Clinical trial NCT04081220
Conditions: Thrombocythemia, Essential
Sponsor: The University of Texas Health Science Center at San Antonio
Start date: 2020-04-09; Completion date: 2023-12-20
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a single-center, open-label investigator-initiated trial evaluating the effects of IMG-7289 administered orally once daily in patients with essential thrombocythemia.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: IMG-7289
Intervention descriptions: intervention 1: Single starting dose with individualized dose titrations throughout

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 57 
IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
CTMS# 19-0078 
 
 
 
 
 
 
 
 
 
COVER PAGE  
 
 
 
 
 
Official Study Title: AN INVESTIGATOR INITIATED PHASE 2 TRIAL 
OF THE LSD1 INHIBITOR IMG-7289 (BOMEDEMSTAT) IN 
ESSENTIAL THROMBOCYTHEMIA 
 
 
NCT number: NCT04081220 
 
IRB Approval Date: 11.01.2023 
 
 
Unique Protocol ID: CTMS# 19-0078  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complion Document ID: 7005814 


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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AN INVESTIGATOR INITIATED PHASE 2 TRIAL OF THE LSD1 INHIBITOR IMG-7289 
(BOMEDEMSTAT) IN ESSENTIAL THROMBOCYTHEMIA 
 
 
Zohra Nooruddin, MD 
Professor of Medicine 
Mays Cancer Center 
UT Health San Antonio 
7979 Wurzbach Rd 
San Antonio, TX 78229-3900 
Email: nooruddinz@uthscsa.edu 
Joel E. Michalek, Ph.D. F.A.S.A, Biostatistics Core 
Mays Cancer Center 
UT Health San Antonio 
Office: 210-567-0886 
 
 
CTMS# 19-0078 
IND# 145325 
 
PROTOCOL Version 13 
DATE: 7/27/23 


Page 3 of 57 
IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
INVESTIGATOR’S AGREEMENT 
 
I have read and understand the contents of this clinical protocol for Protocol “An Investigator Initiated Phase 2 
Trial Of The LSD1 Inhibitor IMG-7289 (bomedemstat) In Essential Thrombocythemia” CTMS# 19-0078 and will 
adhere to the study requirements as presented, including all statements regarding confidentiality. In addition, I 
will conduct the study in accordance with current international conference on harmonization (ICH) guidance, 
Good Clinical Practice (GCP) guidance, the Declaration of Helsinki, US Food and Drug Administration (FDA) 
regulations and local IRB and legal requirements. 
 
Name of Investigator: Zohra Nooruddin, MD 
Institution: Mays Cancer Center 
 
See attached electronic signature 
Investigator Signature 
Date 
Complion Document ID: 7005814 


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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Table of Contents 
1 
Abbreviations ............................................................................................................................... 6 
2 
Study Synopsis ............................................................................................................................ 8 
3 
Background ................................................................................................................................ 15 
3.1 
Background on the Disease to be Treated ......................................................................... 15 
3.2 
Study Rationale .................................................................................................................... 15 
3.3 
Background on IMG-7289 .................................................................................................... 16 
3.4 
Rationale for and Safety of the Proposed Starting Dose .................................................. 16 
3.5 
Justification of the Dose and Regimen .............................................................................. 17 
4 
Statement of Study Objectives ................................................................................................. 18 
4.1 
Study Aims and Hypotheses ............................................................................................... 18 
4.2 
Endpoints.............................................................................................................................. 18 
4.2.1 
Primary Endpoint ........................................................................................................... 18 
4.2.2 
Secondary Endpoints .................................................................................................... 19 
5 
Investigational Plan.................................................................................................................... 19 
5.1 
Overview ............................................................................................................................... 19 
5.2 
Initial Treatment Period ....................................................................................................... 19 
5.3 
Additional Treatment Period for Qualifying Patients Only ................................................ 20 
5.4 
Inclusion and Exclusion Criteria ......................................................................................... 20 
5.4.1 
Inclusion Criteria ........................................................................................................... 20 
5.4.2 
Exclusion Criteria .......................................................................................................... 21 
5.5 
Guidelines ............................................................................................................................. 21 
5.6 
Prohibited Medications/Treatments .................................................................................... 21 
6 
Study Treatment ......................................................................................................................... 22 
6.1 
Dosing and Administration.................................................................................................. 22 
6.2 
Dosage: Initial Treatment Period ....................................................................................... 23 
6.3 
Dosage: Additional Treatment Period ............................................................................... 24 
6.4 
Missed Doses ....................................................................................................................... 24 
6.5 
Dose Modification Guidelines ............................................................................................. 24 
6.5.1 
Hematologic Toxicities .................................................................................................. 24 
6.5.2 
Dose Limiting Toxicities ............................................................................................... 25 
6.5.3 
Stopping Rules .............................................................................................................. 25 
6.5.4 
Interruption of Dosing ................................................................................................... 25 
7 
Study Assessments and Procedures ....................................................................................... 26 
7.1 
Informed Consent ................................................................................................................ 26 
7.2 
Screening (Day -28 to Day -1) .............................................................................................. 26 
7.3 
Initial Treatment Period ....................................................................................................... 27 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
7.3.1 
ITP Day 1 - Treatment Start ........................................................................................... 27 
7.3.1.1 
ITP Pre-dose Day 1 .................................................................................................. 27 
7.3.1.2 
ITP Dosing Day 1 ..................................................................................................... 27 
7.3.1.3 
ITP Post-dose Day 1 ................................................................................................ 27 
7.3.2 
ITP Weekly Visits - Days 8, 15, 22, 29, 36, 43, 50 and 57 (± 1 day*) ............................ 27 
7.3.2.1 
ITP Days 29 and 57 Only ......................................................................................... 28 
7.3.2.2 
ITP Day 57 Only ....................................................................................................... 28 
7.3.3 
ITP Bi-Weekly Visits - Days 71, 85, 99 and 113 (± 2 days*) ......................................... 28 
7.3.3.1 
ITP Day 85 Only ....................................................................................................... 29 
7.3.3.2 
ITP Days 85 and 113 Only ....................................................................................... 29 
7.3.3.3 
ITP Day 113 only ...................................................................................................... 29 
7.3.4 
ITP Monthly Visits Days 141 and 169 (± 3 days*) ........................................................ 29 
7.3.4.1 
ITP Day 141 Only ..................................................................................................... 30 
7.3.4.2 
ITP Day 169 Only ..................................................................................................... 30 
7.4 
Additional Treatment Period (ATP; for qualifying patients only) ..................................... 30 
7.4.1 
ATP Day 1 Treatment ‘Re-start’ (± 3 days) ................................................................... 31 
7.4.2 
ATP Monthly Visits Days 29, 57, 85, 113, 141 and 169 (± 3 days*) ............................. 31 
7.4.2.1 
ATP Day 169 Only ................................................................................................... 32 
7.5 
Suspected Relapse .............................................................................................................. 32 
7.6 
Follow-up Period Visits ....................................................................................................... 33 
7.6.1 
End of Treatment Visit ................................................................................................... 33 
7.6.2 
Pre-End of Study Visit ................................................................................................... 33 
7.6.3 
End of Study / Early Termination Visit ......................................................................... 34 
7.7 
Schedule of Events – Initial Treatment Period ................................................................... 35 
7.8 
Schedule of Events – Additional Treatment Period........................................................... 37 
8 
Study Design/Data Collection ................................................................................................... 38 
9 
Minority Accrual ......................................................................................................................... 38 
9.1 
Purpose ................................................................................................................................. 38 
10 Statistical Analysis .................................................................................................................... 41 
11 Data and Safety Monitoring Oversight ..................................................................................... 41 
11 References/Bibliography ............................................................................................................. 46 
12 Appendices ................................................................................................................................. 47 
12.1 
Revision History................................................................................................................ 48 
7.3.4 ITP Monthly Visits Days 141 and 169 (± 3 days) ............................................................................48 
7.3.2.3 ITP Day 57 Only ...........................................................................................................................49 
7.3.3.3 ITP Day 113 only ..........................................................................................................................49 
12.2 
The 2016 WHO Diagnostic Criteria for ET (Arber et al., 2016) ....................................... 50 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
12.3 
Criteria for Intolerance/Resistance to Hydroxyurea ....................................................... 50 
12.4 
ELN Response Criteria for ET (Barosi et al, 2013) ......................................................... 51 
12.5 
Eastern Cooperative Oncology Group (ECOG) Performance Status Scale ................. 52 
12.6 
MPN-SAF Symptoms/Quality of Life ................................................................................ 53 
12.7 
Bone Marrow Fibrosis Grading ........................................................................................ 55 
12.8 
Adverse Event Tracking Log ............................................................................................ 56 
12.9 
Data Collection and Submission ..................................................................................... 57 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
1 
Abbreviations 
AE 
Adverse Event 
AML 
acute myelogenous leukemia 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ATP 
Additional Treatment Period 
ATRA 
all-trans retinoic acid 
CBC 
complete blood count 
CR 
complete remission 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose limiting toxicity 
DNA 
deoxyribonucleic acid 
Dpi 
dose of pharmacodynamic inhibition; 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 
DSM 
Data Safety Monitoring 
DSMB 
Data Safety Monitoring Board 
DSMC 
Data Safety Monitoring Committee 
DSMP 
Data Safety and Monitoring Plan 
Ds 
starting dose 
DQA 
Director of Quality Assurance 
ECOG 
Eastern Cooperative Oncology Group 
ELN 
European Leukemia Net 
EPO 
erythropoietin 
ET 
early termination 
ET 
Essential Thrombocythemia 
EoS 
End of Study 
EoT 
End of Treatment 
FDA 
Food and Drug Administration 
G-CSF 
gram colony stimulating factor 
GCP 
Good Clinical Practice 
GM-CSF 
granulocyte-macrophage colony stimulating factor 
GMP 
Good Manufacturing Practice 
H 
histone 
Hy 
hypothesis 
Hb 
hemoglobin 
HU 
hydroxyurea; hydrea®, hydroxycarbamide 
IB 
Investigator’s Brochure 
IIT 
Investigator Initiated Trial 
IL 
interleukin 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IPSET 
International Prognostic Score for Thrombosis in Essential Thrombocythemia 
IRB 
Institutional Review Board 
ITP 
Initial Treatment Period 
JAK 
Janus kinase 
K 
lysine 
KD 
knockdown 
KDM1A 
lysine-specific demethylase 1 
LPE 
limited physical examination 
LSD1 
lysine-specific demethylase 1 
MAOIs 
monoamine oxidase inhibitors 
MDS 
myelodysplastic syndromes 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
MEP 
megakaryocyte-erythroid progenitor 
MF 
myelofibrosis 
MPN 
myeloproliferative neoplasms, myeloproliferative diseases 
MPN-SAF 
Myeloproliferative Neoplasm Symptom Assessment Form 
NIH 
National Institutes of Health 
NCI 
National Cancer Institute 
NOAEL 
no-observed-adverse-effect-level 
NSAID 
non-steroidal anti-inflammatory drug 
OSP 
Office of Sponsored Programs (UTHSA) 
PALS 
Priority of Audit Level Score 
PD 
pharmacodynamics 
PE 
physical examination 
PI 
Principal Investigator 
PK 
pharmacokinetics 
PMF 
primary myelofibrosis 
PR 
partial remission 
PSD 
Pharmacokinetic Sampling Department 
PV 
polycythemia vera 
RNA 
ribonucleic acid 
SAE 
Serious Adverse Event 
STAT 
Signal Transducer and Activator of Transcription 
TSS 
Total Symptom Score; is derived from the MPN-SAF 
UPIRSO 
Unanticipated Problem Involving Risks to Subjects or Others 
UTHSA 
UT Health San Antonio 
WOCBP 
Women of child-bearing potential 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
2 
Study Synopsis 
 
Protocol Title: AN INVESTIGATOR INITIATED PHASE 2 TRIAL OF LSD1 INHIBITOR IMG-7289 
(BOMEDEMSTAT) IN ESSENTIAL THROMBOCYTHEMIA 
Protocol No:CTMS#19-0078, NCT04081220 
Investigator/Study Centers: Single site institutional study at the Mays Cancer Center in San Antonio, TX. 
Study Objectives/Hypotheses: We propose to determine the effects of IMG-7289 (Imago BioSciences, 
Inc.’s bomedemstat), an irreversible inhibitor of the enzyme lysine-specific demethylase 1 (LSD1, or 
KDM1A) as a treatment of essential thrombocythemia (ET). ET is an indolent hematologic cancer 
characterized by reduced quality of life, thrombocytosis, elevated cytokines, and increased rates of 
thrombosis and bleeding that can evolve to myelofibrosis and/or acute myeloid leukemia. LSD1 is an 
enzyme that regulates the maturation of megakaryocytes from progenitor cells, as well as the function of 
mature megakaryocytes. In ET, acquired mutations cause JAK/STAT activation which results in an over- 
abundance of activated megakaryocytes that in turn produce an excess of platelets, growth factors and 
inflammatory cytokines. The primary hypothesis is that pharmacologic inhibition of LSD1 will reduce both 
the number of megakaryocytes and their capacity to secrete growth factors and inflammatory cytokines to 
the clinical benefit of ET patients. 
Study Aims and Hypotheses (Hy): 
Aim 1. To assess the hematologic effects of IMG-7289 in a population of ET patients requiring platelet 
control who are resistant to or intolerant of hydroxyurea per ELN criteria. 
Hy1: IMG-7289 will induce complete hematologic response in >10% of this study population by 24 weeks. 
Aim 2: To qualitatively examine markers of disease burden including patient-reported symptom burden, 
standard ARUP testing of mutant (variant) allele burden in granulocytes (baseline and Week 24), spleen 
size, and bone marrow histology. Hy2: ET patients treated with IMG-7289 will experience improved 
symptom burden, reduced mutation allele burden, improved spleen size if enlarged at baseline, and reduced 
megakaryocyte hyperplasia following the 24-week treatment course. 
Investigational Drug: The active drug substance is identified as IMG-7289 (bomedemstat). IMG-7289 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. 
IMG-7289 will be supplied as capsules in multiple strengths. These strengths, based on IMG-7289 free 
base, i.e., the active substance, may include: 5 mg, 10 mg, 25 mg, and 50 mg. Capsule strengths provided 
may change throughout the duration of the study. 
Study Population: Twenty patients eighteen years of age or older with hydroxyurea resistant or intolerant 
ET per ELN criteria will be treated. 
Duration of Participation: Study participants will initially be treated in the study for 24 weeks. If 
participants are deriving clinical benefit from IMG-7289, the drug can be continued for an additional 24 
weeks; this is an iterative process and may repeat indefinitely if there is clinical benefit in the absence of 
excess toxicity. 
Methodology: This is a single-center, open-label investigator-initiated trial evaluating the effects of 
IMG-7289 administered orally once daily in patients with essential thrombocythemia. Preclinical testing of 
LSD1 inhibition in myeloproliferative neoplasm models induced apoptosis in mutant stem/progenitor cells, 
reduced inflammatory cytokines, reduced spleen length, decreased bone marrow fibrosis, and reduced 
extramedullary hematopoiesis. Additionally, LSD1 inhibition with IMG-7289 was shown in a Jak2V617F mouse 
model of ET/polycythemia vera (PV) to selectively decrease the number of malignant megakaryocytes as 
well as reduce elevated platelets, red cells, and granulocytes (Jutzi et al. 2018). To date, IMG-7289 has 
been investigated in acute myeloid leukemia, myelodysplastic syndrome, and myelofibrosis patients, with 
notable changes in the myelofibrosis population including dose-dependent decreases in IL-8, platelets, and 
neutrophils. This Phase 2 prospective single arm study is the first proposed study to determine the 
hematologic effects of IMG-7289 in a population of ET patients. The primary aim of this study is to 
determine the effects of IMG-7289 in a population of ET patients requiring platelet control who are resistant 
to or intolerant of hydroxyurea, per ELN criteria, over a period of 24 weeks. Secondary aims are to explore 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
the effects of IMG-7289 on disease-related symptom burden, mutant (variant) allele burden in granulocytes, 
spleen size, and bone marrow histology. If successful, this study will help to meet an unmet need for 
therapeutic interventions that reduce thrombocytosis and improve symptom burden among individuals with 
HU-resistant or intolerant ET per ELN criteria. 
The therapeutic goal for the treatment of ET is to inhibit the activity of LSD1 in hematopoietic cells for only a 
fraction of the 24-hour dosing cycle, sufficient to reduce the production of platelets and granulocytes whose 
over-production characterizes this condition. Considerations leading to the choice of a safe starting dose 
include chronic toxicology studies in conjunction with the clinical experience of the eighty-five patients who 
have received IMG-7289 to date in IMG-7289-CTP-101 and -102. Using all available information in 
conjunction with the therapeutic goal for the treatment of ET, the starting dose of IMG-7289 of 0.6 mg/kg QD 
has been selected to enable ET patients to reach the optimum dose sufficient to reduce platelets below 
400 k/μL while still maintaining an adequate safety margin. 
Study Conduct: This study consists of two treatment periods: the Initial Treatment Period (ITP), followed 
by the Additional Treatment Period (ATP). In the ITP, patients will be treated daily for 169 days. The ATP 
offers treatment to qualifying patients for additional 169 day cycles for those patients deriving clinical benefit, 
as determined by the Principal Investigator. 
During the ITP, patients will initially return for study assessments weekly for the first 8 weeks (ITP Days 8, 
15, 22, 29, 36, 43, 50 and 57), at least bi-weekly for 8 weeks with the start of video visits every other 
assessment point if deemed applicable by the Principal Investigator (ITP Days 71, 85, 99 and 113) and then 
monthly for 8 weeks (ITP Days 141 and 169). It is anticipated that by Week 8 (Day 57) patients will have 
achieved a stable dose, with weekly visits no longer necessary. For safety purposes, weekly visits may 
continue at the PI’s discretion (note: bi-weekly visits may also continue post Week 16 (Day 113)) if 
necessary. On Day 169 bone marrow sampling is also required. At the Day 169 visit, a ‘qualification’ 
assessment will be made to determine whether the patient is deriving clinical benefit and safely tolerating 
IMG-7289. Such patients qualify for entry into the ATP, a transition which should occur without interruption 
in dosing. Patients not deriving clinical benefit, or who achieve complete remission (CR) or partial remission 
(PR) and subsequently relapse (Section 12.4) the equivalent of treatment failures, will discontinue IMG-7289 
and undergo End of Treatment (EoT), pre-End of Study (pre-EoS) and End of Study (EoS) visits. 
In the ATP, treatment may continue for an additional 169 days in those patients deriving clinical benefit, as 
determined by the Principal Investigator. Qualifying patients will return for study assessments monthly (ATP 
Days 1, 29, 57, 85, 113, 141 and 169). It is anticipated that patients continuing in the ATP will have already 
achieved a stable dose, with bi-weekly visits no longer necessary. For safety purposes, bi-weekly visits may 
continue at the PI’s discretion, if necessary. Optional on every other Day 169 (i.e., ATP2 Day 169, ATP4 
Day 169) for as long as the patient continues to qualify for treatment, patients will undergo bone marrow 
sampling. At the Day 169 visit, a ‘qualification’ assessment will be made to determine whether the patient is 
continuing to derive clinical benefit. Such patients thereby qualify for re-entry into the ATP, which is iterative; 
patients may continue to receive IMG-7289 for as long as they continue to qualify. 
Patients will be followed closely throughout the study for both Adverse Events (AEs) and signs of toxicity by 
frequent monitoring of clinical signs and symptoms as well as safety labs. Pharmacodynamic effects will be 
closely monitored by frequent hematology assessments of peripheral blood, and optional requisite bone 
marrow aspirates (optional in the ATP period only) and biopsies. Throughout dosing, transfusions may be 
administered if needed in accordance with standard institutional guidelines. 
IMG-7289 Dosing: 
Initial Treatment Period (ITP): All patients will be treated daily, for up to 169 days of dosing. Treatment will 
begin on Day 1 at the starting dose (Ds) of 0.6 mg/kg QD. Details on the selection and rationale for the 
starting dose and dosing schedule can be found in Sections 3.4 and 3.5. 
Through the use of dose titration, all patients will be dosed to the IMG-7289 Dpi; the dose needed to safely 
inhibit normal thrombopoiesis for a fraction of the dosing cycle. Dose-titration, both upward and downward, is 
contingent on the hematology assessment and comparison of hematology values from the prior study visit. 
 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Up-titrations may begin on ITP Day 29 and occur no more frequently than every 4 weeks from the previous 
up- or down-titration. Down-titrations can be made at any time in the best interest of the patient. Up- 
titrations will be made in increments of 0.2 mg/kg/d and down-titrations in decrements of 0.1 or 0.15 mg/kg/d. 
 
