Inclusion Criteria:

• - Age ≥18 years.

• - 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 (European Leukemia Net) criteria, or in the Investigator's judgment are not candidates for available approved therapy. The ELN definitions of resistance/intolerance to HU (hydroxyurea) requires the fulfillment of at least one of the following criteria:

• - Platelet count greater than 600 × 109/L after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); - Platelet count greater than 400 × 109/L and leukocytes less than 2.5 × 109/L or hemoglobin (Hb) less than 100 g/L at any dose of HU; - Presence of leg ulcers or other unacceptable mucocutaneous manifestations at any dose of HU; - HU-related fever.

• - Requires treatment in order to lower platelet counts based on the Clinically Relevant IPSET (International Prognostic Score for Thrombosis in Essential Thrombocythemia) -Thrombosis Guidelines.

• - Platelet count >450 x 109/L pre-dose Day 1.

• - Peripheral blast count <10% pre-dose Day 1.

• - ANC (absolute neutrophil count) ≥0.5 x 109/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 spleen size determination, bone marrow evaluations, and peripheral blood sampling during the study.

• - Must have discontinued ET therapy at least 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.

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).

• - 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:

• - Greater than 3 separate transfusion episodes over the last 6 months and/or any transfusion over the last 4 weeks.

• - Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater.

• - Currently pregnant or 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 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: 1.

Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal. 2. International normalized ratio (INR) >1.3 x the local upper limit of normal. 3. Known Acquired Von Willebrand's disorder.

Arms

Experimental: IMG-7289

Interventions

Drug: - IMG-7289

Single starting dose with individualized dose titrations throughout