- The posters present the clinical and preclinical pipeline at an early stage.
- Focus on ATG-037, ATG-018, ATG-022, ATG-012 and ATG-008.
SHANGHAI and HONG KONG, March 9, 2022 /PRNewswire/ — Antengene Corporation Limited (“Antengene” SEHK: 6996.HK), a leading innovative global biopharmaceutical company dedicated to the discovery, development and commercialization of first-in-class and/or order against cancer, announced today the publication of the abstracts of five posters that will be presented at the next 2022 American Association for Cancer Research Meetings (AACR 2022), which will take place from April 8 to April 13 in New Orleans via in person or virtually.
“The preclinical studies we will present at AACR 2022 will provide a window into the scope of targets and the in vitro and live data that supports five programs in Antengene’s pipeline,” said Bo ShanPh.D., scientific director of Antengene. “The data from these studies has been instrumental in guiding our clinical development plans for each program, including information on potential combination therapy regimens and novel biomarkers or genetic alterations that could be used to predict the 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:
Jtitle : ATG-037, a very potent small molecule CD73 inhibitor, has superior immunosuppression reversal activity in high AMP environments compared to anti-CD73 antibodies
Abstract: 2576
Session: Cell cycle, replication inhibitors and immunotherapy agents
Date and time: 9:00 a.m. – 12:30 p.m. CST, April 12, 2022
Location: Section 21 Poster
This study was designed to compare the activity of ATG-037, a highly potent and selective oral small molecule inhibitor of CD73, and two CD73 inhibitor antibodies. CD73 is an enzyme highly expressed in the tumor microenvironment and allows the degradation of AMP to adenosine, leading to immunosuppression and cancer progression. In vitoo assays were used to assess each compound’s ability to inhibit CD73 function and reverse AMP/adenosine-mediated T cell suppression. Compared to both antibodies, ATG-037 demonstrated more potent and comprehensive cell surface CD73 inhibitory activity in this study. Additionally, the authors concluded that ATG-037 had a stronger ability to restore T cell function in higher AMP environments than other anti-CD73 clinical antibodies. These data highlight the potential therapeutic advantages of small molecule CD73 inhibitors over blocking antibodies. ATG-037 is being evaluated by Antengene in a phase I trial like mas onotherapy and in combination with an anti-PD-1 antibody in patients with locally advanced or metastatic solid tumors.
JTitle: Novel ATR inhibitor ATG-018 is effective in preclinical cancer models
Abstract: 2604
Session: DNA damage response and repair
Date and time: 9:00 a.m. – 12:30 p.m. CST, April 12, 2022
Location: Section 22 Poster
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-proliferative efficacy and 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 CDX models. The authors concluded that ATG-018 demonstrated potency in vitro and live the efficacy of monotherapy in models of solid tumours/hematological cancers with certain homologous recombination deficits. Additionally, 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 deficits/genetic alterations.
JTitle: ATG-022, an antibody-drug conjugate targeting Claudin 18.2, has been shown to be potent live efficacy in xenografts derived from gastric cancer patients
Abstract: 1143
Session: Preclinical and clinical pharmacology
Date and time: 9:00:00 – 12:30 CST, April 11, 2022
Location: Section 25 Poster
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 expression levels of CLDN18. 2. Human CLDN18.2 is overexpressed in a large proportion of gastric and pancreatic cancers. Studies with a monoclonal antibody (IMAB362) targeting CLDN18.2 have demonstrated promising clinical benefit in combination with chemotherapy. But it showed suboptimal efficacy in patients with low expression levels of CLDN18.2. In this AACR study, ATG-022 shows high affinity (sub-nanomolar level) against CLDN18.2 and demonstrated in vitro potency and live antitumor effects, with live efficacy observed in PDX models with low CLDN18.2 expression. The authors concluded that ATG-022 shows promise for gastric cancer patients with a wide range of CLDN 18.2 expression levels. Antengene is conducting preclinical studies for ATG-022.
JTitle: Synergistic effects of the combination of Kras (G12C) with SHP2ERK1/2, mTORC1/2 or XPO1 for the treatment of Kras (G12C) mutated cancer
Abstract: 2679
Session: Signaling pathway inhibitors
Date and time: 9:00 a.m. – 12:30 p.m. CST, April 12, 2022
Location: Section 25 Poster
This preclinical study was conducted to identify the combination therapy regimen that could overcome the short progression-free survival that is a feature of KRAS G12C inhibitors. The study evaluated the antitumor activity of ATG-012, a KRAS G12C inhibitor, along with four other agents involved in multiple pathways: i) a 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 models solid tumor preclinical CDX. While ATG-012 monotherapy induced tumor growth inhibition, the authors concluded that a strong live synergy was continuously observed throughout the study period when each of these four agents was combined with ATG-012 in 2-agent combinations. These data provide several promising combination strategies for ATG-012 that could be used in clinical trials for cancer patients with the KRAS G12C mutation.
JTitle: Identification of the 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 a.m. – 12:30 p.m. CST, April 13, 2022
Location: Section 26 Poster
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 the MUC5B mutation has been identified as a positive predictive biomarker for ATG-008 (Onatasertib) and potentially improves the proportion of lung cancer patients who respond to treatment. ATG-008 is an mTOR 1/2 complex dual kinase inhibitor. The mTOR complex regulates cell growth, metabolism, proliferation and survival. While the mTOR pathway is frequently dysregulated in cancers, the 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 gene mutation, amplification and expression with ATG-008 susceptibility. The results were validated in cell-derived xenograft (CDX) mice bearing lung cancer cell lines with or without the MUC5B mutation. CDX mice carrying the Muc5B mutation exhibited higher tumor growth inhibition than wild-type Muc5B cell lines. The authors concluded that the presence of the Muc5B mutation was correlated with more potent antitumor efficacy of ATG-008 in mouse models of lung cancer. These data support the ATG-008 test in the clinic. ATG-008 is being evaluated by Antengene in several phase I and II clinical trials.
About Antengene
Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a leading R&D-driven global biopharmaceutical company focused on first-in-class/best-in-class innovative therapeutic drugs for cancer and other diseases potentially fatal. . Driven by his vision of “Treating patients across borders“, Antengene aims to provide the most advanced cancer drugs to patients in the Asia-Pacific region and around the world. Since beginning operations in 2017, Antengene has obtained 22 Investigational New Drug (IND) approvals in the United States. and in Asiasubmitted 6 new drug applications (NDAs) in several Asia Pacific markets, with 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 preclinical assets. Antengene holds worldwide rights to 10 programs and Asia Pacific rights, including Greater China region, on 5 programs.
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