On October 31, 2023 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 medicines for cancer, reported that it has presented results from five programs by poster presentation, including two clinical programs on the anti-CD24 monoclonal antibody ATG-031 and the PD-L1/4-1BB bispecific antibody ATG-101; two preclinical programs on the LILRB4 antagonist antibody ATG-034 and the GPRC5D/CD3 T-cell engager ATG-021; and the Company’s proprietary novel AnTenGagerTM platform, at the 2023 Society of Immunology in Cancer Annual Meeting (SITC 2023) (Press release, Antengene, OCT 31, 2023, View Source [SID1234636574]). The SITC (Free SITC Whitepaper) Annual Meeting is a widely recognized and respected international event that brings together cutting-edge presentations by multidisciplinary experts in basic and applied cancer immunotherapy with a goal of improving outcomes for cancer patients.
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"Thanks to Antengene’s robust R&D capabilities and its proprietary technology platforms, we have released the exciting results from multiple studies at the SITC (Free SITC Whitepaper) Annual Meeting this year. Among them, preclinical results on the pharmacokinetics, pharmacodynamics, and toxicology of ATG-031, the world’s first anti-CD24 monoclonal antibody entering clinical development, deserve particular attention as they demonstrated ATG-031’s ability to systemically enhance antitumor immunity and its favorable safety profile. Moreover, CD24 is highly expressed in a variety of solid tumors and hematologic malignancies, thus indicating the drug’s broad therapeutic opportunity. The U.S. Food and Drug Administration (FDA) has already cleared an Investigational New Drug (IND) application for a Phase I study of ATG-031 in patients with advanced solid tumors or B-cell non-Hodgkin lymphoma (B-NHL). The study, led by the MD Anderson Cancer Center, along with three other clinical centers in the U.S., is currently ongoing," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO. "Also at the meeting, we released results on AnTenGagerTM, an inhouse-developed and fully-patented T cell engager (TCE) platform that offers target-dependent T cell activation and enhanced antitumor activity with reduced risk of cytokine release syndromes. Building on the progress, we will continue to accelerate our development of cutting-edge therapies and showcase our innovative prowess on the global stage."
Details of the Poster Presentations:
ATG-031(anti-CD24 monoclonal antibody)
Title: The preclinical characterization and translational research of ATG-031, a first-in-class humanized anti-CD24 antibody, for the treatment of solid tumors and hematological malignancies
Abstract: 1337
CD24 is a small, highly glycosylated cell adhesion protein that functions as a novel "don’t eat me" target in cancer, where it is the dominant innate immune checkpoint. CD24 is extensively expressed in a variety of tumor types, whereas its distribution in normal tissues is limited.
Therapeutic antibodies blocking "don’t eat me" signals exhibited potent preclinical and early clinical efficacy against solid tumors and hematological malignancies.
As the first-in-class anti-CD24 monoclonal antibody entering clinical development, ATG-031 has demonstrated potent anti-tumor activity as a single agent and in combination with chemotherapies and checkpoint inhibitors, as well as excellent safety and PK properties in pre-clinical studies. It induces macrophage mediated phagocytosis of tumor cells, and boosts T cell dependent anti-tumor immunity in the tumor microenvironment.
These pre-clinical data support the further development and evaluation of ATG-031 in the Phase I, multicenter, dose escalating clinical trial in patients with solid tumors and hematological malignancies. To date, the U.S. Food and Drug Administration (FDA) has already cleared an Investigational New Drug (IND) application for a Phase I study of ATG-031 in patients with advanced solid tumors or B-cell non-Hodgkin lymphoma (B-NHL). The study, led by the MD Anderson Cancer Center, along with three other clinical centers in the U.S., is currently ongoing.
ATG-101(PD-L1/4-1BB bispecific antibody)
Title: Single-cell RNA sequencing reveals the positive feedback activation loop between T and dendritic cells induced by PD-L1x4-1BB bispecific antibody
Abstract: 1112
Single-cell RNA-sequencing (scRNAseq) was used to better understand the biology of immune responses induced by ATG-101.
Transcriptional profiling of the tumor microenvironment (TME) revealed that ATG-101 reversed T cell exhaustion, increased T cell cytotoxicity, and reduced tolerogenic dendritic cells (DCs).
Due to the increased gene expression of PD-L1 in DCs and 4-1BB in T cells following ATG-101 treatment, it is anticipated that ATG-101 will promote greater T cell-dentritic cell crosslinking over time, further activating 4-1BB signalling, strengthening T cell-DC interaction, and generating a positive feedback loop.
Currently, ATG-101 is being assessed in a dose-escalation study in the Mainland of China, Australia, and the U.S.
ATG-034 (LILRB4 antagonist antibody)
Title: Antibody targeting a specific epitope of LILRB4 induces potent ADCC/ADCP effect against leukemia cells
Abstract: 1391
Acute myeloid leukemia (AML) patients, especially those with monocytic AML subtypes have poor treatment outcomes. Existing therapies targeting CD33 and CD123 has demonstrated hematological toxicities. Moreover, the antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis (ADCC/ADCP) effect of current therapeutic mAbs targeting LILRB4 antigen on AML is relatively weak.
ATG-034-S3 potentiates NK-mediated ADCC, macrophage-mediated ADCP, cytotoxicity of CD8+ T cells and reverses AML-mediated T cell suppression, thus enhancing anti-tumor immunity and demonstrating potent in vivo anti-tumor efficacy.
ATG-034-S3 may be a promising strategy for the treatment of monocytic M4/M5 AML and other LILRB-positive hematological malignancies.
ATG-021 (GPRC5D/CD3 T-cell engager)
Title: ATG-021, a novel 2+1 CD3-based T-cell engager (TCE) targeting GPRC5D, demonstrates potent in vivo anti-tumor efficacy with low cytokine release
Abstract: 1191
GPRC5D is expressed on malignant bone marrow plasma cells, whereas normal tissue expression is limited to the hair follicle; Upregulation of GPRC5D expression has been associated with unfavorable prognosis.
As a novel 2+1 GPRC5DxCD3 T cell engager, ATG-021 has demonstrated optimum efficacy and safety through its GPRC5D-dependent CD3 binding. It has demonstrated potent in vivo anti-tumor efficacy with reduced cytokine release in pre-clinical studies.
These pre-clinical data warrant further clinical evaluation of ATG-021 against multiple myeloma.
AnTenGager Platform
Title: A novel "2+1" bispecific T cell engager platform, enables enhanced anti-tumor activity with reduced risk of CRS
Abstract: 1190
Multiple T-cell engaging bispecific antibodies have demonstrated promising therapeutic efficacy in the treatment of hematological malignancies. However, suboptimal efficacy in the treatment of solid tumors and the risk of cytokine release syndrome (CRS) continue to be major challenges.
AnTenGagerTM is a novel "2+1" T cell engager platform developed by Antengene, and molecules developed through this platform have exhibited limited binding to CD3-positive cells before tumor-associated-antigen (TAA) crosslinking, suggesting reduced risk of CRS caused by systemic CD3 activation.
Compared to clinical benchmarks targeting the same tumor associated antigen (TAA), molecules developed by the AnTenGagerTM platform demonstrated substantially lower binding capacity to CD3+ before TAA-crosslinking, while inducing increased cytotoxicity against target-positive tumor cells, less ex-vivo cytokine release by human peripheral blood mononuclear cells (PBMCs), and enhanced in vivo efficacy in a PBMC humanized mouse tumor model.
These results suggest that AnTenGagerTM is a promising platform to develop next generation T cell engagers, with improved efficacy and safety profiles.