Bioray Biotech Achieves Breakthrough with Next-Gen Quikin CART® Platform, Files for IPO

Leading the World: China's CAR-T Achievements First Published in Nature

ShanghaiSeptember 1, 2022/PR Newswire/ -- September 1, 2022,BRL Medicine Inc., Focusing on Gene and Cell Therapy(hereinafter referred to as "BRL Medicine") announced its collaboration with East China Normal University and the First Affiliated Hospital of Zhejiang University School of Medicine.Non-viral Targeted IntegrationCAR-T Technology (Quikin CART^®）The research成果 was officially published in the international top academic journal on August 31.NaturePublished on.It is worth mentioning that this is the first publication in a top-tier journal in China.NatureCAR-T Research Achievements.This not only represents a significant breakthrough for BRL Medicine in the CAR-T field but also signifies that BRL Medicine has successfully advanced to the forefront of the international gene and cell therapy sector.

Nature Publishes Article

(Link: https://www.nature.com/articles/s41586-022-05140-y)

Quikin CART^®It is a non-viral targeted integration CAR-T platform with independent intellectual property rights built by BRL Medicine.Can be achieved without the use of viral vectors, throughOne-step preparationCAR-T cell products with genomic site-specific integration have the advantages of low cost, short preparation time, simple process, and high safety and efficacy. In May 2020, a trial was initiated at the First Affiliated Hospital of Zhejiang University School of Medicine.The World's First"Clinical Trial of PD1 Knockout Non-Viral Site-Specific Integration CD19-CART Cell Therapy for Relapsed and Refractory Non-Hodgkin Lymphoma"In China, the product demonstrated outstanding clinical safety and efficacy,The first patient to receive the treatment has been in complete remission ever since.(CR) exceeds 2 years.

Quikin CART^®All-New Upgrade, Faster and More Efficient

The preparation of traditional CAR-T products is mainly achieved through viral vectors,This will bring the following issues:

1. Since the virus uses a random insertion method to integrate the CAR sequence into the cell genome, it may alter the expression of normal genes; therefore,There is a potential risk of tumorigenicity,And the uniformity of CAR-T products prepared in this way is very low; secondly, from the perspective of the production process, traditional CAR-T products...The preparation time is relatively long.The preparation time for several CAR-T products currently on the market is approximately 15-28 days, which greatly increases the waiting time for patients to receive medication and also means that such CAR-T products cannot be used for patients with very rapidly progressing tumors.Greatly increased production costs,Currently, several CAR-T products that have been launched in the U.S. market are priced between $373,000 and $475,000, equivalent to RMB 2.562 million to 3.263 million. The first CAR-T product approved in China in 2021 was also priced at a staggering RMB 1.2 million, setting a record for the pricing of domestically produced drugs. Such high prices are unaffordable for many families.

By comparison,Quikin CART^®Can effectively solve several major problems brought by the use of viral vectors, demonstrating significant advantages.Targeted integration allows each CAR sequence to be precisely inserted into a specific site of the genome, avoiding the risk of tumorigenicity caused by random insertion, and maximizing the safety and efficacy of CAR-T products. With just one step of preparation, it can simultaneously achieve continuous CAR expression and regulation of endogenous genes in T cells, significantly shortening the entire CAR-T production process, allowing more patients to benefit. Additionally, using a non-viral production process can greatly reduce the high costs associated with the use of viral vectors.

Breaking the Shackles of Relapse and Refractory Challenges, Igniting Hope for More Patients

Non-Hodgkin lymphoma is a malignant tumor of the hematologic system that originates in lymphoid tissue, accounting for 80%-90% of all lymphomas. Although patients often achieve remission after initial treatment, recurrence frequently occurs thereafter. Despite the approval of CAR-T products for the clinical treatment of relapsed or refractory non-Hodgkin lymphoma, the overall efficacy remains limited. The PD-L1/PD1 signaling pathway is an important immune checkpoint that suppresses T-cell function, and several studies have reported that knocking out PD1 can effectively enhance the function of CAR-T cells.

Therefore,BRL Medicine UtilizesQuikin CART^®The platform has developed a targeted CD19 non-viral PD1 site-specific integration CAR-T product (BRL-201).In preclinical studies, compared with CAR-T cells using lentiviral infection and gene-editing technology to knock out PD1, BRL-201 demonstrated stronger and more durable killing effects on both high and low PD-L1 expressing tumor cells, significantly improving the survival rate of mice. Mechanistic studies show that Quikin CART^®The technology itself can significantly increase the proportion of memory T cells, and the downregulation of PD1 expression can effectively enhance the anti-tumor immune function of T cells. In the clinical trial of BRL-201 for the treatment of relapsed and refractory non-Hodgkin's lymphoma, no CAR-T-related neurotoxicity or cytokine release syndrome above grade 2 was observed in the 8 patients treated, demonstrating the excellent clinical safety of BRL-201. According to the test results, CAR-T cells can rapidly expand and persist for a relatively long time after infusion into patients.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 time for patients receiving this CAR-T therapy has exceeded 2 years, and they are still in a state of complete disease remission.It is worth mentioning that,Whether it is forIn the treatment of patients with high PD-L1 expression tumors, even under conditions of low CAR-T cell infusion dose and positivity rate, BRL-201 still demonstrated good efficacy, proving its powerful tumor-killing ability.

