IDEAYA Biosciences Announces US FDA IND-Clearance for IDE849, a Potential First-in-Class DLL3 TOP1 ADC, for a Phase 1 Study in Solid Tumors

Rhea-AI Summary

IDEAYA Biosciences (NASDAQ: IDYA) has received FDA IND clearance for IDE849, a potential first-in-class DLL3 TOP1 ADC, to begin Phase 1 clinical trials in solid tumors. The drug targets DLL3, which is upregulated in multiple cancer types including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), and non-small cell lung cancer (NSCLC). In ongoing Phase 1 trials by partner Hengrui Pharma, IDE849 has shown multiple partial responses with predominantly Grade 1 or 2 treatment-related adverse events. Clinical data from over 40 SCLC patients will be presented in Q3 2025. IDEAYA plans to evaluate IDE849 as both a monotherapy and in combination with their PARG inhibitor IDE161 in the second half of 2025, with the U.S. trial starting at a dose equivalent to current expansion doses showing confirmed partial responses.

Positive

• FDA IND clearance received for IDE849, enabling Phase 1 trials in the U.S.
• Multiple partial responses observed in ongoing Phase 1 trials
• Favorable safety profile with predominantly Grade 1-2 adverse events and no drug-related discontinuations
• Broad potential application across multiple cancer types (SCLC, NETs, NSCLC, melanoma)
• Clinical data from 40+ SCLC patients to be presented in Q3 2025

Negative

• Maximum tolerated dose not yet determined
• Early-stage development (Phase 1) with efficacy still to be proven
• Common adverse events include decreased blood cell counts and nausea

Insights

Oncology Clinical Development Expert

FDA clearance for IDE849, a novel DLL3-targeting ADC, shows promising early efficacy signals with manageable safety profile in cancer patients.

IDEAYA Biosciences has achieved an important regulatory milestone with the FDA clearance of their Investigational New Drug (IND) application for IDE849, a delta-like ligand 3 (DLL3)-targeting antibody-drug conjugate (ADC) with a topoisomerase I inhibitor payload. This clearance enables the initiation of a Phase 1 clinical trial in the United States.

The DLL3 target is particularly significant in oncology because it's selectively expressed in multiple tumor types including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), non-small cell lung cancer, and melanoma, while showing limited expression in normal tissues. This selective expression pattern potentially allows for targeted treatment with reduced impact on healthy cells.

The preliminary clinical data from Hengrui's ongoing Phase 1 trial shows encouraging signs. The company reports multiple partial responses at therapeutic dose levels, with predominantly Grade 1-2 treatment-related adverse events. The most common side effects observed include decreased white blood cell count, anemia, decreased neutrophil count, decreased platelet count, and nausea - a profile consistent with topoisomerase I inhibitor payloads. Importantly, no drug-related discontinuations have been reported, and the maximum tolerated dose has not yet been reached, suggesting potential for dose optimization.

A particularly interesting aspect of IDEAYA's development plan is the combination strategy with IDE161, their PARG inhibitor. Preclinical data suggests synergy between TOP1-based ADCs and PARG inhibition, potentially enhancing response durability. For aggressive cancers like SCLC, improving durability of response represents an important clinical goal.

Biotech Industry Analyst

IDEAYA's FDA clearance for novel DLL3 ADC expands pipeline with dual potential as monotherapy and combination treatment across multiple cancers.

This IND clearance represents a significant milestone for IDEAYA's oncology pipeline development. The company is pursuing a dual development strategy for IDE849: as a monotherapy in multiple DLL3-expressing tumors, and in combination with their Phase 1 PARG inhibitor IDE161. This approach creates multiple potential paths to market while addressing the critical need for more effective therapies in difficult-to-treat cancers like small cell lung cancer.

The partnership with Hengrui Pharmaceuticals (SHA: 600276) appears to be accelerating development timelines. Hengrui's ongoing Phase 1 trial has already enrolled over 40 SCLC patients, with data expected at a medical conference in Q3 2025. Importantly, the FDA is allowing IDEAYA to begin its U.S. trial at a dose equivalent to an expansion dose in Hengrui's trial where responses have already been observed, potentially streamlining the development process.

