Rigel to present new data in MDS and AML from IRAK1/4 inhibitor R289 and REZLIDHIA at ASH 2025

Rigel Pharmaceuticals, Inc. a commercial stage biotechnology company focused on hematologic disorders and cancer, announced that data from the ongoing Phase 1b study of R289¹, a potent and selective inhibitor of dual interleukin receptor-associated kinases 1 and 4 (IRAK1/4), in patients with lower-risk myelodysplastic syndrome (MDS) who are relapsed or refractory (R/R) to prior therapies will be presented in an oral session at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition on Sunday, December 7, 2025. In addition, the ASH Annual Meeting will feature four poster presentations with data for REZLIDHIA^® (olutasidenib) for the treatment of R/R mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML). The ASH Annual Meeting is being held December 6-9, 2025, in Orlando, Florida and virtually.

“We are very pleased to have the opportunity to highlight our hematology and oncology portfolio at ASH this year,” said Lisa Rojkjaer, M.D, Rigel’s chief medical officer. “In particular, we are delighted that updated results from our Phase 1b study in patients with relapsed or refractory lower-risk MDS have been accepted for oral presentation. Despite the availability of approved agents, there remains an unmet need for additional therapies to treat patients with transfusion dependent lower-risk MDS, and we look forward to advancing the dose expansion phase of the study to completion.”

ASH Annual Meeting abstracts may be accessed online at www.hematology.org. Details of the oral and poster presentations, which will be available in the poster hall and via the virtual event platform, are as follows:

Oral Presentation

Sunday, December 7, 2025, 9:45am to 10:00am ET
Publication #: 489
Session Name: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Moving the Needle Through Novel Approaches in MDS and CMML
Presentation Title: An Update of Safety and Efficacy Results from a Phase 1b Study of R289, a Dual IRAK 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower Risk Myelodysplastic Syndrome (LR-MDS)
Presenter: Guillermo Garcia-Manero, M.D.

• As of the data cutoff date (July 15, 2025), 33 patients were enrolled in the dose escalation part of the study. Patients had a median age of 75 with a median of 3 prior therapies and 61% were high transfusion burden at baseline.
• Patients received R289 at doses ranging from 250 mg QD (once daily) to 500 mg BID (twice daily). For the 500 mg BID dose group, five patients were not yet evaluable (<16 weeks follow up) for determination of hematologic responses and one patient withdrew consent.
• R289 was generally well tolerated across all dose groups, with the most frequent treatment emergent adverse events (≥20%) being diarrhea (28.1%), constipation/fatigue (25% each), and creatinine/alanine aminotransferase (ALT) increased (21.9% each), the majority being Grade 1/2. One (1) dose limiting toxicity (DLT) (Grade 4 aspartate aminotransferase (AST) increase/Grade 3 ALT increase) was reported in the 750 mg dose group.
• For evaluable transfusion dependent patients (≥16 weeks follow up) at dose levels of at least 500 mg QD and higher, 4/13 patients (31%) achieved durable red blood cell transfusion independence (RBC-TI) for >8 weeks (500 mg QD [1/3], 750 mg QD [2/5], 500/250 mg QD [1/5]). Duration of RBC-TI was >16 weeks in 3 patients, >24 weeks in 2 patients, and >12 months in 1 patient. The median time to onset of RBC-TI was 2.2 months and the median duration of RBC-TI was 24.3 weeks.
• All responding patients had R835 plasma concentrations similar to those at which ≥50% LPS-induced inhibition of cytokine release was observed in healthy volunteers, indicating a potential threshold for dose response (≥500 mg QD).
• Updated data as of an October 28, 2025, data cutoff will be presented during the oral presentation.

Poster Presentations

Saturday, December 6, 2025, 5:30pm to 7:30pm ET
Publication #: 1659
Title: Clinical Characteristics and Response in Olutasidenib-Treated Relapsed/Refractory mIDH1 Acute Myeloid Leukemia (AML) Patients With Stable Disease Following Two Treatment Cycles
Presenter: Justin M. Watts, M.D.

