IDEAYA Biosciences Achieves Phase 1/2 Enrolment for IDE892 PRMT5 Inhibitor in MTAP-Deleted Cancers

Formulation decisions made during early ADME optimisation are now shaping the combination oncology strategy at IDEAYA Biosciences, as the company confirms first-patient enrolment in a Phase 1/2 trial evaluating IDE892, its MTA-cooperative PRMT5 inhibitor, alongside MAT2A inhibitor IDE397 in MTAP-deleted NSCLC and pancreatic cancer.

For CMC and regulatory teams tracking combination IND packages, the CYP inhibition profile of IDE892 warrants attention. The compound demonstrated a CYP3A4 IC50 greater than 45 micromolar and showed no time-dependent inhibition across all seven major cytochrome P450 enzymes, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, based on full kinetic CYP inactivation assays. That profile directly reduces the drug-drug interaction burden in a combination regimen, a consideration that surfaces early in 21 CFR Part 312 IND submissions and carries forward into Phase 3 protocol design.

Phase 1 monotherapy dose escalation has cleared multiple cohorts, with maximally efficacious target exposures projected at a pill size IDEAYA describes as favorable; the maximum tolerated dose has not yet been reached. Monotherapy expansion is anticipated in Q3 2026. In preclinical MTAP-deleted tumour models, dual PRMT5 and MAT2A inhibition with IDE892 plus IDE397 produced complete and durable responses at doses below those required for monotherapy activity, providing the mechanistic basis for the combination hypothesis.

The selectivity engineering also has downstream process implications. IDE892 was designed with approximately 1,400-fold selective MTA-PRMT5 cooperative binding versus SAM-PRMT5 cooperative binding, a specificity margin intended to widen the therapeutic window and support rational co-administration with pan-RAS inhibitors. IDEAYA has entered a clinical collaboration with Roche to evaluate IDE892 alongside RG6505, Roche's Phase 1 pan-RAS inhibitor, in MTAP-deleted pancreatic ductal adenocarcinoma, where MTAP and KRAS co-alterations are a defined genetic subset.

MTAP deletion occurs in approximately 15% of all solid tumours, including 15–20% of NSCLC and up to 40% of pancreatic cancer. No approved therapies exist for MTAP-deleted cancers. IDEAYA is also advancing a third proprietary MTAP programme targeting CDKN2A through preclinical toxicology studies, with an IND application targeted for the first half of 2027.

The Q3 2026 monotherapy expansion readout will be the next measurable checkpoint for teams monitoring IDE892's dose-exposure relationship ahead of any combination dose-escalation decisions.

Source: IDEAYA Biosciences newsroom via PR Newswire, 15 June 2026.