IDE161 / Ideaya Biosci - LARVOL DELTA

KEYNOTE-F86: A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=216 | Active, not recruiting | Sponsor: IDEAYA Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • BARD1 • BRCA1 • BRCA2 • BRIP1 • CDK12 • CHEK1 • CHEK2 • FANCA • FANCL • HRD • NBN • PPP2R2A • RAD51B • RAD51C • RAD51D • RAD54L

IDE849 (DLL3 TOP1 ADC): targeting to provide a clinical data update from the ongoing IDEAYA-sponsored global Phase 1/2 trial of IDE849 in small-cell lung cancer (SCLC) and neuroendocrine carcinomas (NEC) by the end of 2026. (IDEAYA Biosciences Press Release) - "The company is planning to initiate a monotherapy registrational trial by the end of 2026...Achieved first-patient-in (FPI) in Phase 1 combination trial of IDE849 and IDE161, IDEAYA's proprietary inhibitor of poly(ADP-ribose) glycohydrolase (PARG)."

New trial • P1/2 data • Trial status • Neuroendocrine Carcinoma • Small Cell Lung Cancer

PARG inhibition provokes a DNA damage-dependent innate immune reaction that enhances ICI-driven anti-tumor immunity (AACR 2025) - P1 | "These cumulative observations suggest that IDE161 can induce an innate-immune-pathway-mediated priming of an antitumor adaptive immune response, and thus may deliver both tumor autonomous and nonautonomous therapeutic benefits. This relationship is currently under evaluation with IDE161/pembrolizumab combination therapy In patients with advanced endometrial cancer who have previously progressed on anti-PD-1 therapy (NCT05787587)"

Endometrial Cancer • Oncology • Solid Tumor • IFNB1

QLS1403, a novel and potent PARG inhibitor with robust anti-tumor efficacy in homologous recombination deficient cancer models (AACR 2026) - "IDE-161, a first-in-class PARG inhibitor has entered clinical trials. QLS1403 demonstrates superior potency, sustained efficacy in PARPi-resistant and T-Dxd-resistant cancer cell lines, while displaying favorable safety. These compelling data support its clinical evaluation as a new therapeutics for patients with HRD-positive cancers with acquisition of resistance to PARPi or potentially other existing treatments, such as T-Dxd."

Clinical • Preclinical • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HRD

IDE034, A bispecific antibody-drug conjugate co-targeting PTK7 and B7-H3, exhibits avidity-driven selectivity and enhanced antitumor activity versus mono-specific ADCs (AACR 2026) - "Given the reported frequency of detection of B7H3 and PTK7 protein expression across numerous tumor samples, double positive disease is anticipated to be prevalent in colorectal, non-small cell lung, and breast cancers. Together, these findings support IDE034 as a potential first-in-class bispecific TOP1i-ADC with broad opportunity across disease indications as a monotherapy and in combination with IDE161."

ADC • Bispecific • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD276 • PTK7

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 (PRNewswire) - "The study will be enrolling patients globally, including in North America, Europe, Australia, South America, and Asia....Targeting IDE849 monotherapy, and IDE849 and IDE161 combination clinical data update in H2 2026."

P1 data • Trial status • Melanoma • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Small Cell Lung Cancer

IDEAYA Biosciences Announces First-Patient-In for Phase 1 Trial of IDE034, a Potential First-In-Class B7H3/PTK7 Bispecific TOP1 ADC (PRNewswire) - "The company is planning to evaluate safety, tolerability and PK of IDE034 as a monotherapy in the Phase 1 trial, and also plans to test combinations with agents that target the DNA damage response (DDR) pathway, such as their proprietary PARG inhibitor, IDE161. Dosing of the first patient with IDE034 triggers a $5 million milestone payment from IDEAYA to Biocytogen, pursuant to the Option and License Agreement between the companies."

Financing • Trial status • Solid Tumor

2026 Corporate Objectives:…Antibody-drug Conjugate (ADC) + DNA damage response (DDR) combinations (PRNewswire) - "(i) IDE849 (DLL3 TOP1 ADC): target to initiate a monotherapy registrational study in the second line/refractory setting (2L+) of small cell lung cancer (SCLC) and/or neuroendocrine carcinomas (NEC) by the end of 2026; (ii) IDE034 (B7H3/PTK7 bispecific TOP1 ADC): initiate Phase 1 dose escalation trial in Q1 '26; (iii) IDE161 (PARG): initiate clinical combination studies with IDE849 in SCLC, NEC and other DLL3-overexpressing solid tumors in Q2 '26."

