- Observed preclinical complete suppression (~95-100%) of tumor
SDMA in multiple MTAP-deleted patient derived xenograft (PDX)
models across indications
- Interim IDE397 clinical data demonstrates robust plasma
pharmacodynamic modulation, exceeding target of >60% reduction
of plasma SAM across all evaluated cohorts
- Observed clinical exposure-dependent reduction of tumor
pharmacodynamic biomarker SDMA in target tumor types, including 95%
reduction of tumor SDMA
- No drug-related Serious Adverse Events (SAEs) observed through
Cohort 5
- Enrolling into Cohort 6 of the dose escalation Phase 1
evaluating IDE397; have not yet determined the maximum tolerated
dose (MTD) through Cohort 5
- Targeting initiation of Phase 1/2 monotherapy cohort expansions
in NSCLC and esophagogastric cancer, as well as initiation of
combination cohorts, in mid-year 2022
- Targeting delivery of option data package to GSK mid-year 2022,
including preclinical, and clinical adverse events,
pharmacokinetic, and plasma and tumor pharmacodynamic data
- If GSK elects to opt-in, IDEAYA entitled to receive a
$50 million option exercise payment,
with ongoing development cost sharing of 80% GSK / 20% IDEAYA, and
aggregate development / regulatory milestones of $465 million
SOUTH SAN FRANCISCO,
Calif., March 15,
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 interim Phase 1 clinical data for
IDE397, a potential best in class methionine adenosyltransferase 2a
(MAT2A) inhibitor. The reported data include a summary of adverse
events, as well as pharmacokinetic (PK) data and plasma and tumor
pharmacodynamic (PD) data.
IDEAYA is evaluating IDE397 in an ongoing Phase 1 clinical trial
in patients with tumors harboring methylthioadenosine phosphorylase
(MTAP) gene deletion, which occurs in approximately 15% of solid
tumors. The company is currently enrolling patients into
Cohort 6 of the dose escalation portion of the clinical trial, with
no observed drug-related SAE's and no observed dose limiting
toxicity (DLT) through Cohort 5.
"We continue to be encouraged by the emerging pharmacokinetic,
pharmacodynamic and safety profile of IDE397. We have
demonstrated preliminary tolerability in a dose range that is
showing evidence of maximal SDMA suppression, and we look forward
to the potential for clinical benefit," said Dr. Matthew Maurer, M.D., Vice President and Head of
Clinical Oncology and Medical Affairs at IDEAYA Biosciences.
Clinical PK exposures of IDE397 exhibit dose-proportional
increases from Cohort 1 through Cohort 5, as measured by
area-under-curve (AUC) and maximum concentration (Cmax).
The clinical PK data support an acceptable dosing
regimen. Clinical plasma PD data for IDE397 demonstrates
robust modulation of plasma S-adenosyl methionine (SAM), a proximal
PD biomarker of target engagement. The observed steady state
plasma SAM exceeds the target of >60% reduction of plasma SAM
across all evaluated cohorts. Cohort 5 showed a mean 77%
reduction of steady state plasma SAM as compared to baseline.
Clinical tumor PD data for IDE397 shows exposure-dependent
reduction of symmetric dimethyl arginine (SDMA) in target tumor
types. SDMA is a tumor PD biomarker that reflects mechanistic
modulation of protein methylation, including for pre-mRNA
splicing. Treatment with IDE397 in Cohort 5 resulted in a 95%
reduction of tumor SDMA in a non-small cell lung cancer (NSCLC) as
measured by immunohistochemistry (IHC) score.
IDEAYA is targeting monotherapy cohort expansion and initiation
of combination cohorts mid-year 2022. The timing of the expansion
and/or combination cohorts may be influenced by observation of the
MTD in the dose escalation portion of the Phase 1 clinical
trial.
"The interim clinical PK/PD data and tolerability profile are
consistent with our robust preclinical data and support our plan to
aggressively advance IDE397 into monotherapy expansion cohorts and
rational combination therapies," said Mike
White, Senior Vice President and Chief Scientific Officer of
IDEAYA Biosciences.
IDEAYA is leading research and development of IDE397 through
early clinical development, in collaboration with GlaxoSmithKline
(GSK), and is targeting delivery of an option data package to GSK
mid-year 2022, following dose selection for an expansion cohort or
establishing the MTD. Subject to GSK's election to opt–in and, if
required, HSR clearance, the company is entitled to receive a
$50 million payment, and ongoing
development costs will be shared as 80% GSK / 20% IDEAYA. In
addition, IDEAYA is entitled to potential development and
regulatory milestones aggregate up to $465
million. Upon commercialization, IDEAYA is entitled to 50%
of U.S. net profits and tiered royalties on global non-U.S. net
sales ranging from high single digit to sub-teen double digit
percentages, as well as certain commercial milestones of up to
$475 million.
IDEAYA will host a conference call and webcast at 8:30 a.m.
ET on Tuesday, March 15, 2022. The agenda topics will
include an update on interim clinical data from the ongoing IDE397
Phase 1 clinical trial dose escalation, including a summary of
adverse events and pharmacokinetic, plasma pharmacodynamic and
tumor pharmacodynamic data. The company will also report
fourth quarter and full year 2021 financial results and provide
other corporate updates.
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 early 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 (i) the timing of initiation of Phase 1/2
monotherapy cohort expansions and combination cohorts and (ii) the
timing of delivery of the option data package to GSK. 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 November 15, 2021, and any current and periodic
reports filed with the U.S. Securities and Exchange Commission.
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SOURCE IDEAYA Biosciences, Inc.