IMG-7289 in Patients With Essential Thrombocythemia (ET) or Polycythemia Vera (PV)

1. Age ≥ 18 years.
2. Diagnosis of Essential Thrombocythemia or Polycythemia Vera per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Arber et al., 2016).
3. Patients that have failed at least one standard therapy (failure is the equivalent of inadequate response or intolerance).
4. Platelet count >400 x 10\^9/L pre-dose Day 1for patients with essential thrombocytopenia.
5. Platelet count >150 x 10\^9/L pre-dose Day 1 for patients with polycythemia vera.
6. Peripheral blast count \< 10% pre-dose Day 1.
7. Absolute neutrophil count (ANC) ≥ 0.5 x 10\^9/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 blood draws, spleen size determination, bone marrow evaluations, and peripheral blood sampling during the study.
12. Must have discontinued prior therapy for condition under study for 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.
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:

1. Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater.
2. Currently pregnant, planning on being pregnant in the following 6 months or currently breastfeeding.
3. Currently residing outside the United States.
4. History of splenectomy.
5. Unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1).
6. Uncontrolled active infection.
7. Known positive for HIV if not well-controlled (i.e., undetectable viral load), or infectious hepatitis, type A, B or C.
8. Current use of monoamine oxidase A and B inhibitors (MAOIs).

9. Evidence at the time of screening of increased risk of bleeding, including any of the following:

   • Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal
   • International normalized ratio (INR) >1.3 x the local upper limit of normal
   • History of severe thrombocytopenia or platelet dysfunction unrelated to a myeloproliferative disorder or its treatment
   • Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, haemophilia, Von Willebrand's disorder, Disseminated Intravascular Coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency)

10. Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to haemolysis, or leukaemic infiltration) as defined by any of the following local lab parameters:

    1. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) \< 40 mL/min or serum creatinine > 1.5 x the local upper limit of normal
    2. Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥ 2 x the local upper limit of normal
11. Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment with the investigational drug.
12. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IMG-7289 or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates their participation.
13. Patients with impaired decision-making capacity.