New trial • Neuroendocrine Carcinoma • Small Cell Lung Cancer

A Study of IDE849 in Patients With DLL3 Expressing Tumors Including Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=208 | Recruiting | Sponsor: IDEAYA Biosciences | N=90 ➔ 208

Enrollment change • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Oncology • Small Cell Lung Cancer • Solid Tumor

IDEAYA plans to initiate a Phase 1 combination trial of IDE849 and IDE161 by the end of 2025. (PRNewswire)

New P1 trial • Solid Tumor

Dual PARG-TOP1 Inhibition Exacerbates Dna-Protein Crosslinks and Replication Stress: A Promising Strategy for Enhancing Top1i-ADC Efficacy (IASLC-WCLC 2025) - "Multiplexed viability screens with combination treatment of IDE161 and topotecan revealed enhanced cellular proliferation defects in multiple tumor models compared to single agent treatment. Importantly, deep, durable, and complete responses were observed with IDE161 in combination with multiple TOP1i-ADCs in lung cancer CDX models, that were not achievable with monotherapy. Conclusions : These findings deliver a strong mechanistic rationale for the use of systemic PARG inhibition to enhance the efficacy and durability of TOP1i-ADC therapies in solid tumors, particularly in the setting of lung cancer."

Clinical • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • TOP1

IDEAYA Biosciences and Hengrui Pharmaceuticals Announce Oral Presentation at IASLC 2025 World Conference on Lung Cancer for IDE849 (SHR-4849), a Potential First-in-Class DLL3-TOP1 ADC (PRNewswire) - "IDEAYA Biosciences...announced the publication of an abstract for an oral presentation on IDE849 (SHR-4849) at the IASLC 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (WCLC)....The presentation will cover efficacy and safety results in SCLC from the Phase 1 trial Hengrui is conducting in China for IDE849 (SHR-4849)....Clinical efficacy and safety data will be presented from over 70 small-cell lung cancer (SCLC) patients in Hengrui's ongoing, multi-site, open label Phase 1 trial. Data will include patients from the dose escalation and at multiple expansion doses. U.S. Phase 1 trial of IDE849 in SCLC patients initiated in 3Q 2025....IDEAYA will also have a poster presentation with data from a second published abstract providing combination mechanism and pre-clinical synergy data between TOP1-payload based ADCs and IDE161, the company's proprietary, potentially first-in-class PARG inhibitor."

P1 data • Preclinical • Small Cell Lung Cancer

IDEAYA Biosciences, Inc. Reports First Quarter 2025 Financial Results and Provides Business Update (PRNewswire) - "IDEAYA plans to enable the wholly-owned IDE397 and IDE892 (PRMT5MTA) combination in patients with MTAP-deletion non-small cell lung cancer (NSCLC) in the second half of 2025....Initiation of evaluation of IDE849 and IDE161 combination targeted in the second half of 2025....Targeting to present preclinical combination mechanism and synergy efficacy data of IDE161 with TOP1-payload based ADCs at a medical conference in the third quarter of 2025."

New trial • Preclinical • Non Small Cell Lung Cancer

IDEAYA Biosciences, Inc. Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (PRNewswire) - "Data highlighting IDE275's differentiated potential best-in-class profile will be presented with GSK at a medical conference in the first half of 2025...First patient dosed in the Phase 1 trial evaluating IDE161 in combination with KEYTRUDA in patients with MSI-High and microsatellite stable (MSS) endometrial cancer. Targeting Phase 1 expansion in 2025...Targeting clinical combination(s) of IDE161 with TOP1i ADCs in solid tumors in 2025."

