Inclusion Criteria:
* 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.
Exclusion Criteria:
* Anemia due to other causes (e.g., iron deficiency).
* Low platelet count
* Low neutrophil count
* History of hemoglobinopathies, intrinsic RBC membrane/enzyme defects, or hemolytic anemia.
* 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.
* Diagnosis of MPN, CMML, or overlap MDS/MPN per WHO classification.
* Any condition or concomitant treatment that may impair absorption of orally administered study intervention.
* Uncontrolled infection or severe organ dysfunction.
* 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.
* History of stem cell, bone marrow, or solid organ transplant.
* Known hypersensitivity to ofirnoflast or its excipients.
* Severe renal or hepatic impairment
* Inability to swallow tablets.
* Participation in another interventional clinical study within 90 days prior to first dose.
* QTcF \>480 ms.
* Prior treatment with ofirnoflast.
* 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.
