IDEAYA Biosciences Reports IDE397 Interim Phase 1 Clinical Data

Rhea-AI Summary

IDEAYA Biosciences, Inc. (NASDAQ: IDYA) announced promising interim Phase 1 clinical data for IDE397, a MAT2A inhibitor targeting solid tumors with MTAP gene deletions. The trial showed preclinical tumor SDMA suppression of 95-100% and robust plasma SAM modulation exceeding a 60% reduction. Cohort 5 reports a 95% reduction in tumor SDMA without drug-related serious adverse events. IDEAYA is expanding into monotherapy cohorts and targeting a data package delivery to GSK by mid-2022, potentially earning a $50 million option payment and up to $465 million in milestones.

Positive

• 95-100% tumor SDMA suppression observed in preclinical models.
• Cohort 5 shows 95% reduction of tumor SDMA with no serious adverse events.
• Plans for Phase 1/2 monotherapy and combination cohort expansions.
• Potential $50 million option exercise payment from GSK.

Negative

• None.

• 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 (C_max).    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.

FAQ

What are the interim results of IDEAYA's IDE397 Phase 1 clinical trial?

The interim results indicate a 95% reduction in tumor SDMA and robust plasma SAM modulation beyond 60% across cohorts.

How is IDEAYA collaborating with GSK for IDE397?

IDEAYA plans to deliver an option data package to GSK mid-2022, entitling them to a $50 million payment and development cost sharing.

What is the target market for IDE397?

IDE397 targets solid tumors with MTAP gene deletions, which occur in approximately 15% of solid tumors.

When will IDEAYA initiate monotherapy cohort expansions for IDE397?

Monotherapy cohort expansions are targeted for mid-2022, depending on the maximum tolerated dose observed.

What pharmacodynamics were observed in the IDE397 trial?

Clinical data shows dose-dependent reduction in SDMA and significant modulation of plasma SAM.