IDEAYA Biosciences Announces IDE892, a Potential Best-in-Class MTA-Cooperative PRMT5 Inhibitor, Initiates Part 2 Monotherapy Expansion in the Phase 1/2 Study in MTAP-Deleted Pancreatic and Lung Cancers

• IDE892 is a potential best-in-class PRMT5 inhibitor with 1,400-fold selective MTA-PRMT5 cooperative binding vs SAM-PRMT5 cooperative binding, and CYP3A4 IC50 greater than 45 micromolar with no time-dependent inhibition of the 7 major cytochrome P450s
• IDE892 Phase 1/2 escalation has cleared multiple dose cohorts and projected efficacious target exposures have been achieved to initiate the Part 2 monotherapy expansion. The IDE892 escalation is ongoing in parallel and the MTD has not yet been reached 
• IDE892 and IDE397 combination escalation are ongoing in MTAP NSCLC and PDAC, and IDE892 and pan-RAS combination FPI in MTAP PDAC is targeted for H2 2026
• MTAP-deletion is estimated to occur in up to 40% of PDAC and ~15% of NSCLC
• IDEAYA is targeting a MTAP/CDKN2A, KRAS, and Pancreatic Cancer R&D Day in Q4 2026. Topics will include rational combination strategies to target the underlying tumor heterogeneity and adaptive plasticity in PDAC and other solid tumor indications

SOUTH SAN FRANCISCO, Calif., July 27, 2026 /PRNewswire/ -- IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a leading precision medicine oncology company, today announced that initiation of Part 2 monotherapy expansion has been achieved in its Phase 1/2 clinical trial evaluating IDE892, a potential best-in-class methylthioadenosine (MTA)-cooperative inhibitor of PRMT5, in MTAP-deleted solid tumors, with a focus on non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC). IDE892 Phase 1/2 monotherapy expansion has been initiated at projected efficacious target human exposures where 24-hours target EC90 coverage have been achieved. The IDE892 maximum tolerated dose (MTD) has not yet been reached in the ongoing dose escalation.

"We are excited to initiate monotherapy expansion evaluating IDE892 in MTAP-deleted PDAC and NSCLC. We designed IDE892 to be a potential best-in-class PRMT5 inhibitor, including approximately 1,400-fold selective MTA-PRMT5 cooperative binding versus SAM-PRMT5 cooperative binding, lack of brain penetrance, and favorable drug-like properties intended to maximize its therapeutic window as both a monotherapy agent and in combination. We are well positioned to have the industry's deepest MTAP-deletion pipeline, with IDE892, MAT2A inhibitor IDE397 in Phase 2, and the potential first-in-class CDKN2A lead molecule advancing in preclinical toxicology studies for a target IND in the first half of 2027," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

Loss of MTAP leads to the accumulation of MTA and increased dependence on PRMT5 and MAT2A, two key enzymes involved in methylation and RNA splicing. In MTAP-deleted tumors, this biology establishes a robust synthetic lethal vulnerability that underpins the mechanistic rationale for combining IDE892 and IDE397, where the first-patient-in (FPI) was achieved in mid-2026. IDEAYA also entered into a clinical collaboration with Roche evaluating IDE892 in combination with RG6505, Roche's Phase 1 pan-RAS inhibitor, in MTAP-deleted pancreatic ductal adenocarcinoma (PDAC) to target the genetic co-alterations of MTAP and KRAS in this indication. Next, IDEAYA is advancing a third proprietary and potential first-in-class program for MTAP-deleted solid tumors targeting CDKN2A, the most common co-alteration of MTAP-deletion, through ongoing preclinical toxicology studies to support an investigational new drug (IND) application in the first half of 2027. IDEAYA anticipates that rational combination doublets may be pursued with IDEAYA's CDKN2A lead molecule and IDE892 to target the co-alterations of MTAP and CDKN2A, and pan-RAS inhibitors, as the key tumor suppressor gene CDKN2A has been reported to be deficient in approximately 70% of PDAC.

MTAP deletion is estimated to occur in approximately 15% of all solid tumors, including 15 to 20% of NSCLC and up to 40% of PDAC. There are no approved therapies for MTAP-deleted cancers, highlighting the significant unmet need and opportunity for new precision therapies for these patients.

