Bioray Biotech's BRL-201 Receives IND Approval: World’s First Non-Viral PD1 Targeted Integration CAR-T Product

ShanghaiDecember 14, 2022PR Newswire -- December 14, 2022, BRL Medicine Inc. (hereinafter referred to as "BRL Medicine"), a Shanghai-based company focusing on gene and cell therapy, announced that it has utilized its proprietary Quikin CART technology.^®The platform developed is namedThe clinical trial application (IND) for "Targeted CD19 Non-viral PD1 Site-specific Integration CAR-T Cell Injection" (Pipeline Code: BRL-201) has been officially approved by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) today.。Indication: Relapsed/Refractory B-cell Non-Hodgkin Lymphoma (R/R B-NHL). This is the world's first autologous CAR-T cell product capable of achieving targeted genomic integration without the use of viral vectors.

IND Approved

The IND application for BRL-201 has been approved.BRL MedicineDr. Zheng Biao, CEO, said:"Non-Hodgkin lymphoma is a malignant tumor of the blood system originating from lymphoid tissue. Although CAR-T products have been approved for clinical treatment of relapsed/refractory non-Hodgkin lymphoma, the overall efficacy remains limited. For this indication, BRL Medicine’s ‘BRL-201’ utilizes Quikin CART."^®The CAR-T product targeting CD19 developed by the platform has the advantages of low cost, short preparation time, simple process, and high safety and efficacy. Currently, it has achieved good results in investigator-initiated clinical trials (IIT) for the treatment of relapsed/refractory non-Hodgkin's lymphoma. After 8 patients received the treatment, no CAR-T-related neurotoxicity or cytokine release syndrome above grade 2 was observed, with a complete response rate exceeding 87%, demonstrating the excellent clinical safety of BRL-201. In summary, as the world’s first non-viral PD1 site-specific integration CAR-T product, BRL Medicine will continue to advance the clinical translation of this product to benefit more cancer patients.

In this regard,Professor Mingyao Liu, founder and chairman of BRL Medicine, also stated:"Very pleased with the CDE's affirmation and recognition, and also thank the CDE for its relentless efforts to protect and promote public health and support new drug development. BRL-201 from BRL Medicine achieves the targeted integration of CAR elements into the genome and the regulatory intervention of endogenous genes in T cells in a single step without using viruses. This can significantly reduce the production cost of CAR-T cells, shorten preparation time, and greatly improve the safety and efficacy of CAR-T cell therapy, benefiting more patients. This provides milestone concept validation for the safety, efficiency, and feasibility of non-viral targeted integration CAR-T technology, and represents the combined application of a new generation of CAR-T and PD1 targeted integration. The approval of this IND also means that BRL Medicine has successfully moved closer to the international first-tier team in gene and cell therapy. As a company committed to becoming a global leader in cell and gene therapy, BRL Medicine will continue to focus on high-quality transformation of gene editing technology in cell and gene therapy applications, and constantly drive innovative product development based on clinical needs and feedback, benefiting patients worldwide with genetic diseases, malignant tumors, and autoimmune diseases."

BRL-201: Safe and Effective, Based on the Next-Generation Quikin CART^®Technology

BRL-201 is a product developed by BRL Medicine using Quikin CART.^®The CAR-T product targeting CD19 developed by the platform is indicated for relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Notably, this is the world's first CAR-T product that targets CD19 with non-viral PD1 site-specific integration. It allows for the production of gene-site integrated CAR-T cells in a single step without using viral vectors, offering advantages such as low cost, short preparation time, simple process, and high safety and efficacy. Traditional CAR-T production primarily relies on viral vectors, which introduces several significant issues: complex production processes, high costs, long preparation cycles, and potential tumorigenic risks. In comparison, BRL Medicine’s BRL-201 effectively addresses the major challenges associated with viral vectors, demonstrating remarkable advantages and potential. Site-specific integration ensures that each CAR sequence is precisely inserted into a specific site in the genome, avoiding the risk of tumorigenesis caused by random insertion, thereby maximizing the safety and efficacy of the CAR-T product. With just one step in preparation, it achieves both sustained CAR expression and regulation of endogenous genes in T cells, significantly reducing the overall preparation time of the CAR-T product. Additionally, the non-viral production method offers potential cost benefits, allowing more patients to benefit.

In the investigator-initiated clinical trial (IIT) of BRL-201 for the treatment of relapsed or refractory non-Hodgkin lymphoma, conducted in collaboration between BRL Medicine and the First Affiliated Hospital of Zhejiang University School of Medicine, 8 patients were treated.Not observedThe neurotoxicity related to CAR-T and cytokine storms above grade 2 have demonstrated that BRL-201 possesses excellent clinical safety.According to the test results, CAR-T cells can rapidly expand and persist for a relatively long time in patients after infusion.After receiving treatment87.5% of patients achieved complete remission (CR), and all patients responded to the treatment, with an objective response rate (ORR) of 100%.To date, the longest cancer-free survival period for patients receiving this CAR-T therapy has exceeded 2 years, and they are still in a state of complete disease remission. Whether treating patients with high PD-L1 expression tumors or under conditions of low CAR-T cell infusion dose and positivity rate, BRL-201 has demonstrated favorable efficacy, proving its powerful tumor-killing ability.This research achievement was published onOn August 31, 2022, officially in the international top academic journalNaturePublished on, this not only represents a significant breakthrough by BRL Medicine in the CAR-T field but also marks the first time in China that such research has been published in a top-tier journal.NatureCAR-T research achievements.A revolutionary breakthrough in technology plus clinical transformation means that BRL Medicine, representing China's gene/cell therapy enterprises, once again leads globally and becomes a new force focusing on revolutionary innovative technologies at a world-class level.(Nature article:https://www.nature.com/articles/s41586-022-05140-y）

Currently, BRL Medicine, as a company focusing on the research and development and transformation of gene therapy and cell therapy drugs, has been adhering to technological innovation. In addition to the non-viral targeted integration CAR-T platform (Quikin CART^®) In addition, a universal cell platform (TyUCell^®) and Enhanced T-cell Platform (HyperTCell^®), etc. technology platforms. Among them, TyUCell^®Mainly utilizing gene editing technology to modify allogeneic immune cells to eliminate immune rejection, ensuring the safety and efficacy of cell products, and achieving the generalization of immune cell therapy products; while HyperTCell^®The platform mainly tackles the world's难题 in solid tumor treatment through gene modification of T cells. In the future, BRL Medicine will continue to overcome industry barriers with a multi-pipeline strategic layout, aiming to solve core issues and bottleneck technical problems encountered in gene and cell therapy, thereby bringing福音 to more patients with genetic diseases, cancer, and autoimmune system diseases.。