On July 27, 2026 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a leading precision medicine oncology company, reported that initiation of Part 2 monotherapy expansion has been achieved in its Phase 1/2 clinical trial evaluating IDE892, a potential best-in-class methylthioadenosine (MTA)-cooperative inhibitor of PRMT5, in MTAP-deleted solid tumors, with a focus on non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC). IDE892 Phase 1/2 monotherapy expansion has been initiated at projected efficacious target human exposures where 24-hours target EC90 coverage have been achieved. The IDE892 maximum tolerated dose (MTD) has not yet been reached in the ongoing dose escalation.
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"We are excited to initiate monotherapy expansion evaluating IDE892 in MTAP-deleted PDAC and NSCLC. We designed IDE892 to be a potential best-in-class PRMT5 inhibitor, including approximately 1,400-fold selective MTA-PRMT5 cooperative binding versus SAM-PRMT5 cooperative binding, lack of brain penetrance, and favorable drug-like properties intended to maximize its therapeutic window as both a monotherapy agent and in combination. We are well positioned to have the industry’s deepest MTAP-deletion pipeline, with IDE892, MAT2A inhibitor IDE397 in Phase 2, and the potential first-in-class CDKN2A lead molecule advancing in preclinical toxicology studies for a target IND in the first half of 2027," 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, where the first-patient-in (FPI) was achieved in mid-2026. 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 and potential first-in-class program for MTAP-deleted solid tumors targeting CDKN2A, the most common co-alteration of MTAP-deletion, through ongoing preclinical toxicology studies to support an investigational new drug (IND) application in the first half of 2027. IDEAYA anticipates that rational combination doublets may be pursued with IDEAYA’s CDKN2A lead molecule and IDE892 to target the co-alterations of MTAP and CDKN2A, and pan-RAS inhibitors, as the key tumor suppressor gene CDKN2A has been reported to be deficient in approximately 70% of PDAC.
MTAP deletion is estimated to occur in approximately 15% of all solid tumors, including 15 to 20% of NSCLC and up to 40% of PDAC. There are no approved therapies for MTAP-deleted cancers, highlighting the significant unmet need and opportunity for new precision therapies for these patients.
IDE892 has potential best-in-class properties, including approximately 1,400-fold selective MTA-PRMT5 cooperative binding versus SAM-PRMT5 cooperative binding and lack of brain penetrance intended to maximize its therapeutic window, and favorable drug-like properties to enable rational combinations with IDE397, pan-RAS inhibitors, KRAS G12D therapies, and IDEAYA’s CDKN2A lead molecule. 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, positioning IDE892 as a potential best-in-class MTA-cooperative PRMT5 combination partner.
(Press release, Ideaya Biosciences, JUL 27, 2026, View Source [SID1234669438])