Clinical • New trial • P1 data • Endometrial Cancer • Microsatellite Instability • Solid Tumor

IDEAYA Biosciences, Inc. Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (PRNewswire) - "Initiation of the Phase 3 registration-enabling trial for darovasertib in neoadjuvant UM is targeted for the first half of 2025...Targeting Phase 1/2 expansion in the first quarter of 2025 and clinical data update for IDE397 in combination with Trodelvy in MTAP-deletion UC in 2025...IDEAYA and Amgen mutually agreed to wind down the IDE397 and AMG 193 clinical combination study in February 2025, and will not pursue dose expansion...IDEAYA plans to submit a U.S. IND for the evaluation of IDE849 as a monotherapy in SCLC in the first half of 2025. Targeting to initiate the evaluation in combination with IDE161 and in NETs in the second half of 2025. Clinical data update targeted in 2025."

Clinical data • IND • New trial • Trial completion • Neuroendocrine Tumor • Small Cell Lung Cancer • Urothelial Cancer • Uveal Melanoma

IDEAYA Biosciences Announces Participation at the 43rd Annual J.P. Morgan Healthcare Conference and 2025 Corporate Guidance (PRNewswire) - "3 IND-filings targeted in 2025, representing IDEAYA's 7th, 8th, and 9th potential clinical stage precision medicine oncology program targeting solid tumors; IDE892, a potential best-in-class MTA-cooperative PRMT5 inhibitor, in mid-year 2025. Combination potential with IDE397; IDE034, a potential first-in-class B7H3/PTK7 TOP1i bispecific ADC, in the second half of 2025. Combination potential with IDE161; IDE251, a potential first-in-class KAT6/7 dual inhibitor development candidate, in the second half of 2025. Combination potential with multiple programs in IDEAYA's pipeline..."

IND • Solid Tumor

IDEAYA Biosciences Enters Exclusive License with Hengrui Pharma for SHR-4849… (PRNewswire) - "IDEAYA Biosciences...announced that it has entered into an exclusive license agreement for SHR-4849, a novel DLL3-targeting Topo-I-payload ADC program with Jiangsu Hengrui Pharmaceuticals..., an innovative global pharmaceutical company headquartered in China focused on unmet clinical needs. Under the terms of the agreement, IDEAYA will develop and commercialize SHR-4849 worldwide outside of Greater China....Under the terms of the agreement, Hengrui Pharma is eligible to receive upfront and milestone payments totaling $1.045 billion, including a $75m upfront fee, up to $200m in development and regulatory milestone payments, plus commercial success-based milestones. Hengrui is also eligible to receive mid-single to low-double digit royalties on net sales outside of Greater China....Rational combination opportunities with IDEAYA's DNA Damage Repair (DDR) clinical pipeline, including Phase 1 PARG inhibitor IDE161."

Licensing / partnership • Solid Tumor

IDEAYA Announces First-Patient-In for Phase 1 Clinical Trial Evaluating IDE161 in Combination with KEYTRUDA (pembrolizumab) in Patients with Endometrial Cancer (PRNewswire) - "IDEAYA Biosciences, Inc...announced that it has dosed the first patient in the IDEAYA-sponsored Phase 1 trial evaluating the combination of IDE161, the company's investigational, potential first-in-class, small molecule poly (ADP-ribose) glycohydrolase, or PARG, inhibitor, in combination with Merck's (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in endometrial cancer patients with high microsatellite instability (MSI-high) and microsatellite stable(MSS)."

Trial status • Endometrial Cancer • Microsatellite Instability

A Study of PARG Inhibitor IDE161 in Participants with Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=216 | Recruiting | Sponsor: IDEAYA Biosciences | N=68 ➔ 216 | Trial completion date: Sep 2025 ➔ May 2027 | Trial primary completion date: Jun 2025 ➔ Oct 2026

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • HRD

IDEAYA Biosciences, Inc. Reports Third Quarter 2024 Financial Results and Provides Business Update (PRNewswire) - "IDE161 in Tumors with Homologous Recombination Deficiency: Targeting Phase 1/2 monotherapy expansion for IDE161 PARG inhibitor in priority solid tumor type(s) in the fourth quarter of 2024. Targeting first-patient-in for the Phase 1 trial evaluating IDE161, IDEAYA's first-in-class potential PARG inhibitor, in combination with Merck's...KEYTRUDA (pembrolizumab), in MSI-High and MSS endometrial cancer (EC) in the fourth quarter of 2024....Targeting Development Candidate nomination for MTAP-deletion, KAT6 pathway and B7H3/PTK7 Topo-Payload Bispecific-ADC programs in Q4 2024."

