Delving into the Latest Updates on Venadaparib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

NOV-1401 (National OncoVenture)

+ [4]

Target

PARP1 x PARP2

Action

inhibitors

Mechanism

PARP1 inhibitors(Poly (ADP-Ribose) polymerase 1 inhibitors), PARP2 inhibitors(Poly (ADP-Ribose) Polymerase 2 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Advanced gastric carcinomaHRD positive cancer

Inactive Indication

Advanced Malignant Solid NeoplasmBreast CancerEsophageal Carcinoma

Originator Organization

Ildong Pharmaceutical Co., Ltd.

Active Organization

Idience Co., Ltd.Startup

Inactive Organization

Syneos Health (Beijing) Inc.Ltd.

EirGen Pharma Ltd.

National OncoVenture

Drug Highest PhasePhase 1/2

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC23H23FN4O2

InChIKeyYNBQAYKYNYRCCA-UHFFFAOYSA-N

CAS Registry1681017-83-3

研究的主要目的是评价IDX-1197的安全性和耐受性，并确定联合卡培他滨和奥沙利铂（Xelox），或伊立替康用于治疗晚期胃癌患者的最大耐受剂量（MTD）和推荐II期剂量（RP2D）。研究的次要目的为：评估IDX-1197与Xelox或伊立替康联合给药时的疗效，疗效是通过按实体瘤疗效评价标准（RECIST）v1.1评价的客观缓解率（ORR）、无进展生存期（PFS）、疾病控制率（DCR）、缓解持续时间（DOR）、缓解时间（TTR）、最佳总缓解（BOR），疾病进展时间（TTP），最低可重复有效剂量（MRAD）以及总生存期（OS）进行定义。评价IDX-1197单次递增剂量（SAD）联合Xelox或伊立替康用于治疗晚期胃癌患者时的药代动力学（PK）（仅剂量探索部分）。评价IDX-1197联合Xelox或伊立替康用于治疗晚期胃癌患者时IDX-1197和伊立替康的群体PK模型。通过评估校正的QT间期，评价IDX-1197联合伊立替康对心脏复极化的影响。通过ECG记录和时间匹配的PK测量来评估QT间期延长的风险。

[Translation]

The primary objectives of the study are to evaluate the safety and tolerability of IDX-1197 and to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of IDX-1197 in combination with capecitabine and oxaliplatin (Xelox) or irinotecan for the treatment of patients with advanced gastric cancer. Secondary objectives of the study are to evaluate the efficacy of IDX-1197 in combination with Xelox or irinotecan, as defined by objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), time to response (TTR), best overall response (BOR), time to disease progression (TTP), lowest repeatable effective dose (MRAD), and overall survival (OS) as assessed by response evaluation criteria in solid tumors (RECIST) v1.1. To evaluate the pharmacokinetics (PK) of IDX-1197 in combination with Xelox or irinotecan as a single ascending dose (SAD) in patients with advanced gastric cancer (dose-finding portion only). Population PK models of IDX-1197 and irinotecan were evaluated in combination with Xelox or irinotecan in patients with advanced gastric cancer. The effects of IDX-1197 plus irinotecan on cardiac repolarization were evaluated by assessing the corrected QT interval. The risk of QT prolongation was assessed by ECG recordings and time-matched PK measurements.

Start Date15 Dec 2023

Sponsor / Collaborator

Idience Co., Ltd.Startup

[+2]

NCT05202912

/ CompletedPhase 1

A Randomized, Open-label, Single-dose, Crossover Phase 1 Clinical Trial to Evaluate the Effects of Food or Ethnicity on the Pharmacokinetics and Safety/Tolerability of IDX-1197 After Single Oral Administration in Healthy Male Korean, Chinese, and Caucasian Volunteers

Study to Evaluate the Effects of Food or Ethnicity on the Pharmacokinetics and Safety/Tolerability of IDX-1197 After Single Oral Administration in Healthy Male Korean, Chinese, and Caucasian Volunteers

Start Date16 Jan 2022

Sponsor / Collaborator

Idience Co., Ltd.Startup

NCT04725994

/ RecruitingPhase 1/2

An Open-Label, International, Multicenter, Phase 1b/2a Study to Assess the Safety, Tolerability, and Efficacy of IDX-1197 in Combination with XELOX (Capecitabine and Oxaliplatin) or Irinotecan in Patients with Advanced Gastric Cancer

This is an open-label, Phase 1b/2a study to evaluate the safety and tolerability of IDX-1197 and determine the MTD and RP2D in combination with XELOX or irinotecan in patients with advanced gastric cancer.

