A Multi-Center, Open Label, Extension Study Evaluating the Safety and Efficacy of Bomedemstat for the Treatment of Patients With Myeloproliferative Neoplasms (MPNs) Enrolled in a Prior Bomedemstat Clinical Study
Phase: PHASE2
Conditions: Thrombocythemia, Essential, Primary Myelofibrosis
Sponsor: Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

Official Protocol Title:
NCT number:
Document Date:
NCT05223920
A Multi-Center, Open Label, Extension Study Evaluating 
the Safety and Efficacy of Bomedemstat for the 
Treatment of Patients with Myeloproliferative Neoplasms 
(MPNs) Enrolled in a Prior Bomedemstat Clinical Study
13-December-2023

Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 1
Protocol Title:
A Multi-Center, Open Label, Extension Study Evaluating the 
Safety and Efficacy of Bomedemstat for the Treatment of 
Patients with Myeloproliferative Neoplasms (MPNs) Enrolled
in a Prior Bomedemstat Clinical Study
Protocol No.:
IMG-7289-CTP-202 / MK-3543-005
Investigational Product:
Bomedemstat (IMG-7289 / MK-3543)
Indication:
Myeloproliferative Neoplasms
Study Phase:
Phase 2
EudraCT Number:
2021-002452-37
IND Number:
130,789
Sponsor:
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc. 126 East 
Lincoln Avenue, Rahway, NJ 07065, USA
Version and Date:
Amendment 02
13 December 2023
08WYVV

Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 2
Sponsor Signatory
Typed Name:
Title:
Date
Protocol-specific Sponsor contact information can be found in the Investigator Study File 
Binder (or equivalent).
Investigator Signatory
I agree to conduct this clinical study in accordance with the design outlined in this 
protocol and to abide by all provisions of this protocol.
Typed Name:
Title:
Date
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 3
DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 2
13-DEC-2023
This change was made to address study extension. 
Participants from this study will be eligible to enroll in 
another bomedemstat extension study at any point 
before this study ends.
Amendment 1
14-JUN-2023
This change was made to address Non-Merck protocol 
template. The rationale is further supported by 
acquisition of Imago BioSciences, Inc. by Merck & Co., 
Inc. This conversion resulted only in an entity name 
change and update to the address.
Original Protocol
11-JUL-2021
Not applicable
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 4
PROTOCOL AMENDMENT SUMMARY OF CHANGES
Amendment: 02
Overall Rationale for the Amendment:
This change was made to address study extension. Participants from this study will be eligible 
to enroll in another bomedemstat extension study at any point before this study ends.
Summary of Changes Table
Section Number 
and Name
Description of Change
Brief Rationale
Primary Reason for Amendment
Section 9.4.1, End 
of Treatment 
(EoT)
Language added to allow eligible participants 
from this extension study to enroll in another 
extension study using bomedemstat 
This change was made to address study 
extension. Participants from this study will be 
eligible to enroll in another bomedemstat 
extension study at any point before this study 
ends.
Section Number 
and Name
Description of Change
Brief Rationale
Additional Changes
Title Page
Added complete address for Sponsor 
To provide complete address for Sponsor
Section 2,
Protocol Synopsis
Language added to allow eligible participants 
from this extension study to enroll in another 
extension study using bomedemstat
Refer to the rationale for Section 9.4.1
Section 5.1,
Overview
Language added to allow eligible participants 
from this extension study to enroll in another 
extension study using bomedemstat
Refer to the rationale for Section 9.4.1
Section 9.4.2, 
End of 
Study/Early 
Termination Visit
Language added to allow eligible participants 
from this extension study to enroll in another 
extension study using bomedemstat
Refer to the rationale for Section 9.4.1
Section 11.2.5, 
For Participants
Who Consent To 
Another 
Bomedemstat 
Extension Study
Added section
To provide guidance for investigator for 
reporting all AEs, SAEs, and other reportable 
safety events
Throughout
Minor administrative, formatting, grammatical, 
and/or typographical changes were made 
throughout the document.
To ensure clarity and accurate interpretation of 
the intent of the protocol
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 5
Table of Contents
DOCUMENT HISTORY.................................................................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES...............................................................................4
1
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS..............................................................9
2
PROTOCOL SYNOPSIS....................................................................................................................................13
3
INTRODUCTION.................................................................................................................................................21
3.1
Background on the Disease to be Treated............................................................................................21
3.2
Background on the Drug Target..............................................................................................................21
3.3
Background on LSD1 in Myeloid Neoplasia Pre-Clinical Studies ..............................................23
3.4
Background on Bomedemstat (IMG-7289/MK-3543).....................................................................24
3.5
Potential Clinical Risks and Benefits when Dosing an LSD1 Inhibitor .....................................24
3.6
Bomedemstat Dose Justification.............................................................................................................25
3.6.1
Rationale for and Safety of the Proposed Bomedemstat Dose.............................................25
3.6.2
Rationale for the Bomedemstat Dosing Schedule....................................................................26
4
HYPOTHESIS AND OBJECTIVES...............................................................................................................27
4.1
Objectives.......................................................................................................................................................27
5
INVESTIGATIONAL PLAN............................................................................................................................27
5.1
Overview.........................................................................................................................................................27
6
STUDY POPULATION......................................................................................................................................29
6.1
Study Entry Criteria.....................................................................................................................................29
6.1.1
Inclusion Criteria................................................................................................................................29
6.1.2
Exclusion Criteria...............................................................................................................................29
6.2
Patient Enrollment .......................................................................................................................................30
6.3
Patient Withdrawal ......................................................................................................................................30
6.4
Patient Care Guidelines..............................................................................................................................30
6.5
Prohibited Medications...............................................................................................................................31
7
STUDY PRODUCT..............................................................................................................................................32
7.1
Formulation, Labeling, Packaging and Storage..................................................................................32
7.1.1
Formulation..........................................................................................................................................32
7.1.2
Packaging and Labeling ...................................................................................................................32
7.1.3
Storage ...................................................................................................................................................32
7.2
Dispensing, Administration, Dosage and Missed Doses.................................................................32
7.2.1
Dispensing ............................................................................................................................................32
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Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 6
7.2.2
Administration.....................................................................................................................................33
7.2.3
Dosage....................................................................................................................................................33
7.2.4
Missed Doses.......................................................................................................................................34
7.2.5
Interruption of Dosing.......................................................................................................................34
8
SAFETY ADVISORY BOARD (SAB) REVIEWS AND MANAGEMENT OF STUDY 
TOXICITIES, INCLUDING STOPPING RULES...............................................................................................34
8.1
Safety Advisory Board (SAB) Reviews................................................................................................34
8.2
Management of Study Toxicities ............................................................................................................35
8.2.1
Hematologic Toxicity........................................................................................................................35
8.2.2
Stopping Rules ....................................................................................................................................35
9
STUDY ASSESSMENTS...................................................................................................................................35
9.1
Enrollment Period........................................................................................................................................37
9.1.1
Informed Consent Visit.....................................................................................................................37
9.1.2
Eligibility Assessment.......................................................................................................................38
.38
.38
.39
.40
.41
.41
.41
.42
.43
.43
.43
.44
.44
.44
.45
10
LABORATORY SAMPLING FOR SAFETY AND PD ANALYSIS ................................................46
10.1
Laboratory Measures...................................................................................................................................46
10.1.1
Local Laboratory Measures.............................................................................................................47
10.1.2
Central Laboratory Measures..........................................................................................................47
11
SAFETY...................................................................................................................................................................48
CCI
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 7
11.1
Pregnancy .......................................................................................................................................................48
11.2
Adverse Events .............................................................................................................................................49
11.2.1
Adverse Event Intensity ...................................................................................................................50
11.2.2
Adverse Event Relatedness .............................................................................................................51
11.2.3
Serious Adverse Events....................................................................................................................51
11.2.4
Reporting Serious Adverse Events ...............................................................................................52
11.2.5
For Participants Who Consent To Another Bomedemstat Extension Study ...................53
12
ANALYSIS AND STATISTICAL CONSIDERATIONS.......................................................................53
12.1
General Considerations ..............................................................................................................................53
12.2
Power ...............................................................................................................................................................53
12.3
Treatment Assignment and Blinding .....................................................................................................53
12.4
Study Endpoints............................................................................................................................................53
12.4.1
Primary Endpoints..............................................................................................................................53
12.4.2
Exploratory Endpoints......................................................................................................................54
12.5
Data Analysis.................................................................................................................................................55
12.5.1
Safety and Tolerability Data Analysis.........................................................................................55
12.5.2
Efficacy Data Analysis .....................................................................................................................56
13
STUDY ADMINISTRATION ..........................................................................................................................57
13.1
Ethical Considerations................................................................................................................................57
13.2
Participation Information Sheet/Consent Form (PISCF).................................................................57
13.3
Institutional Review Board (IRB), Independent Ethics Committee (IEC) and Human 
Research Ethics Committee (HREC)...................................................................................................................57
13.4
Study or Site Termination .........................................................................................................................58
13.5
Study Monitoring Requirements.............................................................................................................58
13.6
Quality Assurance........................................................................................................................................59
13.7
Confidentiality...............................................................................................................................................59
14
INVESTIGATOR REQUIREMENTS............................................................................................................60
14.1
Protocol Adherence.....................................................................................................................................60
14.2
Source Documentation ...............................................................................................................................61
14.3
Direct Access to Source Documentation..............................................................................................61
14.4
Case Report Forms ......................................................................................................................................61
14.5
Study Drug Accountability .......................................................................................................................61
14.6
Disposal of Study Drug..............................................................................................................................62
14.7
Training of Staff ...........................................................................................................................................62
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 8
14.8
Clinical Study Report..................................................................................................................................62
14.9
Retention of Records...................................................................................................................................62
15
REFERENCES.......................................................................................................................................................63
16
APPENDICES ........................................................................................................................................................66
..66
..66
..68
..71
..72
16.2
Criteria for Grading Myelofibrosis (Arber et al., 2016)*................................................................73
16.3
Eastern Cooperative Group Performance Status................................................................................73
16.4
Revised IWG-MRT and ELN Response Criteria for MF................................................................74
16.5
Revised Response Criteria for ET:  IWG-MRT and ELN Consensus 2013 (Barosi et al., 
2013) ............................................................................................................................................................................76
16.6
Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score  (MPN-
SAF TSS) – 7-Day Recall .......................................................................................................................................77
16.7
Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)..................................78
16.8
Patient Global Impression of Change....................................................................................................80
16.9
Remote Data Review ..................................................................................................................................81
16.9.1
Risk Assessment.................................................................................................................................81
16.9.2
Security Measures ..............................................................................................................................81
16.9.3
Processes ...............................................................................................................................................81
16.9.3.1
Direct, Controlled Remote Access to the Systems Used by the Trial Site to
Manage the Source Documents/Source Data..........................................................................................82
16.9.3.2
For Passive Access to Original Documents/Original Data via Live Image
Transmission.....................................................................................................................................................82
16.9.3.3
Passing on Redacted Copies of Original Documents and Documents with Original 
Data
........................................................................................................................................................82
CCI
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Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 9
1
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
Abbreviation
Definition
<, ≤, >, ≥
less than, less than or equal to, greater than, greater than or equal to
±
plus or minus
Ac
acetylation
ADL
activities of daily living
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AML
acute myeloid leukemia
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
AST
aspartate transaminase
ATP
Additional Treatment Period
BCR-ABL
breakpoint cluster region-Abelson
BM
bone marrow
Bomedemstat 
(IMG-7289 / MK-
3543)
N-[(2S)-5-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}-1-(4-
methylpiperazin-1-yl)-1-oxopentan-2-yl]-4-(1H-1,2,3-triazol-1-
yl)benzamide, bis-tosylate salt
BMMC
bone marrow mononuclear cell
BUN
blood urea nitrogen
°C
degrees Centigrade
CALR
calreticulin 
CBC
complete blood count
CD
cluster of differentiation
CFR
Code of Federal Regulations
cGMP
current Good Manufacturing Practices
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
Clinical Benefit
not meeting “progressive disease” criteria as per Section 16.4 (for MF 
patients) and Section 16.5 (for ET patients) and safely tolerating IMG-
7289, as determined by the Principal Investigator
CMH
Cochran-Mantel-Haenszel
CoREST
Co-repressor for RE1-silencing transcription factor
COVID-19
Coronavirus disease-2019
CR
complete remission or response
CRO
contract research organization
CRP
c-reactive protein
CT
computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
CV
co-efficient of variation
Cxcl
chemokine (C-X-C Motif) ligand
CXCR4
chemokine (C-X-C motif) receptor 4
CYP
cytochrome P450
D, d
day
DILI
Drug-induced liver injury
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Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 10
Abbreviation
Definition
DNA
deoxyribonucleic acid
DNMT
DNA-methyltransferase
Dpi
pharmacodynamic dose; the estimated dose of IMG-7289 needed in 
humans that provides sufficient exposure to inhibit normal 
hematopoiesis safely during a fraction of the 24-hour dosing cycle
EC
Ethics Committee 
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
EFS
event free survival
ELN
European Leukemia Network
EMH
extramedullary hematopoiesis
EMR
electronic medical record
EoS
End of Study
EoT
End of Treatment
EPO
erythropoietin
ESC
embryonic stem cell
ET
essential thrombocythemia; Early Termination
FAD
flavin adenine dinucleotide
Free base of IMG-
7289
N-[(2S)-5-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}-1-(4-
methylpiperazin-1-yl)-1-oxopentan-2-yl]-4-(1H-1,2,3-triazol-1-
yl)benzamide, free base
FSH
follicle stimulating hormone
g or gm
gram
g/dL
gram per deciliter
GCP
Good Clinical Practice
G-CSF
gram colony stimulating factor
GFI1
growth factor independent 1 transcription factor
GFP
green fluorescent protein
GGT
gamma glutamyltransferase
GM-CSF
granulocyte-macrophage colony stimulating factor
GMP
Good Manufacturing Practices
H
histone
HAV
hepatitis A virus
Hb
hemoglobin
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDAC
histone deacetylase
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HREC
Human Research Ethics Committee
HSC
hematopoietic stem cell
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
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Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 11
Abbreviation
Definition
IL
interleukin
IMG-7289
bomedemstat, N-[(2S)-5-{[(1R,2S)-2-(4-
fluorophenyl)cyclopropyl]amino}-1-(4-methylpiperazin-1-yl)-1-
oxopentan-2-yl]-4-(1H-1,2,3-triazol-1-yl)benzamide, bis-tosylate salt
INR
international normalized ratio
IRB
Institutional Review Board
ITT
Intent to Treat
IUD
intrauterine device
IWG-MRT
International Working Group for Myelofibrosis Research and 
Treatment
JAK
Janus Kinases
K
lysine
KD
knockdown 
KDM1A
lysine-specific demethylase 1
Kg
kilogram
L
litre
LDH
lactate dehydrogenase
LIC
leukemia initiating cell
LPE
Limited Physical Exam
LSD1
lysine-specific demethylase 1
LSDi
LSD1 inhibition or inhibitors
MAO; MAOI
monoamine oxidase(s); monoamine oxidase inhibitor(s)
MDS
myelodysplastic syndrome
me; Me
methyl; methylation
MedDRA
Medical Dictionary for Regulatory Activities
MF
myelofibrosis
mg
milligram
mg/kg
milligram per kilogram
mg/kg/d
milligram per kilogram per day
mL
milliliter
MPL
myeloproliferative leukemia virus oncogene, thrombopoietin receptor
MPN
myeloproliferative neoplasias or neoplasms, myeloproliferative 
diseases
MPN10
The equivalent of the MPN-SAF TSS
MPN-SAF; 
MPN-SAF TSS
Myeloproliferative Neoplasm Symptom Assessment Form; 
Myeloproliferative Neoplasm Symptom Assessment Form Total 
Symptom Score
MPP
multipotent progenitor
MRI
magnetic resonance imaging
mRNA
messenger RNA
MYB
V-Myb Avian Myeloblastosis Viral Oncogene Homolog
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse 
Events
nM
nanomolar
NSAID
nonsteroidal anti-inflammatory drug
NuRD
nuclear remodeling and histone deacetylase
OCT4
octamer-binding transcription factor 4
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Protocol IMG-7289-CTP-202 / MK-3543-005
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13 December 2023
Page 12
Abbreviation
Definition
ONC
Office of the National Coordinator for Health Information Technology
OS
overall survival
PBMC
peripheral blood mononuclear cell
PD
pharmacodynamics
PE
physical examination
PET-MF
post-essential thrombocythemia myelofibrosis
PFS
progression free survival
PGIC
Patient Global Impression of Change
Ph
phosphorylation 
PI
Principal Investigator (at each site responsible for patient care)
PISCF
Participant Information Sheet/Consent Form
PMF
primary myelofibrosis
PR
partial remission or response
PT
prothrombin time
PV
polycythemia vera
QD
once daily
RBC
red blood cell
REST
RE-1 silencing transcription factor
RNA
ribonucleic acid
SAB
Safety Advisory Board
SABP
Safety Advisory Board Plan
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
sh
short hairpin
SOX2
sex determining region Y-box 2
SRM
Study Reference Manual
SRY
sex determining region Y
STAT
signal transducer and activator of transcription
TCP
tranylcypromine
TF
transcription factor
TP
Treatment Period
µL
microliter
µM
micromolar
Ub
ubiquitination 
VPN
virtual private network
WBC
white blood cell
WHO
World Health Organization
WOCBP
women of child-bearing potential
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Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 13
2
PROTOCOL SYNOPSIS
Protocol Title:  A Multi-Center, Open Label, Extension Study Evaluating the Safety and 
Efficacy of Bomedemstat for the Treatment of Patients with Myeloproliferative Neoplasms 
(MPN) Enrolled in a Prior Bomedemstat Clinical Study
Protocol No:  IMG-7289-CTP-202 / MK-3543-005
Amendment No: 01 
Sites:  Up to 25 sites in Australia, New Zealand, Italy, Germany, Hong Kong, UK and US.  All 
sites will have previously participated in a bomedemstat study.
Study Objectives:  The objectives of this extension study are to:  

