-ATG-101, a novel PD-L1/4-1BB bispecific antibody, shows potent in vivo anti-tumor efficacy in checkpoint inhibitor resistant/relapsed models while mitigating liver toxicity risk, computational analysis adds support to dosing strategy
-ATG-017, an ERK1/2 inhibitor, in vivo combination supports clinical development strategy
SHANGHAI and HONG KONG, Nov. 14, 2021 /PRNewswire/ -- 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 therapeutics in hematology and oncology, today announced the presentation of three posters at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington D.C. (https://www.sitcancer.org/home).
"Antengene is very pleased to present preclinical data on two of our Phase I programs, for ATG-101 and ATG-017, at the 2021 SITC meeting on November 12, 2021. The unique mechanisms, promising preclinical safety and activity of these exciting new compounds are very much in keeping with Antengene's mission to develop first-in-class, best-in-class medicines for cancer," said Jay Mei, M.D., Ph.D., Founder, Chairman and Chief Executive Officer of Antengene.
Dr. Mei continued, "These presentations also highlight the breadth and depth of Antengene's drug development capabilities. The Antengene management team and I look forward to reviewing these posters, detailed below, and the Company's exciting portfolio at our upcoming R&D Day, planned for November 16th (virtual, details below) and November 18th (in person, details below)."
Summary of Poster Presentations
Poster #893: ATG-101: Active in "Cold" tumors, No Preclinical Liver Toxicity
ATG-101 is a PD-L1 / 4-1BB bi-specific antibody that was designed to activate tumor infiltrating lymphocytes and inhibit immune checkpoints, without inducing liver toxicity. Antengene presented data from in vitro and in vivo studies that evaluated ATG-101 activity in several T-cell activation assays and multiple in vivo models, including those resistant to anti-PD(L)1 therapies.
Data in the poster showed that ATG-101 was active in anti-PD-L1 resistant and relapsed tumor models. In addition, ATG-101 increased the activation of T-cells and exhausted T-cells upon PD-L1 crosslinking (required for ATG-101 activity), rendering "cold" tumors "hot". Importantly, ATG-101 showed no liver toxicity in a GLP toxicity study (differentiating the drug vs other 4-1BB targeted monoclonals/bi-specifics) and did not induce cytokine release syndrome in an in vitro assay. ATG-101's unique safety and efficacy properties make it a promising potential therapy for solid tumors and non-Hodgkins lymphoma.
Poster #608:Promising ATG-017 in vivo Combination Study Add to Clinical Strategy
ATG-017 is a potent small molecule kinase inhibitor targeting the extracellular signal-related kinases 1 and 2 (ERK1/2). Antengene presented data on an in vivo study that evaluated ATG-017 in combination with an anti-PD-L1 monoclonal antibody (atezolizumab), in an aggressive, immune checkpoint inhibitor resistant mouse cancer model.
Data in the poster showed that the combination enhanced the antitumor efficacy as well as increasing the percentage of infiltrating CD8+ T cells, NK cells, CD8:CD4 ratio and M1:M2 macrophage ratio in the tumor microenvironment, rendering a "cold" tumor "hot". These results demonstrated that ATG-017 has potential synergy with immune checkpoint inhibitors, providing a rationale for exploring combination therapy in the clinic in the pursuit of improved efficacy in solid tumors, including those resistant to checkpoint inhibitions.
Bispecific antibody ATG-101 acts by forming a trimer (comprised of ATG-101 bound to PD-L1 and 4-1BB expressing cells) that activates tumor infiltrating lymphocytes and inhibits immune checkpoints. Measuring trimeric complexes is important in defining optimal clinical doses but is very challenging to do in the clinic.
Antengene and its collaborators at Applied BioMath, LLC reported on the development of a computational semi-mechanistic pharmacology model that could be used to define the clinical dose of ATG-101. It works by simulating in vivo tumor growth inhibition and predicting trimer formation, free drug levels and receptor occupancy over time. This work has enabled Antengene to define a clinically effective dose range of ATG-101 that induces >90% PD-L1 receptor occupancy, a key metric of drug activity. This valuable pharmacology tool, which may also be applied across other compounds in Antengene's pipeline, reflects the Company's enthusiasm to utilize novel technologies and partnerships to enhance drug development capabilities.
