On June 19, at the first BioChina Summit of China Biopharmaceutical Forum in Suzhou, Akeso, Inc. (9926.HK) was awarded as “Top 10 Chinese Bispecific Antibody Drug Companies” for its cutting edge technology, rich research & development pipelines and indications, focus index of specialized area and investment tags based on Parmcube data base.
This BioChina Summit is themed of “GO FORWARD·Make Innovation Walk with More Power”, focusing on innovative projects and bellwether of next-generation biotech industry development, creating sustainable innovation pattern with quick results, promoting Chinese pharmaceuticals innovation and cooperation.
Bispecific antibodies to lead the immuno-oncology era 2.0
Immuno-oncology therapy has been recognized as the epochal breakthrough in oncotherapy, represented by the development and commercialization of PD-1 drugs, it has brought new therapeutic hope to cancer patients worldwide and marked the immuno-oncology therapy era 1.0. But as a broad-spectrum anti-tumor drug, PD-1 cannot really solve all problems. Seeking a therapy that is better in effectiveness and safety than PD-1 is proposition of immuno-oncology therapy era 2.0. Bispecific antibody drug is one of the core directions for development.
As the pioneer of bispecific antibody drug development in China, Akesobio has established the encompassing drug discovery and development system since founding, the system’s core is composed by comprehensive drug development platform (ACE Platform) and a bispecific antibody drug development technology (Tetrabody). The company’s exclusive “Tetrabody” technology provides druggable bispecific antibody and has tackled bispecific antibody’s major challenges in CMC and clinical aspects. So far the company has independently developed various leading bispecific antibody products, including the globally first-in-class PD-1/CTLA-4 bispecific antibody Cadonilimab (AK104), PD-1/VEGF bispecific antibody (AK112), PD-1/CD73 bispecific antibody (AK131), PD-1/LAG3 bispecific antibody (AK129).
Cadonilimab (PD-1/CTLA-4 bispecific antibody, AK104)
Akesobio’s self-developed globally first-in-class PD-1/CTLA-4 bispecific antibody drug, major indications include liver cancer, cervical cancer, lung cancer, gastric cancer, esophageal squamous cell cancer and nasopharyngeal carcinoma. Relative research data of cervical cancer, gastric cancer and other tumors shows that, as compared with the combination therapy of PD-1 and CTLA-4, Cadonilimab has much lower toxicity and demonstrated promising safety profile and efficacy. Our AK104 project has been incorporated in the Major New Drug Innovation Program under the national 13th Five-year Plan for Major Technology Project (十三五「重大新药创制」科技重大专项支持专案).
Cadonilimab is currently in clinical research simultaneously in China and the U.S., among which 9 clinical trial programs are already at Phase II or later clinical stage. This drug has obtained fast track designation (FTD) and orphan drug designation from the Food and Drug Administration of the United States (FDA) for treating cervical cancer, it also obtained the “Breakthrough Therapy Designation” from the National Medical Products Administration (NMPA) of China. It is expected that the new drug application for Cadonilimab for treatment of cervical cancer will be submitted in 2021. Cadonilimab is expected to become the the first PD-1 based bispecific antibody drug worldwide, leading the immuno-oncology era 2.0.
AK112 (PD-1/VEGF bispecific antibody)
AK112 is a first-in-class and the first to enter clinical trial PD-1/VEGF bispecific antibody independently developed by Akesobio. AK112 blocks PD-1 binding to PD-L1 and PD-L2, and blocks VEGF binding to VEGF receptors. PD-1 antibody in combination with VEGF blocking agents have shown robust efficacy in various tumor types (including renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma). In the view of the co-expression of VEGF and PD-1 in the tumor micro environment, AK112, as a single agent to block these two targets, may block these two pathways more effectively and enhance the anti-tumor activity, as compared to combination therapy.
Currently 6 of AK112 clinical trials are at Phase Ib/II stage, for treatment of lung cancer, solid tumor, gynecological tumor, etc. in China and the U.S.
AK131 (PD-1/CD73 bispecific antibody)
Developed by Akesobio independently, AK131 is a bispecific antibody targeting human CD73 and PD-1. AK131 can inhibit the exonucleotidase activity of CD73 and reduce the accumulation of adenosine, thereby releasing the suppression of anti-tumor immune activity. At the same time, it can block the binding of PD-1 and its ligands PD-L1 and PD-L2 to relieve immunosuppression. In addition, the antibody can also promote the activation of B lymphocytes through a pathway independent of CD73 enzymatic activity and shows potent anti-tumor activity in preclinical in vivo studies. The bispecific antibody AK131, which targets human CD73 and PD-1, can simultaneously bind to human CD73 and PD-1, and relieve tumor immunosuppression through complementary and non-overlapping pathways. It is expected to become a new method for the treatment of tumors.
AK129 (PD-1/LAG3 bispecific antibody)
Independently developed by Akesobio, AK129 is a bispecific antibody targeting human PD-1 and LAG3. AK129 can simultaneously target two immunosuppressive receptors PD-1 and LAG3, block the binding of PD-1 to its ligands PD-L1 and PD-L2, and block the binding of LAG3 to its ligands like MHCII, to relieve the Immunosuppression in tumor microenvironment. LAG3 and PD-1 synergistically inhibit the anti-tumor immune response. AK129 can block LAG3 to increase the T cell immune response and block PD-1 to promote the synergistic enhancement of immune response, and further improve the activity of immune cells and enhance the anti-tumor immune response. AK129 is expected to show a better therapeutic effect.