How's Sanofi's research and development reformgoing? Take a look at the six-month "report card"

MrHudson said Sanofi's research and development philosophy is based on three drivers: expanding the technology platform for drug discovery, deepening the signaling pathways for diseases, and relentlessly focusing on patientsLet's take a look at what the company's three drivers have madethe technology platform for expanding drug discovery
currently, 85% of the protein in the human protein group is still untargeted by traditional methods, which means that a variety of new technology platforms are needed to target these "non-drug" targetsOne of the important factors driving Sanofi's research and development is the expansion of a technology platform that can be used to target these difficult targetsThe technology platforms highlighted on the research and development day include the multi-specific antibody platform, the nano-antibody platform, and the company's $250 million acquisition of Synthorx's synthetic biology platformmulti-specific antibody platform
Sanofi executives introduced a three-specific T-cell activation platform for multispecific antibodiesTT(T cell engagers),TCD3。 Although these molecules can activate T cells, they can also induce cell death due to T-cell activation without simultaneously activating the costimulation signaling pathwayThis limits the anti-cancer activity of T cells to some extentthe three-specific T-cell bonding protein developed by Sanofi, in addition to binding to the CD3 receptor, also carries a protein domain that binds to the co-stimulation receptor CD28, while activating the CD28 signaling pathway promotes the survival of activated T-cell and the production of "T-cell memory"at the same time, CD28 is also expressed on the surface of a variety of myeloma cells and blood cancer cells, and this three-specific antibody has the potential to improve the targeting of tumor cells by targeting two different targets expressed on the surface of tumor cellsSAR442257, developed on the basis of this technology platform, is a three-specific antibody that targets CD38In vitro tests, it showed 1000 to 10,000 times higher myeloma cell killing activity than CD38 monoclonal antibodiesThis three-specific antibody has entered clinical trials for patients with recurrent/refractive multiple myeloma (MM) and non-classic Hodgkin's lymphoma (NHL)Synthetic Biology Platform, which produces more sample protein drugs by expanding gene coding
Synthorin's technology platform, acquired by Sanofi, significantly expands the number of coders (codons) of encoded amino acids by designing a new pair of base pairs (X-Y) Using this system, researchers can position the introduction of non-natural amino acids into proteins, which can accurately improve the nature and function of protein drugs using this platform, Sanofi developed the IL-2 protein that precisely activates the IL-2 signaling pathway Il-2, by combining with different receptors, can mediate downstream reactions that are opposite When it binds to an IL-2 receptor consisting of a beta-pyridine chain, it activates CD8-positive T-effect cells and natural killer cells (NK), thus promoting an anti-cancer immune response This is why a number of biopharmaceutical companies develop IL-2 signal path agonists However, the binding of IL-2 to the receptors of the alpha beta chain causes the proliferation of CD4-positive regulatory Tcells (Treg), which may inhibit the anti-cancer immune response, and this signaling pathway can cause the proliferation of eosinophils, leading to other toxic side effects This is an important obstacle to the development of IL-2 signal path agoagotics Synthorin's technology platform introduces polyglycol modification at specified sites of the protein by replacing specific amino acids in the IL-2 protein with non-natural amino acids These polyglycol chains introduced in specific sites can block the binding of IL-2 to the alpha chain of the IL-2 receptor, thereby specifically promoting the proliferation of CD8-positive T-cells and NK cells with anti-cancer effects At the same time, it does not promote the proliferation of immune-suppressing Treg cells, as well as the eosinophil response that causes other side effects in a non-human primate model, THOR-707, developed on this platform, stimulates lymphocyte proliferation without stimulating an increase in the number of eosinophils In contrast, the natural IL-2 protein aldesleukin also raised levels of lymphocytes and eosinophils At present, this research therapy has entered human clinical trials, preliminary results show that it has good safety, and show positive biomarker data Sanofi believes that this in-therapy may become "best-in-class" IL-2 signaling pathway-specific agonists In addition to retrofitting IL-2, Synthorx's technology platform can also be used to improve the characteristics of a wide range of clinical-phased therapies the signaling pathways of deep-cultivated diseases Sanofi has extensive experience in immunology and monogenic diseases During the research and development day, the company's executives said that by deepening their understanding of the signaling pathways associated with these diseases, researchers were able to expand the scope of application of the therapy, one example being the company's glutamine syntine (GCS) inhibitor venglustat This oral GCS inhibitor, which crosses the blood-brain