Antengene Announces Five Upcoming Presentations at the 2022 American Association for Cancer Research Annual Meeting
Release date：
2022-03-09
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-Posters Showcase Early-Stage Clinical and Preclinical Pipeline.
-Focus on ATG-037, ATG-018, ATG-022, ATG-012 and ATG-008.
Shanghai and Hong Kong, PRC, March 9, 2022 — Antengene Corporation Limited (“Antengene” SEHK: 6996.HK), a leading innovative, global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, today announced the publication of abstracts for five posters that will be presented during the upcoming 2022 American Association for Cancer Research Meetings (AACR 2022), taking place from April 8th to April 13th in New Orleans via in person or virtual attendance.
“The preclinical studies that we will present at 2022 AACR will provide a window into the breadth of targets and the in vitro and in vivo data that support five programs in Antengene’s pipeline,” said Bo Shan, Ph.D., Chief Scientific Officer of Antengene. “The data from these studies have been instrumental in guiding our clinical development plans for each program, including insights on potential combination regimens and novel biomarkers or genetic alterations that could be used to predict efficacy or improve the proportion of patients who respond to treatment. We are very pleased to share these results with the oncology community.”
Details of the posters and corresponding abstracts are shown below:
Title：ATG-037, a highly potent small molecule CD73 inhibitor has superior activity of reversing immunosuppression in higher-AMP environments compared with anti-CD73 antibodies
Abstract: 2576
Session: Cell Cycle, Replication Inhibitors, and Immunotherapy Agents
Date and Time: 9:00 AM - 12:30 PM CST, April 12, 2022
Venue: Poster Section 21
This study was designed to compare the activity of ATG-037, a highly potent and selective oral small molecule inhibitor of CD73, and two antibody inhibitors of CD73. CD73 is an enzyme that is highly expressed in the tumor microenvironment and enables the degradation of AMP into adenosine, resulting in immunosuppression and cancer progression. In vitro assays were used to assess each compound’s ability to inhibit CD73 function and reverse AMP/adenosine mediated T-cell suppression. Compared to the two antibodies, ATG-037 demonstrated more potent and complete inhibitory activity of cell surface CD73 in this study. In addition, the authors concluded that ATG-037 had a stronger ability to restore T-cell function in higher-AMP environments compared with other clinical anti-CD73 antibodies. These data highlight the potential therapeutic advantages of small molecule inhibitors of CD73 over blocking antibodies. ATG-037 is being evaluated by Antengene in a Phase I trial as monotherapy and in combination with anti-PD-1 antibody in patients with locally advanced or metastatic solid tumors.
Title: The novel ATR inhibitor ATG-018 is efficacious in preclinical cancer models
Abstract: 2604
Session: DNA Damage Response and Repair
Date and Time: 9:00 AM - 12:30 PM CST, April 12, 2022
Venue: Poster Section 22
In this preclinical study, the data set supporting the development of ATG-018, a small molecule ATR inhibitor, was reviewed. ATR kinase (ataxia telangiectasia and Rad3 related kinase) plays a role in the DNA damage response (DDR). ATG-018 was tested in a panel of 143 tumor cell lines and three CDX mouse models to assess anti-proliferation efficacy and to identify potential predictive biomarkers. ATG-018 was a potent inhibitor of cancer cell proliferation without affecting the viability of normal PBMCs and a dose-dependent inhibitor of tumor growth in the CDX models. The authors concluded that ATG-018 demonstrated potent in vitro and in vivo monotherapy efficacy in solid tumor/hematologic cancer models with certain homologous recombination deficiencies. In addition, a series of genetic alterations were discovered that correlated with ATG-018 sensitivity and could be potential predictive biomarkers. These data suggest that ATG-018 could be a promising therapeutic agent for patients with such homologous recombination deficiencies/genetic alterations.
