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

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

• Diagnosis of MDS with or without RS (as determined in an evaluable bone marrow aspirate, read by an independent central reader to confirm diagnosis at Screening) according to the World Health Organization 2016 classification that meets the IPSS-R classification of very low, low, or intermediate risk disease.

• Transfusion dependence assessed in the 16 weeks immediately preceding randomization in two 8-week blocks, classified as either:

• a. LTB, defined as 4 to 7 RBC units per 16 weeks; or b. HTB, defined as ≥ 8 RBC units per 16 weeks; and c. For all participants: i. Only transfusion events for a pretransfusion Hgb \< 10 g/dL are counted toward eligibility; ii. At least 1 transfusion event in each 8-week period and a minimum of 2 transfusion events separated by ≥ 7 days within the 16-week period immediately preceding randomization; and iii. No consecutive 56-day period can be RBC transfusion-free during the 16-week period immediately preceding randomization.

• Refractory or intolerant to prior ESA treatment (discontinued ≥ 8 weeks before randomization), or unlikely to respond to ESA treatment, defined as follows:

• a. Refractory to prior ESA treatment: documentation of nonresponse or a response that was no longer maintained with a prior ESA-containing regimen, either as a single agent or combination (e.g., with granulocyte colony-stimulating factor \[G-CSF\]); ESA regimen must have been either: i. Recombinant human EPO ≥ 40,000 IU/week for ≥ 8 doses or equivalent; or ii. Darbepoetin alpha ≥ 500 μg every 3 weeks for ≥ 4 doses or equivalent.

• b. Intolerant to prior ESA treatment: documentation of discontinuation of a prior ESA-containing regimen, either as a single agent or combination (e.g., with G-CSF), at any time after introduction due to intolerance or an AE.

• c. Unlikely to respond to ESA treatment: low chance of response to ESA based on an endogenous serum EPO level \> 200 U/L.

• Less than 5% blasts in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader.

• Eastern Cooperative Oncology Group performance status of 0 to 2

• Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception

• 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).