IDEAYA Biosciences Announces First-Patient-In for Phase 1 Combination Study of IDE849, DLL3 TOP1 ADC, and IDE161, PARG Inhibitor, in DLL3 Upregulated Solid Tumor Indications, including SCLC, NETs, NECs, and Melanoma

Rhea-AI Summary

IDEAYA (NASDAQ: IDYA) announced first-patient-in (FPI) for a Phase 1 combination study of IDE849 (DLL3-targeting TOP1 ADC) plus IDE161 (PARG inhibitor) in DLL3-upregulated solid tumors, including SCLC, NETs, NECs, and melanoma.

The ongoing global IDE849 Phase 1 program is evaluating 3.5 mg/kg IV Q3W in dose escalation and a 2.4 mg/kg IV Q3W expansion cohort where multiple RECIST v1.1 partial responses were observed; a clinical data update is planned for H2 2026.

Positive

• First-patient-in for IDE849+IDE161 Phase 1 combination study
• Global Phase 1 trial evaluating IDE849 at 3.5 mg/kg IV Q3W
• Multiple RECIST v1.1 partial responses in 2.4 mg/kg expansion cohort
• Preclinical synergy: IDE161 induces persistent TOP1 lesions enhancing TOP1 ADC durability

Negative

• Clinical data are preliminary and early-stage (Phase 1) with limited patient numbers
• Observed responses include a very small SCLC cohort (3 PRs out of 4 patients), limiting generalizability
• No reported randomized or long-term efficacy or safety outcomes yet; RP2D not finalized

Key Figures

IDE849 dose: 3.5 mg/kg IV Q3W IDE849 expansion dose: 2.4 mg/kg IV Q3W SCLC responses: 3 PRs out of 4 patients +5 more

8 metrics

IDE849 dose 3.5 mg/kg IV Q3W Current Phase 1 dose escalation evaluation

IDE849 expansion dose 2.4 mg/kg IV Q3W Expansion cohort to determine RP2D

SCLC responses 3 PRs out of 4 patients SCLC patients pre-treated with IMDELLTRA at 2.4 mg/kg cohort

Trial phase Phase 1 Combination study of IDE849 and IDE161 in DLL3-upregulated tumors

Data update timing H2 2026 Planned IDE849 monotherapy and combination clinical data update

Trial identifier NCT07174583 Global Phase 1 IDE849 study in DLL3-upregulated tumors

Geographies North America, Europe, Australia, South America, Asia Planned enrollment regions for IDE849 Phase 1 trial

Conference reference WCLC 2025 Clinical and preclinical IDE849/IDE161 data previously presented

Market Reality Check

Price: $30.46 Vol: Volume 687,368 vs 20-day ...

normal vol

$30.46 Last Close

Volume Volume 687,368 vs 20-day average 975,272 suggests subdued trading into this update. normal

Technical Shares at $30.46 are trading above the 200-day MA at $29.27, despite a -5.08% daily move.

Peers on Argus

IDYA fell 5.08% with several biotech peers also down: DNLI -7.3%, GLPG -3.5%, TV...

1 Up

IDYA fell 5.08% with several biotech peers also down: DNLI -7.3%, GLPG -3.5%, TVTX -1.34%, while BLTE +3.41% and FOLD -0.1% were more mixed, indicating a largely risk-off biotech backdrop.

Previous Clinical trial Reports

5 past events · Latest: Mar 09 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Mar 09	Phase 1 FPI IDE892	Positive	+5.7%	First-patient-in for IDE892 Phase 1 and MTAP/CDKN2A pipeline update.
Feb 27	Phase 1 start IDE034	Positive	+2.6%	Partner announced first patient dosed in IDE034 Phase 1 with milestone payment.
Feb 25	Phase 1 FPI IDE034	Positive	-1.3%	IDEAYA announced first-patient-in for IDE034 bispecific TOP1 ADC trial.
Dec 11	Pivotal trial enrollment	Positive	-0.2%	Completed targeted enrollment of 435 patients in darovasertib Phase 2/3 OptimUM‑02.
Oct 20	Positive Phase 2 data	Positive	+4.3%	Presented positive Phase 2 darovasertib data in primary uveal melanoma at ESMO.

