Inclusion Criteria:

• Age ≥ 18 years old.
• Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post-PV/ET MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT criteria).
• Symptomatic, defined as a MFSAF TSS of ≥ 10 units assessed by a single MFSAF v4.0 assessment during Screening, prior to Day BL1.
• Anemic, defined as any of the following:
  • For any subject; having received a transfusion within 28 days prior to the first day of Baseline assessments (BL1), with pre-transfusion Hgb < 10 g/dL (if a subject receives a transfusion after Day BL1, but prior to Randomization, this pre-transfusion hemoglobin will be used for eligibility); or
  • For subjects without ongoing JAK inhibitor therapy at Screening; Hgb < 10 g/dL during the Baseline Period (Days BL1 to Day BL7);
  • For subjects receiving ongoing JAK inhibitor therapy at Screening; Hgb < 10 g/dL during Screening, prior to the last day of Baseline assessments (Day BL7).
• Previously treated, with an approved JAK inhibitor for PMF or Post-PV/ET MF for ≥ 90 days, or ≥ 28 days if JAK inhibitor therapy is complicated by RBC transfusion requirement of ≥ 4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma a. Subjects who discontinued JAK inhibitor therapy prior to Screening require no additional non-treatment interval b. For subjects with ongoing JAK inhibitor therapy at Screening, JAK inhibitor therapy must be tapered over a period of at least 1 week. Subjects receiving a low dose of JAK inhibitor; e.g., 5 mg QD of RUX, may have a reduced taper period, or no taper, with the sponsor’s approval. A non-treatment interval begins ≥ 7 days prior to Day BL1 (the first of 7 consecutive days of baseline MFSAF assessments).
• Baseline splenomegaly, defined as having a palpable spleen at ≥ 5 cm, below the left costal margin, or with volume ≥ 450 cm³ on imaging (ultrasound, MRI or CT are acceptable), assessed during Screening at any point prior to Randomization.
• High risk, intermediate-2, or intermediate-1 risk MF as defined by DIPSS, or DIPSS-plus.
• No allogeneic stem cell transplant planned.
• Acceptable laboratory assessments:
  • Absolute neutrophil count (ANC) ≥ 0.75 × 10⁹/L;
  • Platelet count (PLT) ≥ 25 × 10⁹/L (without requirement for platelet transfusion;
  • Peripheral blast count < 10%;
  • Aspartate aminotransferase/ glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT) ≤ 3 × ULN (≤ 5 × ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days);
  • Calculated creatinine clearance (CCr) ≥ 30 mL/min according to Cockcroft-Gault;
  • Direct bilirubin ≤ 2.0 × ULN.

Exclusion Criteria:

• Use of the following treatments within the time periods noted:
  • MMB at any time;
  • Approved JAK inhibitor therapy (e.g., fedratinib or ruxolitinib) within 1 week prior to Day BL1;
  • Active anti-MF therapy within 1 week prior to Day BL1. Supportive care including steroids for non-MF indications may be used;
  • Potent cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization;
  • Investigational agent (including investigational JAK inhibitors) within 4 weeks prior to Randomization;
  • Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization;
  • Danazol within 3 months prior to Randomization;
  • Splenic irradiation within 3 months prior to Randomization;
  • Current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin.
• History of prostate cancer, with the exception of localized prostate cancer that has been treated surgically or by radiotherapy with curative intent and presumed cured.
• Prostate specific antigen (PSA) > 4 ng/mL.
• Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI or CT scan for spleen volume measurement per protocol requirements.
• Any of the following:
  • Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (subjects receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial);
  • Significant active or chronic bleeding event ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization;
  • Unstable angina pectoris within 6 months prior to Randomization;
  • Symptomatic congestive heart failure within 6 months prior to Randomization;
  • Uncontrolled cardiac arrhythmia within 6 months prior to Randomization;
  • QTcF interval > 500 msec, unless attributed to bundle branch block;
  • Current progressive thrombosis despite treatment;
  • History of porphyria;
  • Child-Pugh score ≥ 10;
  • Psychiatric illness, social situation, or any other condition that would limit compliance with trial requirements or may interfere with the interpretation of study results, as judged by investigator or sponsor;
  • Inability or unwillingness to comply with the protocol restrictions on MF therapy and other medications prior to and during study treatment.
• Subjects with a prior or concurrent malignancy, whose natural history or treatment has a significant potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding, or thalassemia.
• Known positive status for HIV.
• Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier (testing required for hepatitis B and C).
• Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per CTCAE v5.0.
• Presence of peripheral neuropathy ≥ Grade 2 per CTCAE v5.0.
• Women who are already pregnant or lactating.
• Known intolerance or hypersensitivity to MMB or DAN, their metabolites, or formulation excipients.
• Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
  • Note: DAN capsules contain lactose.