The class 1 innovative drug XZP-KM257 (recombinant anti-HER2 domain II and domain IV bispecific antibody injection)(“KM257”), independently developed by subsidiary Xuanzhu Biopahrmaceutical Co., Ltd. (“Xuanzhu Biopharm”), has been approved by the National Medical Products Administration (“NMPA”) of the People’s Republic of China (“China”) to initiate clinical trials for the treatment of advanced solid tumors with intermediate and high expression of HER2+. The approval of KM257 to initiate clinical trials marks the first macromolecule drug of Xuanzhu Biopharm has entered the clinical development stage.
KM257 is a HER2/HER2 bispecific antibody developed from the proprietary Mebs-lg (Monoclonalantibody Editing Bispecific Immunoglobulin) platform and Mab-Edit (Monoclonalantibody Editing) technology platform of Xuanzhu Kangming, the macromolecule innovative drugcompany under Xuanzhu Biopharm. Possessing a brand new system, it is targeting two different domains of HER2 (domain II and domain IV), and highly innovative. KM257 inhibits the proliferation of tumor cells or induces apoptosis by blocking the heterodimerization of HER2 protein with other HER family members, thereby preventing the efficient transmission of signals.
KM257 is benchmarked against the ZW-25 from Zymeworks Inc. (“Zymeworks”), which is introduced in by BeiGene Ltd.(“BeiGene”) and has the world’s fastest progress in the same target, and showed potential efficacy and good safety. Compared with other HER2/HER2 bispecific antibodies under development, KM257 has the potential to become the Best-in-class with its high stability and efficacy.
HER2 bispecific antibody, the next-generation drug targeting HER2, is the focus of research and development for major domestic and foreign pharmaceutical companies. There is no HER2/HER2 bispecific antibody drug on the global market yet, and all are in the clinical stage. BeiGene acquired the Greater China interests of the bispecific antibody ZW25 and the bispecific antibodydrug conjugates (ADC) from Zymeworks for US$430 million; in 2021, Shanghai Jinmante Biotechnology Co., Ltd., a subsidiary of CSPC Pharmaceutical Group Limited, acquired the exclusive rights in China mainland for KN26 monotherapy and combination with KN046 in the treatment of breast cancer and gastric cancer from Alphamab Oncology with an upfront payment of RMB150 million, a development milestone of RMB450 million and a sales milestone of RMB400 million.
Dr. Che Fengsheng, Chairman and Executive Director of Sihuan Pharmaceutical Holding Group, said: “From the current clinical performance of HER2 bispecific antibodies, the clinical efficacy of bispecific antibodies is expected to be better than that of monoclonal antibodies against HER2-expressing advanced solid tumors. In 2020, the global market size for HER2-targeted monoclonal antibody therapy exceeded US$11 billion. It is expected that in the future, after the HER2 bispecific antibody drug is launched on the market, the sales will increase rapidly in this market of over US$10 billion with great market potential. It will have a positive impact on the Group's operating results in the future.”
Xuanzhu Biopharm
Xuanzhu Biopharm is the innovative drug research subsidiary of Sihuan Pharmaceutical, a large domestic pharmaceutical and medical aesthetic group. After nearly 10 years of construction and development, the company has gathered an outstanding team of nearly 400 led by returned scientists. The company owns the ability to research and develop innovative drugs independently, forms a complete R&D system, with complete drug development and industrialization capabilities, and does not rely on license-in and CRO, with the ability to innovate and produce continuously. Xuanzhu Biopharm owns two first-class innovative drug R&D platforms for both small molecular and large molecular, and is dedicated to the development of category 1.1 innovative drugs for small molecular and bio-macromolecular. It currently has more than 25 innovative drugs in pipeline under development, focusing on tumors, metabolism, anti-infection, digestion, and other fields. Among them, Xuanzhu Biopharm has a full coverage on major targets of breast cancer, and thus becomes one of the companies in China with the most comprehensive coverage in breast cancer therapeutic areas. The R&D of Xuanzhu Biopharm is progressing rapidly, with the NMPA accepted its NDA for Anaprazole Sodium for the treatment of duodenal ulcer and the Class 1 new drug Janagliflozin (transferred to Huisheng Biopharm) for the treatment of diabetes. In addition, it has nearly 10 products in clinical stage. The pipeline layout is complete and balance in long, medium, and short terms, with strong capability to innovate continuously, in order to ensure that at least 1–2 products could apply for IND every year in the future. Riding on the commercialization capabilities of its parent company Sihuan Pharmaceutical, Xuanzhu Biopharm is now transforming from a Biotech company to a Biopharm company, and is gradually becoming a company with excellent R&D and industrialization capabilities.