Pattern Detected

Clinical-trial news for IDEAYA has more often been met with positive than negative price reactions, but selloffs on otherwise constructive updates have occurred.

Recent Company History

Over the past several months, IDEAYA has repeatedly reported clinical milestones across its synthetic lethality and ADC pipeline. Recent FPI announcements for IDE892 and IDE034, and pivotal enrollment completion for darovasertib, all underscored a broad late-stage and early-stage portfolio. Price reactions to these clinical trial updates have been mixed, with several positive moves but also occasional declines. Today’s IDE849/IDE161 combination FPI continues this theme of expanding first-in-class programs within DLL3‑upregulated and other solid tumors.

Historical Comparison

+2.2% avg move · In the past year, IDEAYA’s clinical trial updates produced an average move of 2.22%. Today’s -5.08% ...

clinical trial

+2.2%

Average Historical Move clinical trial

In the past year, IDEAYA’s clinical trial updates produced an average move of 2.22%. Today’s -5.08% reaction to the IDE849/IDE161 FPI skews weaker than prior similar catalysts.

The company has moved from Phase 2 darovasertib data and pivotal enrollment to multiple Phase 1 FPIs (IDE034, IDE892, IDE849/IDE161), illustrating a broadening clinical footprint across ADC and synthetic lethality programs.

Market Pulse Summary

This announcement highlights further execution on IDEAYA’s ADC and DNA damage response strategy, wit...

Analysis

This announcement highlights further execution on IDEAYA’s ADC and DNA damage response strategy, with FPI for a Phase 1 IDE849/IDE161 combination in DLL3‑upregulated tumors and early evidence of partial responses at the 2.4 mg/kg IDE849 dose. In the past year, multiple clinical trial milestones across IDE034, IDE892 and darovasertib have broadened the pipeline. Investors may focus on the planned H2 2026 data update and how emerging safety and efficacy compare to prior datasets.

Key Terms

phase 1, antibody drug conjugate, adc, parg inhibitor, +3 more

7 terms

phase 1 medical

"announced first-patient-in for a Phase 1 clinical trial combination study"

Phase 1 is the first stage of testing a new drug or medical treatment in people, focused primarily on safety, how the body handles the product, and finding a tolerated dose. Think of it as a short, tightly controlled experiment with a small group to check for dangerous side effects before wider testing; for investors it is an early milestone that reduces some uncertainty but still carries high risk and potential for both big value changes and setbacks.

antibody drug conjugate medical

"delta-like ligand 3 (DLL3)-targeting Topo-I-payload antibody drug conjugate (ADC)"

An antibody drug conjugate is a targeted medical treatment that combines a special antibody with a powerful drug, allowing precise delivery of the medicine directly to cancer cells or other harmful cells in the body. For investors, it represents a sophisticated approach to therapy that could improve treatment effectiveness and reduce side effects, potentially leading to significant growth opportunities in the biotech and pharmaceutical sectors.

adc medical

"Top1-payload antibody drug conjugate (ADC) program, and IDE161"

An antibody-drug conjugate (ADC) is a targeted cancer medicine that pairs an antibody that recognizes specific markers on tumor cells with a potent cell-killing drug, connected so the toxic payload is delivered directly to the cancer. For investors, ADCs matter because successful ADCs can improve patient outcomes and reduce side effects compared with traditional chemotherapy, shaping clinical trial success, regulatory approval chances, commercial demand, and a company’s valuation much like a guided missile versus a general bomb.

parg inhibitor medical

"IDE161 (PARG) induced accumulation of TOP1 lesions enhances the efficacy"