Details on the posters, published on the SITC website, are shown below:
Abstract Number: 227 Title: A computational semi-mechanistic pharmacology model of ATG-101, a PD-L1/4-1BB bispecific antibody for treatment of solid tumors and NHL Time: 7:00-17:00 EST, November 12-14, 2021 Presenter：Dr. David C. Flowers, Applied BioMath, LLC First Author: Dr. David C. Flowers, Applied BioMath, LLC
Abstract Number: 608 Title: Synergistic effect of the combination of ATG-017, an ERK1/2 inhibitor, and immune checkpoint inhibitor in preclinical cancer models Time: 7:00-17:00 EST, November 12-14, 2021 Presenter：Dr. Bing Hou, Antengene Corporation Limited First Author: Dr. Peng Chen, Antengene Corporation Limited
Abstract Number: 893 Title: ATG-101, a novel PD-L1/4-1BB bispecific antibody, augments anti-tumor immunity through immune checkpoint inhibition and PDL1-directed 4-1BB activation Time: 7:00-17:00 EST, November 12-14, 2021 Presenter：Dr. Bing Hou, Antengene Corporation Limited First Author: Dr. Hui Yuwen, Antengene Corporation Limited
ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of multiple kinds of cancer. ATG-101 can activate anti-tumor immune effectors by simultaneously blocking the binding of PD-L1/PD-1 and inducing 4-1BB stimulation. In PD-L1 over-expressed cancer cells, ATG-101 has shown potent PD-L1 crosslinking-dependent 4-1BB agonist activity, thus potentially enhancing therapeutic efficacy, whilst mitigating risk of hepatoxicity. Antengene has received U.S. FDA approval for the IND for a Phase I trial of ATG-101 in solid tumors and non-Hodgkins lymphoma and is currently conducting a Phase I study of ATG-101 in Australia for the treatment of patients with metastatic/advanced solid tumors and non-Hodgkin lymphoma.
ATG-017 is a potent and selective small molecule extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor. ERK1/2 are related protein-serine/threonine kinases that function as terminal kinases in the RAS-MAPK signal transduction cascade. This cascade regulates a large variety of cellular processes, including proliferation. The RAS-MAPK pathway is dysregulated in more than 30% of human cancers with the most frequent alterations being observed in RAS or BRAF genes across multiple tumor types. An ERK inhibitor enables the targeting of both RAS and BRAF mutant diseases. In nonclinical pharmacology studies, ATG-017 has demonstrated potent inhibition of ERK1/2 enzyme activity and tumor growth in vitro and in vivo. Antengene is conducting an open-label Phase I, dose-escalation study of ATG-017 in Australia for the treatment of patients with advanced solid tumors and hematologic malignancies.
About Antengene's R&D Day
Antengene's R&D Day will include presentations from Dr. Jay Mei, Founder, Chairman and CEO; Mr. John Chin, Chief Business Officer; Dr. Kevin Lynch, Chief Medical Officer; Dr. Bo Shan, Chief Scientific Officer, and other Company management.
The meetings will be held virtually in English on November 16, 2021, and on-site in Mandarin on November 18, 2021. A live webcast will be available on the Antengene website under "Investor Relations", on the Event Calendar page.
To attend the event, please register in advance at links below:
R&D Day English Session – Virtual Conference
Date: Tuesday, November 16, 2021
Time: 8:30 am – 11: 30 am, Eastern Time / 9:30 pm – 12: 30 am, Beijing Time
Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage R&D- driven global biopharmaceutical company focused on innovative first-in-class/best-in-class therapeutic medicines for oncology 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 18 investigational new drug (IND) approvals, submitted 6 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for selinexor/ATG-101 in South Korea already approved through a priority review process. Leveraging partnerships as well as in-house drug discovery, Antengene has built a broad and expanding pipeline of 13 clinical and pre-clinical assets. The Company has global rights on 8 programs and Asia Pacific rights, including the Greater China region, on 5 programs.
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