NORTH BRUNSWICK, NJ and HANGZHOU, China, February 21, 2022 /PRNewswire/ — recently — Adlai Nortye Ltd. (“Adlai Nortye”), a clinical-stage biopharmaceutical company focused on the development of innovative cancer therapies, announced the publication of preclinical research on AN3025 (anti-hTNFR2) in the revised -journal Frontiers in immunology.
The article titled “Antagonistic Antibody Targeting TNFR2 Inhibits Regulatory T Cell Function to Promote Anti-Tumor Activity” is authored by Dr. Nanhai He, Head of Drug Discovery at Adlai Nortye, and colleagues including Dr. Yonglin ChenDr. Manxue Jia, Sharon Wang and dr. Sherry Xu. In this study, Dr. He and his team present the preclinical results of in vitro and in vivo characterization of AN3025, an anti-TNFR2 antibody with high potential in the field of immunotherapy. Observations include, but are not limited to, the following:
AN3025 treatment can reduce the proportion of regulatory T cells (Treg), increase CD4 effector infiltration+ T cells and CD8+ T cells and upregulates the expression of immune activation genes such as interferon-γ (IFN-γ) and granzyme K (Granzyme K) in the tumor microenvironment, resulting in potent anti-tumor effects.
AN3025 monotherapy significantly inhibited tumor growth in both PD-1 sensitive MC38 animal tumor models and PD-1 resistant B16F10 animal tumor models.
The combination of AN3025 and a PD-1 inhibitor shows superior antitumor effect compared to monotherapies in preclinical.
Corresponding author, Dr. Nanhai He, Head of Drug Discovery at Adlai Nortye, said: “Our in-house developed TNFR2 antagonist antibody, called AN3025, has demonstrated encouraging anti-tumor activities in animal models, and We are committed to advancing this exciting project through preclinical evaluation and looking forward to clinical development in the near future.”
The lead author of the article, Dr. Yonglin ChenDr. Adlai Nortye, added: “Immune Checkpoint Inhibitors (ICIs) are important steps in modern immunotherapy and have been approved for the treatment of various human tumors. However, not all patients respond to ICI and, in addition, many patients develop acquired resistance to ICI. The exploration of new targets and new treatments has become increasingly important in the field of cancer immunotherapy. The TNFR2 antagonist antibody AN3025 has shown great potential for tumor control in preclinical studies, and we look forward to the clinical development of AN3025.”
TNFR2 is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and is highly expressed on the surface of regulatory Treg cells in the tumor microenvironment. Mechanically, TNFR2 plays a key role in maintaining Treg cell proliferation, stability, and activation, and TNFR2-expressing Treg cells are considered the most immunosuppressive Treg population. Therefore, TNFR2 has been proposed as one of the most promising Treg targets in cancer immunotherapy.
AN3025 is a new humanized IgG1 antibody that recognizes human TNFR2 and is currently in preclinical development. The antibody binds to the extracellular domain of human TNFR2 with sub-nanomolar affinity and blocks the signaling pathway downstream of TNFR2 by preventing TNFR2 from binding to its ligand TNF. AN3025 effectively inhibits Treg cells in the tumor microenvironment and enhances anti-tumor immune response. In PD-1 sensitive and PD1 resistant animal tumor models, AN3025 monotherapy shows potent anti-tumor activities. The combination of AN3025 and a PD-1 inhibitor demonstrates superior antitumor effects to monotherapies in preclinical studies.
About Adlai Nortye
Adlai Nortye is a clinical-stage biopharmaceutical company focused on the development of innovative cancer therapies, with its R&D centers in China and the United States. With a strategic focus on oncology, the company has built a global pipeline through collaborations and internal discoveries with more than 10 drug candidates in development. Currently, four of them are in multiple clinical trials, including (i) buparlisib (AN2025) which received Fast-Track designation from the FDA and was in a global Phase III clinical trial ; (ii) Pelareorep (AN1004), an intravenously administered oncolytic virus that has received Fast-Track designation from the FDA and has completed a Phase II clinical trial; (iii) Palupiprant (AN0025), an oral EP4 antagonist which has completed the phase Ib trial in a neoadjuvant setting in advanced localized rectal cancer and is in the phase Ib trial in combination with Keytruda® in patients with multiple solid tumors; and (iv) AN4005, an orally available small molecule PD-L1 inhibitor that was currently in phase Ia and has been shown to functionally overcome inhibition derived from the PD-1/L1 interaction in reporter and human PBMCs (hPBMCs). cell assays. Additionally, Adlai Nortye has also completed the first patient assay for its Phase I clinical trial in collaboration with Roche to evaluate the triple combination of AN2025, AN0025 and Tecentriq® (PD-L1 inhibitor) for a variety of mutant solid tumors PIK3CA in September 2021 in the United States
Adlai Nortye has assembled an experienced management team, built its own immuno-oncology platforms and partnered with several large pharmaceutical companies to drive innovation. Adlai Nortye is committed to becoming an innovative biopharmaceutical company with a global vision and strives to benefit patients around the world. The Society’s mission is to transform deadly cancer into a chronic and eventually curable disease. For more information, please visit: www.adlainortye.com.
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SOURCEAdlai Nortye Biopharma Co., Ltd.