Highlights 

  • R289 shows encouraging early efficacy at doses of 500 mg QD and above. 
  • One-third of evaluable transfusion-dependent patients achieved RBC-TI. 
  • Elderly, heavily pre-treated lower-risk MDS patients demonstrated meaningful hemoglobin increases. 
  • R289 maintained a manageable safety profile across dose groups. 
  • Phase 2 dose selection is expected in the second half of 2026. 

Rigel Pharmaceuticals (NASDAQ:RIGL) presented updated data from its ongoing Phase 1b study evaluating R289, an oral prodrug of the dual IRAK1/4 inhibitor R835, in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome. The findings were shared during an oral session at the 67th American Society of Hematology Annual Meeting. 

The dataset highlights a challenging patient group: the median age was 75, and participants had undergone a median of three prior treatments. A significant majority had previously been treated with luspatercept, erythropoiesis-stimulating agents, or hypomethylating agents. Additionally, 61 percent entered the study with a high transfusion burden. 

In this population, R289 demonstrated early signals of benefit. Among evaluable transfusion-dependent patients receiving doses of 500 mg QD or higher, 33 percent (6 of 18) achieved red blood cell transfusion independence (RBC-TI) lasting more than eight weeks. Several sustained responses extended beyond 16 and 24 weeks. Hemoglobin levels rose by 2.9 to 6.1 g/dL in those achieving RBC-TI, reflecting meaningful clinical improvement. 

Safety Profile Supports Continued Clinical Development 

Across all dose groups, R289 remained generally well tolerated. Median treatment duration was 5.5 months, and most adverse events were low-grade. Common treatment-emergent adverse events include diarrhea, constipation, fatigue, cough, and mild creatinine elevation. Higher-grade adverse events, such as anemia or neutrophil count decreases, were manageable and aligned with expectations for this disease population. 

Only one dose-limiting toxicity—elevated AST and ALT—occurred in the 750 mg cohort, reinforcing the suitability of doses at or above 500 mg QD for further evaluation. At these dose levels, R835 plasma concentrations achieved target inhibition thresholds aligned with pharmacodynamic effects seen in earlier healthy volunteer studies. 

Rigel has moved into the dose-expansion phase, where up to 40 patients will be randomized to 500 mg QD or 500 mg BID. These results will guide the selection of the recommended Phase 2 dose, expected in late 2026. 

Advancing a Targeted Approach in an Area of Unmet Need 

R289 is designed to inhibit IRAK1/4 signaling, a pathway implicated in the pro-inflammatory bone marrow environment that contributes to persistent cytopenias in lower-risk MDS. The company emphasizes the therapeutic potential of targeting toll-like receptors and interleukin-1 receptor signaling to address inflammation-driven marrow dysfunction. 

With Fast Track and Orphan Drug designations already secured, Rigel aims to advance R289 as a future treatment pathway for patients with transfusion-dependent disease who have limited alternatives. 

Conclusion 

The updated Phase 1b results support continued advancement of R289 as a potential therapy for lower-risk MDS patients who have exhausted standard options. With meaningful transfusion independence rates, sustained hemoglobin gains, and a manageable safety profile, R289 is positioned for a pivotal next step as Rigel moves toward Phase 2 development. 

Rigels’ shares closed at USD 48.92, marking a 3.25% increase from the prior session.