IDEAYA Advances PRMT5 Inhibitor IDE892 into Monotherapy Expansion
IDEAYA Biosciences has initiated the monotherapy expansion phase of its Phase 1/2 clinical trial for IDE892, a potential best-in-class PRMT5 inhibitor. The treatment targets patients with MTAP-deleted solid tumors, specifically non-small cell lung cancer and pancreatic ductal adenocarcinoma, where the company reports achieving projected efficacious target exposures.
The clinical progression follows successful dose escalation cohorts where the maximum tolerated dose has not yet been reached. IDE892 is designed with high selectivity, featuring approximately 1,400-fold greater binding affinity for MTA-PRMT5 complexes compared to SAM-PRMT5, a property intended to widen its therapeutic window. The drug also demonstrates a favorable profile for combination therapy, showing no time-dependent inhibition of major cytochrome P450 enzymes.
Beyond monotherapy, IDEAYA is exploring combination strategies to address tumor heterogeneity. This includes ongoing testing with the MAT2A inhibitor IDE397 and a collaboration with Roche to evaluate IDE892 alongside the pan-RAS inhibitor RG6505. With MTAP deletions occurring in up to 40% of pancreatic ductal adenocarcinoma cases and 15% of non-small cell lung cancers, the company is prioritizing these indications to address a significant clinical gap in precision oncology. Looking ahead, IDEAYA plans to advance a CDKN2A-targeting program into clinical trials by the first half of 2027.
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