• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local study participant privacy regulations.

• In the opinion of the Investigator, the participant is able and willing to comply with the requirements of the protocol (e.g., all study procedures, return for follow-up visits).

• Male or female ≥18 years of age, at the time of signing informed consent.

• Eastern Cooperative Oncology Group (ECOG) performance score ≤2 (see Appendix 2).

• Life expectancy ≥12 months per Investigator assessment.

• Confirmed diagnosis of PMF (prefibrotic or overtly fibrotic) according to the 2016 World Health Organization (WHO) criteria (see Appendix 3), post-PV MF, or post-ET MF according to the 2008 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria (see Appendix 4).

• Anemia, defined as:

‣ Having received ≥6 units of RBC transfusion for Hgb ≤8.5 g/dL in the 12 weeks prior to the planned C1D1, including ≥1 unit of RBC transfusion in the 28 days prior to C1D1; or

⁃ Having ≥3 evaluable Hgb measurements at \<10.0 g/dL including ≥1 evaluable Hgb measurement assessed 8 to 13 weeks prior to C1D1. Participants receiving RBC transfusions but not meeting criterion a. may enroll under criterion b. following the below parameters:

• All pre-transfusion Hgb values (defined as a Hgb assessed within the 3 days prior to a transfusion) should be recorded, and ≥1 pre-transfusion Hgb value is required.

∙ Hgb values collected within the 28 days following a transfusion will not be considered evaluable unless qualifying as a pre-transfusion Hgb; in cases where multiple transfusions are given in succession due to poor Hgb response, only the first pre-transfusion Hgb will be considered evaluable.

• Arm-specific criteria:

• Arms 1A and 2A:

⁃ Previously treated with JAK inhibitor(s) and, per the Investigator, discontinued due to one of the following reasons:

• Relapsed disease following treatment with JAK inhibitor(s)

∙ Refractory to treatment with JAK inhibitor(s)

∙ Intolerance to treatment with JAK inhibitor(s)

∙ Participant no longer met risk/benefit ratio to continue JAK inhibitor(s) OR

∙ Participant with prognostic score of intermediate-1 or higher per Dynamic International Prognostic Scoring System (DIPSS; see Appendix 7) and is ineligible for JAK inhibitor(s) in the opinion of the Investigator

⁃ Participants previously treated with JAK inhibitor(s) must have discontinued JAK inhibitor therapy ≥8 weeks before C1D1

• Arms 1B and 2B:

⁃ Has been receiving ruxolitinib prescribed for a diagnosis of PMF (prefibrotic or overtly fibrotic), post-PV MF, or post-ET MF for ≥8 weeks prior to C1D1 and on a stable dose for ≥4 weeks prior to C1D1. In Arm 2B only, at least 10 participants should have been on ruxolitinib for \<6 months prior to C1D1.

⁃ Meets ≥1 of the following criteria in the opinion of the Investigator:

• Current ruxolitinib treatment is considered to be providing insufficient control of the disease

∙ The participant's cytopenias are limiting the participant's ruxolitinib dose intensity

∙ The participant's disease is symptomatic and warrants additional therapy

• Arm 2C (Brazil only):

⁃ No prior treatment with JAK inhibitor(s) and no access to JAK inhibitor therapy as determined by the Investigator

⁃ Platelet count ≥ 50 × 109/L

⁃ Spleen volume ≥ 450 cm3 as assessed by CT or MRI collected during the pretreatment period

⁃ MF-SAF-TSS meeting at least one of the following criteria during the pretreatment period:

• 2 symptoms with average score ≥ 3

∙ Average total score ≥ 10

• Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception as described in the protocol.