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

On June 15, 2026 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a leading precision medicine oncology company, reported 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.

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"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.

(Press release, Ideaya Biosciences, JUN 15, 2026, View Source [SID1234668742])