Start Date28 Jun 2021

Sponsor / Collaborator

Idience Co., Ltd.Startup

100 Clinical Results associated with Venadaparib

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100 Translational Medicine associated with Venadaparib

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100 Patents (Medical) associated with Venadaparib

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7

Literatures (Medical) associated with Venadaparib

01 Feb 2025·Cancer Medicine

First‐In‐Human Dose Finding Study of Venadaparib (IDX‐1197), a Potent and Selective PARP Inhibitor, in Patients With Advanced Solid Tumors

Article

Author: Kim, Sung‐Bae ; Bang, Jeongsook ; Lee, Won Sik ; Lim, Jong‐Ha ; Lee, Myong‐Jae ; Kim, Yong‐Man ; Lee, Jae Lyun ; Ha, Kyoung Soo ; Bae, Kyun‐Seop ; Hong, Min Ju ; Roh, Eun‐Jihn ; Ock, Chan‐Young

ABSTRACTBackgroundVenadaparib, a novel poly (ADP‐ribose) polymerase (PARP) inhibitor, has demonstrated high PARP‐1/2 selectivity over other PARP family members and exhibited strong PARP‐trapping activity, effectively inhibiting tumor growth in homologous recombination deficient (HRD) cancer in vitro and in vivo.MethodsThis phase 1, dose‐finding study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and anticancer efficacy of venadaparib as monotherapy in patients with advanced solid tumors that progressed after standard‐of‐care therapy. The study employed a conventional 3+3 design, with doses ranging from 2 mg/d to 240 mg/d.ResultsAmong the 32 enrolled patients, the most common tumor types were breast (16 patients) and ovarian (12 patients) cancers. No dose‐limiting toxicities (DLTs) were observed up to 240 mg/d. The most frequent grade 3 or 4 adverse events were anemia (50%), neutropenia (22%) and thrombocytopenia (6%). Tumor shrinkage by Response Evaluation Criteria in Solid Tumours (RECIST) was observed at doses ≥ 40 mg/d, regardless of BRCA mutation status.Two partial responses out of four ovarian cancer patients receiving venadaparib ≥ 40 mg/d were reported. Clinical benefit, defined as stable disease or partial response, was observed at the lowest tested dose. Venadaparib exhibited ≥ 90% PAR inhibitory effect in pharmacodynamic analysis from 10 mg/d based on tumor samples. The recommended phase 2 dose (RP2D) was defined as 160 mg once daily.ConclusionsFurther 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).

01 Dec 2024·Purinergic Signalling

Machine learning-aided search for ligands of P2Y6 and other P2Y receptors

Article

Author: Gao, Zhan-Guo ; Lewicki, Sarah A ; Puhl, Ana C ; Ekins, Sean ; Makarov, Vadim ; Jacobson, Kenneth A ; Pramanik, Asmita

AbstractThe P2Y6 receptor, activated by uridine diphosphate (UDP), is a target for antagonists in inflammatory, neurodegenerative, and metabolic disorders, yet few potent and selective antagonists are known to date. This prompted us to use machine learning as a novel approach to aid ligand discovery, with pharmacological evaluation at three P2YR subtypes: initially P2Y6 and subsequently P2Y1 and P2Y14. Relying on extensive published data for P2Y6R agonists, we generated and validated an array of classification machine learning model using the algorithms deep learning (DL), adaboost classifier (ada), Bernoulli NB (bnb), k-nearest neighbors (kNN) classifier, logistic regression (lreg), random forest classifier (rf), support vector classification (SVC), and XGBoost (XGB) classifier models, and the common consensus was applied to molecular selection of 21 diverse structures. Compounds were screened using human P2Y6R-induced functional calcium transients in transfected 1321N1 astrocytoma cells and fluorescent binding inhibition at closely related hP2Y14R expressed in CHO cells. The hit compound ABBV-744, an experimental anticancer drug with a 6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine scaffold, had multifaceted interactions with the P2YR family: hP2Y6R inhibition in a non-surmountable fashion, suggesting that noncompetitive antagonism, and hP2Y1R enhancement, but not hP2Y14R binding inhibition. Other machine learning-selected compounds were either weak (experimental anti-asthmatic drug AZD5423 with a phenyl-1H-indazole scaffold) or inactive in inhibiting the hP2Y6R. Experimental drugs TAK-593 and GSK1070916 (100 µM) inhibited P2Y14R fluorescent binding by 50% and 38%, respectively, and all other compounds by < 20%. Thus, machine learning has led the way toward revealing previously unknown modulators of several P2YR subtypes that have varied effects.

