The general trend of "double resistance"! Many MNCs, such as Aberdeen and Sanofi, have invested heavily in the layout

Paper dividend < br / > suffered from the periodic disturbance of the epidemic situation, the investment and transaction of the pharmaceutical industry experienced a short dormancy, and entered the post epidemic era, when the opportunity came to a crisis, all major enterprises have thrown olive branches to their promising projectsIt's worth noting that Roche, Sanofi and Aberdeen all focused on this field this week - bispecific antibody (BsAb)< br / > bispecific antibody refers to the artificial antibody containing two specific antigen binding sites, which can interact with target cells and functional cells (usually T cells) at the same time, and mediate a series of immune reactionsCompared with monoclonal antibody, bispecific antibody increases a specific antigen binding site, so it has a significant advantage in treatmentAt the end of May, Science reported a healing story of BsAbAmy Boland, a woman who had been treated with car-t for many years, had relapsedAfter receiving bispecific antibody treatment, the lymphoma disappeared and has not recurred until now< br / > the huge therapeutic potential makes bispecific antibody become the "new pet" of new drug R & D investment< br / > bispecific antibodies do not exist in the natural state and need to be prepared manually by recombinant DNA or cell fusion technology, so it is relatively difficult to develop, so it is wise to choose a partner in the research and development processThis week, a number of cooperation involving BsAb were reached< br / > on June 11, Alberto and genmab jointly announced that they had reached a broad cooperation agreement to jointly develop and commercialize three new generation bispecific antibody products under genmabUnder the agreement, Alberto will pay genmab a $750 million down payment, as well as development, registration and sales milestones totalling $3.15 billion< br / > on June 9, Cinda biology announced a strategic R & D cooperation with Roche Group, focusing on research, clinical development and commercialization of multiple bispecific antibodies and cell therapy productsCinda will use Roche's technology platform to be responsible for product development, production and commercializationRoche reserves the exclusive option to repurchase its rights and interests in the development and commercialization of these products outside ChinaIf Roche exercises all of its options, it will make a down payment of US $140 million to Cinda and a milestone payment of US $1.96 billion in total< br / > on the same day, Sanofi and corningeri announced that they had signed an agreement to reach strategic cooperation: the two sides will jointly promote the clinical trial of the combination of bispecific antibody kn026 and docetaxel for HER2 positive breast cancer patients After reaching a specific clinical milestone, Sanofi will have the right to negotiate for the exclusive license of kn026 during the exclusive period < br / > two months further, on April 9, zaiding pharmaceutical and Zaiyuan reached strategic cooperation on the development and commercialization of cd20xcd3 bispecific antibody regn 1979 in mainland China, Hong Kong, Taiwan and Macao; on March 24, cytomx therapeutics and Ansteel reached a strategic cooperation with a total value of about 1.7 billion US dollars, The two sides will work together to discover, develop and commercialize new T cell bispecific antibodies < br / > this paper lists only a small part of many related transactions, but to some extent, it can reflect the investment heat of dual characteristic antibody < br / > when the trade of candidate bispecific antibody is booming, the world's first bispecific antibody is ready to start again On June 4, CDE website showed that catumaxamab injection, the world's first bispecific antibody, was approved by two implicit clinical trials in China The indication was "not suitable for the treatment of advanced gastric cancer with peritoneal metastasis and systemic treatment" In 2009, catumaxomab was approved by European EMA for the treatment of malignant ascites, but it did not perform well after being put on the market, and finally announced its delisting and shutdown in 2017 < br / > bispecific antibody is developed on the basis of monoclonal antibody, and the therapeutic effect may be better It is regarded as the second generation of antibody therapy for tumor treatment, so its market prospect can be predicted from the sales of monoclonal antibody In 2018, the global market size of monoclonal antibody drugs has increased from 88.3 billion US dollars in 2014 to 144.8 billion US dollars in 2018, with a compound growth rate of 13.2%, far higher than the 7.7% compound growth rate of global biological drugs In addition, among the top 20 drugs in global sales in 2019, monoclonal antibodies occupy 9 positions < br / > at present, only three bispecific antibody drugs have been approved for marketing in the world In addition to the catumaxomab mentioned above, the other two are Amgen's blincyto and Roche's hemlibra < br / > So what about the two bispecific antibody drugs on the market? In 2019, blincyto's sales volume is US $312 million, which has entered the priority review in China and will be approved soon Since its listing in 2017, hemlibra's sales have grown rapidly, reaching CHF 1.38 billion in 2019, an increase of 516% year on year < br / > although blincyto and hemlibra are "getting better", especially hemlibra's performance is remarkable, but this is only the tip of the iceberg for the whole bispecific antibody market, and a broader space is waiting to be explored In recent years, the research and development pipeline of bispecific antibody has witnessed a big explosion Last year, Nature Reviews Drug Discovery published a review on bispecific antibodies Data shows that since 2014, bispecific antibodies have entered a high-speed development period As of March 2019, there are 85 bispecific antibodies in clinical development stage At present, there are more than 100 bispecific antibody drugs in clinical stage in the world < br / > < br / > < br / / > according to statistics, about 20% of the antibody drugs in the pre clinical stage in the world belong to bispecific antibody, which is slightly higher in China, about 22% < br / > next, we will interpret the situation of bispecific antibody under research from different perspectives < br / > from the perspective of disease field, the main research direction of bispecific antibody in the world is still focused on tumor (86%) (as of March 2019), followed by blood diseases and autoimmune diseases However, most of the bispecific antibody programs in China are aimed at cancer, and most of them are breast cancer and gastric cancer < br / > < br / > < br / > from the point of view of the target, the global bispecific antibody projects entering the clinical stage mainly focus on PD-1 / PD-L1, HER2, CTLA4, CD19, BCMA Chinese enterprises have the most HER2 layout < br / > from the perspective of enterprises, according to nextpharma, the global new drug database of medicine magic cube, the number and development progress of the projects are in the first echelon, mainly including Amgen, Roche, genmabogenics, xencor, Johnson & Johnson, AstraZeneca, and Zaiyuan, while the domestic ones mainly include Corning Jerry, Baiji Shenzhou, Anmai biology, Cinda biology, etc < br / > < br / > < br / > from the perspective of research and development progress, nearly 80% of bispecific antibody drugs under research in the world are also in phase I clinical stage The world's fastest-growing research projects are AstraZeneca and Zaiyuan, each with a project in the clinical phase III The fastest development in China is corning Jerry and Baiji Shenzhou, with 2 and 1 projects in clinical phase II respectively < br / > although we all hope to enjoy the first mover advantage and early layout of the market, most of the products under research are in the early stage and concentrated in the direction of tumor, so we can foresee the fierce competition in the global bispecific antibody market in the future.