South San Francisco-based Ideaya Biosciences (Nasdaq: IDYA) has entered a clinical collaboration with Roche to test whether combining an MTA-cooperative PRMT5 inhibitor with a pan-RAS inhibitor can generate meaningful responses in a tumor type with no approved targeted options. The agreement pairs Ideaya's IDE892, currently in Phase I dose escalation, with Roche's Phase I pan-RAS inhibitor RG6505 in patients with MTAP-deleted, RAS-mutant pancreatic ductal adenocarcinoma. Financial terms were not disclosed, consistent with a clinical supply arrangement rather than a licensing transaction.
Under the agreement, Ideaya will sponsor the combination trial while Roche supplies RG6505. Each company retains full commercial rights to its own compounds, including both monotherapy and combination uses. A joint governance committee will oversee the study, and the collaboration includes a provision to evaluate a triplet regimen — IDE892, RG6505, and Ideaya's Phase II MAT2A inhibitor IDE397 — subject to mutual approval by both parties.
MTAP deletion occurs in an estimated 40% of pancreatic ductal adenocarcinoma cases, and nearly all MTAP-deleted PDAC tumors carry co-occurring RAS mutations, making the genetic intersection a logical combination target. IDE892 is described by Ideaya as an MTA-cooperative PRMT5 inhibitor, designed to exploit the accumulation of methylthioadenosine that results from MTAP loss. When MTAP is deleted, MTA builds up intracellularly and cooperatively inhibits PRMT5; IDE892 is engineered to bind selectively to the MTA-PRMT5 complex, with the company reporting approximately 1,400-fold selectivity for MTA-bound PRMT5 over the SAM-bound form in preclinical studies. Ideaya enrolled its first patient in the IDE892 Phase I monotherapy trial in March 2026.
RG6505 targets RAS broadly across isoforms, distinguishing it from approved mutation-specific inhibitors such as sotorasib and adagrasib, which are limited to KRAS G12C. The rationale for combining a PRMT5 inhibitor with a pan-RAS inhibitor in MTAP-deleted PDAC is that the two agents address distinct oncogenic dependencies — synthetic lethality through MTAP deletion on one axis, and direct suppression of RAS-driven proliferation on the other. The triplet option adds IDE397, Ideaya's MAT2A inhibitor, which amplifies MTA accumulation and could theoretically deepen the PRMT5 inhibitory effect.
Ideaya has used IDE397 to establish the clinical proof-of-concept for its MTAP-deletion franchise. The company reported a 33% objective response rate for IDE397 monotherapy in heavily pretreated MTAP-deletion urothelial and lung cancer patients at the EORTC-NCI-AACR 2024 symposium, and subsequently expanded the Phase I/II combination program with Gilead Sciences' Trodelvy in urothelial cancer, where a 57% response rate was reported at the highest dose level evaluated.
Industry and transaction context
The structure of this agreement — mutual drug supply, retained commercial rights, and joint governance without financial transfers — mirrors a pattern that has become increasingly common in early-phase oncology combination testing. A directly comparable arrangement emerged in March 2026, when San Diego-based Erasca (Nasdaq: ERAS) and Boston-based Tango Therapeutics (Nasdaq: TNGX) entered a clinical collaboration to evaluate Erasca's pan-RAS molecular glue ERAS-0015 alongside Tango's PRMT5 inhibitor vopimetostat — an almost structurally identical scientific hypothesis pursued through the same deal architecture. The existence of two separate pan-RAS plus PRMT5 inhibitor combination trials, announced within three months of each other, indicates that the mechanistic rationale has reached a threshold of scientific credibility sufficient to draw multiple independent development programs.