PD-1 resistance is expected to be solved! TIM-3 Target approved clinical, Hengrui, BMS, Roche latest progress...

Introduction: PD-1/L1 first echelon, competition for new directions
foreword: Recently, Novartis in the study of TIM-3 monoclonal antibody MBG453 obtained a clinical trial license, and this antibody has high hopes that it may become the cornerstone of the treatment of a variety of myelin diseasesThe news once again brings the TIM-3 target to the public's viewin the field of TIM-3 antibodies, Novartis has laid out more than ten patent applications around the world, covering everything from monoclonal antibodies, bispecific antibodies to TIM-3 antibodies and PD-1 antibodies and other combination of drugsFor the hot pD-1/L1 in recent years, the drug is nothing short of a new competitive channel for pharmaceutical companies entering the first circuit of PD-1/L1PD-1/L1 Track - 8 competingSince 2018, China's cancer treatment has entered the immune agePD-1/PD-L1 antibody drugs have brought a new cancer treatment model, a time "cure myth" constantlyUp to now, China has listed 4 imported PD-1/PD-L1 mono-resist, 4 domestic PD-1 mono-resist, details of the following table:Table 1: At present, the current domestic PD-1/PD-L1 antibody list
with more and more enterprise layout, PD-1///p L1 track is becoming increasingly crowded, the major pharmaceutical companies in the new indications, large-scale indications to expand the energy, the current Mercadon "k drug" approved the most adaptation, and there are three lung cancer large-scale indications plus, 2019 global sales for the first time exceeded 10 billion U.Sdollars, far more than other pharmaceutical companiesUnder such circumstances, other pharmaceutical companies, while taking into account indications, have also begun to explore other competitive advantageswith clinical verification, PD-1/L1 is more prominent problem is: single drug for most solid tumors have an efficiency of only about 20%, and 15%-35% of patients use a period of time after the recurrence of PD-1/L1 disease, the industry said drug resistanceSo far, scientists and clinicians around the world are studying how to improve the effectiveness of PD-1/PD-L1 antibodies and their resistanceMajor drug companies are also looking for opportunities to lay out drugs that break down resistance and improve their efficiencyTIM-3 Enhanced Efficacy ResistanceStudies have found that T cells that express TIM-3/PD-1 show editing more severe failure, and patients who are not responding to PD-1 treatment are often highly correlated with the expression of TIM-3, while patients who are resistant to PD-1 treatment are also due to the high expression of TIM-3, which leads to tumor immunityTIM-3 (T cell-cell-betaglobulin domain and mucin domain-3) full name T lymphocyte immunoglobulin viscoprotein 3, is a negative lymphocyte immune checkpoint, expressed on the surface of T cells, Treg cells and other congenital immune cells, which can cause the failure of T cells during cancer and chronic viral infectionsTIM-3's ligand is a widely expressed soluble molecule, semi-lactocosin 9 (Gal-9), which binds to oligosaccharides in the variable region of the TIM-3 molecule and in turn negatively regulates the immune response driven by Th1in addition, ossetu has published an experiment using B-hPD-1/hTIM3 mice to perform anti-human PD-1 antibody (keytruda) with TIM3 antibody co-drug effect sin- and effectsThe results of theshowed that the anti-human PD-1 antibody (keytruda) and THE TIM3 antibody combination drug group showed more obvious tumor inhibition effect compared with the PD-1 individual drug group, and its combined anti-tumor effect was better than pD-1 single use, studies have also found that more immune responses can be caused when antitim-3/combined with other checkpoint inhibitors, although most of the currently available TIM-3 antibody research projects are associated with PD-1 antibodiesTIM-3 enterprise layoutup to now, there is no TIM-3 single resistance approved for listing in the world, the layout of this target of the pharmaceutical companies are not many, if the approved PD-1/L1 first echelon of 8 pharmaceutical companies if they can explore joint development, with its effectiveness and the characteristics of drug resistance, in the PD-1 market will be a major competitive advantagethe current TIM-3 target rapid progress of multinational pharmaceutical companies have 4, of which Novartis MBG453 is the fastest progress, in early June this year has launched the drug randomized, double-blind, blank control of the global multi-center III clinical trial, this time approved in China clinical, meaning that Novartis TIM-3 monotonica has started the global process of promotionTable 2: TIM-3 Single Anti-Transnational Pharmaceutical Enterprise first echelon
Roche, BMS both PD-1/L1 drugs have been approved, the rapid layout of TIM-3, may also drive its PD-1 inhibitors to generate new opportunities, ushering in new breakthroughsOn the other hand, there is more room for growth in the development of TIM-3 targets than currently hot immune checkpoints such as PD-1/CTLA-4in China, there are also a number of pharmaceutical companies layout TIM-3 monotonica, the fastest progress is Hengrui Pharmaceuticals, in April last year launched SHR1702 single medicine or joint PD-1 antibody Carellizumab to treat late-stage solid tumor sepsis and pharmacology researchIn the future, the combination of SHR1702 with other drugs will also be the focus of Hengrui's development of TIM-3 monotoreactor, Colum Pharmaceuticals' KL-A293 injection, Zhikang Hongyi Bio's WBP3425 injection, Baiji Shenzhou's BGB-A425, etc have been approved clinically References: