First and only TIGIT/TGF-β dual-targeting antibody fusion protein of Akeso demonstrated promise in preclinical results published at ESMO
- Category: Antibodies
- Published on Tuesday, 13 September 2022 10:23
- Hits: 617
HONG KONG, China I September 13, 2022 I Akeso, Inc. (9926.HK) ("Akeso"), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, published encouraging preclinical results in poster featuring its Fc-mutant anti-TIGIT antibody fused with TGF-βRII protein (AK130) at the European Society for Medical Oncology (ESMO) Congress 2022.
AK130 is the first and only TIGIT/TGF-β dual-targeting antibody fusion protein and the first novel dual-targeting antibody fusion protein developed in-house by Akeso. The clinical trial application for AK130 was just accepted by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) not long ago, demonstrating Akeso's ability to develop breakthrough drugs with complete independence and autonomy.
Details of the poster are as follows:
- Poster: AK130, a first-in-class Fc-mutant anti-TIGIT antibody fused with TGF-βRII protein, elicits potent anti-tumor efficacy in preclinical studies.
- Abstract: #486P
- Presenters: Jing Min, Vice President of Akeso
Although TIGIT is considered a promising immune checkpoint molecule, the single-agent efficacy of anti-TIGIT therapy is limited. AK130, a novel anti-TIGIT antibody fused with TGF-βRII protein, was designed to inhibit TIGIT-mediated immunosuppression while decreasing the TGF-β levels in the tumor microenvironment (TME). Mutations were introduced in the Fc region of the antibody with IgG4 backbone to avoid antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to minimize lymphocyte loss.
The encouraging observations from preclinical results of AK130 supports its clinical development for the treatment of human cancers:
- AK130 could specifically bind to human TIGIT and TGF-β with high affinity.
- In reporter gene assays, AK130 efficiently blocked the interaction between TIGIT and CD155, as well as TGF-β1/TGF-β3 and TGFβ-RII.
- As expected, AK130 did not show ADCC or CDC activity compared to tiragolumab.
- AK130 shows great anti-tumor efficacy in a mouse tumor model.
About AK130 (TIGIT/TGF-β dual-targeting antibody fusion protein)
AK130 is a bifunctional antibody-fusion protein entirely independently developed by Akeso. It consists of an anti-TIGIT monoclonal antibody fused to the extracellular domain of human transforming growth factor-β receptor II (TGFβ-RII). TIGIT is an emerging immune checkpoint that blocks TIGIT-CD155 interaction, relieves the inhibition of tumor-infiltrating CD8 + T cells and NK cells and promotes their anti-tumor function. TGF-β signaling can lead to immunosuppression, cancer immune escape, and immune checkpoint inhibitor resistance. Dual blockade of TIGIT and TGF-β activates T cell immune responses and reduces TGF-β-mediated immunosuppressive activity of Tregs, thereby achieving better antitumor effects.