in the same manner as the duration of response. 
Laboratory results and change from baseline will be summarized with descriptive statistics for 
neutrophils and platelets. On-study use of iron chelation therapies will also be summarized with 
descriptive statistics. The study SAP will detail chelation therapy strata and summary methods as 
required. 
For LTB and HTB patients, RBC transfusions will be summarized by both unit and volume with 
descriptive statistics by nominal visit. The incidence of 56-day transfusion independence by Week 
16, Week 24, and Week 48 and duration of transfusion independence will be summarized with 
descriptive statistics. 
9.6.3 
PK/PD and Exploratory Efficacy Analyses  
Etavopivat plasma concentrations will be summarized descriptively by time point, disease strata 
(NTD, LTB, and HTB), and overall. 
Pharmacokinetic parameters will be based on the actual sample collection times and determined 
using standard noncompartmental methods. Pharmacokinetic analyses will be conducted on patients 
in the Pharmacokinetic Set and will be detailed in a separate PK plan.  
Pharmacodynamic (PD) results will include RBC 2,3-DPG and ATP levels over time. All PD 
endpoints will be based on the efficacy evaluable set and will be summarized with descriptive 
statistics by time point, disease strata, and overall. 
9.6.3.1 
Pharmacokinetic and/or Pharmacodynamic Modelling  
Data from the study may be used for exploratory pharmacokinetic and/or pharmacodynamic 
analysis as needed. 
9.7 
Analysis of Study Population Endpoints  
All study population analyses will be conducted on the Full Analysis Set.   
9.7.1 
Disposition and Reasons for Discontinuation  
The number of patients completing informed consent, dosed, completing the study, early 
discontinuation, and treatment discontinuation will be summarized with descriptive statistics for 
each disease strata (NTD, LTB, and HTB) and overall. The number of patients in each analysis 
population will also be summarized. 
All protocol deviations related to study inclusion or exclusion criteria, conduct of the trial, patient 
management, or patient assessment will be listed, as well as the major/minor status and the effect on 
the per-protocol set (PP). 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
60 of 77 
Version 3.0; 31 July 2023 
9.7.2 
Demographics and Other Baseline Characteristics  
Demographics and baseline characteristics will be summarized for each disease strata and overall 
using descriptive statistics.  
9.7.3 
Study Drug Compliance  
Study drug compliance will be assessed by examination of the dispensed and returned pills. Percent 
compliance will be calculated based on comparing the returned pills to the expected number of pills 
to be taken between visits. 
Study drug compliance will be summarized using descriptive statistics for each disease strata and 
overall.  
9.8 
Analysis of Safety Assessments  
All Safety analyses will be performed on the Safety Set. 
9.8.1 
Adverse Events  
Original verbatim terms used in the eCRFs by Investigators or designees to identify AEs will be 
coded using Medical Dictionary for Regulatory Activities (MedDRA), version 21.0 or higher. 
Summaries of AEs will be based on TEAEs. A TEAE is an AE that begins or worsens following 
first dose of study drug and prior to 28 days after the last dose of study drug. The number and 
percentage of patients with TEAEs will be summarized for each disease strata, and overall, by 
MedDRA System Organ Class (SOC) and Preferred Term (PT) for the following categories: 
 TEAEs 
 Drug-Related TEAEs 
 Grade 3 or Higher TEAEs 
 Grade 3 or Higher Drug-Related TEAEs 
 Serious TEAEs 
 Serious Drug-related TEAEs 
 TEAEs Leading to Dose Reduction 
 TEAEs Leading to Dose Interruption 
 TEAEs Leading to Dose Discontinuation 
 
