IDEAYA Biosciences Reports IDE397 Interim Phase 1 Clinical Data

• 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

Excerpt from the Press Release:

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.

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