IDEAYA Biosciences, Inc., a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced the clearance of an investigational new drug (IND) application with the US Food and Drug Administration (FDA) for the initiation of a Phase 1 clinical trial to evaluate IDE849 (SHR-4849).

It is a potential first-in-class delta-like ligand 3 (DLL3)-targeting Topo-I-payload antibody drug conjugate (ADC) program, in solid tumours.

Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences said, “We are excited to advance IDE849, a potential first-in-class DLL3 TOP1 ADC, into a Phase 1 study in the US DLL3 is upregulated in multiple solid tumour types, including small cell lung cancer (SCLC), neuroendocrine tumours (NETs), non-small cell lung cancer (NSCLC), melanoma, among other solid tumours, highlighting the potential to have a pipeline in a single asset. We look forward to the IDE849 clinical data update in SCLC at a medical conference in Q3 2025, including at multiple expansion doses.”

Dr. Darrin M. Beaupre, Chief Medical Officer, IDEAYA Biosciences added, “IDE849 is a potential first-in-class DLL3 TOP1 ADC, a target antigen that has demonstrated preliminary monotherapy clinical validation in SCLC. In addition, IDE849 aligns with our strategy to develop rational combination therapies, particularly with our potential first-in-class Phase 1 PARG inhibitor IDE161, where we have generated preclinical combination data with TOP1-based ADCs that demonstrates combination synergy and enhanced durability.”

IDE849 is in an ongoing multi-site open label Phase 1 clinical trial for advanced solid tumours by Jiangsu Hengrui Pharmaceuticals Co., Ltd. In this ongoing Phase 1 study, IDE849 has reached therapeutic dose levels where multiple partial responses have been observed as of the data cut-off date of December 10, 2024.

As of the data cut-off date, treatment related adverse events (TRAEs) were predominantly Grade 1 or 2, and the Phase 1 dose escalation is ongoing with no reported drug-related discontinuations, and the maximum tolerated dose has not yet been reached. The most common TRAEs observed were white blood cell count decreased, anaemia, neutrophil count decreased, platelet count decreased, and nausea.

Hengrui Pharma is targeting to present clinical efficacy and safety data on IDE849 in over 40 SCLC patients from a multi-site open label Phase 1 trial, including from the dose escalation phase and at multiple expansion doses, at a medical conference in Q3 2025.

In addition, IDEAYA is targeting to present preclinical combination mechanism and synergy efficacy data of IDE161/PARG with TOP1-payload based ADCs at a medical conference in the third quarter of 2025. We believe this potential first-in-class combination has the potential to enhance durability of IDEAYA's TOP1-payload based ADC pipeline, including IDE849 and IDE034.

DLL3 has been reported to be upregulated in multiple solid tumour types, including in SCLC, NETs, NSCLC, melanoma, among others. DLL3 has limited extracellular expression in normal tissues, making it a promising potential therapeutic target in these solid tumours, for which there remains significant unmet medical need.

IDEAYA is targeting to evaluate IDE849 clinically in a multi-site global clinical trial as a monotherapy agent in SCLC, NETs and multiple DLL3 upregulated solid tumour types, and to evaluate IDE849 in a clinical combination with IDEAYA's potential first-in-class Phase 1 PARG inhibitor, IDE161, in the second half of 2025.