AK112 (PD-1/VEGF Bi-Specific Antibody) in Combination with AK117 (CD47 Monoclonal Antibody) Obtained Approval to Initiate Clinical Trial for the Treatment of Advanced Malignant Tumors

(HONG KONG, 11 Oct 2021) Akeso, Inc. (the Company, 9926.HK) announces that the AK112 (PD-1/VEGF bi-specific antibody), the novel core immuno-oncology drug independently developed by the Company, obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China to initiate a phase Ib/II clinical trial in combination with AK117 (CD47 monoclonal antibody) for the treatment of advanced malignant tumors.


This phase-Ib/II clinical trial aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and anti-tumor activity of AK112 in combination with AK117 for the treatment of advanced malignant tumors.


This is another combination therapy of AK117 in combination with bi-specific antibodies after being in combination with Cadonilimab (AK104, PD-1/CTLA-4 bi-specific antibody) for the treatment of advanced solid tumors and in combination with azacitidine for the treatment of hematologic tumors. The Company fully leverages its own rich research pipelines to promote clinical trials on multiple combination therapies of AK117 for hematologic tumors and solid tumors in order to accelerate the development of AK117.


CD47 is highly expressive on the surface of tumor cells. CD47 blockade stimulates the phagocytosis of tumor cells by macrophages and promotes adaptive immune responses through dendritic cells. Current preliminary studies have shown that the combination therapy with anti-PD-1 drugs and targeted CD47 yields synergistic anti-tumor effect through activation of adaptive immune responses and has demonstrated satisfactory anti-tumor efficacy in selected patients with solid tumors with no additional safety risk.


Meanwhile, related studies have also shown that the up-regulation of CD47 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 the up-regulation of CD47, thereby inhibiting the anti-tumor function of macrophages. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway (the up-regulation of CD47) induced by anti-angiogenesis therapy while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.


Currently, AK112 has taken the lead in entering the phase III clinical trial in the world, and AK117 is also one of the world’s leading CD47 monoclonal antibodies in clinical research and development progress. The combination therapy of AK112 in combination with AK117 is expected to activate both innate and adaptive immune pathways and enhance the targeted recognition of tumors by the immune system. The combined application of these two drugs will be able to bring the three tumor immune targets of PD-1, VEGF and CD47 into play to achieve better anti-tumor effects than existing therapies.



About AK112 (PD-1/VEGF Bi-Specific Antibody)

AK112 is a first-in-class and the first to enter clinical trial PD-1/VEGF bi-specific antibody independently developed by the Company. Engineered with our unique Tetrabody technology, 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 microenvironment, 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.



About AK117 (CD47 Monoclonal Antibody)

AK117 is a novel humanized IgG4 mAb independently developed by the Company. It can bind with CD47 expressed on tumor cells to prevent the interaction between CD47 and its receptor, SIRPα, expressed on macrophages so as to enhance phagocytosis to inhibit the growth of tumor cells. Previously published data demonstrated exceptional safety profile. AK117 resulted in no dose-limiting toxicity and no anemia of clinical significance in subjects in all doseescalation cohort (the highest dose cohort was 45 mg/kg once-weekly), and was well tolerated by subjects in all cohorts. The CD47 receptor occupancy rate (RO) of the peripheral blood T cells has reached and maintained at 100% in the 3 mg/kg cohort.



About Akeso, Inc.

Akeso, Inc. is a biopharmaceutical company dedicated to the research, development, manufacturing and commercialization of new innovative antibody drugs that are affordable   to patients worldwide. Since the Company’s establishment, the Company has established an end-to-end comprehensive drug development platform (ACE Platform) and system, encompassing fully integrated drug discovery and development functions, including target validation, antibody drug discovery and development, CMC production process development, and GMP compliant scale production. The Company has also successfully developed a bi-specific antibody drug development technology (Tetrabody technology). The Company currently has a pipeline of over 20 innovative drugs for the treatment of major diseases like tumors, autoimmune diseases, inflammation and metabolism diseases, 13 of which have entered clinical stage, including two first-in-class bi-specific antibody drugs (PD-1/CTLA-4 and PD-1/VEGF). In Aug 2021, the Company’s first in-house innovatively researched and developed differentiated PD-1 monoclonal antibody Penpulimab monoclonal antibody injection (安尼可®) was approved to the market. The Company’s vision is to become a global leading biopharmaceutical company through research and development of high efficacy and breakthrough new drugs that are first-in-class and best-in-class therapies.