New molecule • Trial status • Endometrial Cancer • Microsatellite Instability

A novel small molecule inhibitor of PARG, YL-18319, promotes tumor regression in BRCAmutated, Homologous Recombination Deficient, and PARP-inhibitor resistant cancer models (EORTC-NCI-AACR 2024) - "In contrast, niraparib or olaparib PARP inhibitor treatments failed to exhibit sensitivity in tumor cell proliferation assays (IC50, 0.3-4.6 mM). A differentiated tumor regression was observed in BRCAmutant (HCC1428 breast, HCC1395 breast) and HRD (SNU-601 ovarian) in vivo models treated with YL-18319 compared with niraparib or IDE-161 (PARG inhibitor)... The small molecule PARG inhibitor, YL-18319, demonstrated a highly potent activity in vitro and in vivo, as well as favorable pharmacologic properties. The evaluation of YL-18319 in a phase 1 dose escalation clinical trial for patients with advanced cancers is warranted."

Preclinical • Oncology • BRCA • HRD

IDE161, a potential first-in-class clinical candidate PARG inhibitor, selectively targets solid tumors with replication stress and DNA repair vulnerabilities (EORTC-NCI-AACR 2024) - P1 | "Finally, the singular consequences of PARG inhibition, in the context of drug-induced DNA damage, offers mechanism-based combination hypotheses for both approved and investigational new drugs in biomarker populations beyond those responsive to IDE161 monotherapy- several of which have been evaluated in relevant CDX models and demonstrated to deliver deep and durable responses including complete responses. These findings underpin the clinical development strategy currently underway for evaluation of IDE161 in biomarker selected patients with advanced or metastatic cancer."

Clinical • Oncology • Solid Tumor

IDEAYA Biosciences Announces Late-Breaker Oral Presentation of IDE397 Phase 1 Expansion Results in MTAP-Deletion Lung and Urothelial Cancer at the 36th Edition of the EORTC-NCI-AACR Symposium (PRNewswire) - "IDEAYA Biosciences, Inc...announced a late-breaking oral presentation of the Phase 1 expansion results of IDE397, a first-in-class, oral, MAT2A inhibitor in methylthioadenosine phosphorylase (MTAP)-deletion urothelial and non-small cell lung cancer (NSCLC) patients at the 36th edition of the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics taking place on October 23 to 25, 2024, in Barcelona, Spain. In addition, IDEAYA will also have additional poster presentations at the EORTC-NCI-AACR Symposium highlighting preclinical data for the MAT2A and PARG programs."

P1 data • Preclinical • Non Small Cell Lung Cancer • Urothelial Cancer

IDEAYA Biosciences, Inc. Reports First Quarter 2024 Financial Results and Provides Business Update (PRNewswire) - "IDE161 is currently being evaluated in IDE161-001 (NCT05787587), a Phase 1/2 trial of IDE161 in solid tumors with HRD...Selection of an initial Phase 2 monotherapy expansion dose in HRD solid tumors is targeted in the second half of 2024. The Company is currently validating IDE161 combination opportunities preclinically and targeting identification of additional combination(s) in 2024....The Company is planning to evaluate IDE161 in a combination study with KEYTRUDA in patients with MSI-high and MSS endometrial cancer. A first-patient-in for this study is targeted in the second half of 2024."

New trial • Trial status • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Uterine Cancer • HRD

IDEAYA Announces Clinical Collaboration to Evaluate IDE161 in Combination with KEYTRUDA (pembrolizumab) in Patients with Endometrial Cancer (PRNewswire) - "IDEAYA Biosciences, Inc...announced that it has entered into a clinical trial collaboration and supply agreement with Merck (known as MSD outside the US and Canada) to evaluate IDE161, the company's investigational, potential first-in-class, small molecule poly (ADP-ribose) glycohydrolase, or PARG, inhibitor, in combination with KEYTRUDA (pembrolizumab) Merck's anti-PD-1 therapy, in patients with microsatellite instability-, or MSI-, high and microsatellite stable, or MSS, endometrial cancer, in a Phase 1 clinical trial....Under the clinical trial collaboration and supply agreement, Merck will provide KEYTRUDA to IDEAYA, which will be the sponsor of the Phase 1 clinical combination trial."

Licensing / partnership • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor