IDEAYA Biosciences Announces First-Patient-In for Phase 1 Trial of IDE892, a Potential Best-In-Class PRMT5 Inhibitor for MTAP-Deleted Solid Tumors, and Provides MTAP and CDKN2A Pipeline Update

Core Insights - IDEAYA Biosciences has initiated a Phase 1 clinical trial for IDE892, a potential best-in-class PRMT5 inhibitor targeting MTAP-deleted solid tumors, including non-small cell lung cancer (NSCLC) and pancreatic cancer [1] - The company plans to deprioritize combination activities with Trodelvy to focus on its proprietary MTAP-deleted and CDKN2A pipeline, aiming for a first-in-class CDKN2A development candidate nomination in H2 2026 and an IND submission in H1 2027 [1] Group 1: IDE892 Development - The first patient has been enrolled in the Phase 1 trial evaluating IDE892, which will assess safety, tolerability, pharmacokinetics, and pharmacodynamics as a monotherapy and in combination with IDE397 [1] - IDE892 exhibits approximately 1,400-fold selective binding to MTA-PRMT5 versus SAM-PRMT5 complexes and demonstrates single-digit nanomolar potency in MTAP-deleted cell lines [1] - Preclinical studies show that dual inhibition of PRMT5 and MAT2A with IDE892 and IDE397 resulted in durable tumor regressions in MTAP-deleted tumor models [1] Group 2: CDKN2A Program - IDEAYA is advancing its CDKN2A-deficiency program, targeting a first-in-class development candidate selection in H2 2026 and an IND submission in H1 2027 [1] - CDKN2A deficiency is prevalent in over 80% of pancreatic cancer cases and is often co-deleted with MTAP, creating opportunities for rational combination therapies [1] - The company has demonstrated robust monotherapy efficacy with its CDKN2A lead in multiple preclinical models, including a KRAS mutation pancreatic model [1] Group 3: Strategic Prioritization - As part of its strategic focus, IDEAYA has deprioritized clinical combination activities with Trodelvy and will conclude enrollment in ongoing Phase 1/2 trials with Gilead [1] - The company may explore additional combinations between IDE397 and other TOP1 payload ADCs, including IDE034, in the context of MTAP-deleted cancers [1] - MTAP deletion occurs in 15-20% of NSCLC, up to 40% of pancreatic cancer, and approximately 15% of all solid tumors, highlighting the unmet need for targeted therapies [1]