IDEAYA Biosciences has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration for IDE892, a potential best-in-class MTA-cooperative inhibitor of PRMT5 designed to treat MTAP-deleted solid tumors. The precision medicine oncology company is targeting to begin a Phase 1 dose escalation trial of IDE892 in MTAP-deleted lung cancer in the fourth quarter of 2025.
The development strategy centers on advancing IDE892 into combination trials with IDE397, IDEAYA's proprietary MAT2A inhibitor, planned for the first half of 2026. This dual-targeting approach leverages the synthetic lethality principle, where cancer cells with specific genetic deletions become vulnerable to targeted therapeutic intervention.
Targeting a Significant Patient Population
Approximately 15-20% of non-small cell lung cancer (NSCLC) cases harbor MTAP deletions, representing a substantial patient population with limited treatment options. Extensive studies have demonstrated that elevated MTA/SAM ratios in MTAP-deleted cancers create a tumor-specific vulnerability to MTA-cooperative PRMT5 inhibition.
"We are excited to advance IDE892 into clinical studies for patients with MTAP-deleted lung cancer, where we believe the inhibition of PRMT5 in combination with MAT2A could have synergistic anti-tumor activity," said Michael White, Chief Scientific Officer at IDEAYA Biosciences.
Optimized Drug Design for Combination Therapy
IDE892 represents the culmination of comprehensive optimization efforts focused on biophysical and pharmacokinetic properties required to maximize therapeutic benefit as a combination partner with IDE397. White emphasized that the compound was specifically designed "to generate a potential best-in-class MTA-cooperative PRMT5 inhibitor profile."
The mechanistic rationale underlying this combination approach shows that the anti-tumor effect is substantially enhanced when PRMT5 inhibition is combined with MAT2A inhibition, creating an important combination therapy opportunity in an area of substantial unmet medical need.
Expanding Beyond Lung Cancer
Beyond MTAP-deleted lung cancer, IDEAYA plans to clinically evaluate other high-priority MTAP solid tumor indications using both IDE892 monotherapy and in combination with IDE397. This broader development strategy reflects the company's commitment to addressing multiple cancer types that share this genetic vulnerability.
Upcoming Data Presentation
The preclinical profile of IDE892 and the mechanistic combination rationale with IDE397 will be presented at IDEAYA's 10-Year Anniversary R&D Day on September 8th, 2025. This presentation is expected to provide detailed insights into the scientific foundation supporting the clinical development program.
IDEAYA's approach integrates expertise in small-molecule drug discovery, structural biology, and bioinformatics with robust internal capabilities in identifying and validating translational biomarkers. The company has built a deep pipeline of product candidates focused on synthetic lethality and antibody-drug conjugates for molecularly defined solid tumor indications.
