GenScript's GMP sgRNA Powers Bonovo's Allogeneic CAR-T Therapy Featured in Cell, Pioneering Autoimmune Disease Treatment
BRL Medicine
Cell and Gene Therapy Drug Developer
On July 15, 2024, BRL Medicine Inc., a company deeply engaged in gene and cell therapy,BRL Medicine Inc.(hereinafter referred to as "BRL Medicine") published an article in the international top journal Cell titled "Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis". The article introduces BRL Medicine's self-developed next-generation targeted CD19 universal CAR-T cell therapy (TyU19), which has achieved a critical breakthrough in treating refractory autoimmune diseases.This is the world's first report of successful treatment of autoimmune diseases using allogeneic universal CAR-T.。
GenScript is honored to provide sgRNA synthesis services from R&D to GMP level for BRL Medicine's universal CAR-T product.，Empowering CAR-T to Pioneer New Frontiers in Autoimmune Diseases, Benefiting More PatientsIt is worth noting that in July 2023, BRL Medicine's clinical trial application (IND) for its product "Allogeneic Chimeric Antigen Receptor T-Cell Injection with Targeted CD19 Gene Modification" (pipeline code: BRL-301) was approved by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for the treatment of B-cell Acute Lymphoblastic Leukemia. The research findings published in this Cell article further expand the application scenarios of this product.
World's First! Universal CAR-T Successfully Treats Autoimmune Diseases
Autoimmune diseases are a class of disorders where the body's immune system abnormally reacts to self-antigens, causing damage to the body itself. Conventional treatments often face challenges such as long treatment cycles and a high risk of recurrence. According to Frost & Sullivan estimates, the global biopharmaceutical market targeting autoimmune diseases is expected to reach $145 billion by 2030, potentially becoming the next major market after oncology, leaving vast room for imagination regarding CAR-T cell therapy.
In this study, TyU19 is an allogeneic universal CAR-T cell therapy product targeting the CD19 antigen developed by BRL Medicine based on its proprietary universal cell platform (TyUCell®). It employs a sophisticated multi-gene, selective gene editing strategy (Figure 1), effectively avoiding the risks of graft-versus-host disease (GvHD) and immune rejection of allogeneic cells, and hasHigh accessibility, low cost, stable qualityAnd many other characteristics, which have been reflected in clinical trialsSignificant efficacy and high safety。
Figure 1 Design and in vivo effects of BRL Medicine's UCAR-T product "TyU19"
In this study, the research team successfully used BRL Medicine's UCAR-T product TyU19 to treat three patients with refractory autoimmune diseases, including one case of immune-mediated necrotizing myositis (IMNM) and two cases of systemic sclerosis (SSc).
The 42-year-old female subject with IMNM did not experience any fever or symptoms of cytokine storm after receiving TyU19 cell therapy. Her Total Improvement Score (TIS) rapidly increased from a baseline of 72.5 to 100 within two months and remained at this level throughout the subsequent follow-up period. Imaging and pathological examinations also showed significant relief in muscle inflammation.
This study also enrolled two subjects with severe SSc who, after receiving TyU19 cell therapy, showed significant improvement in CRISS scores within a few months. Additionally, regarding skin fibrosis, the modified Rodnan skin scores (mRSS) of both patients decreased significantly.
In addition,All patients' B cells were completely depleted after TyU19 treatment., the autoantibodies of IMNM patients were completely eliminated (Figure 2); the critical organ fibrosis damage in 2 SSc patients was reversed and continued to improve during the 6-month monitoring period (Figure 3). The entire treatment process was well-tolerated.No cytokine release syndrome (CRS), graft-versus-host disease (GvHD), or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed.。
Figure 2 Clinical Assessment of IMNM Patients
Figure 3 Clinical Assessment of SSc Patients
Genscript GMP sgRNA: Empowering CAR-T to Tackle New Avenues in Autoimmunity
As the number of projects and products using CAR-T for cancer treatment grows rapidly, exploring new indications such as autoimmune diseases not only expands the application areas of cell therapy but also opens up new blue oceans for the industry’s differentiated development.
Genscript is honored to provide the key reagent raw material sgRNA for BRL Medicine's universal CAR-T therapy from the research and development stage to the clinical research stage., as well as customized quality control testing and professional technical support, using high-standard gene editing reagent raw materials to ensure the successful application of downstream high-quality gene therapy products.
With 21 years of deep cultivation in nucleic acid synthesis, GenScript possesses a comprehensive product line of gene-editing nucleic acid raw materials, featuring high editing efficiency, low toxicity, and low off-target effects, includingResearch-grade to GMP-grade chemically synthesized sgRNA, gene knock-in templates (ssDNA single-stranded template/dsDNA double-stranded template/GenCircle dsDNA circular template). Meanwhile,Genscript GMP Business Team: Expert in Navigating Regulatory Updates, Continuous Engagement with Authorities, Proficient in Preparing Submission Documents for China and the U.S., Providing Solutions for Deficiency Letters。
As of May 2024, GenScript has successfully deliveredMore than 120 batchesGMP sgRNA and Gene Knock-in Templates, SupportMore than 40 project applications, successfully passedMore than 30 audits, supporting global customers in obtaining9 IND Approvals, proudly leading the way in the GMP gene-editing nucleic acid raw materials industry.
Figure 4 Genscript Gene and Cell Therapy CRISPR Raw Material Solutions
Genscript Zhenjiang GMP Facility Built to Comply with FDA, EMA, PMDA, and NMPA Requirements for GMP Facilities, Equipped with Advanced Environmental Control Systems, Optimized Aseptic Product Manufacturing Equipment, and Standardized Personnel and Material Flow Management.
Swipe left and right to browse GenScript Zhenjiang GMP Facility
Genscript can deliver up to gram-level sgRNA and HDR gene knock-in templates in a single batch, with GMP-grade products.Support the development of in vitro gene editing therapies (CAR-T, CAR-NK, etc.) and in vivo gene editing therapies based on various gene editing technologies (Cas9 / Cas12 / Base Editing / Prime Editing, etc.), and with sufficient production capacity to support rapid delivery, accelerating the filing and clinical trial progress, assisting GCT companies in the efficient advancement of pipeline development and commercialization, contributing to the goal of gene and cell therapy benefiting more patients.
About BRL Medicine
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. To date, it has generated more than 100 patent achievements. Five projects are currently undergoing investigator-initiated clinical trials at eight renowned hospitals, three projects have been approved for IND and have officially entered the registered clinical trial stage, and several other projects are in the IND application stage. Among these, gene-editing treatments for β-thalassemia, non-viral PD1 targeted integration CAR-T, and UCART have achieved excellent clinical outcomes, demonstrating global leadership. Academic papers on these advancements have been published in prestigious journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell.
BRL Medicine has built five proprietary technology platforms: gene editing technology innovation platform, hematopoietic stem cell platform, non-viral site-specific integration CAR-T platform, universal cell platform, and enhanced T-cell platform. It owns a 7,000-square-meter GMP pilot base and a nearly 200-person operations team, strongly ensuring that innovative research achievements 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. With an attitude of openness, sharing, and win-win cooperation, BRL Medicine is working with global innovative biopharmaceutical ecosystem companies to accelerate the transformation and implementation of innovative drugs for the benefit of patients worldwide suffering from genetic diseases, malignant tumors, and autoimmune diseases!
About GenScript Biotech
Genscript Biotech Corporation (HK.1548) is a leading global provider of life science R&D and manufacturing services. Rooted in robust DNA synthesis technology, Genscript has established four major business units: Life Science Services and Products, Biologics Contract Development and Manufacturing (CDMO), Industrial Synthetic Products, and a Comprehensive Global Cell Therapy Company.
GenScript was founded in 2002 and listed on the Main Board of the Hong Kong Stock Exchange in 2015. Its legal entities span across the United States, China, Japan, Singapore, the Netherlands, Ireland, the United Kingdom, South Korea, Belgium, and Spain. Its business operations cover over 100 countries and regions worldwide, providing high-quality, convenient, and reliable services and products to more than 200,000 customers.
As of December 31, 2023, GenScript has more than 6,900 employees worldwide, and its services and products have been cited in over 88,700 peer-reviewed academic journal articles globally. GenScript owns multiple intellectual property rights, including over 300 authorized patents and more than 900 patent applications, as well as a large number of technical secrets.
