IDEAYA Biosciences, a medicine oncology company, has announced the enrolment of the first patient in its Phase I clinical trial evaluating IDE892, an investigational MTA-cooperative PRMT5 inhibitor designed for patients with MTAP-deleted solid tumours. These include cancers such as Non-Small Cell Lung Cancer and Pancreatic Cancer, where treatment options remain limited.

The Phase I trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of IDE892 when used as a standalone therapy and in combination with IDE397, the company’s MAT2A inhibitor. The combination approach is expected to be explored further in mid-2026 as part of IDEAYA’s strategy to develop targeted therapies for genetically defined cancers.

According to the company, IDE892 has been engineered with potential best-in-class properties, including strong selective binding to MTA-PRMT5 complexes and potent activity in MTAP-deleted tumour cell lines. Preclinical studies have shown that the therapy can inhibit key PRMT5-mediated biological processes linked to tumour growth. IDE892 has also demonstrated tumour regression as a monotherapy in preclinical models, while its combination with IDE397 has produced durable and complete responses in MTAP-deleted tumour models, including those related to lung cancer.

The biological rationale for this strategy lies in the loss of the MTAP gene, which leads to accumulation of methylthioadenosine (MTA) and increased reliance on PRMT5 and MAT2A enzymes involved in methylation and RNA splicing. This dependency creates a synthetic lethal vulnerability in MTAP-deleted cancers, making dual inhibition of PRMT5 and MAT2A a promising therapeutic strategy.

IDEAYA is also advancing its CDKN2A-deficiency programme, with plans to select a potential first-in-class development candidate in the second half of 2026 and target an investigational new drug (IND) filing in the first half of 2027. The company has reported strong monotherapy activity from its CDKN2A lead candidate in several preclinical models, including pancreatic cancer models with KRAS mutations. Future studies may also explore combination approaches with assets in IDEAYA’s MTAP-deletion portfolio and other targeted therapies.

As part of its strategic pipeline prioritisation, IDEAYA will focus on its proprietary MTAP-deleted programmes, including IDE397 and IDE892, along with its CDKN2A-deficiency research. The company has decided to deprioritise certain clinical combination studies with Trodelvy conducted in collaboration with Gilead Sciences and will conclude enrolment in ongoing Phase I/II trials related to that programme.

MTAP deletion is estimated to occur in around 15–20 percent of Non-Small Cell Lung Cancer cases, up to 40 percent of Pancreatic Cancer cases, and roughly 15 percent of all solid tumours. Currently, there are no approved therapies specifically targeting MTAP-deleted cancers, highlighting a significant unmet need for precision oncology treatments.

Through its integrated approach combining drug discovery, structural biology and biomarker development, IDEAYA Biosciences aims to develop first-in-class targeted therapies tailored to the genetic drivers of cancer.