Erasca Presents New Preclinical Data Reinforcing Best-in-Class Potential of RAS-Targeting Franchise at the 2025 AACR Annual Meeting

Core Insights - Erasca, Inc. presented new preclinical data at the AACR Annual Meeting, highlighting the best-in-class potential of its RAS-targeting compounds ERAS-0015 and ERAS-4001, which show robust anti-tumor activity as both monotherapy and in combination therapy [1][2] Group 1: ERAS-0015 - ERAS-0015 is a pan-RAS molecular glue that demonstrated favorable pharmacokinetic properties, including longer residence time and greater tissue exposure, leading to robust anti-tumor activity at lower doses compared to leading competitors [3][5] - The compound forms a ternary complex with active state RAS and cyclophilin A (CypA), effectively blocking downstream effector complex formation and showing potent inhibition of proliferation across diverse tumor tissues and RAS mutations [5] Group 2: ERAS-4001 - ERAS-4001 is a pan-KRAS inhibitor that selectively targets both mutant and wildtype KRAS, potentially offering an expanded therapeutic index and addressing resistance mechanisms associated with mutant-selective KRAS inhibitors [4][6] - The compound exhibited significant tumor growth inhibition and anti-tumor efficacy in KRAS mutant xenograft models, with single-digit nanomolar IC50s observed in various cell lines [6][10] Group 3: SHOC2 Modulators - The company identified direct SHOC2 binders that inhibit the assembly of the SHOC2-MRAS-PP1C complex, representing a novel approach to attenuate RAS/MAPK pathway signaling [7][10] - These compounds are the first examples of direct modulators of the SMP complex, with ongoing optimization for potential protein-protein inhibitors and degrader modalities [10] Group 4: Company Overview - Erasca is a clinical-stage precision oncology company focused on developing therapies for RAS/MAPK pathway-driven cancers, with a strong pipeline and collaboration with leading experts in the field [8]