Inclusion Criteria:

1. 18 years of age or older. 2. Diagnosis of PMF, post-PV MF, or post-ET MF. 3. DIPSS Intermediate-2 or High-risk MF with ≤10% blasts, regardless of JAK2 mutation status. 4. Estimated spleen volume ≥450cm3. 5. MFSAF v.4.0 TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3. 6. ECOG PS of 0, 1, 2, or 3. 7. Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response. 8. ANC ≥1.0×10^9/L. 9. Platelet count ≥75×10^9/L. 10. eGFR ≥45 mL/min/1.73m2. 11. Serum total bilirubin ≤2.0 × upper limit of normal (ULN). 12. AST and ALT ≤3.0 × ULN. 13. QTcF ≤480 msec.

Exclusion Criteria:

1. Prior splenectomy. 2. Splenic irradiation within 3 months prior to first dose of study drug. 3. Ongoing use of systemic corticosteroids at dose equivalent to >10mg/day of prednisone. 4. Uncontrolled intercurrent illness such as an acute infection. 5. Chronic active or acute hepatitis B or C infection. 6. Chemotherapy in the previous 4 weeks prior to first dose of study drug (Hydrea is permitted until 5 days before starting protocol therapy). 7. Use of a JAK2 inhibitor in the previous 10 days. 8. Use of erythropoiesis stimulating agents (unless stable for >8 weeks). 9. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0). 10. Unable or unwilling to undergo CT or MRI for spleen size imaging. 11. Pregnant or breastfeeding. 12. Requirement for therapy with a medication that is a strong CYP3A4 inhibitor as a concomitant medication.

This is a phase 1, non-randomized, open-label study utilizing a 3+3 sequential dose escalation design followed by an expansion phase. The primary objective will be to evaluate the safety and tolerability of AJ1-11095, and establish a Maximally Tolerated Dose (MTD) and/or inform the establishment of a candidate Recommended Phase 2 dose (RP2D). The RP2D may be the maximally tolerated dose (MTD) or may be a dose below the MTD. The candidate RP2D will be based on AE pattern, PK and biomarker information, in addition to all available safety and efficacy data. Expansion cohorts will be enrolled to gather additional safety and efficacy information and to further refine input for future RP2D discussions. Eligible participants will have PMF, PPV-MF or PET-MF and will have either have relapsed after a response, or be refractory to, at least one prior type I JAK2 inhibitor therapy, either administered as monotherapy or in combination with another drug.

Arms

Experimental: Cohort 1

Dose A of AJ1-11095 taken orally by patients.

Experimental: Cohort 2

Dose B of AJ1-11095 taken orally by patients.

Experimental: Cohort 3

Dose C of AJ1-11095 taken orally by patients.

Experimental: Cohort 4

Dose D of AJ1-11095 taken orally by patients.

Experimental: Cohort 5

Dose E of AJ1-11095 taken orally by patients.

Experimental: Dose Expansion Cohort 1

Candidate RP2D of AJ1-11095 taken orally by patients.

Experimental: Dose Expansion Cohort 2

Alternative candidate RP2D of AJ1-11095 taken orally by patients.

Interventions

Drug: - AJ1-11095

Type II JAK2 Inhibitor