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

Inclusion criteria

• Age ≥ 18 years.
• Diagnosis of Essential Thrombocythemia or Polycythemia Vera per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Arber et al., 2016).
• Patients that have failed at least one standard therapy (failure is the equivalent of inadequate response or intolerance).
• Platelet count >400 x 10^9/L pre-dose Day 1for patients with essential thrombocytopenia.
• Platelet count >150 x 10^9/L pre-dose Day 1 for patients with polycythemia vera.
• Peripheral blast count < 10% pre-dose Day 1.
• Absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L pre-dose Day 1.
• 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).
• Life expectancy > 36 weeks.
• Able to swallow capsules.
• Amenable to blood draws, spleen size determination, bone marrow evaluations, and peripheral blood sampling during the study.
• Must have discontinued prior therapy for condition under study for 2 weeks (4 weeks for interferon) prior to study drug initiation.
• Agrees to use an approved method of contraception from Screening until 28 days after last administration of the study drug.
• 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

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

• 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
• Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥ 2 x the local upper limit of normal
• Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment with the investigational drug.
• 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.
• Patients with impaired decision-making capacity.