Title: ATG-022, an antibody-drug conjugate targeting Claudin 18.2, demonstrated potent in vivo efficacy in gastric cancer patient-derived xenografts
Abstract: 1143
Session: Preclinical and Clinical Pharmacology
Date and Time: 9:00 AM - 12:30 PM CST, April 11, 2022
Venue: Poster Section 25
In this preclinical study, ATG-022, an antibody-drug conjugate targeting Claudin 18.2 (CLDN18.2), was evaluated in several gastric cancer patient-derived xenograft (PDX) models with different CLDN18.2 expression levels. Human CLDN18.2 is overexpressed in a large proportion of gastric and pancreatic cancers. Studies with a monoclonal antibody (IMAB362) targeting CLDN18.2 demonstrated promising clinical benefit in combination with chemotherapy. But it showed suboptimal efficacy in patients with low CLDN18.2 expression levels. In this AACR study, ATG-022 is reported to show high affinity (sub-nanomolar grade) against CLDN18.2 and demonstrated potent in vitro and in vivo antitumor effects, with in vivo efficacy observed in CLDN18.2 low expression PDX models. The authors concluded that ATG-022 shows promise for gastric cancer patients with a broad range of CLDN 18.2 expression levels. Antengene is conducting preclinical studies for ATG-022.
Ttitle: Synergistic effects of the combination of Kras (G12C) with SHP2, ERK1/2, mTORC1/2 or XPO1 inhibition for the treatment of Kras (G12C) mutated cancer
Abstract: 2679
Session: Signaling Pathway Inhibitors
Date and Time: 9:00 AM - 12:30 PM CST, April 12, 2022
Venue: Poster Section 25
This preclinical study was conducted to identify combination therapy regimen that could overcome the short progression free survival that is a characteristic of KRAS G12C inhibitors. The study evaluated the anti-tumor activity of ATG-012, a KRAS G12C inhibitor, with four other agents that are involved in the multiple pathways: i) an SHP2 inhibitor, ET0038, ii) an ERK 1/2 kinase inhibitor, ATG-017, iii) an mTORC1/2 kinase inhibitor, ATG-008 or iv) the XPO-1 inhibitor, Selinexor, in preclinical solid tumor CDX models. While ATG-012 monotherapy induced tumor growth inhibition, the authors concluded that strong in vivo synergism was continually observed throughout the study period when each these four agents were paired with ATG-012 in 2-agent combinations. These data provide several promising combination strategies for ATG-012 that could be utilized in clinical testing for cancer patients with the KRAS G12C mutation.
Title: Identification of MUC5B mutation as a positive predictive biomarker for mTORC1/2 inhibition by ATG-008 in lung cancer
Abstract: 4032
Session: Molecular Pharmacology
Date and Time: 9:00 AM - 12:30 PM CST, April 13, 2022
Venue: Poster Section 26
This study was designed to discover genetic alternations that could serve as predictive biomarkers for mTORC1/2 inhibition by ATG-008 (Onatasertib) in lung cancer. And MUC5B mutation was identified as a positive predictive biomarker for ATG-008 (Onatasertib) and potentially improve the proportion of lung cancer patients who respond to therapy. ATG-008 is a dual mTOR complex 1/2 kinase inhibitor. The mTOR complex regulates cell growth, metabolism, proliferation and survival. While the mTOR pathway is frequently deregulated in cancers, efficacy of mTOR inhibitors in lung cancer has been modest. 31 lung cancer cell lines were treated with ATG-008 to determine dose response and correlate the gene mutation, amplification and expression with sensitivity to ATG-008. Results were validated in cell-derived xenograft (CDX) mice bearing lung cancer cell lines with or without theMUC5B mutation. CDX mice that carried the Muc5B mutation had higher tumor growth inhibition compared with wild type Muc5B cell lines. The authors concluded that the presence of the Muc5B mutation correlates with more potent anti-tumor efficacy of ATG-008 in murine lung cancer models. These data support testing ATG-008 in the clinic. ATG-008 is being evaluated by Antengene in multiple Phase I and II clinical trials.
About Antengene
Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on innovative first-in-class/best-in-class therapeutic medicines for cancer and other life-threatening diseases. Driven by its vision of “Treating Patients Beyond Borders”, Antengene aims to provide the most advanced anti-cancer drugs to patients in the Asia Pacific Region and around the world. Since initiating operations in 2017, Antengene has obtained 22 investigational new drug (IND) approvals in the US and in Asia, submitted 6 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for selinexor/ATG-010/XPOVIO® in China, South Korea, Singapore and Australia approved. Leveraging partnerships as well as in-house drug discovery, Antengene has built a broad and expanding pipeline of 15 clinical and pre-clinical assets. Antengene has global rights on 10 programs and Asia Pacific rights, including the Greater China region, on 5 programs.
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