- FPI achieved for first-in-class combination of IDE849 (DLL3 TOP1 ADC) and IDE161 (PARG inhibitor). IDE161 (PARG) induced accumulation of TOP1 lesions enhances the efficacy and durability of TOP1 ADCs in multiple preclinical models
- IDE849 Phase 1 study advancing globally to determine RP2D, including current dose evaluation at 3.5 mg/kg IV Q3W. Multiple PRs observed at 2.4 mg/kg IV Q3W expansion cohort, including 3 PRs out of 4 SCLC patients pre-treated with IMDELLTRA®
- Targeting IDE849 monotherapy, and IDE849 and IDE161 combination clinical data update in H2 2026
SOUTH SAN FRANCISCO, Calif., March 30, 2026 /PRNewswire/ — IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced first-patient-in for a Phase 1 clinical trial combination study to evaluate IDE849, a potential first-in-class delta-like ligand 3 (DLL3)-targeting Topo-I-payload antibody drug conjugate (ADC) program, and IDE161, a potential first-in-class poly(ADP-ribose) glycohydrolase (PARG) inhibitor. The Phase 1 combination study will be evaluated in DLL3 upregulated solid tumor indications, including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and melanoma.
“We are excited about the progress in our Phase 1 IDE849 monotherapy study to determine the RP2D and to initiate a registrational study by year-end, and the advancement of our wholly owned first-in-class clinical combination of IDE849 and IDE161 in DLL3 upregulated solid tumor indications,” said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. “We are leveraging our deep scientific expertise in DNA damage repair to enable this rational combination with IDE161, with the goal of inducing accumulation of TOP1 lesions to enhance the clinical efficacy and durability of our proprietary TOP1-payload ADCs, including IDE849 and IDE034, a Phase 1 B7H3/PTK7 bispecific TOP1 ADC,” said Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences.
IDEAYA is advancing a multi-site global Phase 1 clinical trial for IDE849 in DLL3 upregulated solid tumor indications, including SCLC, NETs, and NECs, and melanoma (NCT07174583). The study will be enrolling patients globally, including in North America, Europe, Australia, South America, and Asia. In this ongoing Phase 1 dose escalation study, IDE849 is currently evaluating a 3.5 mg/kg IV dose once every 3-weeks (Q3W). Next, to determine the recommended Phase 2 dose (RP2D), IDEAYA is also enrolling patients in a IDE849 expansion cohort at the 2.4 mg/kg IV dose Q3W, where multiple partial responses (PRs) have been observed by RECIST 1.1, including 3 PRs out of 4 SCLC patients pre-treated with IMDELLTRA® (tarlatamab-dlle). The preliminary safety and efficacy profile observed to date in the IDEAYA sponsored study is consistent with the clinical data presented by our China-region partner Jiangsu Hengrui Pharmaceuticals Co. Ltd., at the IASLC World Conference on Lung Cancer 2025 (WCLC 2025).
In addition, IDE849 is being evaluated in a clinical combination with IDEAYA’s potential first-in-class Phase 1 PARG inhibitor, IDE161. IDEAYA has presented preclinical combination mechanism and synergy efficacy data of IDE161/PARG with TOP1-payload based ADCs at WCLC 2025. IDE161 prevents the removal of poly(ADP-ribose) chains generated by PARP during the DNA damage response, leading to persistent PARylation and impaired resolution of DNA repair complexes. Together with TOP1-payload ADCs, this unique mechanism-of-action results in sustained TOP1 cleavage complexes and the accumulation of DNA damage that delivers enhanced anti-tumor activity. 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 (Phase 1 B7H3/PTK7 Bispecific TOP1 ADC).
DLL3 has been reported to be upregulated in multiple solid tumor 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 tumors, for which there remains significant unmet medical need.
About IDEAYA Biosciences
IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA’s approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets.
Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to IDEAYA’s expectations, plans, and beliefs related to its clinical development programs, including the ongoing Phase 1 clinical trial evaluating IDE849 as a monotherapy and in combination with IDE161; the potential safety, tolerability, efficacy, and durability of IDE849 and IDE161; the potential therapeutic benefit and mechanism of action of IDE849, IDE161, and their combination; the potential of IDE849 and IDE161 to be first-in-class therapies; IDEAYA’s plans to determine the recommended Phase 2 dose (RP2D) for IDE849; the timing and progress of IDEAYA’s clinical trials, including plans to initiate a registrational study for IDE849; the expected timing of clinical data updates, including potential updates in the second half of 2026; and the potential applicability of IDEAYA’s TOP1-payload ADC platform across multiple tumor types. 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
[email protected]
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SOURCE IDEAYA Biosciences, Inc.