Maximum Severity of TEAEs will also be summarized by SOC and PT. Additional summary 
tabulations of TEAEs may also include:  most commonly reported TEAEs, deaths, serious TEAEs, 
serious drug-related TEAEs, TEAEs leading to dose reduction, TEAEs leading to dose interruption, 
and TEAEs leading to study drug discontinuation will be also provided, summarized by SOC and 
PT.  
All adverse events will be presented in data listings with non-treatment-emergent events being 
included in a separate listing. 
9.8.2 
Other Safety Assessments  
Vital signs may include blood pressure (systolic and diastolic), heart rate, respiratory rate, and oral 
temperature. Descriptive statistics of each collected vital sign will be summarized for each disease 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
61 of 77 
Version 3.0; 31 July 2023 
strata and overall. Temporal assessments will include both raw and change from baseline 
summaries for each time point.  
ECG result interpretations will be summarized with descriptive statistics for each disease strata and 
overall. Quantitative ECG results will be summarized in the same manner as vital signs for the PR, 
QT, QRS, HR, and QT interval corrected using Fridericia's correction formula (QTcF). 
Additionally, categories of quantitative results and shift tables may be included with details 
included in the SAP.  
Laboratory test data will be summarized descriptively by the type of laboratory test and nominal 
visit (absolute value and change from baseline) and disease strata and overall. Shift tables may be 
produced for selected laboratory test results based on clinical interpretations and NCI-CTCAE 
severity level thresholds. Details of these analyses will be included in the SAP. 
Concomitant medications and prior systemic therapies will be coded using the World Health 
Organization Drug Dictionary (WHODrug) into Anatomical Therapeutic Chemical (ATC) and PT. 
The number and percentage of subjects taking concomitant medications will be tabulated by ATC, 
PT, disease strata, and overall.  
Physical examination results will be included in data listings. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
62 of 77 
Version 3.0; 31 July 2023 
10.0 
DATA MANAGEMENT AND RECORD KEEPING  
10.1.1 
Data Handling  
Data will be recorded on eCRFs and reviewed by the clinical research associate (CRA), data 
manager and/or Sponsor representative. The CRAs will verify data recorded in the relevant 
system(s) with source documents. All corrections or changes made to any study data must be 
appropriately tracked in an audit trail in the relevant system. An eCRF will be considered complete 
when all missing, incorrect, and/or inconsistent data has been accounted for. 
10.1.2 
Computer Systems  
Data will be processed using a validated computer system conforming to regulatory requirements. 
10.1.3 
Data Entry  
Data must be recorded using the relevant system while the study is in progress. All site personnel 
must log into the system using their secure username and password in order to enter, review, or 
correct study data. These procedures must comply with Title 21 of the Code of Federal Regulations 
(21 CFR Part 11) and other appropriate international regulations. All passwords will be strictly 
confidential. 
10.1.4 
Medical Information Coding  
For medical information, the following thesauri will be used: 
 MedDRA for medical history and adverse events 
 WHODrug for prior and concomitant medications and prior systemic therapies 
10.1.5 
Data Validation  
Validation checks programmed within the relevant system, as well as supplemental validation 
performed via review of the data, will be applied to the data in order to ensure accurate, consistent, 
and reliable data. Data identified as erroneous, or data that are missing, will be referred to the 
investigative site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 
10.2 
Record Keeping  
Records of patients, source documents, monitoring visit logs, eCRFs, inventory of study product, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in the 
appropriate study files at the site. Source data are defined as all information in original records and 
certified copies of original records of clinical findings, observations, or other activities in a clinical 
study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity to 
further store such records. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
63 of 77 
Version 3.0; 31 July 2023 
11.0 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL  
11.1 
Ethical Conduct of the Study  
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and wellbeing of study subjects 
are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and 
that the clinical study data are credible. 
11.2 
Institutional Review Board/ Independent Ethics Committee  
The IRB/ IEC will review all appropriate study documentation in order to safeguard the rights, 
safety, and well-being of patients. The study will only be conducted at sites where IRB/ IEC 
approval has been obtained. The protocol, Investigator’s Brochure, ICF, advertisements (if 
applicable), written information given to the patients, safety updates, annual progress reports, and 
any revisions to these documents will be provided to the IRB/ IEC by the Investigator. 
Federal regulations and International Council for Harmonisation (ICH) Guidelines require that 
approval be obtained from an IRB/ IEC prior to participation of patients in research studies. Prior to 
study onset, the protocol, any protocol amendments, ICFs, advertisements to be used for patient 
