⁃ Nuvisertib (TP-3654) Monotherapy Arm:

• Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF and intermediate or high-risk primary or secondary MF

• Previously treated with JAK inhibitor(s) and is intolerant, resistant, refractory or has lost response to the JAK inhibitor(s) or is ineligible to be treated with JAK inhibitor

• Fulfill the following clinical laboratory parameters:

• Platelet count ≥ 25 x 10\^9 /L, without assistance of growth factors or platelet transfusions

• ANC ≥ 1 x 10\^9/L without assistance of granulocyte growth factors

• Peripheral blood blast count \< 5%

• ECOG performance status ≤ 1

• Life expectancy ≥ 6 months

• Adequate renal function

• Adequate hepatic function

• Adequate coagulation function

• Splenomegaly (spleen volume of ≥ 450 cm3 by MRI or CT scan) within 2 weeks prior to Cycle 1 Day 1.

• Dose escalation: At least 2 symptoms measurable (score ≥ 1) using the MF-SAF

• Dose expansion: At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF

⁃ Nuvisertib (TP-3654) + Ruxolitinib Arm:

• Confirmed pathological diagnosis of PMF or post-PV-MF/post ET- MF and intermediate or high-risk primary or secondary MF

• On ruxolitinib treatment for ≥ 6 months, and on a stable dose of ruxolitinib (5 to 25 mg BID) for ≥ 8 weeks prior to the first dose of nuvisertib, but has either lost response or had a suboptimal or plateau in response

• Fulfills the following clinical laboratory parameters:

• Platelet count ≥ 50 × 10\^9/L (without assistance of growth factors or platelet transfusions)

• ANC ≥ 1 × 109/L without assistance of granulocyte growth factors

• Peripheral blood blast count \< 5% at screening

• Adequate renal function

• Adequate hepatic function

• Adequate coagulation function

• Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1

• At least 2 symptoms measurable with each score ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0

• ECOG performance status ≤ 1

• Life expectancy ≥ 6 months

⁃ Nuvisertib (TP-3654) + Momelotinib Arm

• Confirmed pathological diagnosis of PMF or post-PV-MF/post ET-MF and intermediate or high-risk primary or secondary MF

• Previously treated with an approved JAK inhibitor (except momelotinib) for PMF or Post-PV/ET MF for ≥ 12 weeks, or ≥ 4 weeks if JAK inhibitor therapy was complicated by a transfusion requirement of ≥ 4 units of red blood cells in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma

• Fulfills the following clinical laboratory parameters:

• Anemic, defined as Hb \<10 g/dL or requiring RBC transfusion at baseline

• Platelet count ≥ 50 × 109/L (without assistance of growth factors or platelet transfusions)

• ANC ≥ 1 × 109/L without assistance of granulocyte growth factors

• Peripheral blood blast count \< 5% at screening

• Adequate renal function

• Adequate hepatic function

• Adequate coagulation function

• Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1

• At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0

• ECOG performance status ≤ 1

• Life expectancy ≥ 6 months