Key

Inclusion Criteria:

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

• - Diagnosis of PMF, post-PV MF, or post-ET MF according to the 2017 World Health Organization criteria.

Arm-specific criteria: Arm 1A:

• - Previously treated with JAK inhibitor(s) or Participant is ineligible for JAK inhibitor(s) - Anemia, defined as hemoglobin ≤10 g/dL during screening, or receiving RBC transfusions.

Arm 2A:

• - Previously treated with JAK inhibitor(s) or Participant is ineligible for JAK inhibitor(s) - Anemia, defined as hemoglobin ≤10 g/dL during screening, or receiving RBC transfusions.

Arm-specific criteria for 1B and 2B:

• - Has been receiving ruxolitinib for ≥8 weeks prior to C1D1 and on a stable dose for ≥4 weeks prior to C1D1.

• - Anemia, defined as hemoglobin ≤10 g/dL during screening, or receiving RBC transfusions.

Key

Exclusion Criteria:

• - Presence of the following cardiac conditions: 1.

New York Heart Association Class 3 or 4 heart failure. 2. QTcF >500 msec on the screening or C1D1 electrocardiogram (ECG) 3. Uncontrolled clinically significant arrhythmia (participants with rate-controlled atrial fibrillation are not excluded) 4. Acute myocardial infarction or unstable angina pectoris <6 months prior to C1D1.

• - History of stroke, deep venous thrombosis, or arterial embolism within 6 months prior to C1D1.

• - Any malignancy other than PMF, post-ET MF, or post-PV MF that has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy, or surgery, within 1 year prior to C1D1.

In-situ cancers, squamous cell, and basal cell carcinomas which have been fully excised, and monoclonal gammopathy of unclear significance are allowed at the discretion of the Investigator.

• - History of solid organ or hematological transplantation.

• - Presence of uncontrolled hypertension, defined as systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg despite adequate treatment.

• - Diagnosis of hemolytic anemia, active bleeding, hemoglobinopathies, or congenital disorders as a cause of the participant's anemia.

• - CTCAE Grade ≥2 bleeding events within the 3 months prior to C1D1.

• - Bone marrow blast percentage >2%.

Participants with blast % between 2-5% are allowed if at least 2 bone marrows >6 months apart demonstrate stability of blast percentage, these participants must be reviewed with the Medical Monitor prior to study entry.

• - Prior treatment with luspatercept, sotatercept, or other commercially available or investigational TGF-β inhibitors (all Arms) - Treatment within 28 days prior to C1D1 with: 1.

Erythropoiesis stimulating agent (ESA) 2. Granulocyte colony-stimulating factor (G-CSF) 3. Granulocyte-macrophage colony-stimulating factor (GM-CSF) 4. Thrombopoietin agonists (TPO) 5. Immunomodulator imide drugs (IMiDs; e.g., thalidomide, pomalidomide, lenalidomide) 6. Interferon

KER-050 is an investigational therapeutic protein designed to increase red blood cell and platelet production by inhibiting the signaling of a subset of the transforming growth factor beta (TGF-ß) family of proteins to promote hematopoiesis. It is being developed for the treatment of low blood cell counts, or cytopenias including anemia and thrombocytopenia in patients with Myelodysplastic Syndrome (MDS) and Myelofibrosis (MF)

Arms

Experimental: Arm 1a

Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) monotherapy

Experimental: Arm 1b

Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)

Experimental: Arm 2a

Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy

Experimental: Arm 2b

Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)

Interventions

Drug: - KER-050 monotherapy

KER-050 administered (SC) for up to 13 cycles

Drug: - KER-050 in combination with ruxolitinib

KER-050 administered (SC) for up to 13 cycles in combination with standard of care ruxolitinib