• In the pivotal cohort of the Phase 2 registrational study, of 147 patients with R/R mIDH1 AML who received olutasidenib, 36 (24%) patients maintained stable disease (SD) after 2 cycles of treatment. Treatment duration ranged from 2.6 to 51.1 months. In these 36 patients, the subsequent response rate was 33% (n=12), including 6 (17%) complete remission (CR), 2 (6%) CR with partial hematologic recovery (CRh), 1 (3%) CR with incomplete recovery, 1 (3%) morphologic leukemia-free state, and 2 (6%) partial remission.
• Median time to best response from the start of treatment was 3.7 months (range: 2.8-5.7). 8 patients (22%) remained in SD and 16 (44%) had subsequent disease progression on study.
• In the 12 late responders, median duration of response (DOR), duration of CR/CRh, and duration of CR were 9.9 months, 17.3 months, and not reached, respectively. Additionally, of the late responders who were transfusion dependent for platelets (n=6) or red blood cells (n=9) at baseline, 5 (83%) and 8 (89%), respectively, became transfusion independent.
• Patients who achieved any late response had a longer median treatment duration (10.1 months) than non-responders. Median overall survival (OS) for late responders was 23.9 months and 32.7 months for those with CR/CRh.
• Patients with SD after 2 cycles of olutasidenib may experience meaningful clinical benefit with continued treatment, as one-third of these patients subsequently achieved a late response, resulting in a lower risk of death compared to patients with no later response. These findings suggest that early SD may not predict treatment failure and support continuing olutasidenib for at least 6 cycles or until disease progression.

Sunday, December 7, 2025, 6:00pm to 8:00pm ET
Publication #: 4616
Title: Assessment of Real-World Treatment Patterns and Outcomes of Olutasidenib in Patients with Mutated Isocitrate Dehydrogenase 1 Acute Myeloid Leukemia Previously Treated with Venetoclax Using Electronic Health Record Data
Presenter: Catherine Lai, M.D., MPH

• This retrospective cohort study analyzed data from Loopback Analytics’ electronic health records data in the U.S. until September 2024, incorporating structured clinical data and abstracted data from physician notes. Fourteen olutasidenib-treated patients in the Loopback database met inclusion criteria for the study.
• The overall response rate (ORR) was 50% (7/14) and the composite complete remission (CRc) rate was 36% (5/14). Among patients who achieved any response, 86% (6/7) received venetoclax immediately prior to olutasidenib.
• Median OS from olutasidenib initiation in the full cohort was 12.2 months, with the proportion of patients surviving 6, 9, and 12 months estimated to be 88%, 70%, and 53%, respectively.
• In this real-world cohort, despite the small sample size, 50% of patients responded to post-venetoclax olutasidenib, consistent with the clinical efficacy observed in the pivotal Phase 2 trial. These findings support the use of olutasidenib as a viable therapeutic option in post-venetoclax treatment settings.

Publication #: 3439
Title: Analysis of Hematologic Improvement (HI) by Time to Response in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients Treated with Olutasidenib
Presenter: Shira N. Dinner, M.D

• In the pivotal cohort of the Phase 2 registrational study (n=147), increases in hemoglobin were seen early in the course of treatment and levels continued to increase over 12 cycles. Similarly, platelet counts increased and blast percentages decreased over the course of treatment.
• A total of 71 patients (48%) achieved an overall response; 47 patients (32%) achieved CR and 51 (35%) achieved CR/CRh. Among CR/CRh responders, 28 (55%) achieved a response in <2 months, 17 (33%) from 2 to 4 months, and 6 (12%) at >4 months.
• Patients with a longer time to response tended to have lower baseline platelet counts and higher bone marrow blast percentages compared with earlier responders, suggesting lower hematopoietic reserve and greater disease burden.
• In 37 patients (25%) who had a best response of SD, several showed improvement in platelets and hemoglobin levels by end of treatment. 7 of 21 (33%) patients with prior platelet transfusion dependence became independent and 7 of 23 (30%) with prior red blood cell transfusion dependence became independent.
• This report highlights the hematological responses to olutasidenib in these patients with R/R mIDH1 AML and suggests that continuing olutasidenib treatment beyond 2 cycles may offer hematologic benefits, even in the absence of an early clinical response.

Monday, December 8, 2025, 6:00pm ET to 8:00pm ET
Publication #: 5213
Title: Olutasidenib Monotherapy in Patients With mIDH1 Acute Myeloid Leukemia Who Received Prior Intensive Chemotherapy
Presenter: Jay Yang, M.D.

• In the pivotal cohort of the Phase 2 registrational study (n=147), in patients with prior intensive chemotherapy (IC), the ORR was 50% with 35/105 (33%) achieving CR and 38/105 (36%) achieving CR/CRh. Median DOR was 15.5 months, with median duration of CR not reached and CR/CRh of 17.6 months.
• After a median follow up of 37.3 months, the median OS was 12.5 months. In comparison, in the 38 patients who received prior non-intensive therapy the ORR was 42%; 9/38 achieved CR and 10/38 achieved CR/CRh. The median DOR in this group was 16.2 months, with a median duration of CR and CR/CRh of 28.1 months and 29.0 months, respectively.
• Among this cohort of patients with R/R mIDH1 AML who had received prior IC, treatment with olutasidenib monotherapy produced clinically meaningful response rates that closely align with those observed in the overall population, with durable responses and acceptable tolerability.