On April 26, 2022 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that it has filed a clinical trial application with the Human Research Ethics Committee (HREC) in Australia in order to initiate the Phase I ATRIUM trial of ATG-018 in patients with advanced solid tumors and hematologic malignancies (Press release, Antengene, APR 26, 2022, View Source [SID1234612993]).

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The primary objective of the study is to evaluate the safety and tolerability of ATG-018 as monotherapy to determine the appropriate dose for Phase II studies and assess preliminary efficacy, if available; the secondary objective is to characterize the pharmacology of ATG-018.

ATG-018 is an orally available, potent, selective small molecule ATR inhibitor. ATG-018 inhibits the ATR (ataxia telangiectasia mutated and Rad3-related) kinase, thus limiting cancer cells’ ability to repair damaged DNA, in a mechanism also known as synthetic lethality.

Dr. Bo Shan, Chief Scientific Officer of Antengene commented, "ATG-018, one of Antengene’s first in-house programs to reach the clinic, targets the DDR pathway that is deregulated in many cancers. DDR inhibitors represent a promising area of drug development and clinical research in oncology, especially in resistant or advanced diseases. The differentiated profile of ATG-018 may enable it to be used as monotherapy and open the door for novel collaborations and combination regimens that could benefit cancer patients around the world."

Dr. Kevin Lynch, Chief Medical Officer of Antengene continued, "Antengene is very excited to submit the ATG-018 Phase I protocol for HREC review, based on its solid preclinical data package including efficacy as a monotherapy in solid tumor models, oral bio-availability and potential biomarkers. The use of biomarker-informed studies may facilitate clinical trial enrollment and provide an additional tool to monitor patients during the trial. As we prepare for the start of this important study, I want to thank all of the investigator sites for their support and enthusiasm, and everyone in Antengene’s R&D organization for their dedication in the preparation for this study."

About the ATRIUM Trial

The ATRIUM trial is a Phase I multi-center, open-label, dose finding study of ATG-018 monotherapy in patients with advanced solid tumors or hematologic malignancies. The primary objective of the study is to evaluate the safety and tolerability of ATG-018 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and/or biologically effective dose of ATG-018 monotherapy and preliminary efficacy, if available; the secondary objective is to characterize the pharmacology of ATG-018. As a Phase I study, there will be intensive safety monitoring throughout the trial.

About ATG-018

Developed by the internal R&D Team at Antengene, ATG-018 is an oral, potent, selective small molecule inhibitor targeting ataxia telangiectasia and Rad3-related (ATR) kinase. ATR kinase belongs to the phosphoinositide 3 kinase-related family. Inhibiting ATR kinase leads to increased accumulation of single-strand DNA breaks, particularly meaningful for tumor cells which rely on DNA damage repair (DDR). Preclinical studies have demonstrated that ATR inhibitor monotherapy or combination with other drugs (including DDR agents) could be promising therapeutic strategies for solid tumors (including gastric, esophageal, squamous cell carcinoma) and hematologic malignancies (chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma [DLBCL] and multiple myeloma [MM]).

According to a preclinical poster presented at AACR (Free AACR Whitepaper) 2022, ATG-018 has demonstrated potent in vitro and in vivo monotherapy efficacy in solid tumor/hematologic cancer models with certain homologous recombination deficiencies. These data were supported by a series of genetic alterations that correlated with ATG-018 sensitivity and could be potential predictive biomarkers. Taken together, these data suggest that ATG-018 could be a promising therapeutic agent for patients with such homologous recombination deficiencies/genetic alterations.

ATG-018 is a development stage product candidate and is not approved by any regulatory agency. Antengene has global rights to ATG-018.