Continue to assess the safety, tolerability and efficacy of bomedemstat in patients who 
received bomedemstat in a prior study

Measure the extent and durability of bomedemstat treatment effects on exploratory 
endpoints including any impact of bomedemstat on the natural history of MF and ET
Investigational Drug: The active drug substance is identified as bomedemstat (also known 
as IMG-7289 / MK-3543). Bomedemstat is an irreversible inhibitor of LSD1. The chemical 
name 
is: 
N-[(2S)-5-{[(1R, 2S)-2-(4-fluorophenyl) cyclopropyl]amino}-1-(4- methylpiperazin-1-yl)-1-
oxopentan-2-yl]-4-(1H-1,2,3-triazol-1-yl)benzamide, bis-tosylate salt.  Bomedemstat will be
supplied as capsules in multiple strengths. Reference the Pharmacy Manual for details.
Study Population: This study will enroll approximately 80 patients with an MPN that meet 
the eligibility criteria.   
Methodology:  This is a multi-center, open-label extension study to assess the long-term 
safety and efficacy of bomedemstat administered orally once daily in patients with an MPN 
who participated in a prior bomedemstat study such as, but not limited to, IMG-7289-CTP-
102 and IMG-7289-CTP-201 (referred to hereafter as ‘feeder studies’).  Details of the 
extension study and a copy of the informed consent form (ICF) should be provided to the 
patient prior to their anticipated final visit in the feeder study. Informed consent should be 
obtained at, or before, the feeder study’s final visit.  It is intended that patients transition 
directly into this extension study with no interruption of dosing.  
Under the following circumstances, provided the Principal Investigator (PI) deems it safe and 
clinically appropriate, patients may remain off bomedemstat for up to 2 weeks prior to 
entering the extension study:   

Patient does not provide consent by their final feeder study visit.  Such patients will 
have an allowance of 14 days to consent to and initiate dosing in the extension study.

Patient requires a dose hold per Titration Assessment

There is an administrative need to interrupt bomedemstat dosing (i.e., pending any 
necessary health authority or local/site approvals).
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Protocol IMG-7289-CTP-202 / MK-3543-005
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13 December 2023
Page 14
Note:  Fourteen (14) days without bomedemstat dosing prior to first dose in the extension 
study may not be exceeded without written Sponsor Medical Monitor approval.
A Safety Advisory Board (SAB) will perform reviews of safety parameters in accordance with 
a Safety Advisory Board Plan to assess the continued use of bomedemstat per protocol.
Study Conduct:  
Eligibility criteria will be assessed based on the patient’s final visit in their feeder study.  The 
first visit in the extension study is the ‘Transition Visit’.  Ideally, patients will commence 
treatment upon completion of a Treatment Period (TP) in the feeder study; however, some 
patients will need to transition to this extension study at differing timepoints and so the final 
feeder study visit and the Transition Visit will need to be linked (i.e., patients completing their 
feeder study at the end of a TP will enter the extension study at TP1 Day 1; patients completing 
their feeder study at a ‘Day 85’ visit will enter the extension study at TP1 Day 85) to maintain 
the correct visit schedule.  Patients will be dosed in TPs, with each TP comprised of daily 
treatment with bomedemstat for 169 days.  Qualifying patients may continue to receive 
bomedemstat for multiple TPs, each comprising an additional 169 days of treatment.
CCI
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Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 15
days) post last procedure date in the feeder study.    
At each Day 169 visit, a Qualification Assessment will be made to determine whether the 
patient is continuing to derive clinical benefit (defined as not meeting “progressive disease” 
criteria, as per Appendices 16.4 and 16.5 for MF and ET patients, respectively, and safely 
tolerating bomedemstat), thereby determining patient qualification for continued 
bomedemstat use via entry into another TP.  Patients who qualify for another TP should
transition without interruption in dosing.  Patients who do not qualify will discontinue 
bomedemstat, immediately undergo an End of Treatment (EoT) visit and have the Follow-up 
Period End of Study (EoS) visit scheduled. If available, patients who qualify for another 
bomedemstat extension study can undergo an EoT visit and transition to the next extension 
study without the need for a Follow up Period/EoS visit.
Bomedemstat Dosing:  All patients will be dosed with bomedemstat daily with dose-titration 
contingent on the Titration Assessment performed at every TP visit.  Patients receiving their 
first extension study dose with no interruption in dosing will have a Titration Assessment 
performed at the Transition Visit to determine if a titration is needed.  Patients requiring an 
interruption in dosing will have a Titration Assessment performed at the Transition Visit to 
determine if they will commence at the same daily dose of bomedemstat being taken at the 
conclusion of their feeder study or if a down-titration or dose hold is needed (up-titrations 
are not permitted).  Titration targets and rules, specific to the underlying MPN, are detailed 
in the Study Reference Manual, Pharmacy Manual, and Appendix 16.1.3 and 16.1.4.  The upper 
limit for titration is 6 mg/kg/day. 
Study Duration:  
 
.
Study Assessments:  The key study assessments outlined below are also summarized in 
Study Assessments, Section 9, and in the Schedule of Assessments, Section 16.1.  
*Patients entering the extension study at the final visit of the feeder study will undergo the asterisked 
procedures in association with the feeder study; the assessments should not be duplicated.  Patients 
entering the extension study that require interruption of dosing must undergo the asterisked 
procedures.
Limited Physical Examinations (LPE):
 
  LPEs include weight, 
vital signs, a review of body systems to assess change from previous LPE and spleen 
measurement.  
 
 
 
  
  
 
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following the last assessment in the feeder study for as long as the patient continues to qualify 
for treatment, and at the Suspected Relapse, EoT, EoS and ET visits. Bone marrow sampling 
will not be repeated if performed in the prior 5weeks.
†Aspirate sample should be optimally obtained within the first pull. Do not collect after a second pull attempt.
Local Laboratory Assessments: The following panels (Section 10.1.1 details analytes) will be 
performed as per below, and at the Transition Visit*, Suspected Relapse, EoT, EoS and ET
visits:
Genomic and Correlative Research Analyses:  The following will be collected at the time-
points noted below, and (unless bone marrow was performed in the prior 5 weeks) at the
Suspected Relapse, EoT, EoS and ET visits.  Genomic mutant allele burden will be analyzed.
Also, some or all of each sample may be placed in long-term storage for potential correlative
research studies.
Titration Assessment:  At every visit during the TP, the local laboratory hematology panel will 
be assessed for potential dose titration in accordance with the titration rules detailed in the 
Study Reference Manual and Pharmacy manual. 
Qualification Assessments:  At Day 169 of each TP completed, Investigators will assess 
whether the benefit-risk of bomedemstat favors continued treatment, thereby determining 
patient qualification for entry into another TP.  Qualifying patients may enter another TP upon 
completing the Day 169 visit. Patients who do not qualify will discontinue bomedemstat,
undergo an EoT visit and proceed with the Follow-up Period EoS visit.
The below assessments are required ONLY if required in the feeder study:
ECOG Performance Status (Appendix 16.3): On Day 169 of each TP completed, and at the 
Suspected Relapse, EoT, EoS and ET visits. 
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Eligibility Criteria: 
Patients must meet all Inclusion and no Exclusion Criteria. 
Inclusion Criteria:
1.
Completed at least one Treatment Period (TP) in a prior bomedemstat MPN protocol 
(such as, but not limited to, IMG-7289-CTP-102 or IMG-7289-CTP-201).
2.
In the estimation of the Investigator, the risk-benefit favors continued dosing with 
bomedemstat.
Exclusion Criteria:
1.
Ongoing participation in another investigational study (except observational studies).
2.
A history of non-compliance in a prior bomedemstat study (excluding dose suspensions 
that were medically warranted).
3.
Current use of a prohibited medication (e.g., romiplostim).
4.
Medical, psychiatric, cognitive, or other conditions that, in the Investigator’s opinion, 
compromise the patient’s safety, ability to give informed consent, or comply with the trial 
protocol.
5.
Females who are pregnant or breastfeeding or plan to become pregnant or breastfeed 
during the study.
6.
 
 
  
 
 
 
  
 
  
Note:  In the UK, male patients with a pregnant partner must agree to use a condom to avoid 
exposure to the developing child.  
Note:  In Germany, use of computerised tomography (CT) is not permitted for patients unable to 
undergo magnetic resonance imaging (MRI).  Only MRI is permitted for study purposes.
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Patient Care Guidelines:  
Patient care guidelines are provided for Investigator and site staff consideration and 
recognize the standard of care across global institutions will vary.  The following are not 
protocol requirements.
For all patients:
1.
In general, supportive care (transfusions, administration of anti-fungals, etc.) should be 
maintained in accordance with institutional policy.  (Note:  Transfusions must be 
adequately recorded in the source documents to facilitate data entry of the study 
required parameters [i.e., type of blood product transfused, units, total volume]).
2.
Patients taking medications with the potential to induce or inhibit CYP3A4 or CYP2D6 
should be monitored closely for potential effects of co-administration; particular 
attention should be given to anti-infectives in the azole class.
3.
There are no restrictions to, or recommendations on the timing of, administration of 
vaccines (i.e., coronavirus disease 2019 [COVID-19] vaccination).
4.
Cessation of bomedemstat is associated with a rebound in thrombopoiesis, and platelet 
counts may exceed baseline in the patient. When bomedemstat is discontinued, 
platelet counts must be monitored closely and the timing of the start of an 
alternative therapy should take the expected rebound of platelets into 
consideration.  

 
 
5.
 
 
 
 
Prohibited Medications/Treatments:  
Please consult the Medical Monitor with any questions pertaining to prohibited medications.
1.
All cytotoxic agents, with noted exception of hydroxyurea for MF patients as per 
Guidelines
2.
All hematopoietic growth factors: romiplostim,
eltrombopag, granulocyte and 
granulocyte-macrophage colony stimulating factor (G-CSF and GM-CSF) and 
erythropoietin (EPO)
3.
Monoamine oxidase A and B inhibitors
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4.
Anticoagulant or nonsteroidal anti-inflammatory drug (NSAID; including aspirin) use,
when patient platelet count is < 50 x 109/L
 
5.
Management of Study Toxicities:  
AE intensity will be evaluated using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 5, published 27-NOV-2017. Refer to Section 8.2
for additional detail on management of study toxicities.
Contact the Medical Monitor to discuss bomedemstat dose modifications for clinically 
significant AE changes in platelets, neutrophil counts, or other hematologic parameters.
Stopping Rules:  
Bomedemstat will be permanently discontinued, and the patients will undergo the Follow-up 
Period Visits (see Section 9.4) in the event of the following:

Investigator or Medical Monitor deem it unsafe for the patient to continue bomedemstat.

Following the temporary interruption of bomedemstat due to platelet counts below 
the applicable threshold (25 x 109/L for MF patients and 50 x 109/L for ET patients), the 
patient's platelet counts do not return to the required threshold (>50 x 109/L for MF 
patients and >150 x 109/L for ET patients) within 21days. Note:  new platelet thresholds 
may apply as additional feeder studies are conducted; such thresholds will be specified 
in the Study Reference Manual and Pharmacy Manual.
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Criteria for Evaluation:  
The parameters comprising safety and efficacy assessments are below.  Details on endpoints 
and data analysis are provided in Sections 12.4 and 12.5, respectively.
 
 
 
Safety
In all patients, safety will be assessed by: 

Evaluation of: 
o
Adverse events (AEs)
o
Serious adverse events (SAEs)
o
Required laboratory tests (hematology, chemistry, coagulation and urinalysis)
o
Physical examinations, including vital signs
Efficacy
In all patients, efficacy will be assessed by evaluation of: 

Constitutional symptoms measured by continued completion of the version of the 
MPN-SAF tool associated with the feeder study

Formal measures of response, including relapse, and disease transformation

Fibrosis score
In MF patients, efficacy will also be assessed by:

Spleen volume reduction 
In ET patients, efficacy will also be assessed by:

Patient reported change in clinical status as measured by the PGIC

Durability in the reduction of platelet counts in the absence of new thromboembolic 
events

Durability in the reduction of white blood cell count 

Evaluation of the incidence of thromboembolic events 
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3
INTRODUCTION
3.1
Background on the Disease to be Treated
The BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are a family of related neoplastic 
disorders of bone marrow.  The three main chronic BCR-ABL1-negative MPNs are polycythemia 
vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF).  The cardinal 
clinical features of these disorders are increased red cell mass in PV, increased platelet count in 
ET, and bone marrow fibrosis in PMF.  The MPNs are clonal disorders arising most frequently 
from acquired (somatic) mutations in a multipotent hematopoietic stem/progenitor cell, 
resulting in abnormalities in red cell, granulocyte and platelet production often in association 
with marrow fibrosis and extramedullary hematopoiesis and, in some cases evolution to acute 
myeloid leukemia (AML).
3.2
Background on the Drug Target
LSD1, also known as KDM1A, is an enzyme that removes mono- and dimethyl groups from 
histone (H) H3 at critical lysines (K), K4 and K9 (Shi et al., 2004).  Methylation of histone H3K4 
and H3K9 is a post-translational modification associated with changes in the confirmation of 
chromatin (Bannister and Kouzarides, 2011; Beisel and Paro, 2011).  Chromatin is collective term 
for the association of nuclear macromolecules consisting of deoxyribonucleic acid (DNA), protein 
scaffolding, enzymes enhancing transcription and synthesis of ribonucleic acid (RNA) (Kornberg, 
1974).  The DNA and its protein scaffold of histones form an ordered complex called the 
nucleosome.  Each nucleosome is composed of two copies of each of the four histone proteins, 
H2A, H2B, H3 and H4, forming an octamer around which DNA is wrapped.  The rates of gene 
transcription are heavily influenced by the accessibility of transcription factors and the RNA 
polymerase complexes to template DNA at promoters (Bannister and Kouzarides, 2011; Beisel 
and Paro, 2011).
Epigenetics refers to the regulation of gene expression resulting from chemical modifications of 
histones, the DNA bases such as cytosine or RNA, changes that do not alter the actual DNA 
sequence (Bird, 2002).  Enzymes that modify these substrates by the addition or removal of these 
chemical changes are called epigenetic regulators.  Histone and nucleic acid modifications 
provide binding sites for proteins and components of the transcriptional machinery that affect 
transcriptional gene silencing or activation (Kouzarides, 2007).  Histone modifications include 
acetylation (Ac), methylation (Me), phosphorylation (Ph) and ubiquitination (Ub).  By virtue of 
altering the local state of chromatin, LSD1 is an epigenetic regulator of gene expression.  The 
primary therapeutic effects of LSD1 inhibition in the treatment of essential thrombocythemia 
come from the down regulation of megakaryopoiesis and thrombopoiesis, functions that require 
LSD1 activity. 
LSD1 is localized to specific sites in the genome through the agencies of proteins that bind DNA 
directly, generally transcription factors (TFs) (Whyte et al., 2012; Whyte et al., 2013).  Many TFs, 
both activators such as V-Myb Avian Myeloblastosis Viral Oncogene Homolog (MYB) and steroid 
hormone receptors, as well as repressors such as growth factor independence 1 transcription 
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repressor (GFI1) and RE-1 silencing transcription factor (REST), recruit LSD1 to specific genomic 
locations (Metzger et al., 2005; Saleque et al., 2007; Lin et al., 2010).  LSD1 is part of a larger 
protein complex, containing, e.g., Co-RE-1 silencing transcription factor (CoREST) or nucleosome 
remodeling and histone deacetylase (NuRD), which dictates the cell- and site-specific chromatin 
remodeling (Lee et al., 2005; Foster et al., 2010).  These complexes may also include DNA 
methyltransferase 1 (DNMT1) and histone deacetylases 1, 2 and 3 (HDAC1, 2, and 3) activities all 
of which contribute to maintaining or modifying the epigenetic state at that specific genomic site 
(Shi et al., 2005; Orkin and Hochedlinger, 2011).  Thus, an important property of LSD1 beyond its 
own enzymatic activity is its function as a scaffold for other proteins and epigenetic enzymes that 
are co-recruited to genomic sites.  Likewise, LSD1 bound to specific sites precludes the binding 
of other factors that may influence transcription. 
LSD1 is unique among the many histone demethylases in that it coordinates flavin adenine 
dinucleotide (FAD) to oxidatively remove one or two methyl groups, in the process producing 
H2O2 and formaldehyde.  As such, FAD is an essential co-factor for LSD1 activity(Shi et al., 2004).  
The other 34 histone lysine demethylases, collectively termed the Jumonji demethylases, employ 
an iron-dependent mechanism to remove methyl groups from histone lysines (Klose et al., 2006). 
LSD1 is an essential gene; loss of LSD1 activity leads to early embryonic lethality (Wang et al., 
2009; Foster et al., 2010).  The protein is also needed for regulating the balance between self-
renewal and proliferation (Wang et al., 2007).  A conditional in vivo LSD1 knockdown (KD) using 
a doxycycline-inducible short hairpin LSD1 (shLSD1) established LSD1 as a central regulator of 
hematopoietic stem cells (HSCs) and progenitor cells (Sprussel et al., 2012). An inducible LSD1
KD resulted in profound but reversible thrombocytopenia, neutropenia and anemia; monocyte 
numbers were increased as monopoiesis does not require LSD1 activity.  LSD1 KD for 27 days led 
to an increase in circulating multipotent progenitors (MPPs) and HSCs with a concomitant down-
regulation of chemokine (C-X-C motif) receptor 4 (CXCR4) without affecting the size of the 
quiescent long-term HSC pool(Sprussel et al., 2012).  
LSD1 plays a key role in regulating the progression from pluripotency to terminal differentiation 
and balancing self-renewal and proliferation (Adamo et al., 2011; Wang et al., 2007; Whyte et al., 
2012).  LSD1 is recruited to “high confidence” promoters and super-enhancers of genes essential 
for normal development by the “master” transcription factors octamer-binding transcription 
factor 4 (OCT4), SRY (sex determining region Y)-box 2 (SOX2), Nanog and the co-activator 
Mediator.  Though not essential for maintenance of the embryonic stem cell (ESC) state, as part 
of the NuRD complex, LSD1 “decommissions” enhancers of genes maintaining the pluripotency 
program allowing ESC to differentiate.  LSD1 is essential for the complete shutdown of the ESC 
gene expression program as cells transition to more differentiated cell states(Whyte et al., 2012).  
The role LSD1 plays in ESCs is phenomenologically similar to the essential role LSD1 plays during 
myeloid hematopoiesis, in which enhancers active in HSCs generating a stem-cell gene 
expression signature are also “decommissioned”, allowing commitment of progenitors to specific 
myeloid lineages (Lara-Astiaso et al., 2014).  Enhancers essential for terminal myeloid 
differentiation in lineage-specific progenitor cells, the so-called de novo enhancers, must be 
poised for activation by the placement of H3K4me1 marks.  As progenitors commit to 
differentiation, LSD1 is down-regulated dramatically allowing de novo enhancers and promoters 
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to be stably activated with progressive methyl or acetyl additions on H3K4 and H3K27, 
respectively (Lara-Astiaso et al., 2014).   
3.3
Background on LSD1 in Myeloid Neoplasia Pre-Clinical Studies
Over-expression of LSD1 messenger RNA (mRNA) and excess LSD1 protein have been observed 
in many tumor types, including poorly-differentiated neuroblastoma, squamous cell carcinoma, 
Ewing’s sarcoma, AML, neuroendocrine carcinomas and epithelial tumors such as breast, 
prostate, bladder, small cell lung and colon cancers (Metzger et al., 2005; Kahl et al., 2006; Schulte
et al., 2009; Lim et al., 2010).  In MPNs, LSD1 was over-expressed mainly in megakaryocytes and 
erythroid precursors and to a lesser degree in early myeloid cells (Niebel et al., 2014). Treatment 
of various tumor types in culture with LSD1 inhibitors (LSDi) has been reported to inhibit tumor 
growth, reduce their potential for migration and invasion, reduce clonogenic potential and 
eliminate cancer stem cells, induce markers of differentiation appropriate to the cell lineage, and 
induce apoptosis (Somervaille and Cleary, 2006; Somervaille et al., 2009; Harris et al., 2012; 
Zhang et al., 2013).  In various models of mouse leukemia, treatment with LSD1 inhibitors 
induced monocytic markers of differentiation, reduced clonogenic potential of leukemia 
initiating cells (LICs), and induced cell death(Harris et al., 2012).  
LSD1 activity is present in a high proportion of malignant myeloid blasts cells (Lin et al., 2011; 
Rhodes et al., 2007; Wouters et al., 2009).  LSD1 gene expression is among the highest in 
immunophenotypically stem/progenitor populations of myeloid neoplastic cells (Goardon et al., 
2011; Somervaille et al., 2009; Harris et al., 2012).  
LSD1 may play a direct role in regulating pathogenic signaling from the activated Janus Kinases 
(JAK) signal transducer and activator of transcription (STAT) pathway.  The JAK-STAT signaling 
pathway is activated by the canonical MPN mutations in MPL, JAK2 and CALR via the 
phosphorylation of STAT3 and STAT5, transcription factors that activate specific sets of genes 
with pleiotropic effects (Chen and Mullally, 2014).  STAT3 activity as a transcription factor is 
modulated by methylation on lysine (K140) and is one of many reported non-histone substrates 
for LSD1 (Yang et al., 2010).  
Proof-of-concept studies of the therapeutic activity of LSD1 inhibition were performed in well 
established, pre-clinical mouse models of MPNs (Jak2V617F, MplW515L).  Compared to mice treated 
with vehicle, LSD1 inhibition (LSDi) in MPLW515L mice markedly suppressed myeloproliferation 
reducing granulocyte and platelet counts, thus establishing therapeutic efficacy. Spleen weights 
in treated animals showed a dose-proportional decrease.  Histopathological analysis of bone 
marrow and spleen confirmed a marked reduction in myeloproliferation, as well as a reversal of 
extramedullary hematopoiesis (EMH).  Most notably, there was near-complete resolution of 
reticulin fibrosis in the bone marrow in the LSDi treatment arm.  LSD1 inhibition had a significant 
impact on serum inflammatory cytokine concentrations as exemplified by a very marked 
reduction in the plasma concentration of the Chemokine (C-X-C Motif) Ligand 5 (Cxcl5 or IL-8 in 
humans), a key participant in the pathologic inflammatory state of MPN.  
LSD1 inhibition also reduced the mutant cell burden.  In a mouse model of AML in which MLL-
AF9 had been virally transduced into transplanted mouse HSCs along with the gene for green 
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fluorescent protein (GFP), in those mice treated with vehicle, 74.6% of circulating cells were 
GFP+, while only 43.2% of circulating cells were GFP+ in LSDi-treated mice.  Flow cytometry 
analysis of spleen and bone marrow revealed reduced numbers of CD11b+/Gr1+ myeloid cells 
and CD41+ megakaryocytes. The numbers of mutant GFP+ myeloid cells and megakaryocytes in 
these tissues were also significantly reduced by LSDi treatment.  The decrease in platelet counts 
and mutant clone burden, and the resolution of fibrosis after 28 days of LSD1 inhibition supports 
targeting LSD1 in patients with MPN.
3.4
Background on Bomedemstat (IMG-7289/MK-3543)
Bomedemstat is an orally available, irreversible inhibitor of LSD1, active against LSD1 and human 
AML cells at concentrations of <5 nM.  Irreversible inhibitors of LSD1 include tranylcypromine 
(TCP) which has been used for the treatment of depression for decades.  The targets of TCP 
therapy, however, include all FAD-dependent monoamine oxidases (MAOs) in addition to LSD1.  
TCP inactivates LSD1 in a manner identical to its action on MAO-A and MAO-B because these 
three enzymes share a similar oxidative chemistry.  Bomedemstat has >4000-fold selectivity for 
LSD over monoamine oxidase A and B, the mostly closely related human enzymes.  
Pharmacokinetic studies in mouse, rat and dog and pharmacokinetic modeling in human systems 
suggest that once-daily dosing in humans would be sufficient to achieve therapeutic exposures.  
Twenty-six and thirty-nine week toxicologic studies in rat and dog, respectively, showed that 
 
 
 
 
.
3.5
Potential Clinical Risks and Benefits when Dosing an LSD1 Inhibitor
The dosing effects with an LSD1 inhibitor (LSDi) are distinct from treatment with standard 
cytotoxic agents or with Janus Kinase (JAK)clo inhibitors.  
LSD1 inhibition has specific effects on each myeloid lineage.  LSD1 activity is needed for the 
differentiation of progenitors to red cells, platelets and granulocytes; LSD1 activity is not needed 
for monopoiesis.  Hence, LSD1 inhibition changes the cellular composition in the marrow and the 
morphology of these cells. Likewise, distribution of blood cells based on lineage is also affected 
with an increase in the production of monocytes and a decreasing in the other myeloid cell types; 
the production of platelets appears to be more sensitive to LSD1 inhibition and red cell 
production the least.  There is no evidence to date that inhibition of LSD1 has an effect on the 
function of platelets or neutrophils.  
 
