- R289 was generally well tolerated and demonstrated signs of
preliminary clinical activity in elderly heavily pretreated LR-MDS
patients
- RBC-TI/HI-E responses occurred in 40% of evaluable TD
patients receiving R289 doses ≥500 mg QD
SOUTH
SAN FRANCISCO, Calif., Dec. 9, 2024
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a
commercial stage biotechnology company focused on hematologic
disorders and cancer, today announced initial data from its
ongoing Phase 1b study evaluating
R2891, an oral prodrug of R835, a potent and selective
dual inhibitor of IRAK1 and IRAK4, in patients with relapsed or
refractory (R/R) lower-risk myelodysplastic syndrome (LR-MDS). The
data is being presented today by Dr. Guillermo Garcia-Manero (Poster #: 4595) at the
66th American Society of Hematology (ASH) Annual Meeting
and Exposition being held December
7-10, in San Diego,
California and virtually.
"Elderly patients with transfusion dependent LR-MDS have few
effective treatment options. We are encouraged by the safety and
tolerability profile demonstrated by R289 thus far, and by the
first evidence of hematologic responses, namely transfusion
independence, observed," said Lisa Rojkjaer, M.D, Rigel's chief
medical officer. "The promising initial safety and efficacy data,
together with the recent Fast Track designation from the FDA,
underscores the potential of R289 as a new treatment option for
these patients."
Rigel's open-label, Phase 1b study
of R289 is enrolling patients with lower-risk MDS who are R/R to
prior therapies (NCT05308264). The primary objective of the study
is to assess the safety and tolerability of R289 with secondary
objectives to assess preliminary efficacy of R289 and characterize
its pharmacokinetic profile.
Key highlights from the interim data as of October 25, 2024, include:
- 22 patients were enrolled. The median age was 76; the median
number of prior therapies was 3 (range: 1-8); 73% and 77% of
patients had received a hypomethylating agent or luspatercept,
respectively; and 73% of patients were high transfusion burden
(HTB) at baseline.
- The median time on therapy was 4.6 months (range: 0.9-22.4
months). R289 was generally well-tolerated in this heavily
pretreated LR-MDS patient population, the majority of whom were
HTB. The most common treatment emergent adverse events (in ≥20% of
patients) were diarrhea and fatigue (each n=6, 27%), and chills,
nausea and pruritus (all n=5, 23%), which were all Grade 1/2. The
most frequent Grade 3/4 adverse events (AEs) were anemia, platelet
count decreased, pneumonia and alanine aminotransferase (ALT)
increased (all n=2,9%). One patient discontinued study drug due to
hyperuricemia (not drug related) and a second patient discontinued
study due to Grade 3 aspartate aminotransferase (AST)/Grade 4 ALT
increase (drug related).
- R835 exposure increased with increasing R289 dose. At doses
≥500 mg QD (once daily), R835 plasma concentrations at steady state
in some patients were ≥ those correlating with 50% or 90%
lipopolysaccharide-induced cytokine inhibition previously observed
in a healthy volunteer study.
- For the 18 efficacy evaluable patients (≥1 dose of R289 with ≥1
efficacy assessment), hematologic responses occurred in 40% (4/10)
of evaluable transfusion dependent patients receiving R289 doses
≥500 mg QD. Red blood cell (RBC)-transfusion independence
(RBC-TI) ≥8 weeks was achieved by three patients (1 at 500 mg QD
and 2 at 750 mg QD); two HTB patients achieved RBC-TI >24 weeks.
The median duration of RBC-TI was 29 weeks (range 12.7-51.9
weeks).
- One HTB patient receiving 500 mg QD achieved a minor
hematologic improvement-erythroid (HI-E) response, with a 64%
reduction in RBC transfusions compared to baseline.
Additional supporting data:
- The patients achieving RBC-TI had peak hemoglobin increases
exceeding 2.0 g/dL compared to baseline.
- There were no RBC-TI/HI-E responses in evaluable transfusion
dependence patients receiving R289 doses of 250 mg QD and 250 mg
BID.
R289 was recently granted Fast Track designation by the
U.S. Food and Drug Administration for the treatment of patients
with previously-treated transfusion dependent LR-MDS.
Poster #: 4595
Title: R289, a Dual IRAK 1/4 Inhibitor, in Patients
with Relapsed/Refractory (R/R) Lower-Risk Myelodysplastic Syndrome
(LR-MDS): Initial Results from a Phase 1b Study
Session: 637. Myelodysplastic Syndromes: Clinical and
Epidemiological: Poster III
Time: Monday, December 9,
2024, 6:00pm to 8:00pm PT
Location: Halls G-H (San
Diego Convention Center)
About R289
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.2
About Rigel
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 www.rigel.com.
- R289 is an investigational compound not approved by the
FDA.
- Sallman DA et al. Unraveling the Pathogenesis of MDS:
The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype.
Front Oncol. June 16, 2016. Accessed
September 30, 2024.
DOI: https://doi.org/10.3389/fonc.2016.00151
Forward-Looking Statements
This press release
contains forward-looking statements relating to, among other
things, clinical information regarding the progress of
Rigel's Phase 1b clinical
trial of R289 for the treatment of lower-risk myeloid dysplastic
syndrome. Any statements contained in this press release that
are not statements of historical fact may be deemed to be
forward-looking statements. Forward-looking statements can be
identified by words such as "plan", "potential", "may", "look to",
"expects", "will" and similar expressions in reference to future
periods. Forward-looking statements are neither historical facts
nor assurances of future performance. Instead, they are based on
Rigel's current beliefs, expectations, and assumptions and hence
they inherently involve significant risks, uncertainties and
changes in circumstances that are difficult to predict and many of
which are outside of our control. Therefore, you should not rely on
any of these forward-looking statements. Actual results and the
timing of events could differ materially from those anticipated in
such forward looking statements as a result of these risks and
uncertainties, which include, without limitation, risks and
uncertainties associated with clinical trials, and risks
that clinical trials may not be predictive of real-world results or
of results in subsequent clinical trials; the availability of
resources to conduct subsequent clinical trials or to develop
Rigel's product candidates; market competition; as well as other
risks detailed from time to time in Rigel's reports filed with the
Securities and Exchange Commission, including its Quarterly Report
on Form 10-Q for the quarter ended September
30, 2024 and subsequent filings. Any forward-looking
statement made by us in this press release is based only on
information currently available to us and speaks only as of the
date on which it is made. Rigel does not undertake any
obligation to update forward-looking statements, whether written or
oral, that may be made from time to time, whether as a result of
new information, future developments or otherwise, and expressly
disclaims any obligation or undertaking to release publicly any
updates or revisions to any forward-looking statements contained
herein, except as required by law.
Contact for Investors & Media:
Investors:
Rigel Pharmaceuticals, Inc.
650.624.1232
ir@rigel.com
Media:
David
Rosen
Argot Partners
646.461.6387
david.rosen@argotpartners.com
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