A Randomized, Open-Label, Phase 1-2 Study of ASTX727 Low Dose (ASTX727 LD) Extended Schedule in Subjects With Lower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS)

• Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.

• Men or women ≥18 years with IPSS low risk or Int-1 MDS (all subjects). Subjects must have had at least 1 of the following disease-related criteria during the 8 weeks before randomization:

‣ Red blood cell (RBC) transfusion dependence of 2 or more units of RBC transfusions (RBC transfusion administered for hemoglobin (Hb) levels ≤9.0 g/dL are counted).

⁃ Hb of \<9.0 g/dL in at least 2 blood counts prior to randomization or in 1 blood count if RBC transfusion was received.

⁃ Absolute Neutrophil Count (ANC) of \<0.5 × 10\^9/L in at least 2 blood counts prior to randomization.

⁃ Platelet counts of \<50 × 10\^9/L in at least 2 blood counts prior to randomization.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

• Adequate organ function.

• Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group \[CTFG\]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.

• Women of child-bearing potential must agree to use contraceptive measures of birth control for 6 months after completing treatment; men must use contraceptive measures and agree not to father a child for at least 3 months after completing treatment.