recruitment, and any other written information regarding this study to be provided to a patient or 
patient’s legal guardian must be approved by the IRB/ IEC. 
No drug will be released to the site for dosing until written IRB/ IEC authorization has been 
received by the Sponsor. 
11.3 
Informed Consent  
The ICF and any changes to the ICF made during the course of the study must be agreed to by the 
Sponsor or designee and the IRB/ IEC prior to its use and must be in compliance with all ICH GCP, 
local regulatory requirements, and legal requirements.  
The Investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
patient has been informed of his/her rights to privacy. The Investigator will obtain written informed 
consent from each patient before any study--specific activity is performed and should document in 
the source documentation that consent was obtained prior to enrollment in the study. The original 
signed copy of the ICF must be maintained by the Investigator and is subject to inspection by a 
representative of the Sponsor, their representatives, auditors, the IRB/ IEC and/ or regulatory 
agencies. A copy of the signed ICF will be given to the patient. 
11.4 
Study Monitoring Requirements  
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, Declaration of Helsinki, ICH GCP, and applicable regulatory requirements, and that 
valid data are entered into the eCRFs. 
To achieve this objective, the monitor’s duties are to aid the Investigator and, at the same time, the 
Sponsor in the maintenance of complete, legible, well organized and easily retrievable data. Before 
the enrollment of any patient in this study, the Sponsor or their designee will review with the 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
64 of 77 
Version 3.0; 31 July 2023 
Investigator and site personnel the following documents: protocol, Investigator’s Brochure, eCRFs 
and procedures for their completion, informed consent process, and the procedure for reporting 
SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source documents 
and requests for clarification or correction may be made. After the eCRF data are entered by the 
site, the CRA will review the data for safety information, completeness, accuracy, and logical 
consistency. Computer programs that identify data inconsistencies may be used to help monitor the 
clinical study. If necessary, requests for clarification or correction will be sent to Investigators. The 
Investigator and his/ her staff will be expected to cooperate with the monitor and provide any 
missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
11.5 
Visits and Assessments in Emergency Situations  
In the event of local or widespread emergencies (eg, COVID-19, weather-related emergencies), in-
person clinic visits may present excessive risks or difficulties for study participants and site staff. In 
these situations, in-person visits may be replaced by alternate methods to assess patients. 
Arrangements should be made to ensure all samples are collected for laboratory analyses and that 
study patients have an adequate supply of study drug. Such changes to the research plan should be 
first discussed with the Medical Lead and must be documented in the study files. 
11.6 
Disclosure of Data  
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB as appropriate. Patients or their legal 
representatives may request their medical information be given to their personal physician or other 
appropriate medical personnel responsible for their welfare. 
Patient medical information obtained during the study is confidential and disclosure to third parties 
other than those noted above is prohibited. 
11.7 
Retention of Records  
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator will 
keep records, including the identity of all participating patients (sufficient information to link 
records, eg, eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE forms, 
source documents, and detailed records of treatment disposition. The records should be retained by 
the Investigator according to specifications in the ICH guidelines, local regulations, or as specified 
in the Clinical Study Agreement, whichever is longer. The Investigator must obtain written 
permission from the Sponsor before disposing of any records, even if retention requirements have 
been met. 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such as 
another Investigator, another institution, or to the Sponsor. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
65 of 77 
Version 3.0; 31 July 2023 
11.8 
Publication Policy  
Following completion of the study, the data may be considered for publication in a scientific journal 
or for reporting at a scientific meeting. Each Investigator is obligated to keep data pertaining to the 
study confidential. The Investigator must consult with the Sponsor before any study data are 
submitted for publication. The Sponsor reserves the right to deny publication rights until mutual 
agreement on the content, format, interpretation of data in the manuscript, and journal selected for 
publication are achieved. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
66 of 77 
Version 3.0; 31 July 2023 
12.0 
REFERENCES  
Ades L, Itzykson R, Fenaux P. Myelodysplastic syndromes. Lancet. 2014;83(9936):2239-52. 
Aizawa S, Harada T, Kanbe E et al. Ineffective erythropoiesis in mutant mice with deficient 
pyruvate kinase activity. Exp Hematol. 2005;33(11):1292-8. 
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization 
classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. 
Banerjee T, Kuypers FA. Reactive oxygen species and phosphatidylserine externalization in murine 
sickle red cells. Br J Haematol. 2004;124(3):391-402. 
Betz T, Lenz M, Joanny JF, Sykes C. ATP-dependent mechanics of red blood cells. Proc Natl Acad 
Sci USA. 2009;106(36):15320-5. 
Brown RC, Cruz K, Kalfa TA, et al. FT-4202, an allosteric activator of pyruvate kinase-R, 
demonstrates proof of mechanism and proof of concept after a single dose and after multiple daily 
doses in a phase 1 study of patients with sickle cell disease. Presented at the 62nd American Society 
of Hematology (ASH) Annual Meeting, December 5-8, 2020. 
Brown RC, Saraf SL, Cruz K, et al. FT-4202 improves hematologic and hemolytic parameters in a 
phase 1 study of patients with sickle cell disease. Presented at the 26th Congress of the European 
Hematology Association (EHA), June 9-17, 2021a. 
Brown RC, Saraf SL, Cruz K, et al. Activation of pyruvate kinase-R with etavopivat (FT-4202) is 
well tolerated, improves anemia, and decreases intravascular hemolysis in patients with sickle cell 
disease treated for up to 12 weeks. Presented at the 63rd American Society of Hematology (ASH) 
Annual Meeting, Atlanta, GA, December 11-14, 2021b. 
Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of 
the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006; 108(2): 
419-25. 
Estepp J, Kalfa T, Saraf S, et al. Phase 1 single (SAD) and multiple ascending dose (MAD) study of 
the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of FT-4202, a PKR activator, in 
healthy and sickle cell disease subjects. EHA Library. 06/12/20; 294015; EP1531. 
Fenaux P, Ades L. How we treat lower-risk myelodysplastic syndromes. Blood. 2013; 121 
(21):4280–4286. 
Fenaux P, Kiladjian JJ, Platzbecker U. Luspatercept for the treatment of anemia in myelodysplastic 
syndromes and primary myelofibrosis. Blood 2019;133(8):790-94. 
Forsyth S, Schroeder P, Geib J, et al. Safety, pharmacokinetics, and pharmacodynamics of 
etavopivat (FT-4202), an allosteric activator of pyruvate kinase-R, in healthy adults: A randomized, 
placebo-controlled, double-blind, first-in-human phase 1 trial. Clin Pharmacol Drug Dev. 2022. 
Grace RF, Rose C, Layton M, et al. Safety and efficacy of mitapivat in pyruvate kinase deficiency. 
NEJM. 2019;381:933-44. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
67 of 77 
Version 3.0; 31 July 2023 
Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F. Revised international 
prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120 (12): 2454–2465. 
Kalfa TA, Kuypers FA, Telen MJ, et al. Phase 1 single (SAD) and multiple ascending dose (MAD) 
studies of the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of FT-4202, 
an allosteric activator of pyruvate kinase-R, in healthy and sickle cell disease subjects. Presented at 
the 2019 ASH Annual Meeting. Orlando, FL, USA. December 09, 2019 (Available online 
November 06, 2019). 
Kim J-W, Dang CV. Multifaceted roles of glycolytic enzymes. Trends Biochem Sci. 
2005;30(3):142-50. 
Kuo KHM, Layton DM, Lal A, Al-Samkari H, Bhatia J, Kosinski PA, et al. Long-term efficacy and 
safety of the oral pyruvate kinase activator mitapivat in adults with non-transfusion-dependent 
alpha- or beta-thalassemia. Blood. 2021;138 (Supplement 1):576. 
Lang KS, Roll B, Myssina S, et al. Enhanced erythrocyte apoptosis in sickle cell anemia, 
thalassemia and glucose-6-phosphate dehydrogenase deficiency. Cell Physiol Biochem. 2002;12 (5-
6):365-72. 
Macdonald R. Red cell 2,3-diphosphoglycerate and oxygen affinity. Anaesthesia 1977;32:544-553. 
Mathias LA, Fisher TC, Zeng L, et al. Ineffective erythropoiesis in β-thalassemia major is due to 
apoptosis at the polychromatophilic normoblast stage. Exp Hematology. 2000;28(12):1343-53. 
Matte A, Brugnara C, De Franceschi L, et al. The pyruvate kinase activator mitapivat reduces 
hemolysis and improves anemia in a β-thalassemia mouse model. JCI. 2021;131(10):e144206. 
Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am. J. Clin Oncol. 1982;5:649-655. 
Platzbecker U, Hofbauer LC, Ehniger G, Holig K. The clinical, quality of life, and economic 
consequences of chronic anemia and transfusion support in patients with myelodysplastic 
syndromes. Leuk Res. 2012;36(5):525-36. 
Platzbecker U, Fenaux P, Adès L, et al. Proposals for revised IWG 2018 hematological response 
criteria in patients with MDS included in clinical trials. Blood. 2019;133(10):1020-1030. 
Schanz J, Tüchler H, Solé F, et al. New comprehensive cytogenetic scoring system for primary 
myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived 
from an international database merge. J Clin Oncol 2012;30(8):820-9. 
Schroeder P, Fulzele K, Forsyth S, et al. Etavopivat, a pyruvate kinase activator in red blood cells, 
for the treatment of sickle cell disease. J Pharmacol Exp Ther. 2022;JPET-AR-2021-00743. 
Zanella A, Fermo E, Bianchi P, Valentini G. Red cell pyruvate kinase deficiency: molecular and 
clinical aspects. Br J Haematol. 2005;130(1):11-25. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
68 of 77 
Version 3.0; 31 July 2023 
Zeidan AM, Linhares Y, Gore SD. Current therapy of myelodysplastic syndromes. Blood Rev. 
2013;27(5):243-59. 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
69 of 77 
Version 3.0; 31 July 2023 
13.0 
APPENDICES  
APPENDIX A: 
RESPONSE CRITERIA FOR MDS  
Adapted from IWG Response Criteria for MDS (Cheson et al. 2006)  
Response Category 
Response criteria (responses must last at least 4 wks) 
Complete remission (CR) 
 
Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines* 
Persistent dysplasia will be noted* 
 
Peripheral blood‡: 
o 
Hb ≥ 11 g/dL 
o 
Platelets ≥ 100 × 109/L  
o 
Neutrophils ≥ 1.0 × 109/L  
o 
Blasts 0% 
Partial remission (PR) 
All CR criteria if abnormal before treatment except: 
 
Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5% 
 
Cellularity and morphology not relevant 
Marrow CR 
Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment 
Peripheral blood: if HI responses, they will be noted in addition to marrow CR 
Stable disease (SD) 
Failure to achieve at least PR, but no evidence of progression for > 8 wks 
Relapse after CR or PR 
At least 1 of the following: 
 
Return to pretreatment bone marrow blast percentage 
 
Decrement of ≥ 50% from maximum remission/response levels in 
granulocytes or platelets  
 
Reduction in Hb concentration by ≥ 1.5 g/dL or transfusion dependence 
Disease progression (PD) 
For patients with: 
 
Less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts  
 
5%-10% blasts: ≥ 50% increase to > 10% blasts 
 
10%-20% blasts: ≥ 50% increase to > 20% blasts 
 
20%-30% blasts: ≥ 50% increase to > 30% blasts 
Any of the following: 
 
At least 50% decrement from maximum remission/response in granulocytes or 
platelets  
 
