Where are the differences between PD-1/L1 and domestic companies?

Guide: Multinational enterprises: In addition to chemotherapy, the preference for "immune and immunity" combination therapy, and the majority of monoanti-drugs, of which the number of combined with CTLA-4 targetsdomestic enterprises: chemotherapy is the pD-1/PD-L1 inhibitor combination drug research project, VEGF has become the most popular joint drug target of domestic enterprises, most of which are small molecules multi-target tyrosine kinase inhibitors!----However, despite the continuous development of immunocheckpoint inhibitors such as PD-1/PD-L1, the efficacy of immunotherapy is still limited, such as PD-1/PD-L1 inhibitors single-drug treatment of liver cancer objective mitigation rate of only about 10% to 20%, more and more companies are experimenting with combined drug regimensa large number of clinical studies have shown that the combination of immunotherapy and other drugs can achieve better anti-tumor effectthaner than monotherapy, as of September 2019, 76% of clinical trials of PD-1/PD-L1 inhibitors are active worldwidepopular combinations include tumor immunotherapy, targeted therapy, chemotherapy, or radiotherapythe top three were chemotherapy, CTLA-4 and VEGF in terms of target distributionto undertake the american Cancer Institute's analytical dimensions and ideas, this paper separately statistics multinational enterprises and domestic enterprises PD-1/PD-L1 inhibitors of the joint drug use, statistical standards for the highest stage of the same indications (if the indications have reached Phase III, then phase II is not included in the statistics), to explore domestic enterprises and multinational enterprises in the joint drug selection target selection of similaritiesmultinationals' target selection of the global clinical layout of The Global Combination Drug Use of PD-1/PD-L1 Inhibitors by Multinational Corporations is basically the same as the global segment of all enterprises at the beginning of the article: in addition to chemotherapy, the preference for "immune-and-immune" combination therapy is preferred, and is dominated by mono-anti-drugs, which are associated with CT LA-4 target joint the largest number of, listed and in the study of the indications project reached 35, mainly concentrated in Navuli u-singof s-opi-mono-sing (30), the degree valulyu sing-singhamab (5)the combination of NavuliU ssupinate and ipitizumab has been approved by the FDA for the treatment of melanoma, renal cell carcinoma, rectal cancer, liver cell carcinoma and non-small cell lung cancer five types of cancerIn addition,, atlizumab and beva-bead singofa "PD-L1-VEGF" combination of therapeutic effect is also very bright, the development of listed and in the study of indications has 13, and in May 2020 was approved by the FDA first-line treatment of liver cell cancer, the world's first and currently the only approved first-line liver cancer treatment of the tumor immunotherapyin contrast, pabolizumab in the choice of combination drugs, the choice of chemotherapy and small molecule-targeted drugs, has been listed and in the study of indications projects, chemotherapy has 24, small molecule-targeted drugs have 15, of which the reveritinib participated in 14 research projectsmultinationals are exploring more joint possibilities, such as HER2, ICOS, CD38, and PD-1 and PD-L1, in addition to the two most popular targets, CTLA-4 and VEGFthe joint selection of small molecule-targeted drugs, in addition to VEGF, the other target selection is mostly distributed in RET, c-Kit, PDGFR, c-Met, HER2 and so on the target selection of domestic enterprises as a whole, domestic enterprises and multinational enterprises have the same point is that chemotherapy is the most common research project of PD-1/PD-L1 inhibitor combination one of the differences is that VEGF has become the most popular joint drug target for domestic enterprises, mostofly small molecules multi-target tyrosine kinase inhibitors, such as TQB2450 , Anrotini, Carellizumab and Apatinib are among the joint choices to carry out research projects in addition, domestic enterprises' choice of small molecule-targeted drug targets is also mostly distributed in PDGFR, c-Kit, RET and SRC and multinational enterprises are the biggest difference in the mono-anti-drug, domestic enterprises CTLA-4 target to carry out very few projects, can be counted only Cindili salinating sbis310, and is still in the clinical I stage jointly target veGF's beva-beadmonol-resistant research projects are also small, and