Rigel targets 2026 R289 dose-expansion data after 33% transfusion independence
Rigel plans to report Phase 1b dose-expansion results for R289 in lower-risk MDS by year-end 2026, building on a 33% transfusion-independence rate seen in dose escalation.
Executive Summary
- Rigel is running the dose-expansion phase of a Phase 1b study of R289 in patients with lower-risk MDS who have already exhausted approved therapies, and plans to disclose preliminary results before the end of 2026.
- Earlier dose-escalation data gave R289 a transfusion-independence signal in a subset of patients, setting a concrete benchmark the larger expansion cohort must reproduce or improve on to matter.
- Because the registered primary endpoint is safety and tolerability rather than efficacy, the trial is built to select a recommended dose, and transfusion independence is being tracked as a secondary measure.
- No competitor in this indication shares R289's dual kinase target, leaving the drug without a direct mechanistic precedent, while newer disease-modifying candidates from larger sponsors are advancing through later-phase trials in the same population.
The catalyst
Rigel Pharmaceuticals said it plans to share preliminary data from the dose-expansion phase of its Phase 1b study of R289 by the end of 2026, according to its January 2026 business update and a subsequent first-quarter 2026 disclosure. The trial, NCT05308264, enrolls adults with very low, low, or intermediate-1-risk MDS by the International Prognostic Scoring System who have relapsed on, are refractory to, or are intolerant of therapies with established clinical benefit in MDS, including erythropoiesis-stimulating agents, luspatercept, and hypomethylating agents. Rigel said enrollment in the dose-expansion phase is ongoing and it expects to complete enrollment and select a recommended Phase 2 dose in the second half of 2026. Rigel+1Rigel Provides Business Update and 2026 OutlookJan 12, 2026Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)NCT05308264
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What dose escalation showed
In the dose-escalation phase, R289 was, in Rigel's words, "generally well tolerated," and red blood cell transfusion independence was achieved by 33% (6 of 18) of evaluable transfusion-dependent patients receiving doses of 500 mg once daily or higher, including 40% (2 of 5) in the 500 mg twice-daily group. Those are dose-escalation results in a small cohort, not the dose-expansion data the trial is designed to report next; the expansion phase is the test of whether that signal holds at a larger scale and informs the dose Rigel selects for future studies. RigelRigel Provides Business Update and 2026 OutlookJan 12, 2026
The trial design
The registered primary endpoint for NCT05308264 is safety and tolerability, with pharmacokinetics and red blood cell transfusion independence at Week 24 tracked as secondary measures. The study is Phase 1, Phase 2, not registrational, and enrolls an anticipated 86 patients through a single experimental arm with an oral formulation. Enrollment has grown from an original target of 40 patients to 86 as the trial expanded scope, and the primary completion date has moved from January 2024 to August 2026 over three separate registry updates, alongside three enrollment revisions. The most recent enrollment count held flat at 86, a change the operational baseline for this design flags as routine rather than a deviation from plan. NCT05308264Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)NCT05308264
The regulatory and competitive frame
R289 carries FDA Fast Track and Orphan Drug designations for previously treated, transfusion-dependent lower-risk MDS, reflecting an unmet-need read in a population that has exhausted ESAs, luspatercept, and hypomethylating agents. No competitor in the supplied MDS trial landscape shares R289's dual IRAK1/4 kinase target; the closest active programs in the indication, including Bristol-Myers Squibb's luspatercept and Takeda's elritercept, work through different mechanisms such as TGF-beta superfamily ligand and activin receptor pathways. That leaves R289 without a direct mechanistic comparator, so the expansion cohort's transfusion-independence data will be read against the drug's own dose-escalation result rather than against a peer readout.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.