Bioray Biologics Announces IND Approval of World’s First Non-Viral PD-1 Targeted Integration CAR-T Therapy for Autoimmune Indication
BRL Medicine
Cell and Gene Therapy Drug Developer
On November 5, 2024, the Investigational New Drug (IND) application for the CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection (pipeline code: BRL-203), independently developed by BRL Medicine Inc., was officially approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) (acceptance number: CXSL2400533). The indication is moderate to severe refractory systemic lupus erythematosus (SLE). This therapy is reported to be the world’s first non-viral site-specific integrated PD1-CAR-T product targeting autoimmune diseases to receive IND approval, providing a breakthrough option for the treatment of autoimmune conditions.
BRL-203 is a non-viral PD1-CAR-T product targeting CD19 developed by BRL Medicine using its proprietary non-viral targeted integration CAR-T platform (Quikin CART). This product utilizes CRISPR/Cas9 gene editing technology to precisely edit the PD1 site in T lymphocytes and insert the CAR molecule targeting CD19 at a specific location. Compared with traditional viral vector-loaded CAR molecules, this method avoids the risk of tumorigenicity caused by random insertion, ensuring the safety and efficacy of the CAR-T product to the greatest extent. Additionally, the non-viral preparation method is simple in process, requiring only one step to simultaneously achieve sustained CAR expression and regulation of endogenous genes in T cells, significantly reducing the cost and preparation time of the CAR-T product.
Kactus Bioscience provided GMP-grade Cas9 protein for gene editing in this project, as well as corresponding document support for IND submission.
In September this year, the first non-Hodgkin's lymphoma (NHL) patient treated with BRL Medicine's another non-viral PD1-CAR-T product targeting CD19 (pipeline code: BRL-201) has been cancer-free for over four years, demonstrating excellent clinical safety and efficacy. This proves that the non-viral site-specific integration PD1-CAR-T therapy has outstanding clinical effectiveness.
For non-viral CAR-T products, gene editing enzymes are key tools for the site-specific integration of CAR molecules, and the industry has set high standards for their quality. Kactus Bio, as a protease raw material company, has now established a layout includingGMP-grade Cas9 Protein、High-fidelity hfCas12Max®(Developed independently by Huigene),GMP-Grade Cytosine Base Editor AccuBase®(Independently developed by Baceonco) and new toolsYolCas12TM(Yao Tang Biotech's self-developed) and other gene editing tool enzymes. Among them, the GMP-grade Cas9 protein has completed FDA DMF registration and provided strong support for IND applications of multiple projects.
BRL Medicine Inc. is committed to becoming a globally leading cell and gene therapy company in the era of new commercial civilization. With the mission of "leading innovation with gene editing technology, developing breakthrough therapies, and benefiting all humanity," BRL Medicine relies on its self-developed center and the "Shanghai Gene Editing and Cell Therapy Research Center" co-built with universities. It has generated more than 100 patent achievements so far. Currently, 19 projects are undergoing clinical trials in over 20 well-known hospitals, four of which have been approved for IND and have officially entered the registration clinical trial stage, while several other projects are in the IND application phase. Among these, gene-editing treatments for β-thalassemia, non-viral PD1 site-specific integration CAR-T, and UCART projects have achieved excellent clinical results with global leadership. These accomplishments have been published in multiple academic papers in prestigious journals such as Nature, Cell, Nature Medicine, and Nature Biotechnology. BRL Medicine has established five proprietary technology platforms: a gene-editing technology innovation platform, a hematopoietic stem cell platform, a non-viral site-specific integration CAR-T platform, a universal cell platform, and an enhanced T-cell platform. The company also operates a 7,000-square-meter GMP pilot production base and has a nearly 100-person operations team, ensuring that innovative research results can be quickly transformed and applied. BRL Medicine continuously drives rapid updates and iterations of its R&D products based on patient needs and clinical feedback. Upholding an attitude of openness, sharing, and win-win cooperation, BRL Medicine collaborates with global innovative biopharmaceutical ecosystem enterprises to accelerate the transformation and implementation of innovative drugs, benefiting patients worldwide who suffer from genetic diseases, malignant tumors, and autoimmune system disorders!
KACTUS Biosystems is a recombinant protein and protease raw material company driven by independent innovation, focusing on serving the development and production of biopharmaceuticals. Since its establishment in 2018, KACTUS Biosystems has relied on its unique protein research and development platform SAMS, which is based on structural design.TM, accumulating rich experience in protein R&D and production. Kactus Biosystems owns self-built GMP facilities and a certified quality system, providing a variety of GMP-grade raw material proteins and enzymes to meet the development needs of cell and gene therapy drugs. Several GMP-grade products have completed FDA DMF registration, supporting projects for applications in both China and the US. Kactus Biosystems has gathered a technical and professional team of nearly 200 people, establishing a research and production center in the Shanghai Pujiang Caohejing Development Zone and a GMP-grade protease industrialization base covering tens of thousands of square meters in the Lingang New Area. Additionally, an overseas market commercial operations and logistics center has been set up in the Boston area of the United States to provide strong support for global drug R&D.