most companies choose to combine with self-developed belavzumab biosimilars, such as Cindilly's combination of IBI305, HLX10-HLX04 in addition to the combination of immunology, immunity, and targeted, immuno-targeted, immuno-and-chemotherapy, scientists are also actively exploring other combination of treatment options, such as soyoma virus, RNA therapy, cell therapy, and so on compared with the difference of target layout , domestic enterprises in PD-1/PD-L1 combined drug research and development strength is relatively backward, the joint drug is mostly concentrated in chemotherapy and small molecule target drugs only carellizumab combined chemotherapy is currently approved for advanced or metastatic non-small cell lung cancer , Cindy sepsis and forreire monotonica in combination chemotherapy treatment of non-squamous non-small cell lung cancer and squamous non-small cell lung cancer were also submitted for listing applications research and development strength is backward, the main reason is that China's antibody drug research and development is still in the initial stage, the development of targets are highly concentrated, most enterpriseantibody drugs in the research pipeline is relatively limited, there is no energy radiation to CTLA-4 and other targets , when choosing a combination drug, is more likely to choose combination with chemotherapy or self-developed products based on cost considerations also has a small number of local enterprises joint drug target layout is more complete, combined drug diversification, such as Cinda Bio's Cindy sepsal, combined with chemotherapy, IBI310 (targeted CTLA-4), IBI305 (target VEGF), IBI110 (target LAG-3), elynini and Sofentinib Of baiji Shenzhou's TerelliZhumonoistainis also has a joint treatment plan for drugs such as chemotherapy, BGB-A3333 (targeted PD-L1), BGB-3111 (target BTK), Target (BGB-290), Motolimod (Target TLR8), Sitravatinib (multi-target), rofatini and rigofini why these targets were chosen for combinations of immunoassays and chemotherapy, first proposed by Roche for the treatment of non-small cell lung cancer with atlizumab combined chemotherapy, and the results of clinical trials benefited the main scientific basis for supporting this result is that immunocheckpoint inhibitors need immunogenicity of the tumor to function when anti-tumor, and the use of low-dose chemotherapy can remove immunosuppression, enhance immunogenicity and regulate the immune response to enhance the effectiveness of immunotherapy , immunotherapy can reverse the resistance of tumor cells to chemotherapy, thereby increasing tumor cell sensitivity to chemotherapy drugs and reducing the toxic effects of chemotherapy , one of the great advantages of using immunoandological and chemotherapy combination therapies is the lower additional costs, which are in stark contrast to mono-anti-combination therapies PD-1/PD-L1 inhibitors and CTLA-4 and other mono-antidrugs, the main reason is the same immunoasiography inhibitors, but the effect of the two unrelated signaling pathways, the combination of the two can produce a good synergy, give full play to the complementary role of immunocheckpoint inhibitors in killing tumor cells, improve the anti-tumor effect T-cell immune response, and thus break the bottleneck of insufficient rate targetveGF's beva-bead sepsis itself has an anti-angiogenesis effect, and when combined with PD-1/PD-L1 inhibitors, it can promote T-cell tumor immersion and activate and activate T-cell responseto tumor antigens to further enhance pD-1/PD-L1 inhibitor's ability to activate the immune system to kill tumor cells the combined therapeutic effects of immunity and targeted therapy are complementary, one of the greatest benefits is that it can improve the acquired drug resistance of targeted drugs in the course of treatment, improve the therapeutic efficiency of targeted therapy, while targeted drugs can play the role of "vaccine", killing tumor cells and releasing targeted antigens to improve the therapeutic effectiveness of immunodrugs References: S1 Xin Yu Jia, Jeffrey P, Oliva Cristina, Neftelinov Svetoslav T, Hubbard-Lucey Vanessa M, Jun Jun Trends in clinical for development PD-1/PD-L1 (J.) Nature reviews Drug discovery, 2020, 19 (3) Liu Yang, Cao Xuetao Synergies in tumor immunotherapy and chemotherapy and their mechanisms of action J., Chinese Journal of Oncology Biotherapy, 2014, 21 (01): 98-103 [3] PD-1/PD-L1 Group Therapies From: Li Jiexuan, Chen Wei, Yang Yu Progress in the treatment of PD-1/PD-L1 inhibitors in the treatment of advanced liver cancer.