IDEAYA Biosciences Announces IDE892, a Potential Best-in-Class MTA-Cooperative PRMT5 Inhibitor, Initiates a Phase 1/2 Clinical Combination Study in MTAP-Deleted Pancreatic and Lung Cancers

• IDE892 is a potential best-in-class MTA-Cooperative PRMT5 combination partner with MAT2A and pan-RAS inhibitors, with favorable drug-like properties
• IDE892 has a CYP3A4 IC50 greater than 45 micromolar, and did not show time dependent inhibition of any of the 7 major cytochrome P450s (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4) based on full kinetic CYP inactivation assays
• IDE892 monotherapy Phase 1 escalation has cleared multiple dose cohorts with maximally efficacious target exposures anticipated at a favorable pill size and the MTD has not yet been reached. IDE892 monotherapy expansion is anticipated in Q3 2026
• MTAP-deletion is estimated to occur in up to 40% of pancreatic cancer and ~15% of non-small cell lung cancer (NSCLC)

SOUTH SAN FRANCISCO, Calif., June 15, 2026 /PRNewswire/ -- IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a leading precision medicine oncology company, today announced that the first patient has been enrolled in its Phase 1 clinical trial evaluating IDE892, a potential best-in-class methylthioadenosine (MTA)-cooperative inhibitor of PRMT5, in combination with IDE397, a potential first-in-class and best-in-class inhibitor of MAT2A, in MTAP-deleted solid tumors, with a focus on NSCLC and pancreatic cancer. In preclinical studies, dual inhibition of PRMT5 and MAT2A with the combination of IDE892 and IDE397 resulted in potent anti-tumor activity in MTAP-deleted tumor models, including complete and durable responses at well-tolerated doses below those required for monotherapy activity.

"We are excited to begin enrolling this Phase 1 combination trial evaluating IDE892 in MTAP-deleted pancreatic cancer and non-small cell lung cancer. We designed IDE892 with potential best-in-class properties, including approximately 1,400-fold selective MTA-PRMT5 cooperative binding versus SAM-PRMT5 cooperative binding intended to maximize its therapeutic window and favorable drug-like properties to enable rational combinations with IDE397 and pan-RAS inhibitors. This trial exemplifies our clinical development strategy of enabling rational combinations to deliver deeper and more durable responses for MTAP-deleted pancreatic cancer and lung cancer patients where there are currently no approved treatment options," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

Loss of MTAP leads to the accumulation of MTA and increased dependence on PRMT5 and MAT2A, two key enzymes involved in methylation and RNA splicing. In MTAP-deleted tumors, this biology establishes a robust synthetic lethal vulnerability that underpins the mechanistic rationale for combining IDE892 and IDE397. IDEAYA also entered into a clinical collaboration with Roche evaluating IDE892 in combination with RG6505, Roche's Phase 1 pan-RAS inhibitor, in MTAP-deleted pancreatic ductal adenocarcinoma (PDAC) to target the genetic co-alterations of MTAP and KRAS in this indication. Next, IDEAYA is advancing a third proprietary program for MTAP-deleted solid tumors targeting CDKN2A, the most common co-alteration of MTAP, through ongoing preclinical toxicology studies to support an investigational new drug (IND) application in the first half of 2027.

MTAP deletion is estimated to occur in approximately 15% of all solid tumors, including 15-20% of NSCLC and up to 40% of pancreatic cancer. There are no approved therapies for MTAP-deleted cancers, highlighting the significant unmet need and opportunity for new precision therapies for these patients.

About IDEAYA Biosciences

IDEAYA is a precision medicine oncology company committed to the discovery, development, and commercialization of transformative therapies for cancer. Our approach integrates expertise in small-molecule drug discovery, structural biology and bioinformatics with robust internal capabilities in identifying and validating translational biomarkers to develop tailored, potentially first-in-class targeted therapies aligned to the genetic drivers of disease. We have built a deep pipeline of product candidates focused on synthetic lethality and antibody-drug conjugates, or ADCs, for molecularly defined solid tumor indications. Our mission is to bring forth the next wave of precision oncology therapies that are more selective, more effective, and deeply personalized with the goal of altering the course of disease and improving clinical outcomes for patients with cancer.

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to the potential therapeutic benefits, safety, efficacy, tolerability, therapeutic window, selectivity, drug-like properties and best-in-class potential of IDE892; the potential of IDE892 as a combination partner with IDE397, RG6505 and other therapies; the anticipated enrollment, conduct, progress and timing of IDEAYA's Phase 1 clinical trials evaluating IDE892 as monotherapy and in combination with IDE397 and RG6505; expectations regarding the achievement of maximally efficacious target exposures, favorable pill size, dose escalation, maximum tolerated dose and clinical expansion cohorts; the potential for IDE892 and IDE397 to produce deeper, more durable or improved anti-tumor responses; the translational relevance of preclinical data and the ability of such data to predict future clinical outcomes; the prevalence of MTAP deletion in various tumor types and the associated market opportunity; the potential therapeutic utility of targeting MTAP-deleted cancers and related synthetic lethal vulnerabilities; the anticipated benefits of IDEAYA's collaboration with Roche; the advancement of IDEAYA's CDKN2A-targeted program and the anticipated timing of IND-enabling activities and regulatory submissions. Such forward-looking statements are based on management's current expectations, assumptions and beliefs and involve substantial risks and uncertainties that could cause actual results, including, but not limited to, those related to IDEAYA's clinical programs, commercial activities, and performance and/or achievements, to differ significantly and/or materially 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 the process of designing and conducting preclinical and clinical trials, enrollment rates, safety outcomes, efficacy results, regulatory interactions and decisions, and the ability to translate preclinical findings into clinical benefit, manufacturing and supply risks, competition, changes in standard of care, the timing and success of commercialization efforts, the outcome of collaborations and licensing arrangements, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of financial resources to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. A further description of 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, are in IDEAYA's filings with the Securities and Exchange Commission, including IDEAYA's most recent Annual Report on Form 10-K and any current and periodic reports filed with the U.S. Securities and Exchange Commission.

Investor and Media Contact

IDEAYA Biosciences
Joshua Bleharski, Ph.D.
Chief Financial Officer
[email protected]

SOURCE IDEAYA Biosciences, Inc.