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IDE892 + RG6505 is an investigational combination regimen consisting of IDE892, an orally bioavailable, methylthioadenosine (MTA)-cooperative inhibitor of protein arginine methyltransferase 5 (PRMT5), and RG6505, a pan-RAS inhibitor. Developed through a clinical collaboration between IDEAYA Biosciences and Roche, this combination is designed to exploit synthetic lethality in cancers with co-occurring genetic alterations. Specifically, MTAP deletion leads to a buildup of MTA, which cooperates with IDE892 to selectively inhibit PRMT5, while RG6505 blocks all forms of mutated RAS proteins that drive tumor growth. The combination is being evaluated in Phase 1 clinical trials for the treatment of MTAP-deleted, RAS-mutant pancreatic ductal adenocarcinoma (PDAC).
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