Clinical application of the first PD-L1 monoclonal antibody in China

　 On April 28, the new generation of PD-L1 monoclonal antibody injection kn035 jointly developed by thinkti and Corning Jerry made important progress -- its clinical application has passed the formal examination and registration site examination of Jiangsu food and drug administration, and has been reported to the State Food and drug administration, with the acceptance number of cxsl1600033 Su, marking the first PD-L1 monoclonal antibody in China Clinical application succeeded! At present, there are two monoclonal antibodies of PD-1 in the world, namely, opdivo of Bristol Myers Squibb and keytruda of mosadong The approved indications are melanoma and non-small cell lung cancer However, PD-L1 mAb has not yet been put on the market, and PD-L1 mAb of Roche, AstraZeneca and Merck / Pfizer has entered the phase III clinical research stage Among them, atezolizumab (mpdl3280a) of Roche has submitted BLA application for bladder cancer and non-small cell lung cancer to the US FDA The successful products declared by thinkti and Corning Jerry belong to the first new generation PD-L1 humanized monoclonal antibody independently innovated and developed in China Compared with the current PD-1 and PD-L1 antibodies that have been listed and under development in the world, which need intravenous injection and cryopreservation, they have the advantages of stability at room temperature and subcutaneous injection, so as to greatly reduce the cost of drug production, transportation and use, and improve drug compliance According to the relevant registration laws and regulations of the state, the above drugs have been accepted for registration, and will be reviewed by the State Food and drug administration, and the clinical trial approval documents will be issued after the review According to Dr Gong Zhaolong, CEO of thoughtway, the company has launched the global synchronous clinical development of the product It is planned to enter the group of patients in the third quarter of 2016 after submitting the ind declaration to the US FDA, which will be the first new generation of PD-L1 antibody to enter clinical development in the world At present, drug development in the field of PD-1 / PD-L1 immunotherapy is extremely hot, with a market peak of US $35 billion According to the data released by GBI, the global business intelligence agency, it is estimated that by 2022, the global immunotherapy market will expand to US $74.2 billion, which is likely to account for half of the tumor treatment market The leading players in this field include Bristol Myers Squibb, MSD, Roche and AstraZeneca At present, two PD-1 antibodies have been listed in the world, namely, opdivo of Bristol Myers Squibb and keytruda of MSD According to a number of clinical research data, the response rate of these two PD-1 antibodies in different tumor indications is only about 20%, and the incidence of drug-related adverse reactions is high in Level 3 / 4, and the death cases caused by drug-related pulmonary toxicity are observed However, three anti-PD-L1 monoclonal antibodies in the third phase of clinical study showed that they were more safe and no serious pulmonary toxicity was observed Therefore, even if there are two PD-1 antibodies on the market, FDA still grants PD-L1 antibody "breakthrough treatment status" This also shows the differentiation advantage of PD-L1 compared with PD-1, and it has been approved by FDA Through the early layout of integrated services of precise diagnosis and treatment of tumor (gene detection, drug recommendation and prognosis tracking), thoughtway accumulated and established a database of high-quality tumor gene variation and clinical drug use Relying on the company's professional and efficient data mining ability and precision drug development platform, thougdi introduced the concept of precision medicine in the pre clinical research and development stage of the new generation of PD-L1 antibody, created a marker driven immunotherapy drug development model, and will run through the whole clinical development process of new drugs, which will greatly improve the efficiency of clinical trials and the success rate of new drug development Thingdi has reached cooperation with a number of well-known pharmaceutical companies and research institutes at home and abroad to jointly develop a variety of new anti-cancer drugs Corning Jerry Suzhou Corning Jerry Biotechnology Co., Ltd was founded in April 2009 by Dr Xu Ting, a special expert of the thousand talents program Suzhou R & D center has a total area of more than 6000 square meters More than 100 high-end talents have been gathered and a postdoctoral workstation has been established; a university enterprise technology center has been established with Southeast University; a strategic cooperation of biomacromolecule drugs has been formed with Shanghai Institute of Pharmaceutical Sciences, Chinese Academy of Sciences, and a technology platform has been established with thermo company of the United States There are 18 doctors in the R & D team, more than 10 with overseas experience and more than 60 masters At the same time, the company has a consulting team composed of world-class scientists In terms of hardware, the R & D center has invested 300 million yuan, which can complete the whole production process from early screening and engineering of antibody / protein drugs, cell line construction and small-scale test technology, to pilot scale-up and clinical trial drugs The company's analysis and quality control platform can independently complete the comprehensive and in-depth characterization of biomacromolecule drugs Early process development platform includes 50L, 130L, 250L mammalian cell production line and 100L prokaryotic production line The pilot plant conforms to cGMP standards of CFDA, EMA and FDA, and is composed of 4 original solution workshops including 250L and 2 1000L mammalian cell production lines and 6000 bottles / hour aseptic preparation filling workshops Animal experimental center can complete the early evaluation of the efficacy, pharmacology, pharmacokinetics and pharmacokinetics of innovative macromolecular drugs In 2011, the company formed strategic cooperation with Shi Huida Pharmaceutical Group The cooperation includes the introduction of funds to rapidly develop the R & D center in Suzhou; the preparation of kangningjierui (Jilin) macromolecular drug production base in Changchun, Jilin Province, and the construction of a factory building in line with CFDA, EMA and fdacgmp standards, with a planned investment of 1 billion yuan in the first phase; the gradual integration of the nationwide sales network of shihuida drug industry to prepare for the listing of monoclonal antibodies and new protein drugs, At the same time, actively explore foreign markets and participate in international competition In 2011, Corning Jerry and internationally renowned scholars in the field of tumor immunity jointly established Dingfu target biotechnology company to focus on tumor immunotherapy R & D pipeline, biological innovative medicine, biological analog