venadaparib (NOV 1401) / National OncoVenture, Ildong - LARVOL DELTA

A Phase IIb Randomized Clinical Trial of Immune Checkpoint Inhibitor-based Maintenance Therapy in Patients With Advanced Biliary Tract Cancer (clinicaltrials.gov) - P1/2 | N=160 | Not yet recruiting | Sponsor: Yonsei University

Checkpoint inhibition • New P1/2 trial • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

Idience Co. Licenses Anti-cancer Drug Candidate in Russia, Middle East (Business Korea) - "The total contract value, including upfront payment and milestones, amounts to $50 million....According to the agreements, when Venadaparib is commercialized, Idience will supply the finished pharmaceutical product to the partner companies, who will then pursue local approval and registration of the product and be responsible for marketing and sales."

Commercial • Breast Cancer • Gastric Cancer

Synthesis and Preliminary Evaluation of Novel PSMA-targeting Small Molecule Drug Conjugate Using the Highly Potent PARP inhibitor Venadarib for Treatment of Prostate Cancer (SNMMI 2025) - "For this preliminary study, rucaparib (Ruc) was chosen as PARPi, which, due to its intrinsic fluorescence, enabled tracking of specific Ruc delivery to the cell nucleus in PSMA-positive cells. Synthesis of PSMA-Vena-16 yielded 1.04 mg peptide (>95% pure). GSH cleavage over time was confirmed, resulting in no detectable intact peptide after 240 min, while increasing amounts of free Vena were observed. Compared to our previously developed PSMA-Ruc-16 compound (3,3'-disulfanediyldipropionic acid), an optimized dithiolinker unit was used in this current study."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Efficacy of venadaparib plus irinotecan in homologous recombination deficiency (HRD) gene mutations as 3+ line treatment in patients with metastatic gastric cancer (mGC). (ASCO 2025) - P1/2 | "Venadaparib in combination with irinotecan demonstrated promising efficacy in patients with mGC, particularly those with HRD gene mutations. Further development of this combination may warrant a biomarker-based approach. Efficacy results in patients with homologous recombination deficiency mutation."

Clinical • Metastases • Gastric Cancer • Oncology • Solid Tumor • ATM • ATR • BARD1 • BRCA1 • BRCA2 • CHEK2 • HRD

Next-gen Korean cancer fighters to showcase innovation at ASCO 2025 (Korea Biomedical Review) - P1/2 | N=100 | NCT04725994 | Sponsor: Idience Co., Ltd. | "...Idience...will report updated phase 2 results for venadaparib, a PARP1 inhibitor being tested in third-line metastatic gastric cancer patients. Among those with homologous recombination deficiency (HRD) mutations, the drug combined with irinotecan achieved an overall response rate (ORR) of 35.7 percent and a median progression-free survival of 5.6 months."

P2 data • Gastric Cancer

Ildong Ideas, Anticancer Drug 'Venadaparib' Research Results Published in International Journal [Google translation] (Medipana) - "The clinical trial was conducted primarily on patients with solid cancers such as breast cancer and ovarian cancer who had failed conventional chemotherapy, and the daily dose was set from 2 mg to 240 mg and the course of venadaparib administration was observed. The clinical results showed that venadaparib had a wide drug safety margin, and showed sufficient PARP inhibition even at a low dose of 10 mg. In addition, a tumor reduction response was confirmed in breast cancer and ovarian cancer patients who had not responded to conventional therapy."

P1 data • Breast Cancer • Ovarian Cancer

First-In-Human Dose Finding Study of Venadaparib (IDX-1197), a Potent and Selective PARP Inhibitor, in Patients With Advanced Solid Tumors. (PubMed, Cancer Med) - P1 | "Further studies are warranted to explore efficacy and safety of venadaparib in other tumor types and in combination with various agents, as well as to explore relevant biomarkers. (ClinicalTrials.gov ID: NCT03317743)."