 
  
The morphologic and clinical pathology changes may not be familiar to clinicians and 
hematopathologists.  
 
 
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1.
2.
3.
4.
Please refer to the Investigator’s Brochure, Section 6.3 for Reference Safety Information.
3.6
Bomedemstat Dose Justification
A summary of the starting dose and dosing schedule are provided below.  Further information, 
including additional relevant data, can be found in the Investigator’s Brochure.
3.6.1
Rationale for and Safety of the Proposed Bomedemstat Dose
In the Phase 2 study in MF patients (IMG-7289-CTP-102), the daily dose of bomedemstat needed 
by most patients to achieve a platelet count in the target range (50-75 x 109/L) is between 
0.6 to 0.8 mg/kg/d with a dosing spectrum investigated of 0.4-1.5 mg/kg/d.  
In the Phase 2 study in ET patients (IMG-7289-CTP-201), the daily dose of bomedemstat needed 
to reduce platelet counts into the target range (200-400 x 109/L) is also currently between 
0.6 to 0.8 mg/kg/d.  
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To date, for both patient populations evaluated in clinical studies IMG-7289-CTP-102 and -201, 
the doses needed to reduce the platelet count to the target range do not appear to be correlated 
with the starting platelet count or antecedent hematologic history.  
In the Phase 1 study in high-risk AML/ myelodysplastic syndrome (MDS) patients (IMG-7289-
CTP-101), there was no maximum tolerated dose observed with doses up to 6 mg/kg/d.  
Patients entering this study will have received bomedemstat for at least 6 months in their feeder 
study.  All patients will be dosed with bomedemstat daily in the extension study, with dose-
titration contingent on the Titration Assessment performed at every TP visit.  Patients receiving 
their first extension study dose with no interruption in dosing will have a Titration Assessment 
performed at the Transition Visit to determine if a titration is needed.  Patients requiring an 
interruption in dosing will have a Titration Assessment performed at the Transition Visit to 
determine if they will commence at the same daily dose of bomedemstat being taken at the 
conclusion of their feeder study or if a down-titration or dose hold is needed (up-titrations are 
not permitted).  
The dose of bomedemstat needed to reduce platelets to the applicable target range is anticipated 
to be up to approximately 2 mg/kg once daily (QD); however, this is not the upper limit for 
titration purposes as the dose needed to achieve a therapeutic effect will vary among patients 
and may change over time.  The upper limit for titration purposes is 6 mg/kg/d (note: this dose 
cannot be exceeded during the dose titration process).  
3.6.2
Rationale for the Bomedemstat Dosing Schedule
This is an open-label extension study that intends to continue to dose patients with bomedemstat
for as long as they are safely tolerating and receiving clinical benefit from its use. Patients 
entering this study will have received bomedemstat for at least 6 months in their prior feeder 
study.  Dose-titration will continue to be contingent on the hematology assessments, specifically:  
platelets, hemoglobin and absolute neutrophil count (ANC).  Titration targets and rules, including 
the frequency with which up- and down-titrations are permitted, and the associated titration 
increments/decrements are specific to the underlying MPN and are detailed in the Study 
Reference Manual and Pharmacy Manual.  
Chronic daily administration of bomedemstat in rat, dog and humans has been well tolerated.  No 
safety signals, per Safety Advisory Board reviews to date, have been observed in either the 
AML/MDS, myelofibrosis, or essential thrombocythemia studies with bomedemstat at doses up 
to 6 mg/kg/d and for
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4
HYPOTHESIS AND OBJECTIVES
Hypothesis: Bomedemstat is safe and tolerable when administered long-term to patients with 
MPNs; inhibition of LSD1 by bomedemstat will provide long-term clinical benefit to patients with 
MPNs.
4.1
Objectives
The objectives of this extension study are to:  

Continue to assess the safety, tolerability and efficacy of bomedemstat in patients who 
received bomedemstat in a prior study

Measure the extent and durability of bomedemstat treatment effects on exploratory 
endpoints including any impact of bomedemstat on the natural history of MF and ET
5
INVESTIGATIONAL PLAN
5.1
Overview
This is a Phase 2 multi-center, open-label extension study for patients with myeloproliferative 
neoplasms dosed with bomedemstat in a prior clinical study.   
This study consists of Treatment Periods (TP) where patients will be treated daily for 169 days.  
The TPs are iterative and treatment may continue for an additional 169 days in those patients 
deriving clinical benefit (defined as not meeting “progressive disease” criteria as per applicable 
Appendix 16.4 or 16.5) and safely tolerating bomedemstat, as determined by the Investigator; 
this definition applies throughout the document and will not be repeated with each reference to 
clinical benefit. 
Eligibility criteria will be assessed based on the patient’s final visit in their feeder study.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6
STUDY POPULATION
6.1
Study Entry Criteria
For purposes of eligibility, the following definitions apply:

A woman is considered of childbearing potential (WOCBP), i.e., fertile, following 
menarche and until becoming post-menopausal unless permanently sterile. Permanent 
sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral 
oophorectomy. 

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a post-menopausal state in women not using hormonal 
contraception or hormonal replacement therapy. However, in the absence of 12 months 
of amenorrhoea, a single FSH measurement is insufficient. 

A man is considered fertile after puberty unless permanently sterile by bilateral 
orchidectomy.

Abstinence is defined as refraining from heterosexual intercourse.  True abstinence, when 
this is in line with the preferred and usual lifestyle of the subject is permitted. Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of 
abstinence for the duration of the Treatment and Follow-up Periods, and withdrawal are not 
acceptable methods of contraception.
6.1.1
Inclusion Criteria
Patients must meet all of criteria to be eligible for study enrollment:
1.
Completed at least one Treatment Period (TP) in a prior bomedemstat MPN protocol (such
as, but not limited to, IMG-7289-CTP-102 or IMG-7289-CTP-201).
2.
In the estimation of the Investigator, the risk-benefit favors continued dosing with 
bomedemstat.  
6.1.2
Exclusion Criteria
Patients will be excluded from the study if they meet any of the following criteria:
1. Ongoing participation in another investigational study (except observational studies).
2. A history of non-compliance in a prior bomedemstat study (excluding dose suspensions that 
were medically warranted).
3. Current use of a prohibited medication (e.g., romiplostim).
4. Medical, psychiatric, cognitive, or other conditions that, in the Investigator’s opinion, 
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compromise the patient’s safety, ability to give informed consent, or comply with the trial 
protocol.
5. Females who are pregnant or breastfeeding or plan to become pregnant or breastfeed during 
the study.
6.
 
 
 
 
 
 
 
 
  
6.2
Patient Enrollment
This study will enroll approximately 80 patients with an MPN that meet the eligibility criteria.   
6.3
Patient Withdrawal
In accordance with the Declaration of Helsinki, Good Clinical Practice (GCP), and International 
Council for Harmonisation (ICH) Guidelines and applicable regulations governing human subject 
protection, a subject has the right to withdraw from the study at any time for any reason. The
patient’s reason for withdrawal, if given, will be documented in the electronic case report form 
(eCRF).  Patients will be requested to complete the Follow-up Period visits for post-dosing safety 
assessments as per Section 9.4.  
Subjects may also be removed from the study by the Sponsor or Investigator. The Sponsor or 
Investigator may remove patients from the study for various reasons, including: 

Taking another investigational medicinal agent during the study;

Use of a prohibited medication;

Major violation of, or deviation from, study protocol procedures which, in the judgment of the 
Medical Monitor, could adversely affect the patient or the integrity of the study including 
missing an extended duration of bomedemstat doses or other evidence of major non-
compliance; 

Withdrawal from the study is, in the Investigator’s judgment, in the patient’s best interest.
6.4
Patient Care Guidelines
Patient safety is paramount. The patient care guidelines below are intended to facilitate some 
consistency across sites by providing guidance to be used by the Investigator and the study staff 
Note:  In the UK, male patients with a pregnant partner must agree to use a condom to avoid 
exposure to the developing child.  
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to ensure patient safety and recognize the standard of care across global institutions will vary.  
The guidelines are not protocol requirements and are not intended to supersede best clinical 
judgment by the Investigator.  Please contact the Medical Monitor with any questions.
For all patients:
1.
In general, supportive care (transfusions, administration of anti-fungals, etc.) should be 
maintained in accordance with institutional policy.  (Note:  Transfusions must be adequately 
recorded in the source documents to facilitate data entry of the study required parameters 
[i.e., type of blood product transfused, units, total volume]).
2.
Patients taking medications with the potential to induce or inhibit CYP3A4 or CYP2D6 
should be monitored closely for potential effects of co-administration; particular attention 
should be given to anti-infectives in the azole class.
3.
There are no restrictions to, or recommendations on the timing of, administration of 
vaccines (i.e., COVID-19 vaccination).
4.
Cessation of bomedemstat is associated with a rebound in thrombopoiesis, and platelet 
counts may exceed baseline in the patient. When bomedemstat is discontinued, platelet 
counts must be monitored closely and the timing of the start of an alternative therapy 
should take the expected rebound of platelets into consideration.  

5.
6.5
Prohibited Medications
Please consult the Medical Monitor with any questions pertaining to prohibited medications. 
1.
All cytotoxic agents with noted exception of hydroxyurea for MF patients as per Guidelines
2.
All hematopoietic growth factors: romiplostim, eltrombopag, granulocyte and granulocyte-
macrophage colony stimulating factor (G-CSF and GM-CSF) and erythropoietin (EPO)
3.
Monoamine oxidase A and B inhibitors
4.
Anticoagulant or nonsteroidal anti-inflammatory drug (NSAID; including aspirin) use, when
patients platelet count is < 50 x 109/L
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For MF patients only:
5.
Prednisone or prednisolone > 10 mg/day or dexamethasone > 4 mg/day (doses exceeding 
these thresholds are permitted for management of gout). Maintenance supplemental 
corticosteroid therapy such as prednisone ≤ 10 mg/day or corticosteroid equivalent is
allowed.
7
STUDY PRODUCT
7.1
Formulation, Labeling, Packaging and Storage
7.1.1
Formulation
The drug product bomedemstat (IMG-7289 / MK-3543) is a bis-tosylate salt.  The free base of 
bomedemstat is the active moiety.  
Bomedemstat will be supplied in capsules of multiple strengths.  These strengths are based on 
bomedemstat free base (the active substance).  The strengths may change over the duration of 
the study.  Details on capsules strengths, colours and sizes, can be found in the Pharmacy Manual.  
The capsules will be manufactured in accordance with Annex 13 and principles of cGMP.
7.1.2
Packaging and Labeling
Bomedemstat capsules will be supplied to the site pharmacy department by sponsor (or 
designee) in packaging in accordance with all applicable local regulatory requirements. 
Packaging labels will also be in accordance with all applicable local regulatory requirements for 
the labeling of active pharmaceutical ingredients and with Annex 13 of cGMP.  Labels will contain 
the drug name, protocol number, lot number, expiry date, storage conditions, name of the (local)
Sponsor and a caution that the investigational drug product is for clinical trial use only.
7.1.3
Storage
The recommended long-term storage condition for bomedemstat is a temperature not to exceed 
25°C. Bomedemstat must be stored in a secure area with access limited to the Investigator and 
authorized staff and under the physical conditions that are consistent with bomedemstat-specific 
requirements.  Bomedemstat supplies will be stored securely under the appropriate conditions 
according to the country, state and regional laws. Procedures for bomedemstat storage and 
accountability will be detailed in a Pharmacy Manual.
7.2
Dispensing, Administration, Dosage and Missed Doses
7.2.1
Dispensing
All material supplied is for use only in this clinical study and should not be used for any other 
purpose.  Only patients enrolled in the study may receive bomedemstat, in accordance with all 
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applicable regulatory requirements. Only authorized site staff may dispense bomedemstat.
The Investigator must provide a prescription form every time bomedemstat is dispensed, 
including (but not limited to) the identification of the patient to whom bomedemstat is to be 
dispensed, the patient’s weight, the requested dose in mg/kg/d and the Investigator (or 
designee’s) signature. 
Bomedemstat will be dispensed at doses in accordance with the dose chart provided and at the 
quantities detailed in the Pharmacy Manual.  Since the bomedemstat dose and associated capsule 
strengths for each patient may change over time, minimize the patient retaining excess study 
drug capsules in their home.
Patients will be instructed to bring any unused bomedemstat in its dispensed packaging to each 
study visit for drug accountability.  New bomedemstat supply will be dispensed at each visit.  The 
Investigator and designated staff will maintain study drug accountability records (Section 14.5).
7.2.2
Administration
Appropriately trained study site personnel will provide patient instructions pertaining to 
bomedemstat administration and supervise the administration of bomedemstat, if taken in the 
clinic.  It is, however, not required that bomedemstat be taken in the clinic; this will be 
determined based on the patient’s regular daily dosing time.  When applicable, the date and time 
of each administration in the clinic will be recorded in the source notes.
Bomedemstat dosing will be based on the patient’s established Dosing Weight from their feeder 
study.  If during treatment the patient’s weight changes by more than 10% from the established 
Dosing Weight, the amount of bomedemstat dispensed should be adjusted per the dose chart.
The dispensing prescription form and source data must clearly document the weight used to 
calculate the dispensed daily dose.
Patients should be instructed to:

Swallow the bomedemstat capsule(s) once daily, at approximately the same time.  
o
While it would be recommended to take at night before bed, dose can be taken at 
any time during the day when convenient.

Swallow the bomedemstat capsule(s) whole.

Fast for 1 hour prior to and 30 minutes after a daily dose. 

Clear liquids are allowed during the fasting period.
7.2.3
Dosage  
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7.2.4
Missed Doses
Patients who do not take their bomedemstat dose at the usual required time should take it 
immediately upon noting that it was not taken; the patient should not take the dose more than 
12 hours after the usual dosing time.  If a patient misses a dose, they should not take two doses 
the following day, but should notify their study coordinator and continue with their normal daily 
dose the following day.  For a temporary dosing interruption due to a medical or unforeseen 
patient situation, please consult the Medical Monitor for guidance on re-start of dosing.  Patients 
who miss an extended duration of bomedemstat doses or exhibit serial non-compliance with 
treatment may be removed from the study at the discretion of the Investigator or Sponsor.
7.2.5
Interruption of Dosing
Patients requiring a Dose Hold according to the Titration and Rechallenge Rules, due to an (S)AE,
or other unforeseen patient situation that interrupts daily dosing should undergo complete blood 
counts at least weekly for safety purposes and to enable re-challenge to commence as soon as 
counts return to the required level, if it is safe to do so. 
8
SAFETY ADVISORY BOARD (SAB) REVIEWS AND MANAGEMENT OF 
STUDY TOXICITIES, INCLUDING STOPPING RULES
8.1
Safety Advisory Board (SAB) Reviews
Safety will be monitored throughout the study in accordance with a Safety Advisory Board Plan 
(SABP) by a SAB constituted by physicians with hematology expertise and clinical study 
experience.  SAB reviews will occur at least quarterly as per the SABP. Reviews may also occur 
on an ad hoc basis when one of the following scenarios occurs:

Fatal or life-threatening reaction assessed as related to bomedemstat (possibly, probably 
or definitely), regardless of expectedness, is reported

Occurrence of other safety-related issues for patients receiving bomedemstat, such as 
evidence of unexpectedly severe effects on hematopoiesis, which pose a medical concern,
and which may necessitate bomedemstat dose adjustment or discontinuation.
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SAB responsibilities will remain in effect until the study has ended.
8.2
Management of Study Toxicities
Expected bomedemstat toxicities based on non-clinical and clinical studies are reported in the 
latest available edition of the Investigator’s Brochure.  
AE intensity will be evaluated using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 5, published 27-NOV-2017.
Stopping rules are defined in Section 8.2.2.  
8.2.1
Hematologic Toxicity
Hematologic values outside of the normal reference range are inherent features of MPNs and are 
expected effects of many therapeutic attempts to manage these diseases. MPN patients require 
doses of bomedemstat that are sufficient to reduce platelet counts and, to a lesser degree, 
absolute neutrophil counts.  Any resulting reversible cytopenias can be managed clinically as 
needed with transfusions as well as broad-spectrum antibiotics, as per standard practice. 
The effects of bomedemstat on normal myeloid hematopoiesis observed in non-clinical and 
clinical studies are expected; these are pharmacodynamic effects of LSD1 inhibition by 
bomedemstat, thus not regarded as adverse.  Refer to the Investigator’s Brochure for additional 
information.
8.2.2
Stopping Rules
Bomedemstat will be permanently discontinued and the patients will undergo the Follow-up 
Period visits (see Section 9.4) in the event of the following:

PI or Medical Monitor deem it unsafe for the patient to continue bomedemstat. 

Following the temporary interruption of bomedemstat due to platelet counts below the 
applicable threshold (25 x 109/L for MF patients and 50 x 109/L for ET patients), the patient's 
platelet counts do not return to the required threshold (>50 x 109/L for MF patients and >150 
x 109/L for ET patients) within 21 days.  Note: new platelet thresholds may apply as 
additional feeder studies are conducted; such thresholds will be specified in the Study 
Reference Manual and Pharmacy Manual.
9
STUDY ASSESSMENTS 
This section provides comprehensive detail on the visits and assessments required and should 
serve as the main guidance for use during study visits.  The Schedule of Assessments (Section 
16.1) contains these details in tabular form and is provided for use in a supportive/reference
capacity only.  To maintain clarity while facilitating a modicum of brevity, the ‘Terms’ in Table 1
below will be utilized in this section to encompass the broader ‘Protocol Meaning’ as stated.
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Table 1
List of Protocol Terms and Meanings
Term
Protocol Meaning
Limited Physical Exam, including 
Vital Signs

Spleen measurement. The edge of the spleen shall be 
determined by palpation, measured in centimeters, 
using a soft ruler/tape, from the costal margin to the 
point of greatest splenic protrusion in the mid-
clavicular line.  Measure in the same manner at all 
visits.

Weight, measured (in kg)

Review of body systems for changes from previous 
visit 

Vital signs, after patient has sat semi-supine for ~3 
minutes, of:
o
Heart rate
o
Respiratory rate
o
Temperature
o
Systolic/diastolic blood pressure
Adverse Events and Concomitant 
Medications Collection
Use non-directive questions (i.e., “How are you feeling”) 
to query patient regarding AEs that may have occurred 
and inquire about medication changes.
Full Local Lab Assessment
The following panels performed locally (Section 10.1.1
details analytes):

Hematology with automated differential

Biochemistry

Coagulation

Urinalysis

Serum pregnancy test for WOCBP
MPN Symptom Questionnaires
IRB/EC approved questionnaires will be completed 
based on the version required in the applicable feeder 
study.  For example, the MPN-SAF TSS for IMG-7289-CTP-
102 and the MPN-SAF for IMG-7289-CTP-201.
Questionnaires will be completed weekly, ideally at the 
same time and day each week for consistency, through 
the EoS or ET Visit.  The actual date of questionnaire 
completion, not the planned or collected date, must be 
documented on each questionnaire completed. On visit 
days, the questionnaire should be completed prior to the 
study visit. If the patient arrives without a completed 
questionnaire, the patient will complete it during the 
visit, and it will be collected by study staff prior to the 
patient departing.  
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Term
Protocol Meaning
Importantly, multiple questionnaires will need to be 
provided to the patient for completion on a weekly basis 
between visits.  Note, for patients undergoing monthly 
labs locally, consideration should be given to the use of a 
courier for provision and return of questionnaires.
Bone 
Marrow 
Sampling
and 
Assessments

Aspirate sample should be optimally obtained within 
the first pull. Do not collect after a second pull 
attempt, and biopsy collected as per site standard 
procedure.  

A central laboratory will perform morphology 
review, fibrosis grading and store BMMCs for 
possible correlative research analysis
(Section 
10.1.2).  

Note:  Any results available from site routine bone
marrow 
work-up, 
including 
morphology, 
cytogenetics, other genetic interrogations will be 
collected either via the eCRF or through collection of 
local reports.
Study Drug Dispensing and Dosing 
Instructions

Administer bomedemstat in accordance with the 
Pharmacy Manual instructions.

Instruct patients to refer to their Dosing Card every 
day for details on bomedemstat dosing (Section 7.2.2) 
and handling of missed doses (Section 7.2.4)
Note:  If at any time additional clinical evaluation outside of the visit schedule is deemed 
necessary by the Investigator, then unscheduled visits should occur, and data should be collected.
9.1
Enrollment Period
9.1.1
Informed Consent Visit
Details of the extension study and a copy of the Participant Information Sheet/Consent Form
(PISCF) should be provided to the patient prior to their anticipated final feeder study visit.  
Informed consent should be obtained at, or before, the feeder study’s final visit.  Patients must 
provide documented informed consent before undergoing any study-related procedures. The PI, 
or designee, will explain to the patient the study purpose, the risks and benefits involved and that 
their participation is voluntary.  Each patient will acknowledge receipt of this information and 
that they wish to participate in the study by giving documented informed consent for their 
involvement in the study in the presence of the PI, or designee, who will also sign and date the
PISCF. Time, date, name of the person taking consent and any questions raised by the patient 
must be documented in the source data.
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9.1.2
Eligibility Assessment
Once consent has been obtained for participation in the extension study, the PI will assess 
whether the patient is eligible.  If the patient meets all eligibility criteria, then they will be 
enrolled upon commencement of their first extension study visit (Section 9.1.4).  Patients deemed 
ineligible should have the reason(s) documented in the patient’s source data and on the 
Screening & Enrollment log.
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10 LABORATORY SAMPLING FOR SAFETY AND PD ANALYSIS
Blood, bone marrow and/or their contents may be retained for future exploratory studies.
The average of the blood volumes collected, which varies by local laboratory institution, is 
provided in EC/IRB approved the informed consent. 
See Section 10.1 and 10.2 for the specifics and volumes required for each test.   
10.1 Laboratory Measures
Details on the laboratory assessments performed throughout the study are provided below by 
category of tests (i.e., biochemistry, hematology, etc.).  Details on the specific laboratory 
assessments required at each visit are located in Section 9 and in schematic form in Appendix 
16.1.  When each category of test is required, at a minimum, the following clinical laboratory 
determinations (or their equivalent) will be performed.  Exceptions are noted by asterisk (*) to 
reflect that the particular analyte will only be analysed if the test is available at the particular 
institution.  
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10.1.1 Local Laboratory Measures
Biochemistry: Serum creatinine, uric acid, urea* or blood urea nitrogen (BUN)*, albumin, total 
bilirubin, 
gamma 
glutamyltransferase 
(GGT), 
alkaline 
phosphatase 
(ALP), 
alanine 
aminotransferase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), C-reactive 
protein (CRP) and serum ferritin.
Hematology: Hemoglobin, red blood cell count (RBC) (including nucleated RBC), red cell 
distribution width, hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin 
(MCH), mean corpuscular haemoglobin concentration (MCHC), platelets, mean platelet volume 
(MPV)*, white cell count and automated or manual assessment as needed to ensure the following 
results are generated:
neutrophils, lymphocytes, monocytes, eosinophils, basophils, 
reticulocytes, promyelocytes, myelocytes, metamyelocytes and blasts.  
Coagulation: Prothrombin time (PT)*, activated partial thromboplastin time (aPTT) and 
International normalized ratio (INR).
Serum Pregnancy Test: For WOCBP, a serum pregnancy test will be utilized according to 
institution standard procedure.  The result must be confirmed prior to next scheduled dose of 
bomedemstat.  
Urinalysis: Leucocyte esterase, nitrites, urobilinogen, protein, pH, blood, specific gravity, 
ketones, bilirubin and glucose.
Bone marrow sampling:  At each sample time-point both aspirate (unless there is a dry tap) and 
biopsy samples are required to be obtained as per site standard procedure. Evaluation of 
morphology including fibrosis score will be performed centrally (see Section 10.1.2);.  
Additionally, any locally available cytogenetic or genetic interrogations performed on samples 
obtained at the same time-point as study samples will also be reported in the eCRF or collected 
via local lab reports.  
Additional Tests for Italy:  HIV test, HAV, HBsAg, HBsAb, HBcAb, HCV
Sample Processing: Sponsor will not provide either a laboratory manual or study supplies for 
the collection and handling of samples to be analysed locally.  Local laboratory standard 
procedures should be followed at each site.
Blood sample volume: The volume of blood needed to perform a Full Local Laboratory
Assessment and a Hematology Local Laboratory Assessment varies by institution.
10.1.2 Central Laboratory Measures
Bone Marrow Sampling Requirements:  Approximately 2-3 mL bone marrow aspirate sample 
for central analysis must be collected from the first pull, whenever possible, and no later than the 
second (except in the case of dry tap).  A peripheral blood smear must also be provided the same 
day for review in conjunction with the bone marrow sample; additionally a de-identified copy of 
the hematology (CBC) report from the day of bone marrow sampling should be sent to the central 
lab with the bone marrow samples (or follow by email as soon as available).  A 1-2 cm section of 
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trephine bone marrow sample must also be collected and sent to the central laboratory as a 
formalin fixed, paraffin embedded block (unless alternative arrangements have been agreed with 
sponsor).  Measures to be performed centrally include: myelofibrosis grading and morphology 
review.  Remaining bone marrow aspirate following preparation of the morphology slides may 
be used for analysis of mutant allele burden over the course of bomedemstat treatment.  Genomic 
sample collection, handling, storage, and analysis will conform to all applicable national guidance 
and regulations.
Genomic Testing:  At each required sample time-point approximately 20 mL peripheral blood 
sample will be collected for analysis.  During the feeder protocols germline samples consisting of 
hair roots and a cheek swab were collected for analysis.  If, upon analysis, the sample yield was 
found to be inadequate a repeat sample of either type may be requested as part of their feeder 
study or as part of this protocol. Genomic sample collection, handling, storage, and analysis will 
conform to all applicable national guidance and regulations.  
Future Correlative Studies:  Approximately 10 mL additional blood will be collected and stored 
in conjunction with each genomic blood sampling time-point for the purposes of potential 
correlative studies.  If site process permits, samples collected and stored earlier in the course of 
their MPN, and any available genetic data may be requested.  
Patients at specific sites/countries may need to provide specific consent for the analysis of these 
correlative samples but samples will be collected for all patients. 
Sample Processing: Sponsor will provide a laboratory manual documenting the collection and 
handling of samples to be analysed centrally.  Laboratory supplies will be provided for the 
collection of all central laboratory samples.
11 SAFETY
The Investigator is responsible for monitoring the safety of patients enrolled in this study.  
If the patient is withdrawn from treatment, the patient will discontinue study treatment and on 
that day or as soon as possible thereafter undergo an EoT visit and have the Follow-up Period 
EoS visit scheduled (see Section 9.4).  
11.1 Pregnancy 
 
