Inclusion Criteria for Participants with MF and Anemia:

1. Age 18 years or older at the time of signing the informed consent (ICF).
2. For Phase 1b: Dynamic International Prognostic Scoring System (DIPSS) score of 3 to 4 (intermediate-2 risk) or ≥ 5 (high-risk) primary MF, post-PV MF, and/or post-ET MF, as confirmed in the most recent local bone marrow biopsy report, according to World Health Organization (WHO) 2016 criteria. For Phase 2a: In addition to the criteria above, DIPSS score of 1 to 2 (intermediate-1 risk) may also be included.
3. Washout of at least 28 days prior to Screening of the following treatments: androgens, erythropoietin, cladribine, immunomodulators (lenalidomide, thalidomide), interferon alpha-2a or any other MF-directed therapy. Systemic corticosteroids are permitted for non-hematological conditions if stable or decreasing dose for ≥ 28 days prior to Screening and receiving an equivalent to ≤ 10 mg prednisone for the 28 days immediately prior to Screening.
4. Anemia: For Phase 1b: Hemoglobin (Hgb) \< 10 g/dL on ≥ 3 assessments over 84 days prior to Screening, without RBC transfusion, or Hgb \< 10 g/dL and receiving RBC transfusions periodically but not meeting criteria for TD participant as defined for the TD cohort. The baseline Hgb value for these participants is the lowest Hgb level during the 84 days prior to Screening, or RBC transfusion dependence, defined as an RBC transfusion frequency of ≥ 6 units packed RBCs (PRBC) over the 84 days immediately prior to Screening. There must not be any consecutive 42-day period without an RBC transfusion in the 84-day period, and the last transfusion must be within 28 days prior to Screening. For Phase 2a: RBC transfusion dependence, defined as an RBC transfusion frequency of ≥ 6 units PRBC over the 84 days immediately prior to Screening. There must not be any consecutive 42-day period without an RBC transfusion in the 84-day period, and the last transfusion must be within 28 days prior to Screening.

For Phase 2a: RBC transfusion dependence, defined as an RBC transfusion frequency of ≥6 units PRBC over the 84 days immediately prior to Screening. There must not be any consecutive 42-day period without an RBC transfusion in the 84-day period, and the last transfusion must be within 28 days prior to Screening.
5. Stable dose of JAK inhibitor (except momelotinib) and/or hydroxyurea, or, if taking any other treatment for MF, stable for at least 28 days prior to Screening. Momelotinib use requires 12 weeks of stable dosing prior to Screening. If subject discontinues JAK inhibitor (including momelotinib) and/or hydroxyurea prior to Screening, a 28-day washout period is required.
6. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
7. Infusion of hematopoietic stem cell transplant not anticipated within 8 months after Screening.
8. Transferrin saturation \<75% (local lab acceptable).
9. Liver iron concentration by MRI \< 7 mg/g dry weight within 3 months of eligibility confirmation.
10. Serum ferritin ≥ 30 μg/L at Screening.
11. Platelet count ≥ 25,000/μL and \< 1,000,000/μL; neutrophils ≥ 1,000/μL; and total white blood cell (WBC) count \< 50,000/μL at Screening.
12. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula.
13. Aspartate aminotransferase (AST) and alanine transaminase (ALT) \< 3.0 x upper limit of normal (ULN) at Screening.
14. Direct bilirubin \< 2x ULN at Screening. Higher levels are acceptable if these can be attributed by the Investigator to ineffective erythropoiesis.

Inclusion Criteria for Exploratory Cohort of Participants with MDS and Anemia:

1. Age 18 years or older at the time of signing the ICF.
2. Molecular International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate (ie, lower risk) MDS or MDS/MPN with ringed sideroblasts and thrombocytosis (RS-T) as confirmed in the most recent local bone marrow biopsy report according to WHO criteria.
3. Washout of at least 28 days is required for prior anemia/neutropenia-directed therapies, including:

1. Androgens
2. Erythropoietin-stimulating agents
3. Luspatercept or sotatercept (ACE-011)
4. Granulocyte colony-stimulating factor (G-CSF) OR granulocyte-macrophage CSF (GM-CSF)
5. Systemic corticosteroids (except for participants on a stable or decreasing dose for ≥28 days prior to randomization for non-hematological conditions and receiving an equivalent to ≤10 mg prednisone for the 28 days immediately prior to Screening) Screening can begin before the 28-day washout is completed, but the washout period must be completed prior to collection of Screening blood samples.
4. Anemia:

1. Baseline Hgb of \<10 g/dL on ≥3 assessments over 84 days prior to Screening, without RBC transfusion, or Hgb \<10 g/dL and receiving RBC transfusions periodically during the 84 days prior to Screening or requiring transfusions
2. Medical history of ≤12 units of PRBC for MDS and anemia
5. ECOG performance score ≤2
6. Infusion of hematopoietic stem cell transplant not anticipated within 8 months after Screening
7. Transferrin saturation \<75% (local lab acceptable)
8. Liver iron concentration by MRI \<7 mg/g dry weight within 3 months of eligibility confirmation by central review
9. Serum ferritin ≥30 μg/L at Screening
10. Platelet count ≥25,000 μL and \<1,000,000/μL, and total WBC count \<50,000 μL at Screening or otherwise approved by Sponsor
11. eGFR ≥30 mL/min/1.73 m2 by the CKD-EPI formula
12. AST and ALT \<3x ULN at Screening
13. Direct bilirubin \<2x ULN at Screening. Higher levels are acceptable if these can be attributed by the Investigator to ineffective erythropoiesis.