barrier, has shown efficacy in treating a variety of polysothromets (lysosome storage disorder, LSD) caused by genetic mutations in the metabolic pathways of gsaclyn (GSL), including rare diseases such as Gaucher disease 3 and Fabry disease , however, by analyzing the signaling pathways in the metabolic pathway of glycolipids, the researchers found that in patients with Parkinson's disease whose genes that encode glucose-brain-pooside asase (GBA), the accumulation of GSL in the patient's brain triggered the accumulation of alpha synaptic nucleoproteins due to the absence of GBA Venglustat is expected to be the first innovative treatment to change the course of this type of Parkinson's disease by reducing GSL levels in patients' plasma and cerebrospinal fluid , lysosome pathway defects play an important part in the progression of disease in patients with Parkinson's disease Regulating GSL levels by inhibiting GCS has the potential to improve lysosome and nerve cell function and reduce neurotoxicity caused by alpha synaptic nucleins The FDA has recommended that Sanofi include iexclusivesed Parkinson's patients with glycosinoma pathology in phase 3 clinical trials for venglustat treatment of Parkinson's disease patient-centric Explaining patient-centered research and development strategies, Sanofi executives gave examples of the company developing innovative treatments for haemophilia For haemophiliacs, while there are currently options for coagulation and non-coagulation factor therapy, they still need to weigh the burden of treatment against the level of protection provided by the treatment Treatments that provide a high level of protection and bring patients closer to a normal life require treatment multiple times a week, while treatments that do not require frequent administration provide a low level of protection that prevents them from engaging in many vigorous activities Sanofi's goal in developing innovative therapies is to go beyond the limitations of current on-market therapies The company developed BIVV01 as an alternative treatment for the next generation of coagulation factor VIII for patients with type A haemophilia This innovative fusion protein combines recombinant coagulation factor VIII with Fc, VWF and XTEN protein fragments, significantly extending the half-life of factor VIII This improvement allows BIVV001 to have a half-life in the blood for more than 40 hours, three times the normal recombinant factor VIII After an injection, it allows the level of factor VIII in patients with severe haemophilia to approach normal levels within the next 3.5 days This means they may be able to play more intense sports like normal people and co-developed with Alnylam, fitusiran is a RNAi therapy that provides a higher level of protection with just one monthly injection The results of the phase 2 development label extension trial announced recently showed that the median annual haemorrhage rate (ABR) in patients treated with this treatment was 0.86 times And it can treat patients with type A and B haemophilia, whether or not they have antibodies against exogenous coagulation factors Fitusiran has the potential to become a "best-in-class" non-coagulation factor therapy , Sanofi is working with the San Rafael Trisson Gene Therapy Institute (ST-TIGET) to develop the first invivative haemophilia gene therapy based on the slow virus At present, the rapid progress of hemophilia gene therapy in the research and development pipeline is based on adenosyd-related virus (AAV) vectors Although these gene therapies have shown long-term efficacy in clinical trials, they may not be suitable for treatment with such gene therapy because many patients already have neutralized antibodies against AAV in their bodies And since AAV viruses do not integrate into the genome of cells, the level of coagulation factors expressed by THE gMO decreases year by year after receiving one-time treatment, and may not achieve a true "cure" effect , and the slow-virus-based gene therapy does not have existing neutralizing antibodies in the human body, and because it integrates genetic modifications into the genome of the patient's cell, these gms can grow with the division of the patient's cells, thus providing the possibility of "cure" The gene therapy, developed jointly by Sanofi, has shown lasting efficacy in preclinical models and is expected to enter clinical development by 2022 today's research and development day event, Sanofi also announced that the company and GlaxoSmithKline jointly developed a new coronavirus recombinant protein candidate vaccine further accelerated development, is expected to enter clinical trials in September this year, as soon as January may be the potential emergency authorization The technology platform has been used to produce the company's approved flu vaccine Sanofi expects to produce 100 million doses of vaccine by January 2021 and expand its production capacity to 1 billion doses per year by 2021 "Based on innovative technology platforms and insights from patient needs and disease signaling pathways, we have significantly accelerated our investment in research and development in six key development projects," Saido CEO Paul Hudson said in a press release Our unique research and development strategy will help Sanofi achieve its goal of providing patients with treatments and vaccines that change the medical paradigm "