Journal • P1 data • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • BRCA • HRD

The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells. (PubMed, Cancer Res Treat) - "When treated with 50 nM irinotecan, the IC50 fold changes for PARP inhibitors were: olaparib, 1649 ± 4049; talazoparib, 25 ± 34.21; venadaparib, 336 ± 596.01. This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • BRCA • CHEK1

Basket Trial of IDX-1197, a PARP Inhibitor, in Patients with HRR Mutated Solid Tumors (VASTUS) (clinicaltrials.gov) - P1/2 | N=108 | Completed | Sponsor: Idience Co., Ltd. | Active, not recruiting ➔ Completed | Phase classification: P1b/2a ➔ P1/2 | N=310 ➔ 108 | Trial completion date: Dec 2023 ➔ Jun 2024

Enrollment change • Pan tumor • Phase classification • Trial completion • Trial completion date • Oncology • Solid Tumor

Study to Assess the Safety, Tolerability, and Efficacy of IDX-1197 in Combination with XELOX or Irinotecan in Patients with Advanced Gastric Cancer (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Idience Co., Ltd. | Phase classification: P1b ➔ P1/2 | Trial completion date: Mar 2024 ➔ Jun 2026 | Trial primary completion date: Sep 2023 ➔ Sep 2025

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

BRCAness, DNA gaps, and gain and loss of PARP inhibitor–induced synthetic lethality (J Clin Invest) - "Recent studies have revealed that changes of specific functional defects of BRCA1/2-deficient cells, particularly their defects in suppressing and protecting single-stranded DNA gaps, contribute to the gain or loss of PARPi-induced synthetic lethality. These findings not only shed light on the mechanism of action of PARPis, but also lead to revised models that explain how PARPis selectively kill BRCA-deficient cancer cells. Furthermore, new mechanistic principles of PARPi sensitivity and resistance have emerged from these studies, generating potentially useful guidelines for predicting the PARPi response and design therapies for overcoming PARPi resistance."

Review • Breast Cancer

Novel anti-Acanthamoeba effects elicited by a repurposed poly (ADP-ribose) polymerase inhibitor AZ9482. (PubMed, Front Cell Infect Microbiol) - "Using a homology model of Acanthamoeba poly (ADP-ribose) polymerases (PARPs), molecular docking of approved drugs revealed three potential inhibitory compounds: olaparib, venadaparib and AZ9482. Analyzing gene expression related to DNA damage repair pathway and the rate of apurinic/apyrimidinic (AP) sites indicated DNA damage efficacy and repair modulation in Acanthamoeba trophozoites following AZ9482 treatment. Collectively, these findings highlight AZ9482, as a structurally unique PARP inhibitor, provides a promising prototype for advancing anti-Acanthamoeba drug research."

Journal • Infectious Disease • Oncology • Targeted Protein Degradation • ANXA5

Association between homologous recombination deficiency (HRD) gene mutations and the efficacy of venadaparib in combination with irinotecan as third- or fourth-line treatment in patients with metastatic gastric cancer (mGC). (ASCO 2024) - P1b | "Venadaparib in combination with irinotecan showed promising efficacy outcomes in patients with mGC, especially for those with mutations of HRD-related genes. Further development of this combination may consider a biomarker-based approach. Clinical trial information: NCT04725994."

Clinical • Combination therapy • Metastases • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ATM • ATR • BARD1 • BRCA1 • BRCA2 • BRIP1 • CHEK1 • CHEK2 • HRD • PALB2 • POLD1 • RAD51 • RAD51B

The synergistic potential of PARP inhibitors and irinotecan in small cell lung cancer (AACR 2024) - "Furthermore, we confirmed protein changes in the DDR pathway through western blotting and measured the number of apoptotic cells using Annexin V staining. In our experiments, talazoparib had the most potent effect at low concentrations, while olaparib and venadaparib showed more pronounced synergistic effects (average fold change of IC50: olaparib, 1649±4049; talazoparib, 25±34.21; venadaparib, 336±596.01; see Table). The combination of a PARPi with irinotecan significantly inhibited cell growth more than the use of either agent alone. Our findings indicate that clinical trials are warranted to confirm the effectiveness of combining PARPi with irinotecan in patients with SCLC."

IO biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ANXA5 • BRCA • CHEK1

Predictive role of homologous recombination deficiency (HRD) for irinotecan in combination with venadaparib, a novel PARP1/2 inhibitor, as third- or fourth-line treatment in patients with advanced gastric cancer. (ASCO-GI 2024) - P1b | "Venadaparib in combination with irinotecan showed synergistic effect in vitro assays and promising clinical efficacy in the systemic treatment of refractory GC, particularly in patients with HRD. The dose expansion phase of the study is ongoing to investigate the optimal biological dose and patient selection strategies, in a randomized design. Clinical trial information: NCT04725994."

Clinical • Combination therapy • Metastases • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ATM • BRCA • HRD

Ildong Pharmaceutical Ideas announces new anticancer drug research results at 'ASCO GI' [Google translation] (Hankyung) - P1 | N=100 | NCT04725994 | Sponsor: Idience Co., Ltd. | "At this symposium, Idience presented a poster of the interim results of a phase 1 clinical trial in which the combination therapy of venadaparib and irinotecan, a chemotherapy drug, was administered to patients undergoing third- and fourth-line gastric cancer treatment. In the evaluable patient group (11 patients) who explored the appropriate dose combination of venadaparib and irinotecan and received co-administration, the objective response rate (ORR) was 36.4% and the median progression-free survival (mPFS) was 5.6 months. The group of gastric cancer patients (5 patients) with homologous recombination deficiency (HRD), which serves as a marker for anticancer treatment, had a relatively higher ORR of 60%....The company plans to speed up the development of venadaparib with the goal of entering clinical trials (phases 2 and 3) next year."

New P2 trial • New P3 trial • P1 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects. (PubMed, Invest New Drugs) - "The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased C in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states."

Journal • PK/PD data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Co-mutation of ATM and ASXL1 and relationship to durable response of a novel PARP1/2 inhibitor, venadaparib, in patients with pancreatic cancer. (ASCO 2023) - P1b/2a | "In this exploratory analysis, patients with co-occurring ATMm and ASXL1m showed higher tumor response. This signals potential value from ATM and ASXL1 co-mutation predicting efficacy of Venadaparib in PC and warrants further validation. Clinical trial information: NCT04174716."

Clinical • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • ASXL1 • ATM • BRCA • HRD

Basket Trial of IDX-1197, a PARP Inhibitor, in Patients With HRR Mutated Solid Tumors (VASTUS) (clinicaltrials.gov) - P1b/2a | N=310 | Active, not recruiting | Sponsor: Idience Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2023

Enrollment closed • Pan tumor • Trial completion date • Oncology • Solid Tumor

Venadaparib Is a Novel and Selective PARP Inhibitor with Improved Physicochemical Properties, Efficacy, and Safety. (PubMed, Mol Cancer Ther) - "Venadaparib had wider safety margins than olaparib. Our results suggest the possibility of venadaparib as a next-generation PARP inhibitor. On the basis of these findings, phase Ib/IIa studies on the efficacy and safety of venadaparib have been initiated."

Journal • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • BRCA • HRD

Venadaparib is a novel and selective PARP inhibitor with improved physicochemical properties, efficacy, and safety. (PubMed, Mol Cancer Ther) - "Venadaparib had wider safety margins than olaparib. Our results suggest the possibility of venadaparib as a next generation PARP inhibitor. Based on these findings, phase 1b/2a studies on the efficacy and safety of venadaparib have been initiated."

Journal • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • BRCA • HRD

Ildong’s new anticancer drug Venadaparib draws attention in clinical trial (Korea Biomedical Review) - "The Ministry of Food and Drug Safety approved the drug’s use to treat two patients last Friday. It was the first time that Venadaparib won approvals for treatment purposes. The approval of drugs for therapeutic purposes is a system that allows clinical trial medicines to be used for patient treatment. The ministry introduced the system to treat new infectious diseases and emergency patients with no alternative treatment methods to expand patients’ treatment opportunities....Besides, Idience plans to conduct a phase 1b/2a clinical trial, VASTUS, to evaluate Venedaparib’s safety, tolerability, and efficacy in solid cancer patients with homologous recombination recovery mutation....Idience seeks to submit a new drug application (NDA) to the FDA in 2026 and license out the technology by finding a partner."

NDA • New P1/2 trial • Non-US regulatory • Oncology • Solid Tumor

Study to Assess the Safety, Tolerability, and Efficacy of IDX-1197 in Combination With XELOX or Irinotecan in Patients With Advanced Gastric Cancer (clinicaltrials.gov) - P1b | N=100 | Recruiting | Sponsor: Idience Co., Ltd. | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Jun 2023 ➔ Sep 2023

Combination therapy • Trial completion date • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Food Effect Study of IDX-1197 in Healthy Subjects (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: Idience Co., Ltd. | Recruiting ➔ Completed

Trial completion

Idience's venadaparib wins orphan drug status from US FDA (Korea Biomedical Review) - "Idience said Tuesday that venadaparib...has been designated as an orphan drug by the US Food and Drug Administration....Venadaparib is a novel drug substance with a Poly ADP-ribose polymerase (PARP) inhibitory mechanism, developed as the targeted agent for solid tumors, such as gastric, breast, and ovarian cancer. The FDA approved it as a rare disease treatment substance related to gastric cancer based on the non-clinical research data and the clinical results....'We will seek partnerships and technology transfer while pushing ahead with multinational clinical trials targeted for new drug application (NDA) by 2026'."

NDA • Orphan drug • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor