IDEAYA Biosciences (IDYA) Study Update summary

Market Opportunity and Unmet Need

• MTAP deletion occurs in about 15% of all solid tumors, with higher prevalence in urothelial (>25%) and NSCLC (>15%), representing a significant patient population with unmet need and ~48,000 new cases annually in the U.S.

• No FDA-approved therapies currently exist for MTAP deletion solid tumors, underscoring the importance of new targeted approaches.

• IDE397 targets MAT2A, addressing vulnerabilities in MTAP-deleted tumors, which are present in ~15% of all solid tumors.

Preclinical and Mechanistic Insights

• IDE397 is a selective, allosteric MAT2A inhibitor that disrupts SAM production and inhibits PRMT5 in MTAP-null cells, showing over 2,000-fold selectivity.

• Preclinical studies show durable tumor regressions and synergy with PRMT5 inhibitors and ADCs; combination with Amgen’s AMG 193 and Trodelvy is being pursued.

• Mechanism-based strategy leverages MTA accumulation for monotherapy and combination approaches.

• Squamous NSCLC models show deep PRMT5 pathway suppression, supporting monotherapy proof of concept.

Phase 2 Clinical Trial Design and Patient Characteristics

• Phase 2 monotherapy expansion at 30mg QD in MTAP-deletion NSCLC and urothelial cancer; 18 evaluable patients (7 urothelial, 11 NSCLC) with a median of 2 prior therapies.

• MTAP-deletion detected in 50% of urothelial and 25% of NSCLC tumors screened.