Inclusion Criteria:

1. At least 18 years of age at the time of signing informed consent.
2. Capable of giving signed informed consent
3. Documented diagnosis of very low-, low-, or intermediate-risk MDS
4. Documented diagnosis of anemia
5. Relapsed or refractory disease after 1 to 3 prior lines of therapy for lower-risk MDS
6. Willing to provide a bone marrow aspirate at Screening.
7. Life expectancy of more than 6 months at screening.
8. Participants of childbearing potential must have a negative pregnancy test at screening (serum) and Day 1 (urine).
9. 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.

Exclusion Criteria:

1. Anemia due to other causes (e.g., iron deficiency).
2. Known clinically significant anemia due to iron, vitamin B12, or folate deficiency; autoimmune or hereditary hemolytic anemia; or gastrointestinal bleeding.
3. History of hemoglobinopathies, intrinsic RBC membrane/enzyme defects, or hemolytic anemia.
4. 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.
5. Diagnosis of MPN, CMML, or overlap MDS/MPN per WHO classification.
6. Any condition or concomitant treatment that may impair absorption of orally administered study intervention.
7. Uncontrolled infection or severe organ dysfunction.
8. 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).
9. Prior treatment with disease-modifying agents (e.g., hypomethylating agents) or immunosuppressive therapy, except prior lenalidomide (permitted).
10. Treatment with cytotoxic chemotherapy or experimental agents within 4 weeks prior to first dose.
11. History of stem cell, bone marrow, or solid organ transplant.
12. Known hypersensitivity to ofirnoflast or its excipients.
13. Severe renal or hepatic impairment
14. Inability to swallow tablets.
15. Participation in another interventional clinical study within 90 days prior to first dose.
16. QTcF >480 ms.
17. Prior treatment with ofirnoflast.