A PARG inhibitor is a drug that blocks the enzyme poly(ADP‑ribose) glycohydrolase (PARG), which normally helps cells remove chemical tags used to signal and repair DNA damage. By stopping that cleanup crew, the drug can make damaged cells—often cancer cells—less able to fix themselves and more likely to die when exposed to chemotherapy or other treatments; for investors, successful PARG inhibitors can meaningfully raise a developer’s commercial and clinical value but carry high scientific and regulatory risk.

recist 1.1 medical

"partial responses (PRs) have been observed by RECIST 1.1, including 3 PRs"

RECIST 1.1 is a standardized set of rules used in cancer clinical trials to measure how solid tumors respond to treatment by tracking changes in size on medical scans. Think of it as a consistent ruler and scorecard that tells doctors and regulators whether a drug is shrinking tumors, keeping them stable, or allowing them to grow. Investors care because RECIST-based results are common primary endpoints that influence regulatory decisions, trial success, and a therapy’s commercial prospects.

dna damage response medical

"generated by PARP during the DNA damage response, leading to persistent PARylation"

A DNA damage response is the set of cellular systems that detect and repair breaks or errors in a cell’s genetic material; think of it as a repair crew and alarm system that keeps DNA functioning properly. It matters to investors because drugs that enhance, inhibit, or exploit these repair pathways can change a therapy’s effectiveness, safety, market potential and regulatory risk, affecting the value of biotech and pharmaceutical companies.

parp medical

"chains generated by PARP during the DNA damage response"

PARP is a family of enzymes that help cells detect and repair damaged DNA; think of them as cellular repair crew members that patch small breaks. It matters to investors because medicines called PARP inhibitors can block these enzymes to kill cancer cells or make other treatments work better, so clinical trials, approvals, or setbacks for PARP-targeting drugs can strongly affect the value of companies developing them.

AI-generated analysis. Not financial advice.

• 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
investor@ideayabio.com

View original content to download multimedia:https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-first-patient-in-for-phase-1-combination-study-of-ide849-dll3-top1-adc-and-ide161-parg-inhibitor-in-dll3-upregulated-solid-tumor-indications-including-sclc-nets-necs-and-melanoma-302727304.html

SOURCE IDEAYA Biosciences, Inc.

FAQ

What does IDEAYA announce about the IDE849 and IDE161 combination study (IDYA) on March 30, 2026?

IDEAYA announced first-patient-in for a Phase 1 combination study of IDE849 and IDE161 in DLL3-upregulated solid tumors. According to IDEAYA, the study will enroll globally and evaluate safety, tolerability, and preliminary efficacy with a clinical update expected in H2 2026.

What doses of IDE849 is IDEAYA testing in the Phase 1 program (IDYA) and which cohort showed responses?

IDEAYA is evaluating IDE849 at 3.5 mg/kg IV Q3W in dose escalation and a 2.4 mg/kg IV Q3W expansion cohort. According to IDEAYA, multiple RECIST v1.1 partial responses were observed in the 2.4 mg/kg expansion cohort.

How many partial responses were reported in the IDE849 2.4 mg/kg expansion SCLC cohort for IDYA?

The company reported three partial responses among four SCLC patients pre-treated with IMDELLTRA. According to IDEAYA, these PRs were assessed by RECIST v1.1 in the 2.4 mg/kg expansion cohort.

What is the scientific rationale for combining IDE849 with IDE161 in IDEAYA's study (IDYA)?

IDEAYA says IDE161, a PARG inhibitor, prevents removal of PAR chains, causing persistent PARylation and impaired DNA repair resolution. According to IDEAYA, this produces sustained TOP1 cleavage complexes that may enhance TOP1-payload ADC anti-tumor activity.

When will IDEAYA provide clinical data updates for IDE849 monotherapy and the IDE849+IDE161 combination (IDYA)?

IDEAYA plans a clinical data update in the second half of 2026 for IDE849 monotherapy and the combination. According to IDEAYA, the update will include monotherapy and combination clinical data progress and safety/efficacy summaries.