A Study to Evaluate Ofirnoflast in Adults With Very Low- to Intermediate-risk Myelodysplastic Syndromes Requiring Red Blood Cell Transfusions

Prior treatment

• Prior history of AML, secondary MDS, or other malignancy (except non-melanoma skin cancer or in situ cervical/breast carcinoma) unless disease-free for \>1 year.
• Any condition or concomitant treatment that may impair absorption of orally administered study intervention.
• Concomitant intercurrent illness or condition that, per investigator judgment, would compromise safe participation (e.g., uncontrolled hypertension, uncontrolled seizure, unstable angina, new-onset/exacerbated cardiac arrhythmia).
• Prior treatment with disease-modifying agents (e.g., hypomethylating agents) or immunosuppressive therapy, except prior lenalidomide (permitted).
• Treatment with cytotoxic chemotherapy or experimental agents within 4 weeks prior to first dose.
• Participation in another interventional clinical study within 90 days prior to first dose.
• Prior treatment with ofirnoflast.

Other illness

• History of hemoglobinopathies, intrinsic RBC membrane/enzyme defects, or hemolytic anemia.
• Uncontrolled infection or severe organ dysfunction.
• History of stem cell, bone marrow, or solid organ transplant.
• Known hypersensitivity to ofirnoflast or its excipients.
• Severe renal or hepatic impairment
• Medications or food products that are strong inhibitors, substrates, and inducers of CYP3A4/5, CYP2C9, P-glycoprotein (P-gp) and/or Breast Cancer Resistance Protein (BCRP) may cause drug-drug interactions and should be avoided.

Lab values

• Low platelet count
• Low neutrophil count

Other

• Anemia due to other causes (e.g., iron deficiency).
• Diagnosis of MPN, CMML, or overlap MDS/MPN per WHO classification.
• Inability to swallow tablets.
• QTcF \>480 ms.

• At least 18 years of age at the time of signing informed consent.
• Capable of giving signed informed consent
• Documented diagnosis of very low-, low-, or intermediate-risk MDS
• Documented diagnosis of anemia
• Documented low serum erythropoietin level
• Relapsed or refractory disease after 1 to 3 prior lines of therapy for lower-risk MDS
• Willing to provide a bone marrow aspirate at Screening.
• Eastern Cooperative Group Performance Status (ECOG PS) of 0, 1, or 2
• Life expectancy of more than 6 months at screening.
• Participants of childbearing potential must have a negative pregnancy test at screening (serum) and Day 1 (urine).
• Participants and partners must use contraception consistent with local regulations and protocol-defined criteria during the intervention period and for at least 30 days after the last dose; periodic abstinence and withdrawal are not acceptable methods.