- Initiated monotherapy expansion cohorts with enrollment open
for NSCLC and esophagogastric tumors with MTAP deletion
- Initiated combination dose escalation cohorts with enrollment
open for combinations with taxanes and separately, with potential
first-in-class combinations, including pemetrexed
- Entered into Clinical Trial Collaboration and Supply Agreement
with Amgen to clinically evaluate IDE397 in combination with AMG
193, Amgen's investigational MTA-Cooperative PRMT5 inhibitor
- ctDNA Molecular Responses observed in 3 of 4 (75%) patients in
Cohorts 5 and 6, demonstrating target engagement and tumor
pharmacodynamic modulation
- Delivered Option Data Package to GSK, including preclinical
data and clinical data from the IDE397 monotherapy dose escalation
study of the Phase 1 clinical trial
SOUTH
SAN FRANCISCO, Calif., July 27,
2022 /PRNewswire/ -- IDEAYA Biosciences, Inc.
(Nasdaq:IDYA), a synthetic lethality focused precision medicine
oncology company committed to the discovery and development of
targeted therapeutics, announced clinical program updates for
IDE397, an investigational, potential best-in-class, small molecule
MAT2A inhibitor being evaluated in an ongoing Phase 1/2 clinical
trial (NCT04794699).
"We are excited to advance our clinical development of IDE397
and to progress our strategic collaborations with GSK and Amgen on
this program. Delivery of the IDE397 Option Data Package to
GSK represents an important milestone in our collaboration with
GSK. The clinical collaboration with Amgen enables clinical
evaluation of a potential first-in-class combination to inhibit two
synthetic lethal nodes within the MTAP pathway – MAT2A and PRMT5,
providing a complementary approach for targeting MTAP-null tumors,"
said Yujiro S. Hata, President and
Chief Executive Officer, IDEAYA Biosciences.
"The ctDNA molecular response clinical pharmacodynamic data
reflects evidence of dose-dependent tumor pharmacodynamic
modulation and target engagement at clinically achievable doses in
patients having MTAP-deleted tumors," said Dr. Michael White, Senior Vice President and Chief
Scientific Officer, IDEAYA Biosciences.
IDE397 is a potent and selective small molecule inhibitor
targeting methionine adenosyltransferase 2a (MAT2A), in patients
having solid tumors with methylthioadenosine phosphorylase (MTAP)
deletion. The MTAP deletion patient population is estimated
to represent approximately 15% of solid tumors, including
approximately 15% of NSCLC, 28% of esophageal, 26% of bladder, and
10% of esophagogastric cancers.
IDEAYA is leading early clinical development of IDE397, in
collaboration with GSK, in an ongoing Phase 1/2 clinical
trial. The company has initiated and is actively enrolling
patients into monotherapy expansion cohorts, including in NSCLC and
esophagogastric cancer. The company selected Cohort 5 dose as
its Phase 2 expansion dose, while it continues to dose escalate
into Cohort 6; it has not yet determined a maximum tolerated
dose.
IDEAYA has also initiated and is actively enrolling patients
into combination cohorts to evaluate IDE397 in combination with
docetaxel in NSCLC, with paclitaxel in esophagogastric cancer and
with pemetrexed in NSCLC. IDEAYA also plans to clinically
evaluate IDE397 in combination with AMG 193, Amgen's
investigational MTA-Cooperative PRMT5 inhibitor, pursuant to a
Clinical Trial Collaboration and Supply Agreement with Amgen.
In preclinical studies, IDEAYA observed a complete response
from evaluation of IDE397 and a representative MTA-cooperative
PRMT5 inhibitor combination therapy in in vivo xenograft
models.
IDEAYA reported additional clinical pharmacodynamic (PD) data
from translational analysis of patient liquid biopsy samples based
on circulating tumor DNA, or ctDNA, molecular responses.
These data were obtained using the GuardantOMNI™, a diagnostic
panel for genomic analysis of ctDNA. Molecular responses were
evaluated based on changes in mean variant allele frequency, or
VAF, on-treatment as compared to VAF levels at baseline. Patients
whose ctDNA showed a reduction of greater than 50% mean VAF
following treatment with IDE397 were characterized as having a
molecular response (ctDNA MR) as reported in Zhang et al (Cancer
Discovery, August 2020).
The IDE397 ctDNA molecular response data demonstrates target
engagement and a dose-dependent tumor pharmacodynamic
modulation. Molecular responses based on ctDNA were evaluable
for thirteen patients with liquid biopsy samples available at
baseline and after first treatment cycle. Across dose
escalation Cohort 1 thru Cohort 6, a ctDNA molecular response was
observed in four (4) of thirteen (13) evaluable patients
(31%). Significantly, ctDNA molecular responses were observed
in three (3) of four (4) evaluable patients (75%) treated with
IDE397 at higher doses in Cohorts 5 and 6, as well as in two (2) of
two (2) NSCLC evaluable patients (100%). This is indicative
of a preliminary signal of clinical activity and is consistent with
preclinical in vivo observations in patient-derived xenograft
models.
IDEAYA has delivered an IDE397 option data package to GSK. The
GSK option data package comprises preclinical data and clinical
data from the IDE397 monotherapy dose escalation study of the Phase
1 clinical trial.
About IDEAYA Biosciences
IDEAYA is a synthetic lethality focused 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
research and drug discovery capabilities to 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 clinical
evaluation of IDE397 in combination with AMG 193. Such
forward-looking statements involve substantial risks and
uncertainties that could cause IDEAYA's preclinical and clinical
development programs, future results, performance or achievements
to differ significantly from those expressed or implied by the
forward-looking statements. Such risks and uncertainties include,
among others, the uncertainties inherent in the drug development
process, including IDEAYA's programs' early stage of development,
the process of designing and conducting preclinical and clinical
trials, the regulatory approval processes, the timing of regulatory
filings, the challenges associated with manufacturing drug
products, IDEAYA's ability to successfully establish, protect and
defend its intellectual property, the effects on IDEAYA's business
of the worldwide COVID-19 pandemic, the ongoing military conflict
between Russia and Ukraine, and other matters that could affect
the sufficiency of existing cash to fund operations. 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 recent
Quarterly Report on Form 10-Q filed on May
10, 2022 and any current and periodic reports filed with the
U.S. Securities and Exchange Commission.
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SOURCE IDEAYA Biosciences, Inc.