IDEAYA's characterization of IDE849 as a "pipeline in a single asset" highlights the strategic value they see in targeting DLL3, which is upregulated across multiple solid tumor types. This approach could potentially expand addressable market opportunities beyond the initial SCLC indication.

The combination strategy with IDE161 demonstrates IDEAYA's focus on creating differentiated therapies through rational combinations of internal pipeline assets. The company plans to present preclinical data on this combination in Q3 2025, alongside Hengrui's clinical data presentation. This combination approach could potentially address resistance mechanisms and enhance treatment durability, which remains a significant challenge in advanced cancers.

• Targeting to evaluate IDE849 (SHR-4849) in SCLC, NETs, and other DLL3-upregulated solid tumors, and in combination with IDE161/PARG to potentially enhance durability
  
  
• Targeting to present clinical data of over 40 SCLC patients, including the dose escalation and expansion, from partner Hengrui at medical conference in Q3 2025

SOUTH SAN FRANCISCO, Calif., May 6, 2025 /PRNewswire/ -- IDEAYA Biosciences, Inc. (NASDAQ: IDYA), 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 U.S. Food and Drug Administration (FDA) for the initiation of a Phase 1 clinical trial to evaluate IDE849 (SHR-4849), a potential first-in-class delta-like ligand 3 (DLL3)-targeting Topo-I-payload antibody drug conjugate (ADC) program, in solid tumors.

"We are excited to advance IDE849, a potential first-in-class DLL3 TOP1 ADC, into a Phase 1 study in the U.S. DLL3 is upregulated in multiple solid tumor types, including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), non-small cell lung cancer (NSCLC), melanoma, among other solid tumors, 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," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

"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," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

IDE849 is in an ongoing multi-site open label Phase 1 clinical trial for advanced solid tumors (NCT06443489) by Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma, SHA: 600276). 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, anemia, 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 (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.

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 tumor 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. 

Based on the U.S. FDA guidance, IDEAYA will begin the Phase 1 study in the U.S. at a IDE849 starting dose that is equivalent to one of the expansion doses being evaluated in the ongoing Phase 1 study (NCT06443489) by partner Hengrui Pharma, where multiple confirmed partial responses have been observed by RECIST 1.1.

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 (i) the potential therapeutic benefits of IDEAYA therapeutics, including combination therapies; (ii) the timing and content of clinical trial updates and data readouts, including efficacy and safety data; (iii) the timing of and potential of clinical trials to evaluate IDE849 in SCLC, NETs, and other DLL3-upregulated solid tumors, and in combination with IDE161/PARG to potentially enhance durability. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly 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 IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the 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, see IDEAYA's Annual Report on Form 10-K dated February 18, 2025 and any current and periodic reports filed with the U.S. Securities and Exchange Commission.

Investor and Media Contact
IDEAYA Biosciences
Andres Ruiz Briseno
Chief Accounting Officer
investor@ideayabio.com

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SOURCE IDEAYA Biosciences, Inc.

FAQ

What is IDE849 and what did IDYA receive FDA clearance for?

IDE849 is a potential first-in-class DLL3 TOP1 antibody drug conjugate (ADC). IDEAYA received FDA IND clearance to begin Phase 1 clinical trials in solid tumors in the U.S.

What types of cancers does IDYA's IDE849 target?

IDE849 targets cancers with upregulated DLL3, including small cell lung cancer (SCLC), neuroendocrine tumors (NETs), non-small cell lung cancer (NSCLC), and melanoma.

What are the initial results from IDE849's ongoing Phase 1 trial?

The ongoing Phase 1 trial has shown multiple partial responses, with predominantly Grade 1-2 treatment-related adverse events and no drug-related discontinuations.

When will IDYA present clinical data for IDE849 in SCLC patients?

IDEAYA's partner Hengrui Pharma will present clinical data from over 40 SCLC patients at a medical conference in Q3 2025.

What are IDYA's plans for IDE849 combination therapy?

IDEAYA plans to evaluate IDE849 in combination with their PARG inhibitor IDE161 in the second half of 2025, aiming to enhance treatment durability.