HONG KONG, China I January 18, 2022 I Akeso, Inc. (9926.HK) announces that Ligufalimab (CD47 monoclonal antibody, research and development code: AK117), the novel immuno-oncology drug independently developed by the Company, combined with Ivonescimab (PD-1/VEGF bi-specific antibody, research and development code: AK112) has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People’s Republic of China (”China”) to initiate a phase Ib/II clinical trial with or without chemotherapy for the treatment of advanced malignant tumors, with an aim to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity of Ligufalimab combined with Ivonescimab combined with or without chemotherapy for the treatment of advanced malignant tumors.

The main target subjects of the phase II clinical trial were patients with gastrointestinal tumors. Previously, a phase Ib/II clinical trial of Ligufalimab combined with Ivonescimab has been initiated with main target subjects of patients with head and neck malignant tumors.

Related statistics have shown that malignant tumors have become the major cause of death in the population of China, where deaths from malignant tumors account for approximatelyn23.91% of deaths from all causes of the population. The five-year relative survival rate of malignant tumors in China is approximately 40.5%, which is still far from developed countries. In addition, gastrointestinal tumors account for six out of the top ten death rate of advanced malignant tumors. Among which, treatments for advanced gastric cancer, biliary malignant tumors, pancreatic cancer and other common gastrointestinal tumors are limited and the efficacy is not high, resulting in a huge gap of clinical demand.

Related studies have shown that Ivonescimab can simultaneously stimulate anti-tumor immune response and inhibit tumor angiogenesis through activation of T cells. Since the over-expression of VEGF in the tumor microenvironment has immunosuppressive effects, the use of a bi-specific antibody that blocks both PD-1 and VEGF can achieve synergistic anti-tumor effects of PD-1/PD-L1 antibodies and anti-VEGF antibodies. It is expected to achieve good clinical efficacy and safety. Currently, anti-PD-1/PD-L1 antibody drugs on the market or under research combined with chemotherapy has shown certain clinical benefits for gastrointestinal tumors. For non-small cell lung cancer and hepatocellular carcinoma, the combination of anti-PD-1/PD-L1 antibodies with anti-VEGF antibodies has shown notable synergistic effects.

Related studies have also shown that combination therapy with anti-PD-1 drugs and targeted CD47 drugs yields synergistic antitumor effect through activation of both innate and adaptive immune response, and has demonstrated satisfactory anti-tumor effect in some of the patients with solid tumors with no additional safety risk. CD47 up-regulation can inhibit the phagocytosis of macrophages and the anti-tumor effect of VEGF/VEGFR inhibitors. At the same time, anti-VEGF/VEGFR treatment can also induce CD47 up-regulation, thereby inhibiting the anti-tumor function of macrophages. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway induced by anti-angiogenesis therapy (CD47 up-regulation) while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.

Therefore, the combination therapy of Ligufalimab and Ivonescimab is expected to activate both innate and adaptive immune pathways, so to achieve the synergistic effect of inhibiting the three tumor immune targets of PD-1, VEGF and CD47 through the combination of the two drugs, thus achieving better anti-tumor effects as compared with existing therapies. Furthermore, based on the statistics of the in vitro and in vivo pharmacodynamics and toxicology studies of Ligufalimab and Ivonescimab, the anti-tumor activity and the controlled safety profile in several clinical trials of different types of tumors, it is expected that the combination of Ivonescimab and Ligufalimab and/or chemotherapy will have a positive effect for the treatment of gastrointestinal tumors.

Currently, Ivonescimab has taken the lead in entering the phase III clinical trial globally, and Ligufalimab is also one of the world’s leading CD47 monoclonal antibodies in clinical research and development progress. The clinical trial of Ligufalimab combined with Ivonescimab in the treatment of head and neck malignant tumors and gastrointestinal tumors is another embodiment of the Company’s continuous exploration of the clinical and commercial value of its rich drug pipeline.