South San Francisco-based IDEAYA Biosciences (Nasdaq: IDYA) and Genentech, a member of the Roche Group, announced a clinical collaboration to evaluate IDE892, IDEAYA's 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 — a co-occurring genotype estimated to affect up to approximately 15% of PDAC patients, as per the firms' press release. Genentech will sponsor and fund the combination trial; IDEAYA will supply IDE892. Each company retains full commercial rights to its respective compound.
IDE892 is a Phase I small-molecule MTA-cooperative PRMT5 inhibitor that selectively binds PRMT5 in the presence of methylthioadenosine, exploiting the synthetic lethal vulnerability created when MTAP is deleted in tumor cells. IDEAYA reports approximately 1,400-fold selectivity for MTA-bound PRMT5 over the SAM-bound form, along with a CYP3A4 IC50 greater than 45 micromolar and no time-dependent inhibition across seven major cytochrome P450 enzymes — properties the company said support its use as a combination partner. IDE892 recently initiated Phase I/II monotherapy expansion in MTAP-deleted PDAC and non-small cell lung cancer after clearing multiple dose escalation cohorts. GDC-7035 is a Phase I KRAS G12D-selective inhibitor, targeting the specific mutation that co-occurs with MTAP deletion in the defined PDAC subpopulation enrolled in this study.
Financial terms were not disclosed, consistent with a clinical drug supply arrangement rather than a licensing transaction. Joint governance will oversee the study.