- IDE397 (MAT2A) and AMG 193 (PRMT5) combination being evaluated
in an Amgen-sponsored Phase 1/2 clinical trial in MTAP-deletion
solid tumors
- Potential first-in-class synthetic lethality combination
targets mechanistically complementary nodes of the MTAP methylation
pathway – MAT2A and PRMT5
- Compelling preclinical anti-tumor efficacy presented at AACR
2023 with durable CRs for IDE397 / AMG 193 combination, each at
doses below maximally efficacious dose
SOUTH
SAN FRANCISCO, Calif., May 22,
2023 /PRNewswire/ -- IDEAYA Biosciences, Inc. (NASDAQ:
IDYA), a precision medicine oncology company committed to the
discovery and development of targeted therapeutics, announced that
the U.S. Food and Drug Administration (FDA) has completed its
review of the Amgen-sponsored Investigational New Drug (IND)
application and concluded that the proposed clinical study may
proceed to evaluate IDE397 in combination with AMG 193 in solid
tumors having MTAP deletion.
"We are pleased to collaborate with Amgen to clinically evaluate
the IDE397 and AMG 193 combination as a potential first-in-class
treatment for patients having solid tumors with MTAP deletion. We
believe that evaluation of this combination represents an exciting
and highly rational clinical study for patients with MTAP-deletion
tumors, based on the observed preclinical efficacy, tolerability
and selectivity," said Dr. Darrin M.
Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA
Biosciences.
"We have a deep understanding of the underlying biological
rationale for this combination of a MAT2A inhibitor and an
MTA-cooperative PRMT5 inhibitor. As presented at AACR 2023, gene
expression analysis of hallmark pathways, alternative splicing
analysis and retained intron analysis collectively demonstrate that
combined pharmacological inhibition of MAT2A and PRMT5 deepens the
biological response through maximal pathway suppression. The
enhanced combination effect was observed selectively in MTAP-null
models," said Dr. Michael White,
Ph.D., Chief Scientific Officer, IDEAYA Biosciences.
IDE397 is a potent and selective small molecule inhibitor
targeting methionine adenosyltransferase 2a (MAT2A). IDEAYA is
clinically evaluating IDE397 as monotherapy in a Phase 1/2 clinical
trial in patients having solid tumors with methylthioadenosine
phosphorylase (MTAP) deletion, with ongoing enrollment into Phase 2
monotherapy expansion cohorts in selected indications, including
squamous cell NSCLC, esophagogastric cancer, and bladder cancer.
AMG 193 is the Amgen investigational methylthioadenosine- (MTA-)
cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor.
The clinical evaluation of IDE397 with AMG 193 represents a novel
and potential first-in-class synthetic lethality combination.
Targeting two mechanistically distinct nodes of the MTAP
methylation pathway – MAT2A and PRMT5 provides a synergistic
approach for targeting MTAP-null tumors.
IDEAYA is collaborating with Amgen to clinically evaluate the
IDE397 and AMG 193 combination in patients having tumors with MTAP
deletion in an Amgen-sponsored clinical trial pursuant to a
Clinical Trial Collaboration and Supply Agreement, or CTCSA. The
Phase 1/2 clinical trial will evaluate the safety, tolerability,
pharmacokinetics, pharmacodynamics and efficacy of IDE397 in
combination with AMG 193.
IDEAYA and Amgen co-presented preclinical data at the 2023
Annual Meeting of the American Association for Cancer Research, or
AACR 2023, demonstrating deep and durable anti-tumor efficacy for
the IDE397 and AMG 193 combination in a NSCLC MTAP-null CDX model.
These data showed complete responses following approximately 30
days of combination treatment at doses below the maximally
efficacious preclinical dose for each compound, which were durable
from approximately study-day 40 to study-day 100. The IDE397 and
AMG 193 combination was well tolerated, with no observed body
weight loss through the approximate 30 days of combination
treatment in these models. Additionally, the results of gene
expression analysis of hallmark pathways, alternative splicing
analysis and retained intron analysis collectively demonstrated
that combined pharmacological inhibition of MAT2A and PRMT5 deepens
the biological response through maximal pathway suppression. The
enhanced combination effect was observed selectively in
MTAP-deleted relative to MTAP wild-type models.
Pursuant to the mutually non-exclusive CTCSA, Amgen is the
sponsor of the IDE397 and AMG 193 combination clinical trial and
each of IDEAYA and Amgen will supply their respective compounds,
IDE397 and AMG 193. Each party will pay fifty percent (50%) of the
external third-party costs for conducting the clinical trial and be
wholly responsible for their respective own internal costs and
expenses in support of the clinical trial. The companies will
jointly own clinical data and all intellectual property, if any,
relating to the combined use of IDE397 and AMG 193 from the
clinical trial. Each party retains commercial rights to its
respective compounds, including with respect to use as a
monotherapy or combination agent. The companies have formed a joint
oversight committee responsible for coordinating all regulatory and
other activities in support of the clinical trial.
About IDEAYA Biosciences
IDEAYA is a precision medicine oncology company committed to the
discovery and development of targeted therapeutics for patient
populations selected using molecular diagnostics. IDEAYA's approach
integrates capabilities in identifying and validating translational
biomarkers with drug discovery to select patient populations most
likely to benefit from its targeted therapies. IDEAYA is applying
its early research and drug discovery capabilities to precision
medicine targets, including synthetic lethality – which represents
an emerging class of precision medicine targets.
Forward-Looking Statements
This press release contains forward-looking statements,
including, but not limited to, statements related to the clinical
benefit to patients of the combination of IDE397 and AMG 193.
IDEAYA undertakes no obligation to update or revise any
forward-looking statements. For a further description of the risks
and uncertainties that could cause actual results to differ from
those expressed in these forward-looking statements, as well as
risks relating to the business of IDEAYA in general, see IDEAYA's
Quarterly Report on Form 10-Q filed on May
9, 2023 and any current and periodic reports filed with the
U.S. Securities and Exchange Commission.
Investor and Media Contact
IDEAYA Biosciences
Paul A. Stone
Chief Financial Officer
investor@ideayabio.com
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SOURCE IDEAYA Biosciences, Inc.