Rigel Pharmaceuticals, Inc. recently announced the first patient has been enrolled in the dose expansion phase of the ongoing Phase 1b study of R289 in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome (MDS). R289 is Rigel’s potent and selective dual inhibitor of interleukin receptor-associated kinases 1 and 4 (IRAK1/4).

“Today marks an important step in the evaluation of R289 for the treatment of patients with transfusion dependent lower-risk MDS, a disease with a persistent unmet need despite the availability of approved agents. In the dose expansion phase of this study, patients with transfusion dependent R/R lower-risk MDS will be randomized to receive a 500 mg R289 dose either once or twice daily,” said Lisa Rojkjaer, MD, Rigel’s chief medical officer. “The outcome of this phase of the study will be the selection of the recommended Phase 2 dose of R289 for future clinical studies. We remain grateful to our investigators for their continued support of our program.”

Rigel’s open-label, Phase 1b study of R289 is evaluating the safety, tolerability, pharmacokinetics and preliminary activity in patients with R/R lower-risk MDS (NCT05308264). Enrollment in the dose escalation phase of the study was completed in July 2025, and the company expects to share updated data from the study later this year. In the dose expansion phase of the study, up to 40 patients will be randomized into dose levels of 500 mg once daily or 500 mg twice daily to determine the recommended Phase 2 dose (RP2D) for future development of R289. In addition, once the RP2D has been determined, an exploratory cohort of erythropoiesis-stimulating agent (ESA) R/R, or ineligible, lower-risk MDS patients will be evaluated at the RP2D.

R289 was previously granted Orphan Drug designation for the treatment of myelodysplastic syndromes and granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS by the FDA.

R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro- inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.

Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company’s marketed products and pipeline of potential products, visit http://www.rigel.com.