 
 
 
 
 
 
 
 
 
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11.2 Adverse Events 
The Investigator is responsible for monitoring the safety of patients who have enrolled in the 
study and for accurately documenting and reporting information as described in this section.
Patients will be instructed to report to the Investigator any AE that they experience.  Investigators 
will ask about the occurrence of AEs at each visit.  Investigators are required to document all AEs 
occurring during the clinical study, commencing with the first dose of bomedemstat at the 
Transition Visit through to the EoS Visit (scheduled at 14 days post last bomedemstat dose).  AE
recording will continue for patients who discontinue study drug but remain in Follow-up Period, 
until their EoT and EoS Visits have been completed.  
Note: Any medical event i.e., (S)AE which is ongoing from the feeder protocol study at the time of
dosing with bomedemstat in this protocol must be documented in the patient’s medical notes and 
will be recorded on the appropriate eCRF pages as AEs ongoing at the time of study entry. 
New AEs will be recorded on designated eCRF pages. Each AE is to be characterised (i.e., verbatim 
term) and information provided regarding its seriousness, start and stop dates, intensity, 
outcome, and causal relationship with the study drug. 
An AE is any undesirable physical, psychological or behavioral effect experienced by a patient 
during participation in an investigational study, in conjunction with the use of the drug or 
biologic, whether or not product-related.  This includes any untoward signs or symptoms 
experienced by the patient from the time of first dose with bomedemstat under this protocol until 
completion of the study.
AEs may include, but are not limited to:

Subjective or objective symptoms spontaneously offered by the patient and/or 
observed by the Investigator or medical staff

Findings at physical examinations

Laboratory abnormalities of clinical significance

Overdose defined as any dose exceeding the prescribed dose for bomedemstat
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
Potential DILI events defined as an elevated AST or ALT laboratory value that is 
greater than or equal to 3× the ULN and an elevated total bilirubin laboratory 
value that is greater than or equal to 2× the ULN and, at the same time, an alkaline 
phosphatase laboratory value that is less than 2× the ULN, as determined by way 
of protocol-specified laboratory testing or unscheduled laboratory testing.
It is important Investigators record accurate AE terms in the eCRFs.  Wherever possible, a specific 
disease or syndrome rather than individual associated signs, symptoms or laboratory parameter 
will be identified by the Investigator and recorded in the eCRF.  However, if an observed or 
reported sign, symptom or laboratory parameter is not considered a component of a specific 
disease or syndrome by the Investigator, or is atypical, it should be recorded as a separate AE in 
the eCRF.
Disease signs, symptoms, and/or laboratory abnormalities already existing prior to the use of the 
study drug are not considered AEs after treatment unless they reoccur after the patient has 
recovered from the preexisting condition or in the opinion of the Investigator they represent a 
clinically significant exacerbation in intensity or frequency.  
Clinical significance is defined as any variation in signs, symptoms, or testing that has medical 
relevance and may result in an alteration in medical care.  The Investigator will continue to 
monitor the patient until the assessment returns to Baseline or until the Investigator determines 
that follow-up is no longer medically necessary.
11.2.1 Adverse Event Intensity
AE intensity will be evaluated using the NCI CTCAE version 5, published 27-NOV-2017. For AEs 
not included in the NCI CTCAE, the Investigator will be required to assess the intensity of the 
adverse drug/biologic experience using the following categories and associated guidelines:  
Grade
Guideline
1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated
2
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL*
3
Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL**
4
Life-threatening consequences; urgent intervention indicated
5
Death related to AE
Note 1: A semi-colon indicates ‘or’ within the description of the grade.
Note 2: Activities of Daily Living (ADL) 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc.
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden.
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11.2.2 Adverse Event Relatedness
The Investigator will make a judgment regarding whether or not, in his/her opinion, the AE was 
related to study drug.  The Investigator will also evaluate any changes in laboratory values, make 
a determination as to whether the change is clinically significant, and whether or not the 
change(s) were related to study drug.  However, even if the Investigator feels there is no 
relationship to the study drug, the AE or clinically significant laboratory abnormality MUST be 
recorded in the eCRF.  Below are guidelines for relationship assessment:

Unrelated: There was no relationship of the AE to the use of the drug or biologic. This 
may include, but is not limited, to the adverse experience being an expected outcome 
of a previously existing or concurrent disease, concomitant medication or procedure 
the subject experienced during their treatment period. 

Remote/Unlikely: AEs which are judged probably not related to the drug or biologic. 

Possible: There was no clear relationship of the AE to the use of the drug or biologic; 
however, one cannot definitively conclude that there was no relationship.

Probable: While a clear relationship to the drug or biologic cannot be established, the 
event is associated with an expected AE (per the current Investigator Brochure or 
SAB findings) or there is no other medical condition or intervention which would 
explain the occurrence of such an experience. 

Definite: The relationship of the use of the drug or biologic to the experience is 
considered definitively established.
If a causal relationship is considered probable, possible, or definite by the Investigator or Sponsor 
(dependent on the regional reporting requirements), the AE is considered to be “related” for 
purposes of regulatory reporting. If a causal relationship is considered remote/unlikely or 
unrelated, the AE is considered “unrelated” for purposes of regulatory reporting.  
11.2.3 Serious Adverse Events
SAEs will be reportable from the time of first dose in the extension study through the EoS or ET
Visit or until the Investigator and sponsor determine that follow-up is no longer necessary.  SAEs 
that are suspected to be drug related will be reported even if they occur when the patient is no 
longer on the study.  
An SAE is any AE that results in any of the following outcomes:
Death
Life-threatening experience. Any AE that places the patient, in the view of the reporter, at 
immediate risk of death from the AE as it occurred, i.e., does not include an AE that had it occurred 
in a more severe form, might have caused death.
Required or prolonged inpatient hospitalization¥. The AE resulted in an initial inpatient 
hospitalization or prolonged an existing hospitalization of the patient. If a patient is hospitalized 
as part of the clinical use of the product, a period of normal hospitalization will be outlined in the 
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protocol or by the judgment of the Investigator. Hospitalizations longer than this period will be 
prolonged hospitalizations.
Persistent or significant disability/incapacity. An AE that resulted in a substantial disruption 
of a person’s ability to conduct normal life functions.
Congenital Anomaly. The exposure of the patient to the drug or biologic during pregnancy that 
is judged to have resulted in the congenital anomaly/birth defect.
Important medical events. AEs that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, may 
jeopardise the patient or subject and may require medical or surgical intervention to prevent one 
of the outcomes listed above. Important medical events or interventions may be considered an 
SAE based upon medical judgment of the Investigator.  
11.2.4 Reporting Serious Adverse Events 
SAEs will be reported promptly, using the SAE Report Form, once the Investigator determines 
that the event meets the protocol definition of an SAE.  The Investigator or designee will report 
the SAE within 24 hours of his/her becoming aware of these events regardless of 
relationship of the SAE to the use of study drug, in accordance with the instructions in the 
Study Reference Manual. The Investigator will always provide an assessment of relatedness at 
the time of the initial report as described in Section 11.2.2.  The SAE Report will always be 
completed as thoroughly as possible with all available details of the event within the designated 
time frames. Copies of relevant patient records, autopsy reports, and other documents may be 
requested.  
If the Investigator does not have all information regarding an SAE, he/she will not wait to receive 
additional information before reporting the SAE. The SAE Report will be updated when additional 
information is received within 24 hours of receipt of such information.
Important:  For fatal and life-threatening events, the event should be reported in the EDC system 
immediately or within 24 hours of learning of the event.  A death occurring during the study or 
information related to such occurrence that comes to the attention of the Investigator during the 
study must be reported immediately to the Sponsor.  A detailed SAE reporting procedure and 
contact information will be included in the Study Reference Manual (SRM) and provided to the 
site before any patients are consented.
Additionally, the Institutional Review Board (IRB), Independent Ethics Committee (IEC) and 
Human Research Ethics Committee (HREC), as applicable, must be notified in writing of any SAEs 
that require expedited reporting to Regulatory Authorities.  Depending upon regional 
requirements, it is the responsibility of the Investigator to notify the IRB/IEC/HREC.  All SAEs 
meeting expedited reporting requirements will be reported to appropriate regulatory agencies 
by sponsor or their designee as soon as possible and within the timeframes specified in the 
various regions in which the study is to be conducted.
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11.2.5 For Participants Who Consent To Another Bomedemstat Extension Study
All AEs, SAEs, and other reportable safety events must be reported by the investigator in this 
protocol up to the time of consenting into another bomedemstat extension trial. Laboratory 
values that meet criteria for reporting as AEs performed during this study will be collected in 
this study.
Note: Once consented to another extension study, AEs/SAEs and other reportable safety events 
meeting the reporting criteria of the extension study, including those considered related to 
study intervention, will be collected in the extension study.
12 ANALYSIS AND STATISTICAL CONSIDERATIONS
12.1 General Considerations
Detailed methodology for summary and statistical analyses of the data collected in this trial will 
be documented in a Statistical Analysis Plan (SAP).  This document may modify the plans outlined 
in the protocol; however, any major modifications of the primary endpoint definitions and/or its 
analysis will also be reflected in a protocol amendment.  Additional statistical analyses other than 
those described in this section may be performed if deemed appropriate and included in the SAP.
12.2 Power
There are no sample size calculations for this extension study.  Sample size will be based on 
elective participation of patients who were enrolled into the feeder studies.
12.3 Treatment Assignment and Blinding
This is an open-label study.  The Investigators, other hospital personnel, patients and Sponsor 
will know the identity of the treatment.  
Effort will be made, as appropriate, to maintain continuity of study staff who administer/evaluate 
various assessments at each site (i.e., physical examination, morphology/fibrosis grade review, 
etc.), in order to facilitate consistency of assessments within a patient.
12.4 Study Endpoints
12.4.1 Primary Endpoints
The safety and tolerability of bomedemstat will be assessed by the analysis of adverse events 
(AEs), as well as changes in physical examinations, vital signs and laboratory values as detailed 
below. 

Monitoring of Adverse Events (AEs), serious adverse events (SAEs), and AEs.  AEs will be 
assessed from time of entry into study until EoS or ET in terms of onset, duration, 
seriousness, severity and causality, using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.  
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
Changes in physical examinations, vital signs and laboratory values will also be assessed 
until EoS or ET.  Information on the timing of these assessments is presented in the 
schedule of assessments.  The following laboratory tests will be conducted:
o
Complete blood counts (CBC) and differential
o
Coagulation
o
Chemistry 
o
Urinalysis 
Additionally, in MF patients:

Spleen volume reduction will be assessed based on spleen volume measured by MRI (or 
CT where applicable) approximately every 48 weeks. 
Additionally, in ET patients:

Reduction of platelet counts will be evaluated and assessed based on local laboratory 
measurements of platelet counts collected serially throughout the study.
12.4.2 Exploratory Endpoints
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12.5 Data Analysis
12.5.1 Safety and Tolerability Data Analysis
Demographics will be tabulated and summarized. Adverse events/ongoing medical event data at 
the time of study entry will be listed, as will Physical Examination data at time of study entry, and 
at subsequent visits.  All characteristics at baseline such as age, weight, height and vital signs 
(resting heart rate, semi-supine systolic/diastolic blood pressure, respiratory rate and 
temperature) parameters will be tabulated and summarized.
All patients receiving at least one dose of bomedemstat will be included in the safety analysis.  
Laboratory values outside the laboratory normal ranges will be summarized and assessed for 
change from time of study entry and Day 1 in the feeder study.
Treatment-emergent adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) and summarized for the number of patients reporting the AE and the 
number of AEs reported.  A by-patient AE data listing including (but not limited to) verbatim 
term, coded term, severity, and relationship to treatment will be provided. 
Concomitant medications will be listed by patient and coded using the WHO drug dictionary.  
Medical history will be listed by patient.
Descriptive statistics (arithmetic mean, standard deviation (SD), sample size, CV (coefficient of 
variation), median, minimum, maximum, and number) will be calculated for quantitative safety 
data as well as for the differences to baseline and time of study entry, when appropriate.  In 
addition, a shift table describing out of normal range shifts will be provided for clinical laboratory 
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results and physical examination results.  For safety and tolerability, missing data including those 
not obtained because of death will be the last value carried forward.
12.5.2 Efficacy Data Analysis
The primary efficacy objective for this study is to measure the extent and durability of 
bomedemstat treatment effects on the exploratory endpoints including any impact of 
bomedemstat on the natural history of MF and ET.  The long-term effects of bomedemstat will be 
examined by summarizing the exploratory endpoints from feeder study baseline through the 
extension study.
If applicable, progression free survival (PFS), event free survival (EFS), and overall survival (OS) 
will be calculated using the Kaplan-Meier method.
Additionally, for MF Patients, spleen volume reduction will be assessed based on spleen volume 
measured by MRI (or CT where applicable). 
Additionally, for ET Patients, the below endpoints, proportions and corresponding 95% 
confidence intervals will be based on the Clopper-Pearson method:
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13 STUDY ADMINISTRATION
The names, titles, and addresses of the Investigators and study personnel are available from 
sponsor.
13.1 Ethical Considerations
This research will be carried out in accordance with the protocol, US Code of Federal Regulations, 
GCP, 21 CFR Parts 50, 56, and 312, the ethical principles set forth in the Declaration of Helsinki, 
and the ICH harmonized tripartite guideline regarding GCP (E6 Consolidated Guidance, April
1996).
13.2 Participation Information Sheet/Consent Form (PISCF)
A sample PISCF document will be provided to each site.  No major deviations may be made from 
the sample PISCF other than country- or region-specific formatting or legal requirements.  
Sponsor and its advisors will review the site-specific draft PISCF before it is finalised, and the 
final IRB/IEC/HREC-approved document must be provided to sponsor for regulatory purposes.
The PISCF must be documented by the patient before his or her participation in the study.  A copy 
of the PISCF must be provided to the patient.  If required by local procedure a second original of 
the PISCF may be provided to the patient.  If applicable, it will be provided in a certified 
translation of the local language.
An original signed PISCF must remain in each patient’s study file and must be available for 
verification by study monitors at any time.
13.3 Institutional Review Board (IRB), Independent Ethics Committee (IEC) and Human 
Research Ethics Committee (HREC)
This protocol, the PISCF, relevant supporting information and all types of patient recruitment or 
advertisement information must be submitted to IRB/IEC/HREC for review and must be 
approved before the study is initiated.  Any amendments to the protocol must also be approved, 
where necessary, by the IRB/IEC/HREC prior to implementing changes in the study.
The Investigator is responsible for keeping the IRB/IEC/HREC apprised of the progress of the 
study and of any changes made to the protocol as deemed appropriate, but in any case, at least 
once a year.  The Investigator must also keep the IRB/IEC/HREC informed of any AEs, according 
to the IRB/IEC/HREC policy.
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13.4 Study or Site Termination
 
If Sponsor, an Investigator, or regulatory authorities discover conditions during the study that 
indicate that the study or related activities at a particular site should be terminated, this action 
may be taken after appropriate consultation between Sponsor and the Investigator.  
 