IDE892 has potential best-in-class properties, including approximately 1,400-fold selective MTA-PRMT5 cooperative binding versus SAM-PRMT5 cooperative binding and lack of brain penetrance intended to maximize its therapeutic window, and favorable drug-like properties to enable rational combinations with IDE397, pan-RAS inhibitors, KRAS G12D therapies, and IDEAYA's CDKN2A lead molecule. IDE892 has a CYP3A4 IC50 greater than 45 micromolar and did not show time dependent inhibition of any of the 7 major cytochrome P450s (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4) based on full kinetic CYP inactivation assays, positioning IDE892 as a potential best-in-class MTA-cooperative PRMT5 combination partner.

About IDEAYA Biosciences

IDEAYA is a precision medicine oncology company committed to the discovery, development, and commercialization of transformative therapies for cancer. Our approach integrates expertise in small-molecule drug discovery, structural biology and bioinformatics with robust internal capabilities in identifying and validating translational biomarkers to develop tailored, potentially first-in-class targeted therapies aligned to the genetic drivers of disease. We have built a deep pipeline of product candidates focused on synthetic lethality and antibody-drug conjugates, or ADCs, for molecularly defined solid tumor indications. Our mission is to bring forth the next wave of precision oncology therapies that are more selective, more effective, and deeply personalized with the goal of altering the course of disease and improving clinical outcomes for patients with cancer.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: the potential therapeutic profile, differentiated properties and best-in-class potential of IDE892; the potential of IDE892 as a monotherapy and in combination with other therapies; the significance of IDE892's preclinical characteristics, including its selective MTA-PRMT5 cooperative binding, CYP3A4 profile, lack of time-dependent inhibition of major cytochrome P450 enzymes, and other drug-like properties; the anticipated therapeutic window of IDE892; the ongoing Phase 1/2 clinical trial of IDE892, including dose escalation, monotherapy expansion, achievement of projected target exposures, evaluation of safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity, and the potential determination of a maximum tolerated dose; the clinical development and potential therapeutic benefit of the combination of IDE892 with IDE397 and with Roche's pan-RAS inhibitor RG6505; the anticipated timing of first-patient-in for the IDE892 and pan-RAS inhibitor combination study; the planned advancement of IDEAYA's CDKN2A program, including ongoing preclinical toxicology studies, anticipated IND timing, and potential future combination strategies; the prevalence of MTAP deletion, KRAS and CDKN2A alterations in selected tumor types; the potential applicability of synthetic lethality biology to IDEAYA's development programs; the potential market opportunity and unmet medical need for patients with MTAP-deleted cancers; the expected depth and breadth of IDEAYA's MTAP-deletion pipeline; the anticipated timing and content of IDEAYA's planned MTAP/CDKN2A, KRAS and Pancreatic Cancer R&D Day; and other statements that are not historical facts. Such forward-looking statements are based on management's current expectations, assumptions and beliefs and involve substantial risks and uncertainties that could cause actual results, including, but not limited to, those related to IDEAYA's clinical programs, regulatory activities, commercial activities, and performance and/or achievements, to differ significantly and/or materially from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including the process of designing and conducting preclinical and clinical trials; patient enrollment rates and retention; biomarker identification, patient selection and diagnostic testing; safety, tolerability, and efficacy results; regulatory interactions and decisions; the ability to translate preclinical findings into clinical benefit; manufacturing and supply risks; competition and changes in standard of care; the timing and success of commercialization efforts; the performance of IDEAYA's collaboration partners, including their ability to conduct clinical development activities and achieve anticipated development and regulatory milestones; the outcome of collaborations and licensing arrangements; IDEAYA's ability to successfully establish, protect and defend its intellectual property; and other matters that could affect the sufficiency of financial resources to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. A further description of risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, are in IDEAYA's filings with the Securities and Exchange Commission, including IDEAYA's most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q and current Reports on Form 8-K.

Investor and Media Contact

IDEAYA Biosciences
Joshua Bleharski, Ph.D.
Chief Financial Officer
[email protected]

SOURCE IDEAYA Biosciences, Inc.