Rigel Pharmaceuticals Updates R2891 Clinical Data

Rigel Pharmaceuticals announced updated data from its ongoing Phase 1b study evaluating R2891, an oral prodrug of R835, a potent and selective dual inhibitor of interleukin receptor-associated kinases 1 and 4, in patients with relapsed or refractory lower-risk myelodysplastic syndrome. The data are being presented today in an oral session by Dr. Guillermo Garcia-Manero at the 67th American Society of Hematology, ASH, Annual Meeting and Exposition being held December 6-9, in Orlando, Florida and virtually. Key highlights from the updated data as of October 28, 2025, include: 33 patients were enrolled, representing a difficult-to-treat population. The median age was 75. The median number of prior therapies was 3; 76% of patients had received luspatercept, 73% had received an erythropoiesis stimulating agent, 67% had received an hypomethylating agent and 6% had received imetelstat. 61% of patients were high transfusion burden at baseline. 67% of patients were ring sideroblast negative. Median duration of treatment was 5.5 months. R289 was generally well tolerated across all dose groups in this heavily pre-treated lower-risk MDS patient population, the majority of whom were HTB at baseline. For evaluable transfusion dependent patients at dose levels of at least 500 mg QD and higher, 6/18 patients achieved durable red blood cell transfusion independence of greater than 8 weeks. Duration of RBC-TI was greater than 16 weeks in 4 patients and greater than 24 weeks in 3 patients. Of the 6 patients achieving RBC-TI, 5 had received an HMA. At doses greater than or equal to 500 mg QD, steady state R835 plasma concentrations reached or exceeded those associated with 50-90% inhibition of lipopolysaccharide-induced cytokine release previously observed in healthy volunteers.