Study or site termination and follow-up will be performed in compliance with the conditions set 
forth in 21 Code of Federal Regulations (CFR) Section 312 and/or other national and local 
regulations, as applicable, and in compliance with the principles set forth in ICHGCPs, including 
ICH E6, and ethical principles established by the Declaration of Helsinki.
13.5 Study Monitoring Requirements
Monitoring and auditing procedures developed by sponsor will be followed in order to comply 
with ICH GCP guidelines.  On-site checking of the eCRFs for completeness and clarity, cross 
checking with source documents, and clarification of administrative matters will be performed, 
when possible.  Additionally, off-site or ‘remote’ monitoring visits may be conducted as needed.  
Remote monitoring may consist of centralized monitoring or remote data review. Centralized 
monitoring is the remote, cross-functional review and evaluation of accumulating in-house data 
conducted by data managers, central monitor associates, medical directors, the clinical team, and 
biostatisticians. The review of data within and across sites proactively identifies missing or 
inconsistent data, data trends, systematic or significant errors and enables site performance 
characteristics to be analyzed. Remote data review is intended to encompass as many activities 
performed in a routine on-site monitoring visit as is functionally possible, and as permitted by 
site policy and procedure.  The remote review of data may be actioned via multiple pathways, 
often contingent on site’s capabilities.  Remote data review, specifically, has become critically 
important in the COVID-19 environment as a measure of safeguarding patient safety, while also 
minimizing risks to trial data integrity and facilitating GCP compliance.  Note: Remote data review 
will only be implemented in Germany in times of increased safety measures such as the COVID-
19 pandemic and only in special cases.  Please see Section 16.9 for additional information 
pertaining to remote data review. 
Monitoring visits will consist of periodic visits during the study period and site close-out visits.  
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The Investigator will permit authorised representatives of sponsor and the respective national 
or local authorities to inspect facilities and records relevant to this study.
Sponsor or its designee will monitor the study.  Monitoring will be done by visits from 
representatives of sponsor (monitors) who will review the eCRFs and source documents.  The 
monitors will ensure that the investigation is conducted according to protocol design and 
regulatory requirements by frequent communications (letter, email, telephone, and fax). The 
monitor/representative of sponsor will perform an Investigator Site File review to confirm all 
documents required to reconstruct the conduct of the clinical trial are present.  The Investigator 
Site File supports the validity of the research, as well as the conduct and integrity of the data 
collected, and needs to be maintained by the Investigator (or designee) and inspection ready at 
all times. 
All unused study materials are to be returned to sponsor or its designee after the clinical period 
of the trial has been completed, or be disposed of at the site according to institutional policies but 
not prior to the approval of the Sponsor and with appropriate documentation.  
13.6 Quality Assurance
The study will be initiated and conducted under the sponsorship of sponsor.  Bomedemstat and 
clinical supplies will be supplied by sponsor.  Representatives of sponsor will monitor the study 
to verify study data, medical records, worksheets, and eCRFs are in accordance with current ICH 
GCPs and the respective local and national government regulations and guidelines.
The Investigator will contact the Sponsor immediately if contacted by a regulatory agency about 
an inspection at his or her center. The purpose of Sponsor audit or inspection is to systematically 
and independently examine all study-related activities and documents to determine whether 
these activities were conducted, and data were recorded, analyzed, and accurately reported 
according to the protocol, ICH/GCP guidelines, and any applicable regulatory requirements.
13.7 Confidentiality
The information obtained during the conduct of this clinical study is confidential, and disclosure 
to third parties other than those noted below is prohibited.
The patient’s identifying information will not leave the clinical site at which they are recruited.  
The patient will be identified on all study documentation using a code number and their initials 
(where it is lawful to collect such information).
Information obtained during the conduct of this study will be collected, processed, and 
transmitted to or for the benefit of sponsor in accordance with the applicable regulations and 
principles of confidentiality for each participating country.  Information contained therein will 
be maintained in accordance with applicable law protecting patient privacy, including the 
provisions of 46 CFR Part 164 promulgated under the Health Insurance Portability and 
Accountability Act (HIPAA) and may be inspected by the clinical researcher, the researcher’s staff, 
Sponsor and its representatives, partners, advisors, affiliates, successors, and clinical research 
contractors and subcontractors to check, process, evaluate, and use the information collected 
during the study.  The patient PISCF (or a separate data protection consent form if required 
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locally) will be used to obtain participant consent to authorise transfer and processing of data 
consistent with applicable law.  Processing, evaluation, or use of the information will be 
performed by a health professional for medical purposes and/or by those operating under a duty 
of confidentiality that is equivalent to that of a health professional.  Information obtained from 
the study will likely be used by sponsor or its affiliates or successors in connection with the 
development of study drug, including possible filing of applications with governmental 
authorities for marketing approval, and for other pharmaceutical and medical research purposes.  
The study Investigator is obliged to provide Sponsor with complete test results and all data 
developed in this study.  This information may be disclosed to other physicians who are 
conducting similar studies and to the applicable regulatory authorities as deemed necessary by 
sponsor.  Patient-specific information may be provided to other appropriate medical personnel 
only with the patient’s permission, as necessary and in accordance with other applicable privacy 
laws and regulations protecting patient health information. 
To ensure compliance with the ICH GCP guidelines, data generated by this study must be available 
for inspection upon request by representatives of the appropriate national and local authorities, 
sponsor, and the IRB/IEC/HREC for each study site.
The raw dataset will be available to sponsor on completion of the study.  Sponsor will actively 
pursue publication of the results of the study in cooperation with the Lead Investigators subject 
to the terms and conditions of the clinical trial agreement between sponsor and Investigators.  
The Lead/Coordinating Investigator will have the right to submit for publication any results 
arising from the study subject to the terms and conditions of the Clinical Trial and Confidentiality 
Disclosure Agreements.  The Lead/Coordinating Investigator, with the agreement of sponsor, will 
coordinate the principal publication of the data arising from the study.  Patient names and other 
personal data relating to an identified or identifiable patient (such as photographs, audio, 
videotapes, or other factors specific to physical, physiological, mental, economic, cultural, or 
social identity), may not be disclosed in any publication without prior written authorisation, in 
compliance with patient privacy law, from sponsor and the patient.
14 INVESTIGATOR REQUIREMENTS
14.1 Protocol Adherence
Each Investigator must adhere to the protocol as detailed in this document and agrees that any 
changes to the protocol must be approved by sponsor’s authorised representative in writing 
prior to seeking approval, where necessary, from the IRB/IEC/HREC.  Each Investigator will be 
responsible for allowing only those patients who have met all protocol eligibility criteria to be 
enrolled. 
Modifications to the protocol should not be made without agreement of the Investigators and 
sponsor. Changes to the protocol will require written IRB/IEC/HREC approval/favorable opinion 
prior to implementation, except when the modification is needed to eliminate an immediate 
hazard(s) to patients.  The IRB/IEC/HREC may provide expedited review and approval/favorable 
opinion for minor change(s) in ongoing trials that have the approval/favorable opinion of the 
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IRB/IEC/HREC.  The Investigator will submit all protocol modifications to the IRB/IEC/HREC in 
accordance with the governing regulations.
When immediate deviation from the protocol is required to eliminate an immediate hazard(s) to 
patients, the Investigator will contact Sponsor, if circumstances permit, to discuss the planned 
course of action.  Any departures from the protocol must be fully documented in the eCRF and 
source documentation.
14.2 Source Documentation
The Investigator must maintain detailed records of all study participants who are enrolled in the 
study or who undergo screening. Source documents include patient medical records and 
Investigator’s patient study files, as well as all test results.  Information required for study 
purposes and any data recorded in the eCRF must be supported by appropriate source 
documentation.
14.3 Direct Access to Source Documentation
The Investigator will ensure that the Sponsor, IRB/IEC/HREC and regulatory authorities will 
have direct access to all trial-related sites, source data/documents, and reports for the purpose 
of monitoring and auditing (ICH[E6] 5.1.2 & 6.10).  This includes electronic source data.  
14.4 Case Report Forms
Case report forms (or an electronic data capture system) will be provided to each investigational 
site for the collection of all study data for enrolled patients, with the exception of data that may 
be captured externally to the site (i.e., central laboratory data).  Study site personnel will record 
the data in the source documentation and enter it in the eCRF within, on average, 5 business days 
of the study visit, while carefully reviewing all information recorded for accuracy and 
consistency.  Any required data printouts should be filed in the patient’s source data, 
(i.e., laboratory reports, etc.) and signed/dated by appropriately designated site personnel as a 
true copy of the original.
A clinical study monitor will review the eCRFs and compare the content to the source data.
The eCRFs for each patient must be reviewed and signed by the Investigator.  This should be done 
as soon as possible after the patient has completed the study and all data queries have been 
resolved.  
14.5 Study Drug Accountability
Accountability for study drug at the trial site is the responsibility of the Investigator.  The 
Investigator will ensure that study drug is used only in accordance with this protocol.  Where 
allowed, the Investigator may choose to assign some of the drug accountability responsibilities 
to a pharmacist or other appropriate individual.  Drug accountability records indicating the 
drugs’ delivery date to the site, inventory at the site, use by each patient, and return to sponsor
(or disposal of the drug, if approved by sponsor) will be maintained by the clinical site.  These 
records will adequately document that the patients were provided the drugs and doses as 
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specified in the protocol and should reconcile all study drugs received from sponsor.  
Accountability records will include dates, quantities, batch/serial numbers, expiry dates (if 
applicable), and patient numbers.  Sponsor or its designee will review drug accountability at the 
site on an ongoing basis during monitoring visits.
14.6 Disposal of Study Drug
All unused study drug will be retained at the site until inventoried by sponsor / designee, unless 
otherwise agreed.  All unused or expired study drug will be returned to sponsor or its designee 
or, if authorised by sponsor, will be disposed of at the study site and the disposal will be 
appropriately documented.  Records shall be maintained by the Investigator of any such alternate 
disposition of the test drug.  These records must show the identification and quantity of each unit 
disposed of, the method of destruction (taking into account the requirements of local law), and 
the person/company who disposed of the test substance.  Such records must be submitted to the 
Sponsor and copies on file in the Investigator’s Site File.  All material containing study drug will 
be treated and disposed of as hazardous waste in accordance with governing regulations.
14.7 Training of Staff
The PI is responsible for the conduct of the study at this study site, including delegation of 
specified study responsibilities, and training of study staff.  The PI shall ensure that the study is 
carried out in accordance with the protocol, ICH/GCP guidelines, and regulations.
The PI will maintain a record of all individuals involved in the study (medical, nursing and other 
staff).  He or she will ensure that appropriate training relevant to the study is given to all of these 
staff, and that any new information of relevance to the performance of this study is forwarded to 
the staff involved.
14.8 Clinical Study Report
The Coordinating or Lead Investigator will be designated to review study data outputs and sign 
for the accuracy of any associated interim clinical study reports and the final clinical study report 
at the end of this study.  The signatory Lead Investigator will be identified by the Sponsor in 
advance of study completion.
14.9 Retention of Records
Records and documents pertaining to the conduct of this study, including eCRFs, source 
documents, consent forms, laboratory test results, medication inventory records and Investigator 
Site File, must be retained by the Investigator in accordance with locally applicable regulatory 
requirements, and in any event for a period of at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the investigational product.  No study records shall be destroyed without 
notifying Sponsor and giving Sponsor the opportunity to take such study records or authorizing 
in writing the destruction of records after the required retention period.
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Rhodes, D.R., Kalyana-Sundaram, S., Mahavisno, V., Varambally, R., Yu, J., Briggs, B.B., Barrette, 
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16 APPENDICES
CCI
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CCI
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CCI
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CCI
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CCI
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CCI
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16.2 Criteria for Grading Myelofibrosis (Arber et al., 2016)* 
Fibrosis grade
Definition
MF-0
Scattered linear reticulin with no intersections (crossovers) corresponding to normal bone marrow
MF-1
Loose network of reticulin with many intersections, especially in perivascular areas
MF-2
Diffuse and dense increase in reticulin with extensive intersections, occasionally with focal bundles of thick fibers mostly 
consistent with collagen, and/or focal osteosclerosisa
MF-3
Diffuse and dense increase in reticulin with extensive intersections and coarse bundles of thick fibers consistent with collagen, 
usually associated with osteosclerosis a
*Slightly modified from the European Consensus Criteria as presented in Thiele et al., 2005
Semiquantitative grading of BM fibrosis with minor modifications concerning collagen and osteosclerosis.Fiber density should be assessed only in hematopoietic areas.  
aIn grades MF-2 or MF-3 an additional trichrome stain is recommended.  
16.3 Eastern Cooperative Group 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, e.g., light house work, 
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
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16.4 Revised IWG-MRT and ELN Response Criteria for MF
Response 
categories
Required criteria (for all response categories, benefit must last for ≥12 weeks to qualify as a response)
CR
Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and
Peripheral blood: Haemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 x 109/L and <UNL; Platelet count ≥100 x 109/L and 
<UNL; <2% immature myeloid cells‡ and
Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
PR
Peripheral blood: Haemoglobin ≥100 g/L and <UNL; neutrophil count ≥1 x 109/L and <UNL; platelet count ≥100 x 109/L and 
<UNL; <2% immature myeloid cells‡ and
Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or
Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF†, and peripheral blood: Haemoglobin ≥85 but <100 
g/L and <UNL; neutrophil count ≥1 x 109/L and <UNL; platelet count ≥50, but <100 x 109/L and <UNL; <2% immature 
myeloid cells‡ and
Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH 
Clinical 
improvement (CI)
The achievement of anaemia, spleen or symptoms response without progressive disease or increase in severity of anaemia, 
thrombocytopenia, or neutropenia§
Anaemia response
Transfusion-independent patients: a ≥20 g/L increase in haemoglobin level¶
Transfusion-dependent patients: becoming transfusion-independent{
Spleen response
A baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable** or
A baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50%**
A baseline splenomegaly that is palpable at <5 cm, below the LCM, is not eligible for spleen response
A spleen response requires confirmation by MRI or computed tomography showing ≥35% spleen volume reduction
Symptoms 
response
A ≥50% reduction in the MPN-SAF TSS††
Progressive 
disease‡‡
Appearance of a new splenomegaly that is palpable at least 5 cm below the LCM or
A ≥100% increase in palpable distance, below LCM, for baseline splenomegaly of 5-10 cm or
A 50% increase in palpable distance, below LCM, for baseline splenomegaly of >10 cm or
Leukaemic transformation confirmed by a bone marrow blast count of ≥20% or
A peripheral blood blast content of ≥20% associated with an absolute blast count of ≥1 x 109/L that lasts for at least 2 weeks
Stable disease
Belonging to none of the above listed response categories
Relapse
No longer meeting criteria for at least CI after achieving CR, PR, or CI, or
Loss of anaemia response persisting for at least 1 month or
Loss of spleen response persisting for at least 1 month
EMH, extramedullary haematopoiesis (no evidence of EMH implies the absence of pathology- or imaging study-proven non-hepatosplenic EMH); LCM, left costal margin; 
UNL, upper normal limit. 
*Baseline and post-treatment bone marrow slides are to be interpreted at one sitting by a central review process. 
†Grading of MF is according to the European classiiication Thiele et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. It is 
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underscored that the consensus definition of a CR bone marrow is to be used only in those patients in which all other criteria are met, including resolution of 
leukoerythroblastosis.  
‡Immature myeloid cells constitute blasts + promyelocytes + myelocytes + metamyelocytes + nucleated red blood cells.  In splenectomized patients, <5% immature 
myeloid cells are allowed. 
§See above for definitions of anaemia response, spleen response, and progressive disease. Increase in severity of anaemia constitutes the occurrence of new transfusion 
dependency or a ≥20 g/L decrease in haemoglobin level from pretreatment baseline that lasts for at least 12 weeks.  Increase in severity of thrombocytopenia or 
neutropenia is defined as a 2-grade decline, from pretreatment baseline, in platelet or absolute neutrophil count, according to the Common Terminology Criteria for 
Adverse Events (CTCAE) version 4.0.  In addition, assignment to CI requires a minimum platelet count of ≥25000 x 109/L and absolute neutrophil count of ≥0.5 x 109/L. 
¶Applicable only to patients with baseline haemoglobin of <100 g/L. 
{Transfusion dependency before study enrollment is defined as transfusions of at least 6 units of packed red blood cells (PRBC), in the 12 weeks prior to study
enrollment, for a haemoglobin level of < 85 g/L, in the absence of bleeding or treatment-induced anaemia. In addition, the most recent transfusion episode must have 
occurred in the 28 days prior to study enrollment. Response in transfusion-dependent patients requires absence of any PRBC transfusions during any consecutive “rolling” 
12-week interval during the treatment phase, capped by a haemoglobin level of ≥ 85 g/L.
**Spleen response must be confirmed by imaging studies where a ≥35% reduction in spleen volume, as assessed by MRI or CT, is required. Furthermore, a ≥35% volume 
reduction in the spleen, by MRI or CT, constitutes a response regardless of what is reported with physical examination. 
††Symptoms are evaluated by the MPN-SAF TSS.  The MPN-SAF TSS is assessed by the patients themselves and includes fatigue, concentration, early satiety, inactivity, 
night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers.  Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can 
be) for each item.  The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). Symptoms response requires ≥50% reduction in the MPN-SAF TSS. 
‡‡Progressive disease assignment for splenomegaly requires coniirmation by MRI or computed tomography showing a ≥25% increase in spleen volume from baseline. 
Baseline values for both physical examination and imaging studies refer to pretreatment baseline and not to post-treatment measurements.
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16.5 Revised Response Criteria for ET:  IWG-MRT and ELN Consensus 2013 (Barosi et al., 
2013)
Response 
Categories
Criteria
Complete 
Remission
A
Durable* resolution of disease-related signs including palpable 
hepatosplenomegaly, large symptoms improvement, † AND 
B
Durable* peripheral blood count remission, defined as: 
platelet count ≤400 x 109/L, WBC count <10 x 109/L, absence of 
leukoerythroblastosis, AND 
C
Without signs of progressive disease, and absence of any hemorrhagic or 
thrombotic events, AND 
D
Bone marrow histological remission defined as disappearance of megakaryocyte 
hyperplasia and absence of >grade 1 reticulin fibrosis.
Partial 
Remission
A
Durable* resolution of disease-related signs including palpable 
hepatosplenomegaly, and large symptoms improvement, AND 
B
Durable* peripheral blood count remission, defined as: 
platelet count ≤400 x 109/L, WBC count <10 x 109/L, absence of
leukoerythroblastosis, AND 
C
Without signs of progressive disease, and absence of any hemorrhagic or 
thrombotic events, AND 
D
Without bone marrow histological remission, defined as the persistence of 
megakaryocyte hyperplasia.
No Response
Any response that does not satisfy partial remission 
Progressive 
Disease
Transformation into PV, post-ET myelofibrosis, myelodysplastic syndrome or 
acute leukemia‡
Molecular response is not required for assignment as complete response or partial response. Molecular response 
evaluation requires analysis in peripheral blood granulocytes. Complete response is defined as eradication of a 
preexisting abnormality. Partial response applies only to patients with at least 20% mutant allele burden at 
baseline. Partial response is defined as ≥50% decrease in allele burden. 
WBC, white blood cell. 
*Lasting at least 12 wk. 
†Large symptom improvement (≥10-point decrease) in MPN-SAF TSS. 
‡For the diagnosis of PV see World Health Organization criteria (WHO); for the diagnosis of post-ET 
myelofibrosis, see the 
IWG-MRT criteria; for the diagnosis of myelodysplastic syndrome and acute leukemia, see WHO criteria.
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16.6 Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score 
(MPN-SAF TSS) – 7-Day Recall
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16.7 Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) 
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16.8 Patient Global Impression of Change
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16.9 Remote Data Review
16.9.1 Risk Assessment
Sponsor will remain responsive where possible, to the remote data review requirements of each 
individual site regarding how patient visits and monitoring visits can occur remotely, when 
possible.
16.9.2 Security Measures
Monitors are only permitted to undertake remote data review through the processes detailed
below in Sections 16.9.3.1 and 16.9.3.2 (EMR access or video call/conferencing) where the
following security measures are in place:

Location of Monitor: remote data review activities may be performed in locations that
do not allow access/viewing by unauthorized third parties:
o
Acceptable locations include: closed room in a Syneos Health office, at home in
private area for home-based staff.
o
Examples of prohibited locations include: Open plan desk space in Syneos
Health offices, on public transportation, in airport lounge or other public areas.

Internet connection: remote data review is permitted only through a secure internet
connection (i.e., Syneos Health office internet or secure personal internet after logging
into Syneos Health virtual private network [VPN]). Use of a public internet, hot spot or
hotel internet is prohibited.

Device: remote data review is permitted only through Syneos Health registered device
(e.g., laptop, iPad) or through a device provided by the site.

While the EMR system is accessed or video call/conference are ongoing, the computer
must be locked if left unattended.
16.9.3 Processes
As outlined in Section 13.5, remote data review is intended to encompass as many activities 
performed in a routine on-site monitoring visit as is functionally possible, and as permitted by 
site policy and procedure.  The source documents/source data to be made available for remote 
data review include those related to the primary endpoint and exploratory endpoints, safety, 
study drug dispensation and return and the reasons for exclusion of a subject from the trial.
The remote review of data may be actioned via multiple pathways, often contingent on site’s 
capabilities.  Examples include:

Remote Source Data Review (via Electronic Medical Records (EMR))

Remote Source Data Review (via video call/conferencing)

Remote Data Verification (using redacted source documents)
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
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Additionally, to facilitate continued interaction with and support of the site, phone monitoring 
visits may also periodically be conducted. Remote review of data will not occur during phone 
visits.
16.9.3.1
Direct, Controlled Remote Access to the Systems Used by the Trial Site to
Manage the Source Documents/Source Data
For data review whereby the monitor accesses the EMR system remotely, the following criteria 
are required to be met before this process can be implemented for any subject:

An audit trail is available in the Electronic Medical Records (EMR) system.

There is unique password access to the EMR system assigned to each member of site staff.

There is unique password, read-only access to the EMR system assigned to the Monitor.

EMR access has been granted only to trial subjects’ records and other patient data is not
accessible to the Monitor (unless a procedure is in place to monitor the Monitor’s activity
following each session).   

US sites only: written procedure is in place for the use of EMR system.

US sites only: If the EMR system is certified by the Office of the National Coordinator for
Health Information Technology (ONC) at the Department of Health and Human Services,
it is sufficient to confirm this on the COVID-19 Remote Source Data Monitoring Site
Agreement.
16.9.3.2
For Passive Access to Original Documents/Original Data via Live Image
Transmission
The following controls will be applied for remote data review by video call/conferencing:

The video call/conference may only occur using a Syneos Health approved information
and communication technology.

Video review of documentation only is permitted.

No recording of the interaction is permitted.

No document upload is permitted.

No document storage is permitted.

Usage must comply with applicable local regulations/regulatory guidance.

During remote data review by video call/conferencing care will be taken to avoid
inadvertent viewing of individuals who should not be part of the interaction.
16.9.3.3
Passing on Redacted Copies of Original Documents and Documents with 
Original Data
Note:  In Germany, the sending of redacted source data is generally not permissible as a method 
for the remote review of data; however, single redacted documents may be used at times to 
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 83
confirm an individual data-point. 
The following controls will be applied during for passing on redacted copies of original 
documents:

Process must be allowed by local regulations and in compliance with applicable 
regulatory guidance

PI to document the delegation of creation of Pseudonymized Certified Copies of the 
source documents on the Study Personnel Signature and Delegation Form

Site staff who will provide source documents to Monitor for remote data review will be
trained on the role, responsibility, and process for providing pseudonymized Certified 
Copies of source documents to support remote review of data

Certified Copies of all required original source documents will be prepared
Certified Copy: A copy (irrespective of the type of media used) of the original record that 
has been verified (i.e., by a dated signature or by generation through a validated process) to 
have the same information, including data that describe the context, content, and structure, 
as the original. (International Council for Harmonisation (ICH) Guideline for Good Clinical 
Practice (GCP) Revision 2).
Note: A copy is certified by signing and dating on the first page with a statement “certified 
copy” and adding a note on the first page that the certified copy package consists of # pages.
Each page must be numbered so that, in total, the pages match the full # of pages 
documented on the first page of the package.

All subject direct identifiers (e.g., name, social security/national identification number, 
medical record number, initials, full date of birth, home address, etc.) will be redacted/
obscured (i.e., pseudonymized) on the copies to protect subject confidentiality and 
personal data.

A quality check of the redacted Certified Copies will be performed by a second site staff 
member to confirm all subject directly identifiable information has been redacted, the 
correct subject identification code added and that the copies are legible. 
o
The quality check will be documented by the second site staff member’s initials,
dating of the first page of the package and addition of the statement 
“QC’d/Checked”

A transmittal form will be completed each time Pseudonymized Certified Copies of source 
documents are sent. 

The prepared source document package, including transmittal form, will be provided by 
one of the following methods:
o
Overnight Courier
o
Secure Fax Transmission 
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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
Protocol IMG-7289-CTP-202 / MK-3543-005
Bomedemstat (IMG-7289/MK-3543)
13 December 2023
Page 84
o
Scanned images via secure email (encrypted email or password protected email 
attachment. If the latter, the password will be provided to Monitor via telephone)
o
A secure platform for document exchange

A set of the prepared source document package, including transmittal form, will be 
retained in the Investigator’s Site File. Note: These documents will not be retained in 
Germany.
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