AMG 193 + IDE397

AMG 193 + IDE397 is a combination of two investigational targeted cancer therapies, tested as a synthetic lethality approach in patients with advanced solid tumors characterized by methylthioadenosine phosphorylase (MTAP) deletion. **AMG 193** is a small molecule, MTA-cooperative inhibitor of protein arginine methyltransferase 5 (PRMT5), disrupting a key epigenetic process required for cancer cell survival in MTAP-null tumors. **IDE397** is a small molecule inhibitor of methionine adenosyltransferase 2A (MAT2A), another enzyme involved in methylation biology and essential for MTAP-deleted tumor metabolism. This combination seeks to maximize tumor cell death by concurrently targeting both PRMT5 and MAT2A dependent vulnerabilities in MTAP-deleted cancers. Both medicines are unapproved and have been evaluated in Phase 1/2 studies, particularly in non-small cell lung cancer (NSCLC) and other solid tumors with MTAP loss[1][2][3][5]. As of mid-2025, IDEAYA and Amgen have decided to wind down clinical development of this specific combination after mutual agreement[7][9].