IDEAYA Biosciences Announces First-Patient-In for Phase 1 Trial of IDE892, a Potential Best-In-Class PRMT5 Inhibitor for MTAP-Deleted Solid Tumors, and Provides MTAP and CDKN2A Pipeline Update

PR Newswire

• Potential best-in-class profile, including ~1,400-fold selective binding to MTA-PRMT5 versus SAM-PRMT5 complexes, and single-digit nanomolar potency in MTAP-deleted cell lines
• IDE892 is being evaluated as a monotherapy agent in MTAP-deleted solid tumors, including NSCLC and PDAC, and targeting combination FPI with IDE397 (MAT2A) in mid-2026
• Targeting nomination of a first-in-class CDKN2A development candidate in H2 2026 and IND in H1 2027; prevalence of CDKN2A-deficiency has been reported at over 80% in PDAC
• IDEAYA will deprioritize combination activities with Trodelvy as part of a strategic prioritization of its proprietary MTAP-deleted and CDKN2A pipeline

SOUTH SAN FRANCISCO, Calif., March 9, 2026 /PRNewswire/ -- IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a leading precision medicine oncology company, today announced that the first patient has been enrolled in its Phase 1 clinical trial evaluating IDE892, an investigational MTA-cooperative PRMT5 inhibitor being developed for patients with MTAP-deleted solid tumors, including non-small cell lung cancer and pancreatic cancer.  The trial will assess safety, tolerability, pharmacokinetics, and pharmacodynamics of IDE892 as a monotherapy agent and in combination with IDE397, IDEAYA's MAT2A inhibitor, in mid-2026.  Dual inhibition of IDE892 and IDE397 has demonstrated durable and well-tolerated tumor regressions in preclinical MTAP-deleted tumor models, including in NSCLC.

"We are excited to have enrolled the first patient in our Phase 1 clinical trial evaluating IDE892 in patients with MTAP-deleted solid tumors, including non-small cell lung cancer and pancreatic cancer.  We designed IDE892 with potential best-in-class properties, including specific biophysical and pharmacokinetic properties that we believe will maximize its therapeutic window and clinical efficacy, both as a monotherapy agent and as a combination partner with our MAT2A inhibitor, IDE397.  Next, we look forward to advancing our first-in-class CDKN2A-defiency program to progress our broader corporate strategy of enabling wholly owned rational combinations targeting MTAP-deletion," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

IDE892 was designed to be a potential best-in-class PRMT5 inhibitor, with ~1,400-fold selective binding to MTA-PRMT5 versus SAM-PRMT5 complexes and observed single-digit nano-molar potency in endogenous MTAP-deleted cell lines, and greater than 50-fold potency differential in MTAP-deleted versus MTAP wild type HCT116 isogenic cell lines.  In addition, IDE892 inhibited the arginine dimethylation of a key PRMT5 substrate involved in mRNA splicing, spliceosome protein SmB (SmB-SDMA), with pico-molar potency in MTAP-deleted cell lines with greater than 100-fold potency differential versus an MTAP wild type cell line.  IDE892 has demonstrated monotherapy regressions in MTAP-deleted preclinical models, and durable complete responses in combination with IDE397. 

Loss of MTAP leads to the accumulation of methylthioadenosine (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.  In preclinical studies, dual inhibition of PRMT5 and MAT2A with the combination of IDE892 and IDE397 resulted in potent anti-tumor activity in MTAP-deleted tumor models, including complete and durable responses at well-tolerated doses below those required for monotherapy activity.

IDEAYA has also advanced its CDKN2A-deficiency program and is on track to select a potential first-in-class development candidate in H2 2026 with a target IND in H1 2027.  IDEAYA has demonstrated robust monotherapy efficacy with its CDKN2A lead in multiple preclinical models, including in a KRAS mutation pancreatic model.  IDEAYA plans to evaluate its CDKN2A-deficiency program preclinically as a monotherapy agent, and in combination with assets in its MTAP-deletion portfolio and potentially other RAS and KRAS targeted assets.  CDKN2A-defiency is common in cancer, with a prevalence of over 80% in pancreatic cancer (M. Schutte, et al., Cancer Research, 1997; IDEAYA analysis, TCGA) and is typically co-deleted in MTAP-deletion solid tumors and a common co-alteration with KRAS mutations, particularly in pancreatic cancer, creating rational combination opportunities with MTAP-deletion and KRAS targeted therapies, respectively.

As part of IDEAYA's strategic prioritization of its proprietary MTAP-deleted pipeline, including IDE397 and IDE892, and the advancement of its CDKN2A-deficiency program, the company has deprioritized its clinical combination activities with Trodelvy and will be concluding enrollment in the ongoing Phase 1/2 trials with Gilead.  Based on preliminary data from these trials supporting the mechanistic rationale for the combination in MTAP-deleted cancers, IDEAYA may evaluate additional combinations between IDE397 and other TOP1 payload ADCs in this setting, including IDE034, its B7H3/PTK7 bispecific TOP1 ADC. 

MTAP deletion is estimated to occur in 15–20% of non-small cell lung cancer, up to 40% of pancreatic cancer, and approximately 15% of all solid tumors, and is commonly co-deleted with CDKN2A due to the proximity of the two genes on chromosome 9p21.  There are no approved therapies for patients with MTAP deletion, highlighting the significant unmet need and important new opportunities for precision therapies.

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, including, but not limited to, statements related to the potential best-in-class profile, safety, efficacy and therapeutic benefit of IDE892, IDE397 and IDEAYA's CDKN2A-deficiency program; the mechanistic rationale and potential clinical benefit of PRMT5 and MAT2A co-inhibition; the timing, progress, design and results of IDE892's Phase 1 clinical trial; the anticipated timing of first-patient-in for the IDE892 and IDE397 combination in mid-2026; the timing of CDKN2A development candidate selection in the second half of 2026 and IND submission in the first half of 2027; the potential for combination strategies involving IDE892, IDE397 and CDKN2A assets; the prevalence of MTAP deletion and CDKN2A deficiency in certain cancers; projected cost savings associated with strategic prioritization decisions; and the potential market opportunity for IDEAYA's product candidates. 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, 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,  enrollment rates, safety outcomes, efficacy results, regulatory interactions and decisions, and the ability to translate preclinical findings into clinical benefit, manufacturing and supply risks, competition, changes in standard of care, the timing and success of commercialization efforts, 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 any current and periodic reports filed with the U.S. Securities and Exchange Commission.

Investor and Media Contact

IDEAYA Biosciences
Joshua Bleharski, Ph.D.
Chief Financial Officer  
investor@ideayabio.com

SOURCE IDEAYA Biosciences, Inc.