Collaboration to to evaluate the efficacy and safety of IDE892, its investigational, potential best-in-class MTA-cooperative PRMT5 inhibitor, in combination with GDC-7035 (RG6620), Genentech's KRAS G12D inhibitor, in patients with pancreatic ductal adenocarcinoma (PDAC) harboring both an MTAP-deletion and a KRAS G12D mutation. Genentech will sponsor the clinical combination study, and IDEAYA will supply IDE892.

"We are excited to expand our clinical collaboration with Roche to evaluate a second KRAS combination with potential best-in-class MTA-cooperative PRMT5 inhibitor IDE892 for pancreatic cancer patients, where there remains a high unmet medical need. IDEAYA is advancing multiple rational combination strategies for the IDE892 program, including with MAT2A inhibitor IDE397, pan-RAS inhibitors, KRAS G12D inhibitors, and IDEAYA's lead CDKN2A compound," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

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-mutant specific 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. IDEAYA is evaluating IDE892 in a Phase 1 dose escalation and expansion clinical trial in MTAP-deleted solid tumors and has initiated a Phase 1 combination cohort in NSCLC and other solid tumors with IDE397, IDEAYA's proprietary MAT2A inhibitor. IDEAYA also plans to initiate a Phase 1 combination cohort with Roche's RG6505 in MTAP-deleted, RAS-mutant PDAC in 2H 2026. The collaboration announced today adds GDC-7035 as an additional KRAS-directed combination partner for IDE892 in MTAP-deleted, KRAS G12D positive PDAC.

MTAP deletions and KRAS G12D mutations are estimated to co-occur in up to approximately 15% of PDAC patients. Combining a PRMT5 inhibitor with a KRAS G12D mutant-specific inhibitor may have the potential to drive deeper and more durable responses for those PDAC patients with co-occurring alterations, who currently have no approved targeted treatment options. 

Under the clinical collaboration, IDEAYA and Genentech each retain all commercial rights to their respective compounds, including as monotherapy and as combination therapies. There will be joint governance to oversee the clinical supply collaboration.