JYP-0015 (ERAS-0015): A Pan-RAS Molecular Glue Poised to Redefine the Treatment of RAS-Mutant Cancers

Executive Summary

JYP-0015, also known as ERAS-0015, is a novel, orally bioavailable, small molecule investigational drug that represents a significant advancement in the field of precision oncology. Developed by Guangzhou JOYO Pharma and subsequently in-licensed by Erasca, Inc., JYP-0015 is a pan-RAS inhibitor that functions as a molecular glue. Its mechanism of action is distinct from first-generation targeted therapies; it is designed to inhibit all three major RAS isoforms (KRAS, NRAS, and HRAS) by inducing the formation of a ternary complex between the active, GTP-bound "ON" state of RAS and the intracellular chaperone protein Cyclophilin A (CypA). This action effectively blocks downstream signaling through the critical RAS/MAPK pathway, which is a primary driver of cellular proliferation and survival in a vast number of human cancers.

RAS mutations, present in approximately 21-30% of all human tumors, have long been considered "undruggable" due to the protein's challenging structural characteristics. While the recent development of allele-specific KRAS G12C inhibitors validated RAS as a viable therapeutic target, their clinical utility is confined to a narrow patient population and is often limited by the rapid onset of resistance. JYP-0015 aims to overcome these limitations by targeting a broad spectrum of RAS mutations and isoforms, potentially addressing a patient population of nearly 2.7 million new diagnoses annually worldwide.