The dose of pharmacodynamic inhibition (Dpi) is anticipated to be approximately 2 mg/kg 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 target platelet count range for dose titrations expected to be 
associated with a clinically significant therapeutic effect is: ≥ 200 to ≤ 400 k/μL (200-400 x 109/L). 
Titration and re-challenge rules based on evaluation of platelet, absolute neutrophil (ANC) and hemoglobin 
(Hb) counts are noted below. 
 
Titration and Re-challenge Rules 
Important: ANC ≥0.5x109/L (500 neutrophils /µL) is needed for up-titration. For an ANC below this 
threshold, the current dose should be maintained or down-titrated in accordance with the rules 
detailed below. 
Hematology Assessment 
Titration and Re-challenge Rules 
Plt Count (x 109/µL) 
Hb Level (g/dL) 
Titration?* 
Titration Rule* 
Re-challenge Rule¥ 
> 400 
≥ 10 
Up-titrate¤ 
Increase by 
0.2 mg/kg/d¤ 
N/A 
≥ 200 - ≤ 400 
≥ 10 
Maintain current 
dose 
N/A 
N/A 
50-199 
≥ 10 
Down-titrate 
Decrease by 
0.1 mg/kg/d 
N/A 
N/A 
8.5 to <10 
Down-titrate 
Decrease by 
0.15 mg/kg/d 
N/A 
< 50 
<8.5 
HOLD DOSEɸ 
N/A 
At 50% of prior dose** when: 
- platelets return to ≥ 100 
- Hb returns to ≥8*** 
¤ 
Up-titrations may begin on ITP Day 29 and occur no more frequently than every 4 weeks from the previous 
up- or down-titration. Down-titrations can be made at any time in the best interest of the patient. 
ɸPatients requiring a dose hold should have complete blood counts monitored at least weekly for safety purposes and to 
enable re-challenge to commence as soon as counts return to the required level, if safe to do so. 
*The PI may, upon review of individual patients and patient responses, recommend up- or down-titrations that are not in 
concordance with the above. 
** Re-challenge at 50% of the previous mg/kg dose. 
***PRBC transfusions allowed if at 0.15 mg/kg/d down-titrated dose level transfusions requirement remains stable within 2 
units per month, and no more than 4 units total per 28 days, and patient otherwise has evidence of clinical benefit. 
¥ Upon re-challenge, all of the above rules reapply. 
 
Additional Treatment Period (ATP): Qualifying patients will ‘re-start’ IMG-7289 on ATP Day 1, with dose 
titration continuing as per the Titration Rules table above; there should be no interruption in dosing (i.e., Day 
169 = Day 1 of new ATP). Additional dose-titration may occur in consultation with the Principal Investigator. 
Study Duration: Screening procedures may commence up to 28 days prior to the start of treatment. 
Patients may initially receive up to 24 weeks of dosing while on study. Patients will be followed for 28 days 
post last dose. Therefore, the anticipated duration of participation in the study is expected to be 
approximately 32 weeks from first patient-first visit to last patient-last visit. Additional treatment may be 
given, contingent on an assessment of patient benefit for multiple repeating ATPs 
Study Assessments: The assessments outlined below are also summarized in Section 7 and in the 
Schedule of Assessments Sections 7.7 and 7.8. 
The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) will be completed at Screening 
(as close to Day -7 as possible) and once weekly from Day 1 through the End of Study (EoS) Visit (Appendix 
12.6). Multiple questionnaires will need to be provided to the patient for completion as visit schedule 
decreases over time. 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
ECOG Performance Status will be performed at Screening, and on Days 85 and 169 of the ITP, on Day 169 
of the ATP for as long as the patient continues to qualify, at EoT, EoS/ET, and upon suspicion of relapse. 
Adverse events (AEs) will be assessed at every visit post first IMG-7289 dose through the EoS visit. 
Physical Examinations (PE): a Full Physical Exam, including height, weight, vital signs and spleen 
measurement will be performed at Screening. Limited Physical Exams (LPE) will be performed weekly for 
8 weeksand then monthly throughout the study, unless deemed to be needed more frequently by PI. Limited 
PEs include weight, vital signs, a review of body systems to assess change from previous PE, and spleen 
measurement. The edge of the spleen shall be determined by palpation, measured in centimeters, using a 
soft ruler, from the costal margin to the point of greatest splenic protrusion. The spleen should be measured 
in the same manner at all visits ideally by the same examiner. 
Serum pregnancy testing will be performed for women of child-bearing potential (WOCBP) at Screening and 
pre-dose on Day 1, and if pregnancy is suspected while the patient remains on-study. 
Bone marrow aspirate* and biopsy will be performed**: 
• 
At Screening (no more than 28 days prior to the first IMG-7289 dose). 
• 
At ITP Day 169 visit. 
• 
Optional at approximately every 12 months thereafter, at ATP Day 169 of every other Additional 
Treatment Period (i.e., ATP2, ATP4), for as long as the patient continues to qualify for treatment. 
*Marrow from the first pull whenever possible, but no later than the second pull, is required. 
**The total number of bone marrow evaluations required during the Initial Treatment Phase is 2 in ~32 weeks. 
Additional marrow evaluation is required only if the patient agrees to the optional time points in the Additional Treatment 
Phase. 
Clinical laboratory measures: The following laboratory measures will be performed at Screening, pre-dose 
Day 1, upon suspicion of relapse, at the EoT, pre-EoS, and EoS/ET visits and in accordance with below: 
• 
Biochemistry - monthly throughout the study (i.e., Days 29, 57, 85, 113, 141 and 169) 
• 
Hematology with manual differential - at every clinic visit throughout the study 
• 
C-Reactive Protein - monthly throughout the study (i.e., Days 29, 57, 85, 113, 141 and 169) 
The following laboratory measures will be performed at Screening: 
• 
Coagulation 
The following laboratory measures will be performed at Screening, Week 24 and upon suspicion of relapse: 
• 
Testing of mutant (variant) allele burden in granulocytes 
Qualification Assessments: 
• 
Initial Treatment Period Day 169: Assess whether the patient is eligible for the ATP. If it is 
determined that the patient is deriving clinical benefit and safely tolerating IMG-7289, then the patient 
qualifies for and may enter the ATP upon completion of the Day 169 visit 
• 
Additional Treatment Period Day 169: Assess whether the patient continues to be eligible for the 
ATP. If it is determined that the patient is deriving clinical benefit and safely tolerating IMG-7289, 
then the patient qualifies for and may re-enter the ATP upon completion of the Day 169 visit. 
Titration Assessment: At every visit following Day 1 patients will be assessed for dose titrations using the 
titration and re-challenge rules in Table 1. 
• 
Up-titrations may occur no more frequently than every 4 weeks from the previous up- or down- 
titration 
• 
Down-titrations are permitted at any time in the patient’s best interest. 
 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Eligibility Criteria: Patients must meet all applicable Inclusion and none of the Exclusion Criteria. 
Inclusion criteria are as follows: 
1. Age ≥18 years. 
2. Diagnosis of Essential Thrombocythemia per World Health Organization (WHO) diagnostic criteria for 
myeloproliferative neoplasms (Arber et al., 2016). 
3. Patients who are intolerant or resistant to hydroxyurea per ELN criteria, or in the Investigator’s judgment 
are not candidates for available approved therapy. The ELN definitions of resistance/intolerance to HU 
requires the fulfillment of at least one of the following criteria: 
a. Platelet count >600 × 109/L after daily dose of at least 2 g HU for at least 3 months (2.5 g/day in 
patients with a body weight over 80 kg); 
b. Platelet count >400 × 109/L and WBC <2.5 × 109/L at any dose of HU; 
c. Platelet count >400 × 109/L and hemoglobin <10 g/dL at any dose of HU; 
d. Presence of unacceptable HU-related non-hematologic toxicities, including fever, mucocutaneous 
manifestations or leg ulcers. 
4. Requires treatment in order to lower platelet counts based on the Clinically Relevant IPSET-Thrombosis 
Guidelines. 
5. Platelet count >450 x 109/L pre-dose Day 1. 
6. Peripheral blast count ≤5% pre-dose Day 1. 
7. ANC ≥0.5 x 109/L pre-dose Day 1. 
8. Fibrosis Score <grade 2, as per a slightly modified version (Arber et al., 2016) of the European 
Consensus Criteria for Grading Myelofibrosis, (Thiele et al., 2005). 
9. Life expectancy > 36 weeks. 
10. Able to swallow capsules. 
11. Amenable to spleen size determination, bone marrow evaluations (during the ITP only and optional in 
the ATP), and peripheral blood sampling during the study. 
12. Must have discontinued ET therapy at least 2 weeks (4 weeks for interferon) prior to study drug 
initiation. 
13. Agrees to use an approved method of contraception from Screening until 28 days after last 
administration of the study drug. Acceptable methods of birth control include: birth control pills, depo- 
progesterone injections, a vaginal hormonal contraceptive ring, a barrier contraceptive such as a 
condom with spermicide cream or gel, diaphragms or cervical cap with spermicide cream or gel, or an 
intrauterine device (IUD). 
14. If male, agrees not to donate sperm or father a child for at least one month after the last dose of the 
study medication. 
Exclusion criteria are as follows: 
1. Greater than 3 separate transfusion episodes over the last 6 months and/or any transfusion over the 
last 4 weeks. 
2. Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater. 
3. Currently pregnant or planning on being pregnant in the following 6 months or currently breastfeeding. 
4. Currently residing outside the United States. 
5. History of splenectomy. 
6. Unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1). 
7. Uncontrolled active infection. 
8. Known positive for HIV or infectious hepatitis, type A, B or C. 
9. Current use of monoamine oxidase A and B inhibitors (MAOIs). 
10. Evidence at the time of screening of increased risk of bleeding, including any of the following: 
a. Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal 
b. International normalized ratio (INR) >1.3 x the local upper limit of normal 
c. Known Acquired Von Willebrand’s disorder. 
 
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GUIDELINES: These guidelines are for use by the Investigator, study staff and patient to safeguard patient 
safety while maintaining data integrity. 
1. In general, supportive care (transfusions, administration of anti-fungals, etc.) should be maintained in 
accordance with institutional policy. Additionally: 
a. It is advised that patients with a platelet count ≤ 10 x 109/L (10,000/μL) be transfused. 
2. Patients taking medications that have 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. Cessation of IMG-7289 is invariably associated with a rebound in thrombopoiesis and platelet counts may 
easily exceed the baseline value. When IMG-7289 is discontinued, the platelet count should be monitored 
closely and an alternative cytoreductive therapy to lower platelets should commence within 24-48 hours. 
PROHIBITED MEDICATIONS/TREATMENTS: The PIs will contact Imago staff with any questions 
pertaining to prohibited medications. 
1. All cytotoxic agents, including standard-of-care therapies for ET 
2. All hematopoietic growth factors: romiplostim, eltrombopag, erythropoietin (EPO), granulocyte colony 
stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) 
3. Monoamine oxidase A and B inhibitors 
4. Anticoagulant and nonsteroidal anti-inflammatory drug (NSAID; including aspirin) use are prohibited in 
patients when their platelet count is < 50 x 109/L (50,000/μL) 
Management of Study Toxicities: Adverse event intensity will be evaluated using the National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, published 
27 November 2017. Please refer to Section 8.2 for additional detail on management of study toxicities, 
including reduction of the starting dose based on DLT. 
Definitions: 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. The 
effects of IMG-7289 on normal myeloid hematopoiesis observed in non-clinical and clinical studies are 
expected in humans; these are pharmacodynamic effects of LSD1 inhibition by IMG-7289, thus are not 
regarded as adverse. These events, with the exceptions below, will not be considered DLTs. 
Dose limiting toxicity (DLT): Any one of the following AEs that occurs through Day 7 of the Initial Treatment 
Period will be considered DLTs unless the Investigator deems the AE to be clearly unrelated to IMG-7289: 
• 
Any Grade 3 or above thrombocytopenia associated with clinically significant bleeding*; 
• 
Any Grade 4 thrombocytopenia associated with a requirement for platelet transfusion; 
• 
Any Grade 4 or 5 non-hematologic adverse event; 
• 
Any Grade 3 or above non-hematologic adverse event with the following exceptions: 
o Nausea, vomiting or diarrhea lasting 3 days or less 
o Aesthenia lasting less than 7 days 
• 
Any Grade 3 electrolyte abnormality unrelated to the underlying malignancy and persisting greater than 
24 hours. 
*A clinically significant bleeding event is defined as an event that is life-threatening, cannot be controlled and/or results 
in hemodynamic instability. 
Patients who experience a DLT may have their dose adjusted downward if the Sponsor Investigator (PI) 
deems it safe for the patient to continue on IMG-7289. Any patient that experiences DLT that results in 
discontinuation of IMG-7289 therapy may begin alternative cytoreductive therapy to lower platelets within 
24-48 hours. 
The SI will contact Imago medical staff to discuss IMG-7289 dose modifications for the management of 
clinically significant changes in platelets, neutrophil counts, or other hematologic parameters. 
 