01 Feb 2024·Investigational New Drugs

Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects

Article

Author: Lee, Won Sik ; Jang, In-Jin ; Lee, Soyoung ; Oh, Jaeseong ; Yang, Eunsol ; Lee, Myongjae ; Kim, Hyun Chul ; Ha, Kyoung Soo ; Lee, ChaeEun ; Yu, Kyung-Sang

AbstractAimVenadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects.MethodsIn this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing.ResultsTwelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUClast) of venadaparib for the fed to fasted state were 0.82 (0.7457–0.9094) and 1.02 (0.9088–1.1339) in Koreans, and 0.77 (0.6871–0.8609) and 0.96 (0.9017–1.0186) in Caucasians, respectively. No statistically significant differences were observed in Cmax (P-value = 0.45) or AUClast (P-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated.ConclusionThe overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased Cmax 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.

100 Deals associated with Venadaparib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced gastric carcinoma	Phase 2	China	Idience Co., Ltd.Startup	28 Jun 2021
Advanced gastric carcinoma	Phase 2	United States	Idience Co., Ltd.Startup	28 Jun 2021
Advanced gastric carcinoma	Phase 2	South Korea	Idience Co., Ltd.Startup	28 Jun 2021
HRD positive cancer	Phase 2	South Korea	Idience Co., Ltd.Startup	06 Nov 2019
Breast Cancer	Discovery	South Korea	Idience Co., Ltd.Startup	16 Sep 2021
Esophageal Carcinoma	Discovery	South Korea	Idience Co., Ltd.Startup	01 Jan 2021
Esophageal Carcinoma	Discovery	China	Idience Co., Ltd.Startup	01 Jan 2021
Esophageal Carcinoma	Discovery	United States	Idience Co., Ltd.Startup	01 Jan 2021
Solid tumor	Discovery	South Korea	Idience Co., Ltd.Startup	06 Nov 2019
Advanced Malignant Solid Neoplasm	Discovery	South Korea	Idience Co., Ltd.Startup	29 Aug 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03317743 (Pubmed \| Cancer Med) Manual	Phase 1	Advanced Malignant Solid Neoplasm	32	Venadaparib	(xjyqjehshc) = Not observed up to 240 mg/d. maeumxooxa (unzxwucfqm ) View more	Positive	01 Feb 2025
NCT04725994 (ASCO2024)	Phase 1	Metastatic Gastric Carcinoma HRD gene mutations	26	Venadaparib plus irinotecan	(hysaqfhnrv) = lucfbzhdcn qmwmyuxelk (lkrqniljdg ) View more	Positive	24 May 2024
				Placebo plus irinotecan	(jdvkhuvrum) = hkghyzguek hukcnyqfla (bipexhpdpx, 2.9 - 5.5)
NCT04174716 (ASCO2023) Manual	Phase 1	Pancreatic Cancer \|	8	Venadaparib (ATMmASXL1m)	(xogeydyzlo) = khfgeqgozx ymuifudhif (vpkxwwpxgn ) View more	Positive	31 May 2023
				Venadaparib (ATMmASXL1wt)	(xogeydyzlo) = xnozanmgzk ymuifudhif (vpkxwwpxgn ) View more
NCT04174716 (VASTUS, ESMO2021)	Phase 1/2	Breast Cancer	14	Venadaparib	(pspdyvdgod) = 8/14 (57%) tkobqjsgkd (ruevgwwlfb ) View more	-	16 Sep 2021
NCT03317743 (ASCO 12021 \| ASCO 22021) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	32	Venadaparib	(yewcveknpo) = Frequently observed adverse drug reactions were as follows – Anemia (56%), nausea (38%) and neutropenia (25%). ryvzwhfhus (zoqnxcdysk )	Positive	20 May 2021
				Venadaparib (BRCAm(+))