Reduction in Hb by ≥ 2 g/dL 
 
Transfusion dependence 
 
Hb = hemoglobin; HI = hematologic improvement; IWG = International Working Group; MDS = myelodysplastic 
syndromes; wks = weeks. 
*Dysplastic changes should consider the normal range of dysplastic changes. 
‡ Transient cytopenias during repeated chemotherapy courses should not be considered as interrupting durability of 
response, as long as they recover to the improved counts of the previous course. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
70 of 77 
Version 3.0; 31 July 2023 
RESPONSE CRITERIA FOR MDS (continued) 
Modified International Working Group Response Criteria for Hematologic Improvement 
(Updated 2018) 
Hematologic Improvement 
Response Criteria 
Erythroid 
Response 
(HI-E) 
Non-transfused 
(NTD)* 
At least 2 consecutive Hb measurements ≥1.5 g/dL for a period of minimum 
8 wk in an observation period of 16 to 24 wk compared with the lowest mean 
of 2 Hb measurements (apart from any transfusion) within 16 wk before 
treatment onset 
Low transfusion 
burden (LTB) 
Absence of any transfusions for at least 8 wk in an observation period of 
16-24 wk with the same transfusion policy (defined below) compared with 
16 wk prior to treatment 
High 
transfusion 
burden (HTB) 
Major response: Transfusion independence, defined by the absence of any 
transfusions over a period of minimum 8 wk in an observation period of 
16-24 wk with the same transfusion policy (defined below) compared with 
16 wk prior to treatment 
 
Minor response: Reduction by at least 50% of RBCs over a minimum of 
16 wk with the same transfusion policy (defined below) compared with 16 wk 
prior to treatment 
On-treatment 
RBC 
transfusion 
policy 
Transfusion policy for the individual patient prior to therapy should be 
maintained on treatment if not otherwise clinically indicated (documentation 
by the treating physician required); maximum variation between pre- and on-
study practice of 1 g/dL (or 0.6 mmol/L) in terms of transfusion threshold 
Platelet response (pretreatment, 
<100 × 109/L), HI-P 
 
Absolute increase of 30 × 109/L for patients starting with >20 × 109/L 
PLTs or 
 
Increase from <20 × 109/L to >20 × 109/L and by at least 100% 
In addition, 
 
Evolution of bleeding symptoms is to be taken into account 
Neutrophil response 
(pretreatment, all patients), HI-N 
 
At least 100% increase and an absolute increase >0.5 × 109/L 
(pretreatment, <1.0 × 109/L) 
Progression or relapse after HI 
For HI-N and HI-P: 
 
At least 50% decrement from maximum response levels in 
neutrophils or platelets, and not meet response criteria when 
compared to baseline  
For HI-E: 
 
Reduction in Hb by ≥ 1.5 g/dL, and not meet response criteria when 
compared to baseline 
 
Transfusion dependence 
 
HTB: increase in transfusion burden by at least 50% 
Hb = hemoglobin; HI = hematologic improvement; PLTs = platelets; wk = week(s). 
*If patients received 1 or 2 RBC concentrates during the 16-wk pre-treatment period, it is recommended that HI-E 
achievement requires not only transfusion independence but also an increase of Hb by at least 1.5 g/dL (= 0.9 mmol/L). 
 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
71 of 77 
Version 3.0; 31 July 2023 
APPENDIX B: 
INTERNATIONAL PROGNOSTIC SCORING SYSTEM SCORE – 
REVISED  
IPSS-R Cytogenetic Risk Groups*, ** 
Cytogenetic Prognostic 
Subgroups 
Cytogenetic Abnormalities 
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: 3 abnormalities 
Very poor 
Complex: >3 abnormalities 
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 Blasts (%) 
≤2 
- 
>2 - <5 
- 
5 - 10 
>10 
- 
Hemoglobin (g/dL) 
≥10 
- 
8 - <10 
<8 
- 
- 
- 
Platelets (x 109/L) 
≥100 
50 - <100 
<50 
- 
- 
- 
- 
ANC (x 109/L) 
≥0.8 
<0.8 
- 
- 
- 
- 
- 
IPSS-R Prognostic Risk Categories/Scores* 
Risk Category 
Risk Score 
Very Low 
≤1.5 
Low 
>1.5 - 3 
Intermediate 
>3 - 4.5 
High 
>4.5 - 6 
Very High 
>6 
 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
72 of 77 
Version 3.0; 31 July 2023 
IPSS-R: Prognostic Risk Category Clinical Outcomes* 
No. pts 
Very Low 
Low 
Intermediate 
High 
Very 
High 
Subjects (%) 
7012 
19% 
38% 
20% 
13% 
10% 
Survival*** 
- 
8.8 
5.3 
3.0 
1.6 
0.8 
AML/25%***,^ 
- 
NR 
10.8 
3.2 
1.4 
0.7 
*   Greenberg et al. 2012. 
** Schanz et al. 2012. 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
73 of 77 
Version 3.0; 31 July 2023 
APPENDIX C: 
DIAGNOSIS OF IDIOPATHIC/DE NOVO MDS ACCORDING TO 
WORLD HEALTH ORGANIZATION  
Name 
Dysplastic 
Lineages 
Cytopenias* 
Ring Sideroblasts 
as % of Marrow 
Erythroid 
Elements 
BM and PM Blasts 
Cytogenetics by 
Conventional 
Karyotype Analysis 
MDS with single 
lineage dysplasia 
(MDS-SLD) 
1 
1 or 2 
< 15% / < 5%† 
BM < 5%, PB < 1%, no 
Auer rods 
Any, unless fulfills all 
criteria for MDS with 
isolated del(5q) 
MDS with 
multilineage 
dysplasia (MDS-
MLD) 
2 or 3 
1-3 
< 15% / < 5%† 
BM < 5%, PB < 1%, no 
Auer rods 
Any, unless fulfills all 
criteria for MDS with 
isolated del(5q) 
MDS with ring sideroblasts (MDS-RS) 
MDS-RS with 
single lineage 
dysplasia (MDS-
RS-SLD) 
1 
1 or 2 
≥ 15% / ≥ 5%† 
BM < 5%, PB < 1%, no 
Auer rods 
Any, unless fulfills all 
criteria for MDS with 
isolated del(5q) 
MDS-RS with 
multilineage 
dysplasia (MDS-
RS-MLD) 
2 or 3 
1-3 
≥ 15% / ≥ 5%† 
BM < 5%, PB < 1%, no 
Auer rods 
Any, unless fulfills all 
criteria for MDS with 
isolated del(5q) 
MDS with isolated 
del(5q) 
1-3 
1-2 
None or any 
BM < 5%, PB < 1%, no 
Auer rods 
del(5q) alone or with 1 
additional abnormality 
except -7 or del (7q) 
MDS with excess blasts (MDS-EB) 
MDS-EB-1 
0-3 
1-3 
None or any 
BM 5%-9% or PB 2%-
4%, no Auer rods 
Any 
MDS-EB-2 
0-3 
1-3 
None or any 
BM 10%-19% or PB 
5%-19%, no Auer rods 
Any 
MDS, unclassifiable (MDS-U) 
with 1% blood 
blasts 
1-3 
1-3 
None or any 
BM < 5%, PB = 1%‡, 
no Auer rods 
Any 
with single lineage 
dysplasia and 
pancytopenia 
1 
3 
None or any 
BM < 5%, PB < 1%, no 
Auer rods 
Any 
based on defining 
cytogenetic 
abnormality 
0 
1-3 
< 15% § 
BM < 5%, PB < 1%, no 
Auer rods 
MDS-defining 
abnormality 
Refractory cytopenia 
of childhood 
1-3 
1-3 
None 
BM < 5%, PB < 2% 
Any 
*  Cytopenias defined as: hemoglobin, < 10 g/dL; platelet count, <100 × 109/L; and absolute neutrophil count, <1.8 × 109/L. Rarely, 
MDS may present with mild anemia or thrombocytopenia above these levels. PB monocytes must be < 1 × 109/L. 
†  If SF3B1 mutation is present. 
‡  One percent PB blasts must be recorded on at least 2 separate occasions. 
§  Cases with ≥ 15% ring sideroblasts by definition have significant erythroid dysplasia, and are classified as MDS-RS-SLD. 
 
Abbreviations: BM = bone marrow; MDS = Myelodysplastic Syndrome; PB = peripheral blood.  
 
Adapted from Arber et al. 2016.  
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
74 of 77 
Version 3.0; 31 July 2023 
APPENDIX D: 
ECOG PERFORMANCE STATUS  
Grade 
ECOG Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
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 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities; up 
and about more than 50% of waking hours 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair 
5 
Dead 
Source: Oken et al. 1982. 
 
 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
75 of 77 
Version 3.0; 31 July 2023 
APPENDIX E: 
CLINICAL LABORATORY ANALYSES  
Chemistry 
Alanine aminotransferase 
Ferritin, transferrin (TIBC) and iron level 
(timing per Table 1-1, and Table 1-2) 
Albumin 
Gamma-glutamyl transferase  
Alkaline phosphatase 
Glucose 
Amylase 
Lactate dehydrogenase 
Aspartate aminotransferase  
Lipase  
Bicarbonate  
Magnesium 
Bilirubin – total, direct, indirect  
Phosphorus 
Blood urea nitrogen  
Potassium  
Calcium  
Sodium  
Chloride  
Total protein  
Creatinine  
Uric acid  
Erythropoietin (Screening only) 
 
Hematology 
Hematocrit 
White blood cell (WBC) count and differential: 
 
Basophils 
 
Eosinophils 
 
Lymphocytes 
 
Monocytes 
 
Neutrophils 
 
Blasts 
Hemoglobin 
Red blood cell (RBC) count 
Reticulocyte count (% and absolute) 
Mean corpuscular hemoglobin concentration 
(MCHC) 
Mean corpuscular volume (MCV) 
RBC distribution width (RDW) 
Absolute neutrophil count (ANC) 
Platelets  
 
Hemoglobin Electrophoresis  
Screening only  
Coagulation 
International normalized ratio (INR) 
Partial thromboplastin time (PTT) 
Prothrombin time (PT) 
Fibrinogen 
Serology 
Hepatitis B surface antigen (HepBsAg) 
Hepatitis C virus (HCV) by polymerase chain reaction (PCR) 
Hepatitis B core antibody (HepBcAb) 
Human immunodeficiency virus (HIV) 
Urinalysis 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
pH 
Nitrite 
Specific gravity  
Protein 
 
Urobilinogen 
 
Microscopic analysis (RBCs, WBCs, microalbumin, bacteria, crystals, and casts) will be performed locally as 
clinically indicated. 
Pregnancy Tests (Female patients) 
Serum (Screening) 
Urine (post-Screening) 
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
76 of 77 
Version 3.0; 31 July 2023 
APPENDIX F: 
EXAMPLES OF DRUGS THAT ARE STRONG INDUCERS OF 
CYP3A4/5  
Strong Inducers: 
Apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s wort 
Additional information can be found at: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-
table-substrates-inhibitors-and-inducers#table3-3 
 
  
 
VV-CLIN-180184 3.0
.

 
 
Forma Therapeutics, Inc. 
 
 
Clinical Study Protocol 4202-ONC-203 
 
 
 
 
 
 
77 of 77 
Version 3.0; 31 July 2023 
APPENDIX G: 
SAMPLE TRANSFUSION PLAN: LTB AND HTB PATIENTS  
Patient: 
Date of plan: 
Planned frequency of transfusions:    
Patient will receive transfusions approximately every ________________ weeks 
 
Baseline pre-transfusion Hb threshold   _____________________________________ 
If Hb is below the level above, a transfusion is required. Threshold should be determined based on 
≥ 16 weeks of pre-treatment mean of Hb. 
During treatment, if the pre-transfusion Hb level is increased by ≥ 1 g/dL compared to the 
pre-transfusion Hb threshold for that patient, transfusion may be delayed by a minimum of 7 days 
and/or the number of units transfused may be reduced by 1 or more RBC units. 
Pre-treatment Hb results from ≥ 16 weeks prior to start of study treatment: 
Date 
Hb Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VV-CLIN-180184 3.0
.