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Stopping Rules: 
IMG-7289 will be discontinued in the event of the following: 
• 
Post DLT, the Principal Investigator deem it unsafe for the patient to continue on IMG-7289. 
• 
Post dose reduction due to DLT, the patient either worsens at any time or fails to demonstrate significant 
improvement within 14 days. 
• 
Post temporary interruption of IMG-7289 due to platelet counts below 50 x 109/L (50,000/μL), the 
patient's platelet counts don’t return to > 150 x 109/L (150,000/μL) within 21 days. 
• 
Any Grade 4 non-hematologic adverse event with failure to recover to Grade 3 within 7 days of 
drug cessation. 
Study Design: This study will follow a Simon two-stage design with an anticipated lower limit response rate 
of 10% and a target response rate of >40%. With these parameters, the optimal Simon design with α=0.05 
and 90% power would need 9 patients in the first stage and 11 patients in the second stage. After testing 
oral IMG-7289 on 9 patients in the first stage, the trial will be terminated if 1 or fewer respond. If the trial 
goes to the second stage, a total of 20 patients will be enrolled. If the total number responding is less than 
or equal to 4, oral IMG-7289 will be rejected; if the total number responding is more than 4, oral IMG-7289 
will be considered worthy of further study. 
 
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3 
Background 
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). 
 
ET is an indolent hematologic cancer characterized by reduced quality of life, thrombocytosis, elevated 
cytokines, an increased rate of thrombosis and bleeding and the potential to develop myelofibrosis and acute 
myeloid leukemia (Vannucchi et al. 2017). Transformation to post-ET myelofibrosis and post-ET acute 
leukemia occurs at a rate of 4–11% and 2.1–5.3% at 15 years, respectively (Cerquozzi and Tefferi, 2015). 
Risk factors for poor survival include age over 60, leukocytosis, and a prior history of thrombosis (Barbui et al., 
2012). Indications for pharmacologic treatment in ET include extreme thrombocytosis, elderly age, JAK2V617F 
mutational status, and history of thrombosis or presence of cardiovascular risk factors (Rumi et al., 2017). 
Standard first-line pharmacologic treatment to reduce thrombocytosis is hydroxyurea (HU) which has a low 
incidence of acute toxicity but is regarded by some as mutagenic. However, approximately 20-25% of ET 
patients will be resistant or intolerant of HU per ELN criteria and treatment with HU has been demonstrated to 
worsen symptom burden (Sever et al., 2014; Geyer et al., 2015). Thus, there remains unmet need for 
therapeutic interventions that reduce thrombocytosis and improve symptom burden among individuals with HU- 
resistant or intolerant ET per ELN criteria. 
 
3.2 Study Rationale 
This is an open-label, single-arm, single-site Investigator Initiated Trial (IIT) of the LSD1 inhibitor, IMG-7289. 
ET is characterized by a neoplastic process expanding myeloid lineages including the erythroid progenitor and 
megakaryocyte populations, platelet production and leukocytosis. Growth factors and cytokines synthesized 
by megakaryocytes and granulocytes contribute to symptoms and to bone marrow fibrosis. The disease is 
described as a clonal disorder of hematopoietic stem/progenitor cells that have acquired a somatic mutation 
activating the JAK/STAT pathway. As such, the activated, proliferating megakaryocyte-erythroid progenitor 
and its mature progeny are the pathologic seat of the disease. 
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 a collective term for the association of nuclear macromolecules consisting of 
DNA, protein scaffolding, enzymes enhancing transcription and synthesis of 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). 
LSD1 enzyme activity is essential for the maturation of megakaryocytes and red blood cells from the 
megakaryocyte-erythrocyte progenitor (MEP) cell. In MEPs, LSD1 is recruited to chromatin via the 
transcription factor GFI1b, a protein also essential to MEP differentiation. Genetics studies have shown that 
interference with either GFI1b or LSD1 has similar effects on the maturation of megakaryocytes and production 
platelets. Thus, therapeutically targeting LSD1 effectively reduces megakaryocyte numbers and the growth 
factors and cytokines that drive the secondary clinical effects observed in ET. 
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In myeloproliferative neoplasms including ET, LSD1 is overexpressed in myeloid cell lines including 
megakaryocytes and erythroid precursors (Niebel et al., 2014). LSD1 inhibition has been found to be effective 
in inducing the apoptosis of human Janus kinase (JAK)2V617F cell lines, reducing inflammatory cytokines, 
reducing spleen volumes, decreasing bone marrow fibrosis, and reducing extramedullary hematopoiesis in 
MplW515L or Jak2V617F-mutated murine models. Additionally, LSD1 inhibition with IMG-7289 was shown in a 
Jak2V617F mouse model of ET/PV to selectively decrease the number of malignant megakaryocytes as well as 
reduce elevated platelets, red cells and granulocytes (Jutzi et al., 2018). Toxicologic studies in rat and dog 
demonstrated a decreased red blood cell mass, platelet and neutrophil counts in a dose-dependent manner. 
LSD1 is known to participate in the maintenance of the self-renewal potential in stem/progenitor cells as well 
as enhance an interferon response in malignant cells. Whether the inhibition of LSD1 with IMG-7289 can 
gradually reduce the mutant cell burden as was observed in mice remains to be seen in patients. 
Our proposed study is innovative in that it is the first study to determine the effects of IMG-7289 in a population 
of ET patients. This study will (a) provide data on the utility of IMG-7289 in the reduction of platelet counts in 
patients that have relapsed or are resistant to or intolerant of HU per ELN criteria, (b) determine the effects of 
IMG-7289 on disease-related markers including biomarkers and symptom burden with the aim of filling an 
unmet need in the management of ET. 
At the doses proposed in this study, IMG-7289 is cleared in less than 24 hours allowing LSD1 activity to return 
and resume its function in normal hematopoiesis. Chronic daily administration of IMG-7289 in rat, dog and 
humans has been well tolerated. No safety signals have been observed in either the AML/MDS or 
myelofibrosis studies with IMG-7289 at doses up to 6 mg/kg/d. 
 
3.3 Background on IMG-7289 
LSD1 is a component of chromatin-modifying complex that alters the transcriptional activity of enhancers and 
transcription factors themselves (Rudolph et al., 2013). Hematopoietic cells require LSD1 for stem cell 
maintenance and for progenitor differentiation in the granulopoietic, thrombopoietic, and erythropoietic lineages 
(Kerenyi et al., 2013). In myeloproliferative neoplasms including ET, LSD1 is overexpressed in myeloid cells 
including megakaryocytes/ erythroid progenitors (Niebel et al., 2014). LSD1 inhibition induced apoptosis in 
mutant stem/progenitor cells, 
reduced inflammatory cytokines, 
reduced spleen volumes, 
decreased bone marrow fibrosis, 
and reduced extramedullary 
hematopoiesis in MplW515L 
JAK2V617F-mutated murine models 
of MPNs (Imago Investigator 
Brochure). Long-term toxicologic 
studies in rat and dog 
demonstrated the expected 
pharmacodynamic effects of 
decreased red blood cell mass, 
platelet and neutrophil counts in a 
dose-dependent and reversible manner 
(Figure 1). 
Figure 1. Dose-dependent decrease in platelet counts observed in male 
and female rats treated with IMG-7289 for 13 weeks. 
 
3.4 Rationale for and Safety of the Proposed Starting Dose 
The primary scientific goals of the study are to determine the hematologic effects of IMG-7289 in ET patients, 
and to establish the safety of dose titration based on periodic hematology evaluations and the impact of 
inhibiting LSD1 for a fraction of the dosing cycle (24 hours) sufficient to reduce the production of platelets. 
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The proposed protocol includes patients with ET who have failed at least one standard therapy (failure is the 
equivalent of inadequate response or intolerance). The therapeutic goal for the treatment of ET is to inhibit the 
activity of LSD1 in hematopoietic cells for only a fraction of the 24-hour dosing cycle, sufficient to reduce the 
production of platelets whose over-production characterizes the condition. 
Considerations for a safe and therapeutic starting dose include chronic toxicology studies in conjunction with 
the clinical experience of the patients who have received IMG-7289 to date in IMG-7289-CTP-101 and -102. In 
the CTP-101 protocol, IMG-7289 was administered to patients with high-risk AML and MDS; the therapeutic 
thesis in that study was to completely inhibit LSD1 in all hematopoietic cells, recognizing patients would need 
clinical support for cytopenias. The starting dose was 0.75 mg/kg/d and the effective dose, at which no safety 
signals have been observed, was deemed 6.0 mg/kg/d. Though the great majority of the patients entered the 
study with Grade 3/4 thrombocytopenia, patients at all dose levels of IMG-7289 required platelet transfusions. 
This sensitivity of thrombopoiesis to LSD1 inhibition in high-risk AML/MDS patients reflects the generally 
compromised nature of the bone marrow, including the reduction of megakaryocytes, in that disease. 
Taking this observation into account in association with the therapeutic goal for the treatment of 
myeloproliferative neoplasms -- inhibiting LSD1 activity in hematopoietic cells for only a fraction of the 24-hour 
dosing cycle -- and PK modeling, the original starting dose in the CTP-102 protocol for myelofibrosis patients 
was 0.25 mg/kg/d. Platelet counts in the first twenty patients ranged from 102 to 1039 k/μL and all required a 
dose increase to lower platelet counts. In a recent analysis of the ongoing IMG-7289-CTP-102 study in 
myelofibrosis patients, the daily dose of IMG-7289 needed by a majority of patients to achieve a platelet count 
in the target range (50-75 k/uL) ranged between 0.6 to 0.8 mg/kg/d with the full dosing spectrum of 0.4-1.5 
mg/kg. The dose needed to reduce the platelet count to the target range in patients with myelofibrosis was not 
correlated with the starting platelet count or the antecedent hematologic history. Platelet counts in patients 
with ET will, on average, be significantly higher than those in patients with myelofibrosis who have failed 
treatment with the standard of care. Notwithstanding, the kinetics of changes in platelet counts in patients with 
ET treated with IMG-7289 are expected to be similar to those patients with myelofibrosis. Accordingly, to 
enable ET patients to reach the optimum dose sufficient to reduce platelets below 400 k/μL while still 
maintaining an adequate safety margin, an IMG-7289 starting dose of 0.6 mg/kg QD has been selected. 
Collectively, these studies established some key points. First, inhibition of LSD1 for a fraction of the 24-hour 
dosing cycle can be achieved safely. Second, the platelet count can be targeted to a specific range by 
adjusting the dose of IMG-7289. 
 
To meet the eligibility criterion for enrollment, ET patients must have a platelet count above 450 k/μL. The 
therapeutic target platelet count is between 200 and 400 k/μL. Based on previous clinical experience in 
patients (all with compromised hematopoiesis), a starting dose (Ds) of 0.6 mg/kg, or 42 mg QD for a 70 kg 
patient, is deemed safe in a patient population characterized by an excess of platelets. Dose adjustments in 
increments and decrements of between 0.2, 0.1 and 0.15 mg/kg will allow up- or down-titration of IMG-7289 to 
achieve the target platelet count (Table 1). Hematology assessments will ensure safety and guide dose 
adjustments, which may be made in accordance with the rules detailed in Section 6.2. 
 
3.5 Justification of the Dose and Regimen 
The phenotypic effects of LSD1 inhibition are mediated through changes in the gene expression patterns that 
are a consequence of transcriptional reprogramming that occurs in the absence of LSD1 activity (Harris et al., 
2012). The phenotypic consequences are cell-specific, include differentiation and, ultimately, cell death. In the 
primary pharmacology studies with IMG-7289, these changes take place over a period of days to weeks; in the 
assay for self-renewal potential (clonogenicity), these changes take days or weeks to observe. Complete and 
sustained inhibition of LSD1 may be the best strategy to rapidly reduce the leukemic stem cell burden in the 
case of AML; however, in less aggressive myeloid neoplasms such as ET, chronic treatment at doses that do 
not completely deprive the hematopoietic process of LSD1 activity is anticipated to be well tolerated while 
having a significant impact on disease. In mouse models of myelofibrosis, the gradual loss of cells bearing the 
MPN mutation (Jak2 or Mpl) was observed over the course of modest LSD1 inhibition. What emerges from 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
these mouse studies is a therapeutic strategy that balances safety with clinical efficacy: inhibit the enzyme for 
only a fraction of the 24-hour dosing cycle to allow some normal thrombopoiesis to occur, thus preventing 
profound thrombocytopenia. At this stage of development, this optimal therapeutic dose must be identified in 
each patient because variations in the severity of disease and perhaps other factors will dictate the starting 
platelet count and hence, sensitivity to drug. 
The safety of longer durations of treatment is supported by the 26 and 39-week toxicology studies in rat and 
dog, respectively. Treated animals in which thrombopoiesis is not completely inhibited show no observable 
irreversible adverse effects on hematopoiesis. The primary effects of LSD1 inhibition are confined to the bone 
marrow with expected secondary effects a consequence of cytopenias at higher doses. 
Observations regarding dose-response in patients with MF treated in the CTP-102 study have led to 
modifications of the titration schedule. As additional patients have been treated, it has been noted that for a 
given daily dose, the platelet count continues to fall beyond Day 7 of dosing, i.e., two successive weekly up- 
titrations caused the platelet count to fall more than expected and occasionally led to significant 
thrombocytopenia. In those patients who had received an identical dose for 3 consecutive weeks, each 
experienced a drop (mean -31%; N=20) in the platelet count between Day 7 and Day 14. The mean decrease 
in platelet counts from Day 14 and Day 21, however, was approximately -12%, suggesting that a steady state 
of drug exposure, LSD1 activity and platelet production occurs between Day 21 and Day 28. As such, it 
appears that two or three weeks between up-titrations is an insufficient amount of time for both the plasma 
concentrations of the drug and platelet production to reach a new steady-state necessary to achieve a stable 
platelet count. Therefore, up-titrations may occur no more frequently than every four weeks from the previous 
up- or down-titration. Down-titrations can occur at any time in best interest of the patient. 
 
At the doses proposed in this study, the concentration of IMG-7289 is sufficient to inhibit hematopoiesis for a 
fraction of the 24-hour dosing period, thus allowing LSD1 activity to return and resume its function in normal 
thrombopoiesis. Chronic daily administration of IMG-7289 in rat, dog and humans has been well tolerated. No 
safety signals have been observed in either the AML/MDS or myelofibrosis studies with IMG-7289 at doses up 
to 6 mg/kg/d. Please refer to the Investigator’s Brochure for additional information on the non-clinical 
and clinical studies conducted to date with IMG-7289. 
 
 
4 
Statement of Study Objectives 
4.1 Study Aims and Hypotheses 
Aim 1. To assess the hematologic effects of IMG-7289 in a population of ET patients requiring platelet control 
who are resistant to or intolerant of hydroxyurea per ELN criteria. 
Hy1: IMG-7289 will induce complete hematologic response in >10% of this study population by 24 weeks. 
 
Aim 2: To qualitatively examine markers of disease burden including patient-reported symptom burden, 
standard ARUP testing of mutant (variant) allele burden in granulocytes (baseline and Week 24), spleen size, 
and bone marrow histology. 
Hy2: ET patients treated with IMG-7289 will experience improved symptom burden, reduced mutation allele 
burden, improved spleen size if enlarged at baseline, and reduced megakaryocyte hyperplasia following the 
24-week treatment course. 
 
4.2 Endpoints 
4.2.1 Primary Endpoint 
• 
Determine the proportion of patients who achieve complete hematologic remission at Week 24 using 
ELN response criteria for ET (Barosi et al., 2013), as per protocol appendix 12.4. 
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4.2.2 Secondary Endpoints 
• 
Determine the proportion of patients who achieve a reduction from baseline in TSS derived from the 
MPN-SAF at any time-point within the course of the 24-week study. 
• 
Determine the proportion of patients who achieve a reduction in spleen length for patients with palpable 
splenomegaly (>5 cm below the left costal margin) at any time point over the course of the 24-week 
study. 
• 
Among patients harboring a JAK2V617F mutation, determine the proportion of patients who achieve a 
>25% change in mutant allele burden from baseline to Week 24. 
• 
Assess if there are changes in bone marrow histology between bone marrow biopsies at baseline and 
Week 24. 
5 
Investigational Plan 
5.1 Overview 
This is a single-center, open-label, investigator-initiated trial evaluating the effects of IMG-7289 administered 
orally once daily in patients with essential thrombocythemia (ET). The therapeutic goal for the treatment of ET 
is to inhibit the activity of LSD1 in hematopoietic cells for only a fraction of the 24-hour dosing cycle, sufficient 
to reduce the production of platelets and granulocytes, respectively, whose over-production characterizes the 
condition. Considerations for a safe and therapeutic starting dose include chronic toxicology studies in 
conjunction with the clinical experience of the patients who have received IMG-7289 to date in IMG-7289-CTP- 
101 and -102. Using all of the information available in conjunction with the therapeutic goal for the treatment of 
myeloproliferative neoplasms, an IMG-7289 starting dose of 0.6 mg/kg QD has been selected. Refer to 
Sections 3.4 and 3.5 for additional detail on the rationale for the starting dose and dose regimen. 
This study consists of two treatment periods: the Initial Treatment Period (ITP), followed by the Additional 
Treatment Period (ATP). In the ITP, patients will be treated daily for 169 days. The ATP offers treatment to 
qualifying patients for an additional 169 days. The ATP is iterative and may repeat as long as the patient 
continues to qualify. Patients not deriving clinical benefit, or who achieve complete remission (CR) or partial 
remission (PR) and subsequently relapse (Section 12.4) the equivalent of treatment failures, will discontinue 
IMG-7289 and undergo follow-up. 
 
All patients will undergo follow-up period visits, including an End-of-Treatment (EoT) visit on the day of last 
dose or as soon as possible thereafter, a pre-End-of-Study (EoS) visit approximately 14 days post last dose, 
and an End-of-Study (EoS) visit approximately 28 days post last dose. Patients that do not enter the ATP, or 
discontinue early, will undergo follow-up beginning with an EoT visit. A patient will be considered to have 
completed the study if they have been dosed with IMG-7829 for the full 24 weeks. 
 
Patients will be followed closely throughout the study for both Adverse Events (AEs) and signs of toxicity by 
frequent monitoring of clinical signs and symptoms as well as safety labs. Pharmacodynamic effects will be 
closely monitored by frequent hematology assessments of peripheral blood, and requisite bone marrow 
aspirates and biopsies. Throughout dosing, transfusions may be administered if needed in accordance with 
standard institutional guidelines. 
 
5.2 Initial Treatment Period 
Using dose titration, the dose of IMG-7289 will be adjusted in each patient to that dose that provides sufficient 
exposure to safely inhibit thrombopoiesis for a fraction of the dosing cycle (designated as the Dpi). Treatment 
will begin on Day 1 at the IMG-7289 Ds of 0.6 mg/kg QD for all patients, with dose-titration contingent on the 
comparison of hematology values from the prior visit. Up-titrations may begin on ITP Day 29 and occur no more 
frequently than every 4 weeks from the previous up- or down-titration. Down-titrations can be made at any time 
in the best interest of the patient. Up-titrations will be made in increments of 0.2 mg/kg/d, and down-titrations in 
decrements of 0.1 or 0.15 mg/kg/d. 
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The dose of IMG-7289 needed to reduce platelets to the target range is anticipated to be up to approximately 2 
mg/kg 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 platelet titration target expected to 
be associated with a clinically significant therapeutic effect is: ≥ 200 to ≤ 400 k/μL (200-400 x 109/L). 
During the ITP, patients will initially return for study assessments weekly for the first 8 weeks (ITP Days 8, 15, 
22, 29, 36, 43, 50 and 57), at least bi-weekly for 8 weeks (ITP Days 71, 85, 99 and 113) and then monthly for 8 
weeks (ITP Days 141 and 169). It is anticipated that by Week 8 (Day 57) patients will have achieved a stable 
dose, with weekly visits no longer necessary. For safety purposes, weekly visits may continue at the PI’s 
discretion (note: bi-weekly visits may also continue post Day 113), if necessary. On Day 169 bone marrow 
sampling is required. At the Day 169 visit, a ‘qualification’ assessment will be made to determine whether the 
patient is deriving clinical benefit and safely tolerating IMG-7289. Such patients qualify for entry into the ATP, 
a transition which should occur without interruption in dosing. Patients not deriving clinical benefit, or who 
achieve complete remission (CR) or partial remission (PR) and subsequently relapse (Section 12.4) the 
equivalent of treatment failures, will discontinue IMG-7289 and undergo End of Treatment (EoT), pre-End of 
Study (pre-EoS) and End of Study (EoS) visits. 
 
5.3 Additional Treatment Period for Qualifying Patients Only 
In the ATP, treatment may continue for an additional 169 days in those patients deriving clinical benefit, as 
determined by the Principal Investigator. Qualifying patients will return for study assessments monthly (ATP 
Days 1, 29, 57, 85, 113, 141 and 169). It is anticipated that patients continuing in the ATP will have already 
achieved a stable dose, with bi-weekly visits no longer necessary. For safety purposes, bi-weekly visits may 
continue at the PI’s discretion, if necessary. On Day 169 of every other ATP (i.e., ATP2 Day 169, ATP4 Day 
169) for as long as the patient continues to qualify for treatment, patients will undergo optional bone marrow 
sampling. At the Day 169 visit, a ‘qualification’ assessment will be made to determine whether the patient is 
continuing to derive clinical benefit. Such patients thereby qualify for re-entry into the ATP, which is iterative; 
patients may continue to receive IMG-7289 for as long as they continue to qualify. Patients not deriving clinical 
benefit will discontinue IMG-7289 and undergo EoT, pre-EoS and EoS visits. 
 
5.4 Inclusion and Exclusion Criteria 
5.4.1 Inclusion Criteria 
Inclusion criteria are as follows: 
1. Age ≥18 years. 
2. Diagnosis of Essential Thrombocythemia per World Health Organization (WHO) diagnostic criteria for 
myeloproliferative neoplasms (Arber et al., 2016). 
3. Patients who are intolerant or resistant to hydroxyurea per ELN criteria, or in the Investigator’s judgment 
are not candidates for available approved therapy. The ELN definitions of resistance/intolerance to HU 
requires the fulfillment of at least one of the following criteria: 
o Platelet count >600 × 109/L after a daily dose of at least 2 g HU for at least 3 months (2.5 g/day 
in patients with a body weight over 80 kg); 
o Platelet count >400 × 109/L and WBC <2.5 × 109/L at any dose of HU; 
o Platelet count >400 × 109/L and hemoglobin <10g/dL at any dose of HU 
o Presence of unacceptable HU-related non-hematologic toxicities, including fever, 
mucocutaneous manifestations or leg ulcers. 
4. Requires treatment in order to lower platelet counts based on the Clinically Relevant IPSET-Thrombosis 
Guidelines. 
5. Platelet count >450 x 109/L pre-dose Day 1. 
6. Peripheral blast count ≤5% pre-dose Day 1. 
7. ANC ≥0.5 x 109/L pre-dose Day 1. 
8. Fibrosis Score <grade 2, as per a slightly modified version (Arber et al., 2016) of the European 
Consensus Criteria for Grading Myelofibrosis, (Thiele et al., 2005). 
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9. Life expectancy > 36 weeks. 
10. Able to swallow capsules. 
11. Amenable to spleen size determination, bone marrow evaluations (in the ITP only, optional in the ATPs), 
and peripheral blood sampling during the study. 
12. Must have discontinued ET therapy at least 2 weeks (4 weeks for interferon) prior to study drug 
initiation. 
13. Agrees to use an approved method of contraception from Screening until 28 days after last 
administration of the study drug. Acceptable methods of birth control include: birth control pills, depo- 
progesterone injections, a vaginal hormonal contraceptive ring, a barrier contraceptive such as a 
condom with spermicide cream or gel, diaphragms or cervical cap with spermicide cream or gel, or an 
intrauterine device (IUD). 
14. If male, agrees not to donate sperm or father a child for at least one month after the last dose of the 
study medication. 
5.4.2 Exclusion Criteria 
Exclusion criteria are as follows: 
1. Greater than 3 separate transfusion episodes over the last 6 months and/or any transfusion over the 
last 4 weeks. 
2. Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater. 
3. Currently pregnant or planning on being pregnant in the following 6 months or currently breastfeeding. 
4. Currently residing outside the United States. 
5. History of splenectomy. 
6. Unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1). 
7. Uncontrolled active infection. 
8. Known positive for HIV or infectious hepatitis, type A, B or C. 
9. Current use of monoamine oxidase A and B inhibitors (MAOIs). 
10. Evidence at the time of screening of increased risk of bleeding, including any of the following: 
o Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal 
o International normalized ratio (INR) >1.3 x the local upper limit of normal 
o Known Acquired Von Willebrand’s disorder. 
 
5.5 Guidelines 
These guidelines are for use by the Investigator, study staff and patient to safeguard patient safety while 
maintaining data integrity. 
1. In general, supportive care (transfusions, administration of anti-fungals, etc.) should be maintained in 
accordance with institutional policy. Additionally: 
a. It is advised that patients with a platelet count ≤ 10 x 109/L (10,000/μL) be transfused. 
2. Patients taking medications that have 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. Cessation of IMG-7289 is invariably associated with a rebound in thrombopoiesis and platelet counts may 
easily exceed the baseline value. When IMG-7289 is discontinued, the platelet count should be monitored 
closely and an alternative cytoreductive therapy to lower platelets should commence within 24-48 hours. 
 
5.6 Prohibited Medications/Treatments 
Investigators will contact Imago staff with any questions pertaining to prohibited medications. 
1. All cytotoxic agents, including standard-of-care therapies for ET 
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2. All hematopoietic growth factors: romiplostim, eltrombopag, erythropoietin (EPO), granulocyte colony 
stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) 
3. Monoamine oxidase A and B inhibitors 
4. Anticoagulant and nonsteroidal anti-inflammatory drug (NSAID; including aspirin) use are prohibited in 
patients when their platelet count is < 50 x 109/L (50,000/μL) 
6 
Study Treatment 
IMG-7289, is an irreversible inhibitor of the enzyme LSD1 being developed by Imago BioSciences, Inc. For 
pre-clinical, clinical and formulation information see the most recent Investigator’s Brochure (IB) for IMG-7289. 
The drug product is IMG-7289, a bis-tosylate salt. The free base of IMG-7289 is the active moiety. IMG-7289 
will be supplied to the site pharmacy department by Imago BioSciences (or designee) in bottles containing 
capsules in accordance with all applicable regulatory requirements. The capsule strengths to be provided, 
based on IMG-7289 free base, i.e., the active substance, may include: 5 mg, 10 mg, 25 mg, and 50 mg. 
Additional strengths may be added over the duration of the study. Such details will be included via updates to 
ancillary study documents and not the study protocol. 
The capsules will be manufactured in accordance with Annex 13 and principles of cGMP at: 
Xcelience LLC 
4910 Savarese Circle 
Tampa, FL 33634 USA 
Upon supply to site, labels will be in accordance with all applicable regulatory requirements for the labeling of 
active pharmaceutical ingredients and with Annex 13 of GMP. 
The recommended long-term storage conditions for IMG-7289 is for the storage temperature not to exceed 
25°C. IMG-7289 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 IMG-7289-specific requirements. 
6.1 Dosing and Administration 
Participants will be initiated on a daily oral dose of 0.6 mg/kg/day of IMG-7289. Dose escalation and 
de-escalation rules are detailed below targeting a platelet count of 200 to 400 x 109/L and a hemoglobin of 10- 
13 g/dL via hematology evaluations (evaluations are weekly for the first 8 weeks, bi-weekly for the next 8 
weeks, and then monthly). Up-titrations may begin on ITP Day 29 and occur no more frequently than every 4 
weeks from the previous up- or down-titration. Down-titrations can be made at any time in the best interest of 
the patient. 
Trained personnel will provide instruction pertaining to IMG-7289 administration and supervise the 
administration of IMG-7289 on any day that it is taken in the clinic. With the exception of ITP Day 1 it is not 
required that IMG-7289 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. 
 
IMG-7289 dosing will be based on the patient’s ITP Day 1 weight. If during the study, the patient’s weight 
differs from ITP Day 1 by more than 10%, the amount of IMG-7289 dispensed should be corrected per the 
dose chart provided. In cases where using the ITP Day 1 weight is impractical for dispensing, a weight taken 
as close to ITP Day 1 as possible (e.g., Screening) may be used; weight at a current visit may also 
occasionally need to be used. The source data must clearly document the weight used. 
Patients will be provided supply of IMG-7289 capsules at the time of their visits throughout the study (weekly 
for the first 8 weeks, followed by monthly). There is no additional preparation required. 
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Patients should be instructed to: 
• 
Take their IMG-7289 orally once daily, at approximately the same time 
• 
When possible, take IMG-7289 on an empty stomach (fast for 1 hour prior to and 30 minutes after 
dose). If needed, and at the discretion of the PI, IMG-7289 may be taken with food. 
• 
Swallow their IMG-7289 capsules whole, with an 8oz glass of water 
Patients may have clear liquids prior to and after the fasting periods have been completed. 
6.2 Dosage: Initial Treatment Period 
In the Initial Treatment Period, all patients will be treated daily, for up to 169 days of dosing. Dosing will begin 
on Day 1 at the starting dose, 0.6 mg/kg/d IMG-7289 free base. Details on the selection of and rationale for 
the starting dose and dosing schedule can be found in Section 3.4 and Section 3.5. 
Through the use of dose titration, all patients will be dosed to the IMG-7289 Dpi; the dose needed to safely 
inhibit normal hematopoiesis for a fraction of the dosing cycle. Dose-titration, both upward and downward, is 
contingent on the hematology assessment and comparison of hematology values from the prior visit. 
Up-titrations may begin on ITP Day 29 and occur no more frequently than every 4 weeks from the previous 
up- or down-titration. Down-titrations can be made at any time in the best interest of the patient. 
The Dpi is anticipated to be approximately 2 mg/kg 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 
platelet titration target expected to be associated with a clinically significant therapeutic effect is: 
• 
A platelet count of ≥ 200 to ≤ 400 k/µL (200-400 x 109/L) 
Titration and re-challenge rules based on periodic evaluation of platelet, absolute neutrophil (ANC) and 
hemoglobin (Hb) counts are noted below. 
Table 1: Titration and Re-challenge Rules 
 
Titration and Re-challenge Rules 
Important: ANC ≥0.5x109/L (500 neutrophils/µL) is needed for up-titration. For an ANC below this 
threshold, the current dose should be maintained or down-titrated in accordance with the rules 
detailed below. 
Hematology Assessment 
Titration and Re-challenge Rules 
Plt Count (x 109/L) 
Hb Level (g/dL) 
Titration?* 
Titration Rule* 
Re-challenge Rule¥ 
> 400 
≥ 10 
Up-titrate¤ 
Increase by 
0.2 mg/kg/d¤ 
N/A 
≥ 200 to ≤ 400 
≥ 10 
Maintain current 
dose 
N/A 
N/A 
50-199 
≥ 10 
Down-titrate 
Decrease by 
0.1 mg/kg/d 
N/A 
N/A 
8.5 to <10 
Down-titrate 
Decrease by 
0.15 mg/kg/d 
N/A 
< 50 
< 8.5 
HOLD DOSEɸ 
N/A 
At 50% of prior dose** when: 
- platelets return to ≥ 100 
- Hb returns to ≥8*** 
¤Up-titrations may begin on ITP Day 29 and occur no more frequently than every 4 weeks from the previous 
up- or down-titration. Down-titrations can be made at any time in the best interest of the patient. 
ɸPatients requiring a dose hold should have complete blood counts monitored at least weekly for safety purposes and to 
enable re-challenge to commence as soon as counts return to the required level, if safe to do so. 
*The PI may, upon review of individual patients and patient responses, recommend up- or down-titrations that are not in 
concordance with the above. 
** Re-challenge at 50% of the previous mg/kg dose. 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Titration and Re-challenge Rules 
***PRBC transfusions allowed if at 0.15 mg/kg/d down-titrated dose level transfusions requirement remains stable within 2 
units per month, and no more than 4 units total per 28 days, and patient otherwise has evidence of clinical benefit. 
¥ Upon re-challenge, all of the above rules reapply. 
 
Please consult the Principal Investigator regarding dose modifications of IMG-7289 should an adverse event 
(AE) requiring a dose reduction occur, and also for the management of clinically significant changes in 
platelets, neutrophil counts, or other hematologic parameters. 
 
6.3 Dosage: Additional Treatment Period 
Those patients demonstrating clinical benefit in the absence of toxicity qualify for continued treatment in the 
Additional Treatment Period, which repeats iteratively. For qualifying patients, dose titration will continue as 
per the Titration Rules table (Table 1) above. Additional dose-titration may occur in consultation with the 
Principal Investigator. 
 
6.4 Missed Doses 
Patients who do not take their IMG-7289 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. 
 
6.5 Dose Modification Guidelines 
Adverse event intensity will be evaluated using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0, published 27 November 2017. 
Expected IMG-7289 toxicities based on non-clinical and clinical studies are reported in the latest available 
edition of the Investigator’s Brochure. 
 
6.5.1 Hematologic Toxicities 
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. 
 
Both genetic knockdown (KD) of LSD1 mRNA and pharmacologic inhibition of LSD1 show that the loss of 
LSD1 activity arrests the production of mature red cells, platelets and granulocytes while over-producing 
monocytes (Sprussel et al., 2012; Kerenyi et al., 2013). Production of cells of lymphoid lineage, B and T cells 
is unimpaired indicating that LSD1 has very cell-specific functions and its inhibition also has very specific 
effects. LSD1 inhibition in malignant myeloid cells causes the induction of monocytic differentiation markers, 
as well as a reduction of self-renewal potential of neoplastic cells, all of which eventually result in apoptosis of 
treated cells. Thus, the anemia, thrombocytopenia, neutropenia and monocytosis attending LSD1 inhibition, as 
observed in animals treated with IMG-7289, reflect primary pharmacodynamic effects. The kinetics of anemia, 
thrombocytopenia, and neutropenia following complete LSD1 inhibition are a function of the lifespan of the 
individually affected cell types. Over the course of LSD1 inhibition, platelet and neutrophil counts are the most 
affected, reflecting their short mean lifespans of approximately seven and twelve days, respectively. Recovery 
of peripheral counts is reversible, rapid, and temporarily overshoots baseline hematologic values. At lower 
doses, the effects on hematopoiesis are much less pronounced suggesting that a modicum of residual LSD1 
activity is sufficient to support blood cell formation. Thus, both the duration of LSD1 inhibition as well as the 
degree of inhibition are critical to the pharmacodynamic effects on myeloid lineages. 
The intended dosing plan for ET patients is predicated on the observation that inhibition of LSD1 has a 
therapeutic effect when LSD1 is inhibited for a fraction of the 24-hour dosing cycle. The concentrations of 
IMG-7289 needed to achieve maximal effects on growth, differentiation, and apoptosis in vitro with primary 
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patient-derived malignant myeloid cells as well as JAK2V617F cell lines are similar to concentrations that in vivo 
inhibit red cell, platelet and granulocyte production. It is therefore expected that ET patients will require 
treatment at doses sufficient to reduce platelet counts and hemoglobin counts, respectively, and, to a lesser 
degree, absolute neutrophil counts. These reversible cytopenias can be managed clinically as needed with 
transfusions as well as broad-spectrum antibiotics in the case of febrile neutropenia as are already standard 
practices in the routine management of malignant myeloid diseases. 
 
The effects of IMG-7289 on normal myeloid hematopoiesis observed in non-clinical studies are expected in 
humans; these are pharmacodynamic effects of LSD1 inhibition by IMG-7289, thus are not regarded as 
adverse. These events, with the exceptions below, will not be considered DLTs. 
 
6.5.2 Dose Limiting Toxicities 
DLT is defined as any one of the following AEs per CTCAE version 5.0 criteria that occurs through Day 7 of the 
Initial Treatment Period will be considered DLTs unless the Investigator deems the AE to be clearly unrelated 
to IMG-7289: 
• 
Any Grade 3 or above thrombocytopenia associated with clinically significant bleeding*; 
• 
Any Grade 4 thrombocytopenia associated with a requirement for platelet transfusion; 
• 
Any Grade 4 or 5 non-hematologic adverse event; 
• 
Any Grade 3 or above non-hematologic adverse event with the following exceptions: 
o Nausea, vomiting or diarrhea lasting 3 days or less 
o Aesthenia lasting less than 7 days 
• 
Any Grade 3 electrolyte abnormality unrelated to the underlying malignancy and persisting greater than 
24 hours. 
 
*A clinically significant bleeding event is defined as an event that is life-threatening, cannot be controlled and/or 
results in hemodynamic instability. 
Patients who experience DLT will have their dose adjusted downward by 50% if the Principal Investigator 
deems it safe for the patient to continue on IMG-7289; the titration rules will subsequently be followed. Any 
patient that experiences DLT that results in discontinuation of IMG-7289 therapy may begin alternative therapy 
within 24-48 hours of discontinuation if their physician deems this safe and appropriate regarding the resolution 
of the DLT. 
 
Please consult the Principal Investigator for IMG-7289 dose modifications for the management of clinically 
significant changes in platelets, neutrophil counts, or other hematologic parameters. 
 
6.5.3 Stopping Rules 
IMG-7289 will be discontinued in the event of the following: 
• 
Post DLT, the Investigator deems it unsafe for the patient to continue on IMG-7289. 
• 
Post dose reduction due to DLT, the patient either worsens at any time or fails to demonstrate significant 
improvement within 14 days. 
• 
Post temporary interruption of IMG-7289 due to platelet counts below 50 x 109/L (50,000/µL), the 
patient's platelet counts don’t return to > 150 x 109/L (150,000/µL) within 21 days. 
• 
Any Grade 4 non-hematologic adverse event with failure to recover to Grade 3 within 7 days of drug 
cessation. 
 
Patients who discontinue IMG-7289 will enter follow-up assessments beginning with EoT visit. 
 
6.5.4 Interruption of Dosing 
Patients requiring a Dose Hold according to the Titration and Rechallenge Rules, or due to an (S)AE, should 
be monitored at least weekly for safety purposes and to enable re-challenge to commence as soon as counts 
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return to the required level, if it safe to do so. During these visits, patients are required to undergo complete 
blood counts only. 
 
7 
Study Assessments and Procedures 
This section provides comprehensive detail on the visits and assessments required; this section should serve 
as the main guidance for use during study visits. The Schedule of Events (Sections 7.7 and 7.8) contains 
these details in schematic form and is provided for use in a supportive/reference capacity only. 
Note: If at any time additional clinical evaluation outside of the visit schedule is deemed necessary by the 
Investigator, then unscheduled visits should occur as appropriate. 
 
7.1 Informed Consent 
Patients must provide written informed consent before undergoing any study-related procedures. The Principal 
Investigator (PI), or designee, will explain to the patient the aims of the study, 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 written informed consent for their involvement in the study in the 
presence of the PI, or designee, who will also sign and date the Participant Information Sheet/ Consent Form 
(PISCF). Time, date, name of the person taking consent and any questions raised by the patient must be 
documented in the source data. 
 
7.2 Screening (Day -28 to Day -1) 
• 
Review of all Inclusion and Exclusion Criteria 
• 
Complete medical/medication history including: 
o History of their current disease (see Section 12.2) 
o Calculate ECOG performance status (Section 12.5) 
o History of all treatments for their current disease [including clinical course with hydroxyurea (see 
Section 12.3) and/or other ET therapy] or any previous oncologic conditions; including chemical, 
surgical and/or radiotherapeutic 
o All concomitant medication, in addition to any used in the 15 days prior to Screening 
o Transfusion history, including: the average number of transfusions per month and average volume 
of each transfusion over a 6-month period; and, any transfusions received (RBC, platelets, etc.), 
with approximate volumes, within 30 days prior to Screening 
• 
Full PE, including Vital Signs – review of all body systems as indicated by signs/symptoms 
• 
Spleen length in centimeters for subjects with palpable splenomegaly 
• 
Collect blood for the following Local Laboratory assessments: 
o CBC with manual differential 
o Chem-12 
o Coagulation (PT/INR/aPTT) 
o C-reactive protein 
o Testing of mutant (variant) allele burden in granulocytes 
o Serum pregnancy test for WOCBP 
• 
Bone Marrow Sampling, including additional aspirate for storage 
• 
Collect MPN-SAF as close to Day -7 as possible and provide patient with questionnaire for completion on 
Day 1, prior to or at the start of the visit (i.e., pre-dose) 
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7.3 Initial Treatment Period 
Procedures are presented below for each visit by assessments performed pre-dose, at dosing, and post-dose 
(as applicable). 
7.3.1 ITP Day 1 - Treatment Start 
7.3.1.1 ITP Pre-dose Day 1 
• 
Update medical/medication history with any changes since Screening 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
• 
Collect MPN-SAF and provide patient with questionnaire for completion on Day 8, prior to or at the start of 
the visit 
• 
Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential 
o Chem-12 
o C-reactive protein 
• 
Serum pregnancy test for WOCBP 
• 
Dispense doses sufficient until the next visit and provide Dosing Card/Diary 
• 
Ensure patient continues to meet eligibility criteria prior to dosing 
7.3.1.2 ITP Dosing Day 1 
• 
Administer IMG-7289 
7.3.1.3 ITP Post-dose Day 1 
• 
Patients should remain in clinic for at least 2 hours (plus or minus one hour) post first dose 
• 
Query for Adverse Events, using non-directive questions (i.e., “How are you feeling?”) 
• 
Update concomitant medications if needed 
• 
Schedule Day 8 clinic visit 
7.3.2 ITP Weekly Visits - Days 8, 15, 22, 29, 36, 43, 50 and 57 (± 1 day*) 
*Important: The ±1 day visit window applies to the visit (e.g., ‘Day 8’ visit may be conducted on 
Day 7, Day 8 or Day 9 as dictated by site and patient schedule), and not to individual assessments, unless 
otherwise noted for a specific assessment. To clarify, the expectation is that all required assessments will be 
done on a single visit day with the exception of those specifically noted below. 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
• 
Adverse Events and Concomitant Medications 
• 
Pre-dose: Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential and hematology assessment to determine if dose titration is required** 
(note: up-titrations may occur no more frequently than every 4 weeks from the previous up- or 
down-titration; down-titrations may occur at any time in the best interest of the patient) 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
• 
Collect MPN-SAF and provide questionnaire for completion on the day of the next visit, prior to or at the 
start of the visit 
• 
Pre-dose: Perform drug accountability and collect study medication 
• 
Dispense doses sufficient until the next visit and provide Dosing Card/diary 
• 
Schedule next clinic visit 
**If a patient requires a dose hold, complete blood counts should be monitored at least weekly for safety and to enable re- 
challenge to commence as soon as counts return to the required level, if safe to do so. 
 
7.3.2.1 ITP Days 29 and 57 Only 
• 
Blood samples for the following Local Laboratory assessments 
o Chem-12 
o C-reactive protein 
7.3.2.2 ITP Day 57 Only 
• 
Provide extra MPN-SAF questionnaire to patient for completion during the ‘off’ week (Day 64) 
• 
Dispense doses sufficient for 14 days (this is the last weekly visit; the patient will now be seen every 14 
days) 
7.3.3 ITP Bi-Weekly Visits - Days 71, 85, 99 and 113 (± 2 days*) 
*Important: The ±2 day visit window applies to the visit (e.g., ‘Day 71’ visit may be conducted on 
Day 69, Day 70, Day 71, Day 72 or Day 73 as dictated by site and patient schedule), and not to individual 
assessments, unless otherwise noted for a specific assessment. To clarify, the expectation is that all required 
assessments will be done on a single visit day with the exception of those specifically noted below. 
Note: It is anticipated that by Week 8 patients will have achieved a stable dose, with weekly visits no longer 
necessary. For the exceptional patient whose dose has not stabilized, weekly visits may continue at the PI’s 
discretion. For such patients, the following is required at each weekly visit: 
• 
Pre-dose: Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential and hematology assessment to determine if dose titration is required** 
(note: up-titrations may occur no more frequently than every 4 weeks from the previous up- or 
down-titration; down-titrations may occur at any time in the best interest of the patient) 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
All other patients will undergo the following at bi-weekly visits: 
• 
Limited PE*, including weight*, vital signs*, spleen measurement* and a review of body systems to assess 
change from previous PE 
o (*) assessments may be omitted on Days 71 and 99 as these visits may be conducted utilizing 
telemedicine/video visit option at PI discretion. 
• 
Adverse Events and Concomitant Medications 
• 
Pre-dose: Blood samples for the following Local Laboratory assessments: 
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o CBC with manual differential and hematology assessment to determine if dose titration is required** 
(note: up-titrations may occur no more frequently than every 4 weeks from the previous up- or 
down-titration; down-titrations may occur at any time in the best interest of the patient) 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
• 
Collect MPN-SAF and provide questionnaires for completion on the day of the next visit, prior to or at the 
start of the visit (including one for completion during each ‘off’ week, i.e., Days 78, 92 and 106) 
• 
Pre-dose: Perform drug accountability and collect study medication 
• 
Dispense doses sufficient for 14 days and provide Dosing Card/Diary 
• 
Schedule next clinic visit 
**If a patient requires a dose hold, complete blood counts should be monitored at least weekly for safety and to enable re- 
challenge to commence as soon as counts return to the required level, if safe to do so. 
 
7.3.3.1 ITP Day 85 Only 
• 
Calculate ECOG performance status (Section 12.5). ECOG must be <3 to continue on study drug. 
7.3.3.2 ITP Days 85 and 113 Only 
• 
Blood samples for the following Local Laboratory assessments 
o Chem-12 
o C-reactive protein 
7.3.3.3 ITP Day 113 only 
• 
Provide extra MPN-SAF questionnaires to patient for completion during the ‘off’ weeks (i.e., Days 120, 127 
and 134) 
• 
Dispense doses sufficient for 28 days (this is the last bi-weekly visit; the patient will now be seen every 28 
days). 
7.3.4 ITP Monthly Visits Days 141 and 169 (± 3 days*) 
*Important: The ± 3 day visit window applies to the visit (e.g., ‘Day 141’ visit may be conducted on 
Day 138, Day 139, Day 140, Day 141, Day 142, Day 143 or Day 144 as dictated by site and patient schedule), 
and not to individual assessments, unless otherwise noted for a specific assessment. To clarify, the 
expectation is that all required assessments will be done on a single visit day with the exception of those 
specifically noted below. 
Note: It is anticipated that by Week 16 patients will have achieved a stable dose, with bi-weekly visits no 
longer necessary. For the exceptional patient whose dose has not stabilized, bi-weekly visits may continue at 
the PI’s discretion. For such patients, the following is required at each bi-weekly visit: 
• 
Pre-dose: Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential and hematology assessment to determine if dose titration is required** 
(note: up-titrations may occur no more frequently than every 4 weeks from the previous up- or 
down-titration; down-titrations may occur at any time in the best interest of the patient) 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
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All other patients will undergo the following at monthly visits: 
• 
Limited PE*, including weight*, vital signs*, spleen measurement* and a review of body systems to assess 
change from previous PE 
o (*) assessments may be omitted on Day 141 as this visit may be conducted utilizing 
telemedicine/video visit option at PI discretion. (In person visit is required on Day 169 with all 
assessments needed). 
• 
Adverse Events and Concomitant Medications 
• 
Blood samples for the following Local Laboratory assessments: 
o Pre-dose: CBC with manual differential and hematology assessment to determine if dose titration is 
required** (note: up-titrations may occur no more frequently than every 4 weeks from the previous 
up- or down-titration; down-titrations may occur at any time in the best interest of the patient) 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
o Chem-12 
o C-reactive protein 
• 
Collect MPN-SAF and provide questionnaires for completion on the day of the next visit, prior to or at the 
start of the visit 
• 
Pre-dose: Perform drug accountability and collect study medication 
• 
Dispense doses sufficient for 28 days and provide Dosing Card/Diary (Day 141 only) 
• 
Schedule next clinic visit 
**If a patient requires a dose hold, complete blood counts should be monitored at least weekly for safety and to enable re- 
challenge to commence as soon as counts return to the required level, if safe to do so. 
 
7.3.4.1 ITP Day 141 Only 
• 
Provide extra MPN-SAF questionnaires to patient for completion during the ‘off’ weeks (i.e., Days 148, 155 
and 162) 
7.3.4.2 ITP Day 169 Only 
• 
Calculate ECOG performance status (Section 12.5) 
• 
Blood sample for testing of mutant (variant) allele burden in granulocytes 
• 
Bone marrow sampling, including additional aspirate for storage (-14/+7 days) 
• 
Qualification: Assess whether the patient is eligible for the ATP. If it is determined that the patient is 
deriving clinical benefit and safely tolerating IMG-7289, then the patient qualifies for and may enter the ATP 
upon completion of the Day 169 visit. If the patient is entering the ATP, please proceed to Section 7.4 
below. If the patient is not entering the Additional Treatment Period, please proceed to Follow-up Period 
Section 7.6 below. 
7.4 Additional Treatment Period (ATP; for qualifying patients only) 
Those patients deriving clinical benefit that enter the Additional Treatment Period will “re-start” IMG-7289. For 
the purposes of clarity and efficiency, rather than continuing to present chronological days/weeks, visits are 
presented as ‘ATP Day 1’, followed by, ‘ATP Days 29, 59, 85,’ etc. 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
The visits and procedures contained herein may repeat as long as the patient continues to qualify for additional 
treatment. Continued treatment in the ATP should occur without interruption in dosing; Day 1 assessments 
may be performed on the same day as Day 169 of the prior treatment period. 
Procedures are presented below for each visit by assessments performed pre-dose, at dosing, and post-dose 
(as applicable). 
7.4.1 ATP Day 1 Treatment ‘Re-start’ (± 3 days) 
All assessments should ideally be performed pre-dose; however, with the exception of the hematology blood test 
and determination of the need for a dose titration, the assessments may be performed post-dose if needed. 
The below assessments do not need to be repeated if performed on the same or calendar day prior. 
• 
Verify patient meets the criteria for additional treatment 
• 
Adverse Events and Concomitant Medications 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
• 
Collect MPN-SAF and provide patient with questionnaires for completion on the day of the next visit, prior 
to or at the start of the visit (including one for completion during each ‘off’ week, i.e., Days 8, 15, 22, etc.) 
• 
Blood samples for the following Local Laboratory assessments: 
o Pre-dose: CBC with manual differential and hematology assessment to determine if dose titration is 
required** (note: up-titrations may occur no more frequently than every 4 weeks from the previous 
up- or down-titration; down-titrations may occur at any time in the best interest of the patient) 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
o Chem-12 
o C-reactive protein 
• 
Dispense doses sufficient for 28 days and provide Dosing Card/Diary 
**If a patient requires a dose hold, complete blood counts should be monitored at least weekly for safety and to enable re- 
challenge to commence as soon as counts return to the required level, if safe to do so. 
 
7.4.2 ATP Monthly Visits Days 29, 57, 85, 113, 141 and 169 (± 3 days*) 
*Important: The ± 3 day visit window applies to the visit (e.g., ‘Day 29’ visit may be conducted on 
Day 26, Day 27, Day 28, Day 29, Day 30, Day 31 or Day 32 as dictated by site and patient schedule), and not 
to individual assessments, unless otherwise noted for a specific assessment. To clarify, the expectation is that 
all required assessments will be done on a single visit day with the exception of those specifically noted below. 
Note: It is anticipated that patients continuing in the ATP will have already achieved a stable dose, with bi- 
weekly visits no longer necessary. For the exceptional patient whose dose has not stabilized, bi-weekly visits 
may continue at the PI’s discretion. For such patients, the following is required at each bi-weekly visit: 
• 
Pre-dose: Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential and hematology assessment to determine if dose titration is required** 
(note: up-titrations may occur no more frequently than every 4 weeks from the previous up- or 
down-titration; down-titrations may occur at any time in the best interest of the patient) 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
 
All other patients will undergo the following at monthly visits: 
• 
Limited PE*, including weight*, vital signs*, spleen measurement* and a review of body systems to assess 
change from previous PE 
o (*) assessments may be omitted on Days 29, 85, and141 as these visits may be conducted 
utilizing telemedicine/video visit option at PI discretion. 
• 
Adverse Events and Concomitant Medications 
• 
Blood samples for the following Local Laboratory assessments: 
o Pre-dose: CBC with manual differential and hematology assessment to determine if dose titration is 
required** (note: up-titrations may occur no more frequently than every 4 weeks from the previous 
up- or down-titration; down-titrations may occur at any time in the best interest of the patient) 
Important: may be performed up to 2 days ahead of the main visit to avoid the need for IMG-7289 
dispensation on the day of blood sampling. For example, if a visit is scheduled on a Wednesday, 
the hematology panel and associated titration assessment can be performed Monday or Tuesday, if 
needed, to ensure IMG-7289 is dispensed and available for collection at the Wednesday visit. 
o Chem-12 
o C-reactive protein 
• 
Collect MPN-SAF and provide questionnaires for completion on the day of the next visit, prior to or at the 
start of the visit (including one for completion during each ‘off’ week, i.e., Days 36, 43, 50, etc.) 
• 
Pre-dose: Perform drug accountability and collect study medication 
• 
Dispense doses sufficient for 28 days and provide Dosing Card/Diary 
• 
Schedule next clinic visit 
**If a patient requires a dose hold, complete blood counts should be monitored at least weekly for safety and to enable re- 
challenge to commence as soon as counts return to the required level, if safe to do so. 
 
7.4.2.1 ATP Day 169 Only 
• 
Calculate ECOG performance status (per Section 12.5). 
• 
Optional bone marrow sampling, including additional aspirate for storage (-14/+7 days), may be collected 
every other ATP (ATP2 Day 169, ATP4 Day 169, etc.) for as long as the patient continues to qualify for 
treatment 
• 
Qualification: Assess whether the patient continues to be eligible for the ATP. If it is determined by the 
Investigator that the patient is deriving clinical benefit and safely tolerating IMG-7289, then the patient 
qualifies for and may re-enter the ATP upon completion of the Day 169 visit. If the patient is re-entering the 
ATP, please revert back to Section 7.4 for the ATP visit schedule and associated procedures and 
assessments. If the patient is not re-entering the ATP, please proceed to Section 7.6 below. 
7.5 Suspected Relapse 
If at any time during the study a patient is suspected to have relapsed, which can only occur post remission, 
then a Suspected Relapse visit should be performed with the following assessments: 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
• 
Adverse Events and Concomitant Medications 
• 
Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential 
o Chem-12 
o C-reactive protein 
o Testing of mutant (variant) allele burden in granulocytes 
• 
Collect MPN-SAF and provide questionnaire for completion on the day of the next visit, prior to or at the 
start of the visit 
• 
Calculate ECOG performance status (per Section 12.5) 
• 
Schedule next clinic visit 
7.6 Follow-up Period Visits 
7.6.1 End of Treatment Visit 
For patients completing the study at the end of a 168-day treatment period, the Day 169 visit will substitute for 
the EoT visit. For patients discontinuing before completing a 168-day treatment period but agreeing to enter 
the Follow-Up Period, the EoT visit should be conducted on the day of last dose or as soon as possible 
thereafter. 
 
Patients should return to the clinic for the following assessments: 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
• 
Adverse Events and Concomitant Medications 
• 
Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential 
o Chem-12 
o C-reactive protein 
o Testing of mutant (variant) allele burden in granulocytes 
• 
Collect MPN-SAF and provide questionnaire for completion on the day of the next visit, prior to or at the 
start of the visit (including one for completion during each ‘off’ week) 
• 
Perform drug accountability and collect study medication 
• 
Calculate ECOG performance status (per Section 12.5) 
• 
Schedule the Pre-End of Study visit 14 days post last dose 
7.6.2 Pre-End of Study Visit 
The Pre-EoS visit should be conducted 14 days (± 3 days) post last dose. 
 
Patients should return to the clinic for the following assessments: 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
• 
Adverse Events and Concomitant Medications 
• 
Blood samples for the following Local Laboratory assessments: 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
o CBC with manual differential 
o Chem-12 
o C-reactive protein 
o Schedule the End of Study Visit in 14 days’ time 
• 
Collect MPN-SAF and provide patient with questionnaires for completion on the day of the next visit, prior 
to or at the start of the visit (including one for completion during each ‘off’ week) 
7.6.3 End of Study / Early Termination Visit 
Early Termination: patients should be seen in the clinic as soon as possible after stopping study drug if they 
terminate the study early and refuse to enter the full Follow-Up Period. 
End of Study: patients should be seen in the clinic 28 days (± 3 days) after the last dose of study drug. 
The following assessments are required at the End of Study/Early Termination visit: 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
• 
Adverse Events and Concomitant Medications 
• 
Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential 
o Chem-12 
o C-reactive protein 
• 
Collect MPN-SAF 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
7.7 Schedule of Events – Initial Treatment Period 
INITIAL TREATMENT 
PERIOD 
Weekly Visits (±1 day) 
Bi-Weekly Visits 
(±2 days)a 
Monthly Visits 
(±3 days)a 
Follow-up 
(±3 days) 
Procedures 
Screen 
Day 
1 
Day 8 
Week 
1 
Day 15 
Week 
2 
Day 22 
Week 
3 
Day 29 
Week 
4 
Day 36 
Week 
5 
Day 43 
Week 
6 
Day 50 
Week 
7 
Day 57 
Week 
8 
Day 71 
Week 
10 
Day 85k 
Week 
12 
Day 99 
Week 
14 
Day 
113k 
Week 
16 
Day 
141k 
Week 
20 
Day 169 
or EOT 
Week 24 
Pre- 
EOS 
EOS/ 
ET 
Informed Consent 
1 
Inclusion/Exclusion 
1 
Demographics 
1 
Physical Exameg 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1k 
1 
1k 
1k 
1 
1 
1 
MPN-SAFh 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
Adverse Events 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
Concomitant Medications 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
ECOG 
1 
1 
1 
Bone Marrow Biopsy and 
Aspirate (and pathology)i 
1 
1c 
1c 
Titration Assessment 
1j 
1j 
1j 
1j 
1j 
1j 
1j 
1j 
1j 
1j 
1j 
1j 
1j 
Qualification Assessment 
1d 
Dispense IMG-7289 
1 
1f 
1f 
1f 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
Administer IMG-7289 
Clinical Laboratory 
CBC with manual Diff 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
Chem-12 (CMP) 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
C-reactive protein 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
Testing of mutant allele 
burden in granulocytes 
1 
1 
PT/INR/aPTT 
1 
Pregnancy Test- Serumb 
1 
1 
Data collection may begin after subject has consented to participation; % NCI-CTCAE v5.0 will be used to document adverse events. Adverse events should only be collected starting 
on Day 1 of treatment. 
a: 
 It is anticipated that by Week 8 all patients will have achieved a stable dose, with weekly visits no longer required. For safety purposes, weekly (or bi-weekly, as appropriate) 
visits may continue to be implemented at PI’s discretion, if necessary. CBC with manual diff only is required at weekly visits; at bi-weekly visits, titration assessment is also 
required. 
b: 
Serum pregnancy test for women of childbearing potential (women who are not post-menopausal for 1 year or more) also performed if pregnancy suspected while patient 
remains on-study. 
c: 
Optional not required . 
d: 
 Assess whether patient is deriving clinical benefit and safely tolerating IMG-7289, thereby qualifying for entry into the ATP upon completion of the Day 169 visit. 
e: 
All physical exams done after screening will be a limited PE 
f: 
Up-titrations are not permitted at these visits. Please see ‘j’ below for additional details. 
g: 
 Spleen measurements should be taken during physical exam 
h:  MPN-SAF completed once per week from Day 1 through End of Study. Provide multiple questionnaires to patient for completion during weeks there are no clinic visits. 
i: 
Additional aspirate to be collected and stored for potential single-cell metabolism, inflammatory signaling, or other future studies. 
j: 
Up-titrations may begin at ITP Day 29 and occur no more frequently than every 4 weeks from the previous up- or down-titration. Down-titrations can be made at any time in the 
best interest of the patient. Patients requiring a Dose Hold according to the Titration and Re-challenge Rules, or due to an (S)AE, should be monitored at least weekly for safety 
purposes and to enable re-challenge to commence as soon as counts return to the required level, if it safe to do so. During these visits, patients are required to undergo 
complete blood counts only. 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
k: 
Visit may be conducted utilizing telemedicine/video visit if deemed appropriate by PI. Limited PE, weight, VS, spleen measurement assessments will be omitted if this option is 
utilized. 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
7.8 Schedule of Events – Additional Treatment Period 
 
ADDITIONAL TREATMENT 
PERIOD 
Monthly Visits (±3 days)a 
Suspected 
Relapse 
Follow-up (±3 days) 
Procedures 
Days 1, 29i, 57, 85i, 113 
Weeks 1, 4, 8, 12, 16 
Day 141i 
Week 20 
Day 169 
or EOT 
Week 24 
Pre-EOS 
(EOT + 14 days) 
EOS (Pre-EOS 
+14 days)/ 
ET 
Physical Examd 
1i 
1i 
1 
1 
1 
1 
MPN-SAFe 
1 
1 
1 
1 
1 
1 
Adverse Events 
1 
1 
1 
1 
1 
1 
Concomitant Medications 
1 
1 
1 
1 
1 
1 
ECOG 
1 
1 
1 
Bone Marrow Biopsy and Aspirate 
(and pathology)f 
1h 
Titration Assessment 
1g 
1g 
Qualification Assessment 
1c 
Dispensation of IMG-7289 
1 
1 
Administration of IMG-7289 
Clinical Laboratory 
CBC with manual Diff 
1 
1 
1 
1 
1 
1 
Chem-12 (CMP) 
1 
1 
1 
1 
1 
1 
C-reactive protein 
1 
1 
1 
1 
1 
1 
Testing of mutant allele burden in 
granulocytes 
1 
Data collection may begin after subject has consented to participation; % NCI-CTCAE v5.0 will be used to document adverse events. 
Adverse events should only be collected starting on day 1 of treatment 
a: 
It is anticipated that all patients continuing in the Additional Treatment Period will have achieved a stable dose, with bi-weekly visits 
no longer required. For safety purposes, bi-weekly visits may be implemented at the PI’s discretion, if necessary. CBC with 
manual diff and titration assessment are required. 
b: 
Only if not performed in the prior 5 weeks. 
c: 
 Assess whether patient is deriving clinical benefit and safely tolerating IMG-7289, thereby qualifying for entry into the ATP upon 
completion of the Day 169 visit. 
d: 
Spleen measurements should be taken during physical exam 
e: MPN-SAF completed once per week from Day 1 through End of Study. Provide multiple questionnaires to patient for completion 
during weeks there are no clinic visits. 
f: 
Additional aspirate to be collected and stored for potential single-cell metabolism, inflammatory signaling, or other future studies. 
g: Up-titrations may occur no more frequently than every 4 weeks from the previous up- or down-titration. Down-titrations can be 
made at any time in the best interest of the patient. Patients requiring a Dose Hold according to the Titration and 
Re-challenge Rules, or due to an (S)AE, should be monitored at least weekly for safety purposes and to enable re-challenge to 
commence as soon as counts return to the required level, if it safe to do so. During these visits, patients are required to undergo 
complete blood counts only. 
h: Optional every other Day 169 (i.e., ATP2 Day 169, ATP 4 Day 169) for as long as the patient continues to qualify for treatment. 
i: 
Visit may be conducted utilizing telemedicine/video visit if deemed appropriate by PI. Limited PE, weight, VS, spleen measurement 
assessments will be omitted if this option is utilized 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
8 
Study Design/Data Collection 
Study Design: This study will follow a Simon two-stage design with an anticipated lower limit response rate of 
10% and a target response rate of >40%. With these parameters, the optimal Simon design with α=0.05 and 
90% power would need 9 patients in the first stage and 11 patients in the second stage. After testing oral IMG- 
7289 on 9 patients in the first stage, the trial will be terminated if 1 or fewer respond. If the trial goes to the 
second stage, a total of 20 patients will be enrolled. If the total number responding is less than or equal to 4, 
oral IMG-7289 will be rejected; if the total number responding is more than 4, oral IMG-7289 will be considered 
worthy of further study. 
Engagement Approach: Enrollment will be via MPN Hematology investigators the Mays Cancer Center (Dr. 
Nooruddin) as well as by members of the Mays Cancer Center hematology team. 
Study Population and Setting: See previous section for eligibility criteria. This investigation will identify, 
recruit, enroll and treat through MPN investigators the Mays Cancer Center. 
 
Intervention: Participants will be initiated on a daily oral dose of 0.6 mg/kg/day of IMG-7289. Dose escalation 
and de-escalation algorithms will be similar to the IMG-7289 CTP-102 protocol for MF targeting a platelet count 
of 200 to 400 x 109/L. 
Outcomes: Outcomes for Aims 1 - 2 will be collected pre- and post-intervention. 
 
Duration: Study participants will be initially be treated in the study for 24 weeks. If participants are deriving 
clinical benefit from IMG-7289, the drug can be continued for an additional 24 weeks; this is an iterative 
process and may repeat indefinitely. 
 
Prior Relevant Experience: Our team has extensive experience recruiting and retaining study participants in 
clinical trials. The Mays Cancer Center at UT Health SA is an NCI designated cancer center widely recognized 
for Phase I clinical trials and drug development discovery. Dr. Nooruddin will be the study PI and was formerly 
Deputy Director of the Cancer Center at Mayo Arizona and continues to collaborate closely between both 
institutions. Dr. Nooruddin has worked investigating QOL and symptom burden in MPNs since 2010. Dr. Joel 
Michalek is the project biostatistician and has over 40 years’ experience in the analysis and reporting of clinical 
and epidemiological studies. 
 
9 
Minority Accrual 
9.1 Purpose 
To assist the Principal Investigators (PIs) conducting Investigator Initiated Trials (IIT) in determining whether or 
not they are meeting the NIH and NCI guidelines and recommendations for the inclusion of minorities in 
Clinical Trials. 
 
Preliminary information that Principal Investigators should consider include: 
• 
Overall Representation of Minorities in the target catchment area 
• 
The ethnic/racial distribution of the specific type of cancer that is being targeted 
The following resources can be utilized to determine target sample sizes for ethnic groups: 
o Texas Health Data http://soupfin.tdh.state.tx.us/txhd.htm 
o Texas Cancer Registry www.dshs.tx.us/tcr/ 
o SEER Cancer Statistics Review www.seer.cancer.gov 
o ACS Cancer Statistics www.cancer.org 
*Estimated Target Accrual (Total) 
This section asks for a projection of the total ethnic/racial and gender mix of the subjects 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Breakdown of subjects - Indicate the total targeted/planned accrual by Race & 
Gender 
Race 
% Male 
% Female 
Black or African American 
10 
10 
American Indian or Alaskan Native 
0 
0 
Asian 
0 
0 
Native Hawaiian or Other Pacific Islander 
0 
0 
White 
30 
30 
More Than One Race (Multiracial) 
60 
60 
Total 
100 
100 
 
 
Breakdown of subjects - Indicate the total targeted/planned accrual by Ethnicity & 
Gender. 
Ethnicity 
% Male 
% Female 
Hispanic or Latino 
10 
10 
Not Hispanic or Latino 
40 
40 
Total 
50 
50 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Section 2: Clinical Investigator Tools for Recruitment of Minorities 
 
Tool included 
in study 
LIST OF TOOLS AND ACTIONS FOR INCREASING MINORITY ACCRUAL TO 
CLINICAL TRIALS 
For assistance with submitting IRB documents, developing materials in English 
and Spanish, and scheduling public service announcements, please contact 
MAtools@uthscsa.edu 
Yes 
No 
 
 
1. Include Clinical Trial information on Mays Cancer Center website in both English 
and Spanish (Please notify MAtools@uthscsa.edu). 
Yes 
No 
 
 
2. Use of Bilingual Research Team Member or Translation services 
Yes 
No 
 
 
3. Identification of bilingual Patient Navigator representative of the Target Population 
Please Specify: 
Yes 
No 
 
 
4. Informed Consent available in Spanish 
Yes 
No 
 
 
6. Information Brochures in English and Spanish** (IRB approval required) 
Yes 
No 
 
 
7. Flyers in English and Spanish (two sided, printed in English on one side and 
Spanish on the other).** (IRB approval required) 
Yes 
No 
 
 
8. Public Service Announcements (PSAs) or Advertisements- Spanish Radio** (IRB 
approval required) 
Yes 
No 
 
 
9. PSA’s or Advertisements -Spanish newspapers (e.g., La Prensa)** (IRB approval 
required) 
Yes 
No 
 
 
10. PSA’s or Advertisements -Spanish Television (e.g., Univision)** (IRB approval 
required) 
Yes 
No 
 
 
11. Patient Friendly Fast Facts in English and Spanish ** (IRB approval required) 
Yes 
No 
 
 
12. Outreach to advocacy or community organizations (including presentations or 
awareness campaigns). Please specify: 
We will contact MPN- Research Foundation, MPN forum, and other MPN 
Specific resources to advertise this study. These websites do not target any 
Specific Hispanic or latino populations. 
Yes 
No 
 
 
13. Other. Please Specify: 
** - It is recommended to submit any patient materials to the IRB as an amendment after the initial IRB 
approval has been granted 
Translational Research Component 
 
Translational components of the study include the analysis of bone marrow histology. 
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IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
10 Statistical Analysis 
Analytic Plan: This will be a one arm Simon 2-stage design with up to N=20 subjects. Complete hematologic 
remission (primary outcome) and overall symptom burden (secondary outcomes) will be assessed at weeks 20 
and 24 (response at Week 24 only). 
 
Sample Size and Power: This study will follow a Simon two-stage design with an anticipated lower limit 
response rate of 10% and a target response rate of >40%. With these parameters, the optimal Simon design 
with α=0.05 and 90% power would need 9 patients in the first stage and 11 patients in the second stage. After 
testing oral IMG-7289 on 9 patients in the first stage, the trial will be terminated if 1 or fewer respond. If the 
trial goes to the second stage, a total of 20 patients will be enrolled. If the total number responding is less than 
or equal to 4, oral IMG-7289 will be rejected; if the total number responding is more than 4, oral IMG-7289 will 
be considered worthy of further study. 
 
Publications: 
All protocol- and amendment-related information, with the exception of the information provided by Imago on 
public registry websites, is considered confidential information. Study results may also be presented at one or 
more medical congresses and may be used for scientific exchange and teaching purposes. Additionally, this 
study and its results may be submitted for inclusion in all appropriate health authority study registries, as well 
as publication on health authority study registry websites, as required by local health authority regulations. 
Eligibility for external authorship, as well as selection of first authorship, will be determined by the study 
Principal Investigator(s). 
 
11 Data and Safety Monitoring Oversight 
A Data and Safety Monitoring Plan is required for all individual protocols conducted at Mays Cancer Center. All 
protocols conducted at Mays Cancer Center are covered under the auspices of the Mays Cancer Center 
Institutional Data Safety Monitoring Plan (DSMP). 
 
The Mays Cancer Center Institutional DSMP global policies provide individual trials with: 
• 
institutional policies and procedures for institutional data safety and monitoring, 
• 
an institutional guide to follow, 
• 
monitoring of protocol accrual by the Mays Cancer Center Protocol Review Committee, 
• 
review of study forms and orders by the Forms Committee, 
• 
tools for monitoring safety events, 
• 
independent monitoring and source data verification by the Mays Cancer Center QA Monitor/Auditor 
• 
monitoring of UPIRSO’s by the Director of Quality Assurance and DSMC, 
• 
determining level of risk (Priority of Audit Level Score – PALS), 
• 
oversight by the Data Safety Monitoring Committee (DSMC), and 
• 
verification of protocol adherence via annual audit for all Investigator Initiated Studies by the Mays 
Cancer Center Quality Assurance Division. 
 
Monitoring Progress and Safety 
Due to the risks associated with participation in this protocol, the Mays Cancer Center DSMB in conjunction 
with the Principal Investigator will perform assessment of adverse events, adverse event trends and treatment 
effects on this study. The Mays Cancer Center DSMB acts as an independent Data Safety Monitoring Board 
(DSMB) for IIS conducted at Mays Cancer Center. The Mays Cancer Center DSMB will monitor data 
throughout the duration of a study to determine if continuation of the study is appropriate scientifically and 
ethically. An additional layer of review is provided by the Mays Cancer Center Data Safety Monitoring 
Committee (DSMC) who will review DSMB quarterly reports. 
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Baseline events and adverse events will be captured using the Mays Cancer Center Master Adverse Events 
Document for each patient using CTCAE V.5.0 or most current version for the grading and attribution of 
adverse events. Usage of the Mays Cancer Center Master Adverse Events Document centrally documents: 
• 
the event and evaluates the seriousness, and grades the severity of the event, 
• 
if the event was a change from baseline, 
• 
the determination of the relationship between the event and study intervention, 
• 
if the event was part of the normal disease process, and 
• 
what actions were taken as a result of the event. 
Safety Definitions: 
For this study, the following safety definitions will be applicable: 
 
Adverse Event Definition: An adverse event (AE) is defined as any untoward or unfavorable medical 
occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or 
laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, 
whether or not considered related to the subject’s participation in the research For this study, all adverse 
events will be documented starting with day 1 of treatment and ending 28 days after the last dose of study drug 
is received. Events occurring pre-first dose are baseline events and not AEs. 
 
Serious Adverse Event Definition: is any adverse event that: 
1. results in death; 
2. is life-threatening (places the subject at immediate risk of death from the event as it occurred); 
3. results in inpatient hospitalization or prolongation of existing hospitalization; 
4. results in a persistent or significant disability/incapacity; 
5. results in a congenital anomaly/birth defect; or 
6. based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical 
or surgical intervention to prevent one of the other outcomes listed in this definition 
Adverse event intensity will be evaluated using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0, published 27 November 2017. For adverse events (AEs) not 
included in the CTCAE, the following guidelines will be used to describe severity. 
 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily activities. 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually potentially life-threatening or incapacitating. Of note, the 
term “severe” does not necessarily equate to “serious”. 
 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. The 
degree of certainty about causality will be graded using the categories below. 
• 
Unrelated: There was no relationship of the adverse event 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: Adverse events which are judged probably not related to the drug or biologic. 
• 
Possible: There was no clear relationship of the adverse event to the use of the drug or biologic; 
however, one cannot definitively conclude that there was no relationship. 
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• 
Probable: While a clear relationship to the drug or biologic cannot be established, the event is 
associated with an expected adverse event (per the current Investigator Brochure or DSMC 
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, 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. 
 
Unanticipated Problems Involving Risks to Subjects or Others Definition: Unanticipated problem involving risk 
to subjects or others includes any incident, experience or outcome that meets all of the following criteria: 
A. unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the subject population being studied (note: the 
unfounded classification of a serious adverse event as “anticipated” constitutes serious non- 
compliance); 
B. definitely related or probably related to participation in the research; and 
C. suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
Reporting Requirements 
For this study, the Master Adverse Events Documents collected on patients for this protocol will be reviewed by 
the Principal Investigator on a continuous basis to determine if a serious safety problem has emerged that 
result in a change or early termination of a protocol such as: 
• 
suspending enrollment due to safety or efficacy, or 
• 
termination of the study due to a significant change in risks or benefits. 
The PI will provide the DSMB with the quarterly findings for discussion and review during their meetings. 
 
The PI (or designee) is responsible for notifying sub-investigators regarding recommendations to modify the 
dosage (dose escalate, dose decrease – outside of the per patient defined titration plan) to ensure that 
subsequent subjects are treated at the currently approved dose level. As per the protocol, the PI will contact 
Imago medical staff to discuss protocol modifications for the management of clinically significant changes in 
platelets, neutrophil counts, or other hematologic parameters. Discussions with Imago staff will be 
documented and decisions shared with the DSMB and all sub-investigators. In the event starting doses are 
modified, the PI may delegate the study coordinator to notify other Mays staff, including the Investigational 
Drug Section to ensure that orders are modified timely and appropriately. 
Additionally, this study will have an interim analysis after the first 9 patients to review for response rate. The 
results of the first 9 patients should be shared with the DSMB to approve extending the study to an additional 
11 subjects. The PI is responsible to for notifying sub-investigators of the hold on enrollment until the DSMB 
has recommended continuance of the study. 
 
Stopping rules for this study include 2 DLT’s in the first cohort of 9. A DLT is defined as any one of the 
following AEs that occurs through Day 7 of the Initial Treatment Period unless the event is considered by the 
Investigator to be clearly unrelated to IMG-7289: 
• 
Any Grade 3 or above thrombocytopenia associated with clinically significant bleeding*; 
• 
Any Grade 4 thrombocytopenia associated with the requirement for platelet transfusion; 
• 
Any Grade 4 or 5 non-hematologic adverse event; 
• 
Any Grade 3 or above non-hematologic adverse event with the following exceptions: 
o Nausea, vomiting or diarrhea lasting 3 days or less 
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o Aesthenia lasting less than 7 days 
• 
Any Grade 3 electrolyte abnormality unrelated to the underlying malignancy and persisting greater than 
24 hours. 
*A clinically significant bleeding event is defined as an event that is life-threatening, cannot be controlled and/or results in 
hemodynamic instability. 
 
As per the Mays Cancer Center DSMP, any protocol modifications, problematic safety reports, unanticipated 
problems, and suspension or early termination of a trial must be reported to the DSMB and all members of the 
research team. Furthermore, the PI of this study will promptly notify all study affiliates, the UT Health SA IRB, 
the Mays Cancer Center DSMB, and the FDA via a FDA Form 3500Aa written IND safety report of any serious 
adverse events that are unexpected and also suspected by the Investigator to be related to the use of the 
study treatment (deemed possibly, probably or definitely related). Suspension and early termination of a trial 
must also be reported immediately to the Director of Quality Assurance who will promptly notify the sponsor 
and the UT Health SA IRB. 
The PI will review the Master Adverse Events documents to determine the significance of the reported events 
and will provide findings using the Investigator Initiated Study Quarterly DSMB Report Form on a quarterly 
basis with the DSMB. The DSMB will review the information provided by the PI and report to the Mays Cancer 
Center DSMC on a quarterly basis, unless an emergent issue has been identified. The Investigator Initiated 
Study Quarterly DSMB Report Form includes information on adverse events, current dose levels, number of 
patients enrolled, significant toxicities per the protocol, patient status (morbidity and mortality) dose 
adjustments with observed response, and any interim findings. Any trend consisting of three or more of the 
same event will be reported to the Mays Cancer Center DSMB for independent review outside of the quarterly 
reporting cycle, which begins the quarter after the first patient is enrolled on the protocol. The DSMB will also 
provide its findings to the Mays Cancer Center’s Regulatory Affairs Division so that it may be provided to the 
UT Health SA IRB with the protocol’s annual progress report. Conflict of interest is avoided by the independent 
reviews of the Mays Cancer Center DSMB, Mays Cancer Center DSMC, and by ongoing independent review 
of UPIRSO trends by the Director of Quality Assurance. 
 
All SAE and UPRISO’s will be reported following Mays Cancer Center, UT Health SA institutional and FDA 
guidelines. 
UT HEALTH SA SAE/UPRISO REPORTING REQUIREMENTS For IIS that the PI holds the IND 
Type Event 
Report to 
Timeframe 
All, SAE and UPIRSO 
Regulatory Affairs, Imago BioSciences 
and DQA 
ASAP 
All SAEs deemed both 
unexpected and ‘related*’ to 
study treatment and UPIRSO 
FDA on form 3500A 
within 7 calendar days by 
telephone and 15 calendar days 
using the Form 3500A 
SAE 
PI at UT Health SA 
within 24 hours 
SAE 
UT Health SA IRB 
Annually 
UPIRSO – all 
PI at UT Health SA 
within 24 hours 
UPIRSO – all 
FDA 
within 7 days 
UPIRSO - life threatening 
UT Health SA IRB/UT Health SA OCR 
within 48 hours 
UPIRSO - non-life threatening 
UT Health SA IRB/UT Health SA OCR 
within 7 days 
*deemed possibly, probably or definitely related 
 
SAEs that are unexpected and also suspected by the Investigator to be related to the use of the study 
treatment (deemed possibly, probably or definitely related) that occur during clinical trials with or without an 
Investigational New Drug (IND) application are mandatory reports submitted to FDA via Medwatch FDA 
F3500A within 15 days for events that have at least a possible relationship with the drug. 
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Assuring Compliance with Protocol and Data Accuracy 
As with all studies conducted at Mays Cancer Center, the PI has ultimate responsibility for ensuring protocol 
compliance, data accuracy/integrity and responding to recommendations that emanate from monitoring 
activities. Source to data monitoring will occur after 9 subjects have been enrolled with periodic data quality 
checks. Protocol compliance, data accuracy and reporting of events is further ensured by an annual audit 
conducted by the Quality Assurance Division, whose audit report is shared with the PI, the research team, and 
will be reviewed by the Mays Cancer Center DSMC. 
Mays Cancer Center DSMB Membership 
This Protocol will utilize the Mays DSMB that consists of UT Health SA faculty and staff. 
As per NCI guidelines and to eliminate conflict of interest (financial, intellectual, professional, or regulatory in 
nature), the Mays Cancer Center DSMB specific to this study will not treat patients on this protocol. Usage of 
the Mays DSMB has been created to ensure that experts are represented on the DSMB assembled for this 
protocol, but may be expanded, at the PI’s discretion, to include other members which may include: 
 
• 
experts in the fields of medicine and science that are applicable to the study (if not currently 
represented on the DSMB), 
• 
statistical experts, 
• 
lay representatives, 
• 
multidisciplinary representation, from relevant specialties including experts such as bioethicists, 
biostatisticians and basic scientists, and 
• 
others who can offer an unbiased assessment of the study progress. 
 
Additional or alternate membership of the DSMB is selected by the DSMC chair, in conjunction with the PI of 
this protocol. 
Mays Cancer Center DSMB Charter and Responsibilities 
The Mays Cancer Center DSMB will provide information on the membership composition, including 
qualifications and experience to both the UT Health SA IRB and Mays Cancer Center PRC for review. The 
Mays Cancer Center DSMB for this study will act as an independent advisory board to the PI and will report its 
findings and recommendations to the PI, the UT Health SA IRB and the Mays Cancer Center DSMB. Mays 
Cancer Center DSMB reports will utilize the Investigator Initiated Study Quarterly DSMB Report Form and 
meetings will occur on a quarterly basis to review any updates from the prior meeting. 
Once the protocol is activated, if not already established elsewhere in the protocol the Mays Cancer Center 
DSMB will establish and provide: 
• 
procedures for maintaining confidentiality; 
• 
statistical procedures including monitoring guidelines, which will be used to monitor the identified 
primary, secondary, and safety outcome variables; 
• 
consider factors external to the study when relevant information becomes available, such as scientific 
or therapeutic developments that may have an impact on the safety of the participants or the ethics of 
the study; 
• 
plans for changing frequency of interim analysis as well as procedures for recommending protocol 
changes; 
• 
recommendation of dose escalation, MTD recommendation of early termination based on efficacy results; 
• 
recommendation of termination due to unfavorable benefit-to-risk or inability to answer study questions; 
• 
recommendation of continuation of ongoing studies; 
• 
recommend modification of sample sizes based on ongoing assessment of event rates; and 
• 
review of final results and publications. 
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11 References/Bibliography 
Arber, A.A., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M.J., Le Beau, M.M., Bloomfield, C.D., Cazzola, M., 
Vardiman, J.W. 2016. The 2016 revision to the World Health Organization classification of myeloid 
neoplasms and acute leukemia Blood 127(20), 2391-2405 
Bannister, A.J., Kouzarides, T., 2011. Regulation of chromatin by histone modifications. Cell Res 21, 381-395. 
Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential 
thrombocythemia: an ELN and IWG-MRT consensus project. Blood. 2013;121(23):4778-4781. 
Barosi G, Besses C, Birgegard G, et al. A unified definition of clinical resistance/intolerance to hydroxyurea in 
essential thrombocythemia: results of a consensus process by an international working group. Leukemia. 
2007;21(2):277-280. 
Barbui T, Finazzi G, Carobbio A, et al. Development and validation of an International Prognostic Score of 
thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). BLood. 
2012;120(26):5128-5133; quiz 5252. 
Beisel, C., Paro, R., 2011. Silencing chromatin: comparing modes and mechanisms. Nat Rev Genet 12, 123- 
135. 
Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential 
thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5:e366. 
Geyer H, Scherber R, AC D, R M. Unmet Needs for Symptom Control in Essential Thrombocythemia with Front 
Line Therapy. Blood. 2015;126(3):a408. 
Harris, W.J., Huang, X., Lynch, J.T., Spencer, G.J., Hitchin, J.R., Li, Y., Ciceri, F., Blaser, J.G., Greystoke, B.F., 
Jordan, A.M., Miller, C.J., Ogilvie, D.J., Somervaille, T.C., 2012. The histone demethylase KDM1A 
sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 21, 473-487. 
Kerenyi, M.A., Shao, Z., Hsu, Y.J., Guo, G., Luc, S., O'Brien, K., Fujiwara, Y., Peng, C., Nguyen, M., Orkin, S.H., 
2013. Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during 
blood cell maturation. Elife 2, e00633. 
Kornberg, R. D., 1974. Chromatin structure: a repeating unit of histones and DNA. Science 184, 868–871 
Imago BioSciences Inc. IMG-7289 Investigator Brochure. 2018. 
Jutzi, J.S., Kleppe, M., Dias, J., Staehle, H.F., Shank, K., Teruya-Feldstein, J., Gambheer, S.M.M., Dierks, C., 
Rienhoff, Jr., H.Y., Levine, R,L., Pahl, H.L. 2018 LSD1 inhibition prolongs survival in mouse models of MPN 
by selectively targeting the disease clone Hemasphere 2, 3-16 
Niebel, D., Kirfel, J., Janzen, V., Holler, T., Majores, M., Gutgemann, I. 2014. Lysine-sepcific demethylase 1 
(LSD1) in haematopoietic and lympoid neoplasms Blood 124(1):151-152 
Rudolph T, Beuch S, Reuter G. Lysine-specific histone demethylase LSD1 and the dynamic control of chromatin. 
Biol Chem. 2013;394(8):1019-1028. 
Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative 
neoplasms. Blood. 2017;129(6):680-692. 
Sever M, Newberry KJ, Verstovsek S. Therapeutic options for patients with polycythemia vera and essential 
thrombocythemia refractory/resistant to hydroxyurea. Leuk Lymphoma. 2014;55(12):2685-2690. 
Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J.R., Cole, P.A., Casero, R.A., Shi, Y., 2004. Histone 
demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119, 941-953. 
Sprussel, A., Schulte, J.H., Weber, S., Necke, M., Handschke, K., Thor, T., Pajtler, K.W., Schramm, A., Konig, 
K., Diehl, L., Mestdagh, P., Vandesompele, J., Speleman, F., Jastrow, H., Heukamp, L.C., Schule, R., 
Duhrsen, U., Buettner, R., Eggert, A., Gothert, J.R., 2012. Lysine-specific demethylase 1 restricts 
hematopoietic progenitor proliferation and is essential for terminal differentiation. Leukemia 26, 2039- 
2051. 
Thiele, J., Kvasnicka, H.M., Facchetti, F., Franco, V., van der Walt, J., Orazi, A. 2005. European consensus on 
grading bone marrow fibrosis and assessment of cellularity Haematologica 90(8), 1128-1132 
Vannucchi AM, Guglielmelli P. What are the current treatment approaches for patients with polycythemia vera 
and essential thrombocythemia? Hematology Am Soc Hematol Educ Program. 2017;2017(1):480-488. 
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12 Appendices 
 
Appendix Item 
12.1 Revision History 
12.2 WHO Diagnostic Criteria for ET 
12.3 Criteria for Intolerance/Resistance to 
Hydroxyurea 
12.4 ELN Response Criteria 
12.5 Performance Status Scale (ECOG or Zubrod) 
12.6 MPN-SAF Symptoms/Quality of Life 
12.7 Bone Marrow Fibrosis Grading 
12.8 Adverse Event Tracking Log 
12.9 Data Collection and Submission 
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12.1 Revision History 
Version 12 to Version 13 
 
Please see summary of Changes document. 
Version 11 to 12 
Changed Principal Investigator to Zohra Nooruddin, MD 
Version 10 to 11 
Please see Summary of Changes document. 
Version 9 to 10 
Please see Summary of Changes document. 
Version 8 to 9 
Changed Principal Investigator to Ruben Anthony Mesa, MD 
Version 7 to 8 
Section 7.7 Schedule of Events table was updated to delete dispensing of IMG-7289 on Day 169. 
 
Version 6 to Version 7 
Updated information is bolded. 
7.3.4 ITP Monthly Visits Days 141 and 169 (± 3 days) 
Note: It is anticipated that by Week 16 patients will have achieved a stable dose, with bi-weekly visits no longer 
necessary. For the exceptional patient whose dose has not stabilized, bi-weekly visits may continue at the PI’s 
discretion. For such patients, the following is required at each bi-weekly visit: 
• 
Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential 
• 
Pre-dose: Perform hematology assessment and determine if dose titration is required 
All other patients will undergo the following at monthly visits: 
• 
Limited PE, including weight, vital signs, spleen measurement and a review of body systems to assess 
change from previous PE 
• 
Adverse Events and Concomitant Medications 
• 
Blood samples for the following Local Laboratory assessments: 
o CBC with manual differential 
o Chem-12 
o C-reactive protein 
• 
Collect MPN-SAF and provide questionnaires for completion on the day of the next visit, prior to or at the 
start of the visit 
• 
Pre-dose: Perform hematology assessment and determine if dose titration is required. 
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• 
Pre-dose: Perform drug accountability and collect study medication 
• 
Dispense doses sufficient for 28 days and provide Dosing Card/Diary (Day 141 only) 
Rationale: Clarification of IP dispensing at Day 141, IP is not dispensed on Day 169. 
Version 5 to Version 6 
Updated information is bolded. 
Capitalization errors corrected throughout protocol. 
7.3.2.3 ITP Day 57 Only 
• 
Provide extra MPN-SAF questionnaire to patient for completion during the ‘off’ week (Day 64) 
• 
Dispense doses sufficient for 14 days (this is the last weekly visit; the patient will now be seen every 
14 days) 
 
Rationale: Clarification from the sponsor on the change in the number of days study medication is to be 
dispensed. Additional comment added in the protocol at the specific time point indicating the correct number of 
doses to be dispensed – 14 days. 
7.3.3.3 ITP Day 113 only 
• 
Provide extra MPN-SAF questionnaires to patient for completion during the ‘off’ weeks (i.e., Days 120, 127 
and 134) 
• 
Dispense doses sufficient for 28 days (this is the last bi-weekly visit; the patient will now be seen 
every 28 days). 
 
Rationale: Clarification from the sponsor on the change in the number of days study medication is to be 
dispensed. Additional comment added in the protocol at the specific time point indicating the correct number of 
doses to be dispensed – 28 days. 
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12.2 The 2016 WHO Diagnostic Criteria for ET (Arber et al., 2016) 
Essential Thrombocythemia† 
Major criteria 
1 
Platelet count ≥450 x 109/L 
2 
BM biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers 
of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant left-shift of 
neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin 
fibersɸ 
3 
Not meeting WHO criteria for BCR-ABL1 + CML, PV, PMF, MDS or other myeloid neoplasms 
4 
Presence of JAK2, CALR or MPL mutation 
Minor criteria 
1 
Presence of a clonal marker (e.g., abnormal karyotype) or absence of evidence for reactive 
thrombocytosis 
WHO indicates World Health Organization; PV, polycythemia vera; ET, essential thrombocythemia; PMF, primary 
myelofibrosis; CML, chronic myelogenous leukemia; MDS, myelodysplastic syndrome. 
† ET requires meeting all 4 major criteria or first three major criteria and one minor criterion. 
ɸGrading of BM fibers (Thiele et al., 2005) 
Criterion number 2 (BM biopsy) may not be required in cases with sustained absolute erythrocytosis: hemoglobin levels. 
18.5 g/dL in men (hematocrit, 55.5%) or 16.5 g/dL in women (hematocrit, 49.5%) if major criterion 3 and the minor 
criterion are present. However, initial myelofibrosis (present in up to 20% of patients) can only be detected by performing 
a BM biopsy; this finding may predict a more rapid progression to overt myelofibrosis (post-PV MF) 
 
12.3 Criteria for Intolerance/Resistance to Hydroxyurea 
Intolerance/resistance to hydroxyurea defined using the ELN criteria for ET (Barosi et al., 2007) 
 
For patients with ET, intolerance / resistance to HU is 
defined as one of the following criteria: 
• 
Platelet count >600 ×109/L after a daily dose of at least 2g HU for at least 3 months 
(2.5g/day in patients with a body weight over 80kg) 
• 
Platelet count >400 × 109/L and WBC < 2.5 ×109/L at any dose of HU 
• 
Platelet count >400 × 109/L and hemoglobin <10g/dl at any dose of HU 
• 
Presence of unacceptable HU-related non-hematologic toxicities, including fever, 
mucocutaneous manifestations or leg ulcers 
Note: Updated based on Erratum published 25April2007. 
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12.4 ELN Response Criteria for ET (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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12.5 Eastern Cooperative Oncology Group (ECOG) Performance Status Scale 
The ECOG scale (Oken, 1982) is used to assess a subject’s quality of life in an evaluation by a health 
professional of the daily activities and how the activities are affected by the disease of the subject. 
 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Grade - ECOG Performance Status 
0 
- Fully active, able to carry on all pre-disease performance without restriction. 
1 
- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, eg, light house work, office work. 
2 
- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about 
more than 50% of waking hours. 
3 
- Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. 
4 
- Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair. 
5 
- Dead. 
 
Source: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response 
criteria of the Eastern Cooperative Oncology Group. Am J. Clin Oncol 1982;5(6):649-55. 
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12.6 MPN-SAF Symptoms/Quality of Life 
Myeloproliferative Neoplasm Symptom Assessment Form 
(MPN-SAF) 
Instructions: Please fill out all questions, as best able, reflecting how these symptoms affected you 
over the LAST WEEK unless directed otherwise. Complete forms until the STOP instruction toward 
the end of the packet. 
 
Symptom 
1 to 10 (0 if absent) ranking* 
1 is most favorable and 10 least favorable 
Please rate your fatigue 
(weariness, tiredness) by circling 
the one number that best 
describes your fatigue right NOW 
(No Fatigue) 0 1 2 3 
Imaginable) 
4 5 6 7 8 9 10 (Worst 
Please rate your fatigue 
(weariness, tiredness) by circling 
the one number that best 
describes your USUAL level of 
fatigue during past 24 hours 
(No Fatigue) 0 1 2 3 
Imaginable) 
4 5 6 7 8 9 10 (Worst 
Please rate your fatigue 
(weariness, tiredness) by circling 
the one number that best 
describes your WORST level of 
fatigue during past 24 hours 
(No Fatigue) 0 1 2 3 
Imaginable) 
4 5 6 7 8 9 10 (Worst 
Circle the one number that describes how, during the past 24 hours, 
fatigue has interfered with your 
• 
General activity 
(Does not Interfere) 0 1 2 3 4 5 6 7 8 9 10 (Completely 
Interferes) 
• 
Mood 
(Does not Interfere) 0 1 2 3 4 5 6 7 8 9 10 (Completely 
Interferes) 
• 
Walking ability 
(Does not Interfere) 0 1 2 3 4 5 6 7 8 9 10 (Completely 
Interferes) 
• 
Normal work (includes 
work both outside the 
home and daily chores) 
(Does not Interfere) 0 1 2 3 4 5 6 7 8 9 10 (Completely 
Interferes) 
• 
Relations with other 
people 
(Does not Interfere) 0 1 2 3 4 5 6 7 8 9 10 (Completely 
Interferes) 
• 
Enjoyment of life 
(Does not Interfere) 0 1 2 3 4 5 6 7 8 9 10 (Completely 
Interferes) 
Complion Document ID: 7005814 


Page 55 of 57 
IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Circle the one number that describes how, during the past Week how 
much difficulty you have had with each of the following symptoms 
Filling up quickly when you eat 
(Early satiety) 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Abdominal pain 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Abdominal discomfort 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Inactivity 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Problems with headaches 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Problems with concentration - 
Compared to prior to my MPD 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Dizziness/ Vertigo/ 
Lightheadedness 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Numbness/ Tingling (in my 
hands and feet) 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Difficulty sleeping 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Depression or sad mood 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Problems with sexual desire or 
Function 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Cough 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Night sweats 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Itching (pruritus) 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Bone pain (diffuse not joint pain 
or arthritis) 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
Fever (>100 F) 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Daily) 
Unintentional weight loss last 6 
months 
(Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst Imaginable) 
What is your overall quality of 
life? 
(As good as it can be) 0 1 2 3 4 5 6 7 8 9 10 (As bad as it 
can be) 
 
Complion Document ID: 7005814 


Page 56 of 57 
IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
12.7 Bone Marrow Fibrosis Grading 
 
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 haematopoietic areas. 
aIn grades MF-2 or MF-3 an additional trichrome stain is recommended. 
Complion Document ID: 7005814 


Page 56 of 57 
IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
Adverse Event Tracking Log 
Check box if there were no adverse events to be recorded  
12.8 Adverse Event Tracking Log 
 
HEADER: PI NAME, Protocol or IRB Number, Protocol Short Title 
 
Subject Initials 
Subject ID# 
Page 
 of 
 
 
Insert question to ask participant (e.g. Were there any adverse events? Y/N) 
 
 
 
 
 
# 
Date 
Reported 
Adverse Event Description 
Adverse Event** 
(Select from Safety 
Profiler) 
Start 
Date 
End 
Date 
Ongoing 
(Y or N) 
Outcome1 
Severity/ 
Grade2 
Serious 
(Y or N) 
AE 
Treatment3 
Expected 
(Y or N) 
Study 
Attribution5 
Action 
Taken4 
Drug/Device 
Attribution5^ 
PI Initials 
Date of 
PI Initials 
 
 
 
 
 
# - AE number. “1” indicates the first adverse event documented on the form, 2 = the second, etc. If the adverse event changes in severity, enter it as a separate adverse event row 
on the paper form using the same AE number as the one that ended. 
**look up corresponding AE at: https://safetyprofiler-ctep.nci.nih.gov/ 
 
Outcome1 
Severity/Grade2 
AE Treatment3 
Action Taken4 
with Study Intervention 
Attribution/ 
Relatedness5 
0 – Fatal 
1 – Mild 
0 – None 
0 – None 
0 – Definite 
1 – Not recovered/not resolved 
2 – Moderate 
1 – Medication(s) 
1 – Interrupted 
1 – Probable 
2 – Recovered w/sequelae 
3 – Severe 
2 – Non-medication TX 
2 – Discontinued 
2 – Possible 
3 – Recovered w/o sequelae 
4 – Life Threatening 
3 – Dose reduced 
3 – Unlikely 
4 – Recovering/Resolving 
5 – Death (Fatal) 
4 – Dose increased 
4 – Unrelated 
5 – Not Applicable 
^5 – Not Applicable (did not receive intervention) 
Complion Document ID: 7005814 


Page 57 of 57 
IMG-7289 in ET Patients Protocol V13 July 27, 2023 
 
12.9 Data Collection and Submission 
Study specific instructions for data entry into REDCap will be provided to the study team during the site 
initiation training prior to study activation. 
The Mays Cancer Center IIS and Multi-site Compliance policies and Data Safety Monitoring Plan will be strictly 
enforced. 
Complion Document ID: 7005814 


Protocol Title: AN INVESTIGATOR INITIATED PHASE 2 TRIAL OF THE LSD1 
INHIBITOR IMG-7289 (BOMEDEMSTAT) IN ESSENTIAL THROMBOCYTHEMIA 
 
Version 12 to Version 13 Summary of Changes (7/27/23) 
 
Protocol Change and Location 
Justification 
Allowing telemedicine visits, 
decreasing the frequency of visits 
Page 28, 30, 32, 35, 36, 37 - 
Video/Telemedicine visit during ITP phase 
post Day 57, may occur every other 
assessment timepoint (Days 71/99/141); 
In person visits will continue on (Days 
85/113/169) 
-In ATP, video/telemedicine visits may 
occur at every other assessment 
timepoint (Days 29/85/141) 
Page 11- clarified language to reflect 
above changes. 
Drug is moving into the Phase 3 with a 
published safety profile. 
Remove Spleen measurement from all 
timepoints post 24 week. 
-Spleen measurement to be completed 
during the initial 24 week period at every 
physical visit. 
Endpoint for evaluation per study 
requirement is complete at the 24-week 
timepoint. 
MPN-SAF to be done at every visit 
(removing extra “at home” 
questionnaires) 
Endpoint for collection of the MPN-SAF 
data concludes at 24-week. 
Page 9- clarification of Study Conduct 
time frame to more accurately reflect 
paragraphs below and original study 
intended length. 
Clerical correction. 
Page 22- Dispense language adjusted to 
Monthly/28-day supply after Q1week for 
first 8-weeks of ITP and all of ATP phases 
Dispensing will coincide with all 
physical/In-person visit for the ITP phase 
which also correlates with titration time- 
points. ATP phase dispensing will remain 
at monthly/28-day visits to correspond 
with potential titration. 
This will reduce the need for mail/ship of 
drug. 
Pg 9 
Made a change for language to clarify 
video assessments to be started. 
Pg 22 
Made a change in language to clarify 
dosing/dispensing moving to monthly. 
 
Complion Document ID: 7005814