On March 24, according to the drug rongyun database, the autocrine PD1 antibody targeting mesothelin chimeric antigen receptor T cell injection (BZD1901) independently developed by Shanghai Cell Therapy Group successfully passed the scientific and rigorous review and approval of the National Center for Drug Examination and approval, and was officially approved to carry out phase I / II clinical research.
Source: YinRong Cloud database
Shanghai cell therapy group chairman and CEO professor Qian Qijun in 2010 in the world first proposed the concept of autocrine antibody killer cell drugs, by changing the local microenvironment to improve / improve CAR-T for solid tumor treatment effect, and in March 2015 the Chinese invention patent authorization, this is the concept of white ze T cell prototype. Subsequently, more than 30 related patents were applied for continuously around this unique product concept, forming a systematic patent moat, but there were still some challenges at that time. Technically, CAR T cells are difficult to autocrine high levels of antibodies, which cannot truly achieve effective changes to the local microregional tumor environment.
In 2018, Qian Qijun was awarded to Professor Zhu Weimin, an internationally renowned antibody expert and inventor of rabbit mAb, who met. After in-depth discussion, he believed that a world-class nano-antibody discovery platform should be established, and the characteristics of camel B cell immune bank, gene sequencing and artificial intelligence should be used to find nano-antibodies with high expression and high stability of nano-antibodies on a large scale. This idea was strongly supported by the Shengzhou municipal government of Zhejiang Province, and then established a 4100 mu camel breeding base in Shengzhou, and established a high-level nanoantibody research and development platform in Shanghai and San Francisco. In 2019, the nanoantibody research and development platform successfully screened MSLN, PD-1 and other nano-antibodies that met the expected functional characteristics, and applied them to CAR T cells. The in vitro and in vivo studies showed good antibody secretion level and tumor killing effect.
On October 28,2019, by the Shanghai cell therapy group co-founder, vice President and President led the team to the world's first targeted tumor and its immune suppression microenvironment autocrine nano antibodies CAR-T cell drug products (anti-PD1 MSLN-CAR-T) project formal project, open white ze T cells (autocrine antibody CAR-T) treatment of solid tumor drug development and clinical proof of concept.
According to Sun Yan, BZD1901, as the world's first autocrine nano-antibody CAR-T cell drug independently developed by China, has adopted non-viral gene writing technology and high-expression autocrine nano-antibody technology in the development process. The application of these innovative technologies in this product, on the one hand, brings a great potential to breakthrough the efficacy of solid tumors, and also poses a serious challenge to the whole product development. In particular, how to develop a CAR-T product process whose production success rate is not worse than or even exceeds the viral vector based on innovative non-viral vectors, greatly reduce the cost of CAR-T product through non-viral vectors, and realize the high robustness and high commercialization feasibility of non-viral vector product process. In addition, the development and implementation of clinical development strategies based on CAR-T products also face great challenges. In order to overcome these problems, Shanghai Cell Therapy Group has launched three battles of BZD1901 process, clinical and product supply, and promoted the continuous application and promotion of the series of research work with the help of mature tool methodology. At the beginning of 2021, the process battlefield took the lead in the breakthrough. It only took 3 months to complete the combination of the new process, amplification verification, technology transfer and 100% successful preparation of over 25 batches of clinical samples, and greatly improved the product quality.
Sun Yan said, along with the solution of the problem of product supply, clinical battlefield 3-4 months time touch more than 2800 patients with target indications, rapid push sensitive indications, dose, curative effect, to complete more than two potential sensitive indications of clear, and in mesothelin-positive rare disease to breakthrough curative effect potential, for the product quickly listed to solve some urgent clinical needs, fully prepared. At the same time, translational medicine based on BZD1901 in vivo and clinical data association research, gradually reveals the nano antibody armed cell drug innovation product concept of unique anti-tumor mechanism, promote the drug innovation products of scientific and clinical science research, for nano antibody armed cell drug series products to lay a solid foundation.
On November 20,2022, Shanghai Cell Therapy Group completed the pharmaceutical, non-clinical and clinical studies according to the FDA, Drug Evaluation Center and officially applied for the new drug; on December 16,2022, it passed the examination of the Drug Evaluation Center of State Food and Drug Administration and obtained the acceptance notice.