Exclusion Criteria for Participants with MF and Anemia:

Medical History, Participants with MF and Anemia:

1. Hereditary hemochromatosis
2. Hemoglobinopathy or intrinsic RBC defect associated with anemia
3. Total splenectomy
4. Hematopoietic cell transplant within the past 10 years
5. Current anemia from iron deficiency, vitamin B12 or folate deficiency, infection, or bleeding
6. Active immune-mediated hemolytic anemia
7. Symptomatic bleeding, unrelated to surgery, in a critical area or organ and/or bleeding causing a decrease in Hgb of ≥ 2 g/dL or leading to transfusion of ≥ 2 units of RBCs in the 6 months prior to Screening
8. Major surgery within 8 weeks prior to Screening or incomplete recovery from any previous surgery
9. Malignancy within the past 3 years, other than primary MF, post-ET, or post-PV MF. The following history or concurrent conditions are allowed:

1. basal or squamous cell carcinoma
2. carcinoma in situ of the cervix or the breast
3. histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis \[TNM\] clinical staging system) A history of completed treatment (medical or surgical) of stage 1-2 cancers may be permitted with prior Sponsor agreement.
10. Stroke, deep vein thrombosis, or pulmonary or arterial embolism within 6 months prior to Screening
11. Known allergic reaction to any study drug excipient, or anaphylaxis to any food or drug
12. A history of anti-drug antibody formation
13. Inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or known to have left ventricular ejection fraction \< 35%
14. Active Hepatitis B or C, or human immunodeficiency virus (HIV) with detectable viral load
15. Uncontrolled fungal, bacterial, or viral infection (ongoing signs/symptoms related to the infection, without improvement despite appropriate treatment)

Treatment History, Medical History, Participants with MF and Anemia:
16. Iron chelation therapy in the 28 days prior to Screening
17. Change in anticoagulant therapy regimen within 8 weeks prior to Screening

Laboratory Exclusions, Medical History, Participants with MF and Anemia:
18. Peripheral blood myeloblasts ≥ 10% of WBC differential at most recent evaluation prior to Screening
19. Positive direct antiglobulin test in conjunction with a reactive RBC eluate at Screening

Exclusion Criteria for Exploratory Cohort of Participants with MDS and Anemia:

Medical History, Participants with MDS and Anemia

1. Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation from other diseases
2. Peripheral blasts ≥5%
3. Prior treatment with hypomethylating agent or other acute myeloid leukemia (AML)-like combination chemotherapy
4. Prior treatment with luspatercept or sotatercept (ACE-011) AND erythropoietin -stimulating agent, unless approved by Sponsor
5. Hereditary hemochromatosis
6. Hemoglobinopathy or intrinsic RBC defect associated with anemia
7. Total splenectomy
8. Hematopoietic cell transplant within the past 10 years
9. Current anemia from iron deficiency, vitamin B12 or folate deficiency, infection, or bleeding
10. Active immune-mediated hemolytic anemia
11. Symptomatic bleeding, unrelated to surgery, in a critical area or organ and/or bleeding causing a decrease in Hgb of ≥2 g/dL or leading to transfusion of ≥2 units of RBCs in the 6 months prior to Screening
12. Major surgery within 8 weeks prior to Screening or incomplete recovery from any previous surgery
13. Malignancy within the past 3 years, other than MDS or MDS/MPN without excess blasts. The following history or concurrent conditions are allowed:

1. basal or squamous cell carcinoma
2. carcinoma in situ of the cervix or the breast
3. histologic finding of prostate cancer (T1a or T1b using the TNM clinical staging system) A history of completed treatment (medical or surgical) of stage 1-2 cancers may be permitted with prior Sponsor agreement
14. Stroke, deep vein thrombosis, or pulmonary or arterial embolism within 6 months prior to Screening
15. Known allergic reaction to any study drug excipient, or anaphylaxis to any food or drug
16. A history of antidrug antibody formation
17. Inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or known to have left ventricular ejection fraction \<35%
18. Active hepatitis B or C, or HIV with detectable viral load
19. Uncontrolled fungal, bacterial, or viral infection (ongoing signs/symptoms related to the infection, without improvement despite appropriate treatment) Treatment History, Participants with MDS and Anemia
20. Iron chelation therapy in the 28 days prior to Screening
21. Change in anticoagulant therapy regimen within 8 weeks prior to Screening Laboratory Exclusions, Participants with MDS and Anemia
22. Positive direct antiglobulin test in conjunction with a reactive RBC eluate at Screening