Phase 1b

.Rigel’s Phase 1b trial of oral R289, a dual IRAK1/4 inhibitor, in relapsed/refractory lower‑risk MDS showed good tolerability and preliminary efficacy. In patients ≥ 75 years with a median of three prior therapies, 33 % (6/18) of transfusion‑dependent subjects receiving ≥ 500 mg daily achieved durable red‑blood‑cell transfusion independence, with responders showing 2.9–6.1 g/dL hemoglobin gains. Common adverse events were mild GI symptoms and fatigue; grade 3/4 events included anemia and neutropenia. R289 met target plasma levels and holds FDA orphan‑drug and Fast Track designations.