BRL-201 Demonstrates Excellent Safety and Efficacy in Clinical Trials

It is worth mentioning that this achievement has also been recognized by the University of California.Professor Justin Eyquem andNatureHighly praised by senior editor Victoria Aranda:"Comprehensive and systematic preclinical research has successfully developed non-viral site-specific integration CAR-T therapy, and reportedThe FirstClinical Trial Results of PD1-Downregulated Site-Specific CAR-T Cells. Researchers observed a high proportion of complete tumor remission in clinical treatments, with no severe toxic side effects found. This encouraging outcome demonstrates that this CAR-T therapy possesses excellent clinical safety and efficacy.The researchers also demonstrated the feasibility of non-viral site-specific integration T-cell therapy in clinical applications. This technological innovation lays a solid foundation for the future development of more gene-targeted modified CAR-T therapies and plays an important role in promoting the field.

Regarding this collaboration, the principal investigator of this clinical study (PI) Huang He, President of the First Affiliated Hospital of Zhejiang University School of Medicine, said:"BRL Medicine's non-viral targeted integration CAR-T product has demonstrated excellent safety and efficacy in clinical treatment, bringing hope to lymphoma patients. Our medical team is delighted to see patients recover and return home. In addition to the first cancer patient who has survived cancer-free for over two years, more than twenty other patients have participated in this program and achieved good results after receiving CAR-T cell therapy. Currently, BRL Medicine's CAR-T cell therapy is highly effective for specific types of lymphoma. We look forward to BRL Medicine developing more and better products targeting a wider range of indications to benefit more cancer patients in the future."

Professor Mingyao Liu, founder and chairman of BRL Medicine, also stated,"Two years have passed, and there are no cancer cells in the patient's body. The CAR-T cells are still patrolling and monitoring lymphoma, bringing long-lasting benefits to the patient. These durable results represent a milestone scientific achievement. Although CAR-T products for treating relapsed/refractory lymphoma are already on the market, CAR-T therapy still awaits greater breakthroughs. Quikin CART^®The technology 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 significantly reduces the production cost of CAR-T cells, shortens the preparation time of CAR-T cells, makes CAR-T cells safer, more powerful, and effective, allowing more patients to benefit. In the future, BRL Medicine will always be "patient-centered" and actively promote the development of the CGT industry, bringing good news to more patients with genetic and tumor diseases.

BRL MedicineThe Innovation of CAR-T Technology is Diversified, and the Future is Promising

For the Chinese market, the exploration of the path from technological innovation to industrialization and commercialization in cell therapy has just begun., so while seeing the future development prospects, it is also necessary toRecognizing the current dilemmas and challenges in CAR-T cell therapy to proactively implement technological advancements.

Quikin CART^®The technical inventor, the first author and co-corresponding author of the paper, Dr. Zhang Jiqin, Vice President of R&D at BRL Medicine and Associate Researcher at the School of Life Sciences, East China Normal University, said:"In recent years, the continuous maturation and development of CRISPR/Cas9 gene editing technology have inspired us to consider its application in CAR-T therapy. Through an in-depth analysis of existing CAR-T technologies and a systematic review of current issues in the CAR-T treatment field, we realized that using gene editing technology to prepare non-viral site-specific integrated CAR-T cells is a direction with great potential. After extensive method exploration and condition optimization, we have established a mature Quikin CART platform."^®Technology Platform. Quikin CART^®The technology can simultaneously achieve stable CAR expression and endogenous gene regulation in a single step without the use of viral vectors, allowing for more precise modifications of CAR-T cells. As a result, it possesses many advantages that current CAR-T technologies lack. We are hopeful to leverage this next-generation CAR-T technology to develop more successful and effective CAR-T products to benefit more patients. Meanwhile, with the recent development of emerging biotechnologies such as gene editing, we believe that more advanced and powerful technology platforms will be developed in the future. We will also strive to make more breakthroughs in technological iteration, with the aim of bringing more hope to the clinical treatment of diseases.

Currently, BRL Medicine is addressing the technical bottlenecks of CAR-T therapy, besidesNon-viral Site-specific Integration CAR-T Platform (Quikin CART^®）"In addition, it has also built"Universal Cell Platform (TyUCell)"^®）"AndEnhanced T-cell Platform (HyperTCell^®）"...and other technical platforms. Among them, TyUCell^®Mainly using gene editing technology to transform allogeneic immune cells to eliminate immune rejection, ensuring the safety and efficacy of cell products, and realizing the generalization of immune cell therapy products; while HyperTCell^®The platform mainly tackles the world's难题 in solid tumor treatment through genetic modification of T cells.

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. It not only continuously overcomes industry barriers for multi-pipeline strategic layout but also is committed to developing world-leading gene editing tools to obtain core technologies with independent intellectual property rights. The current research achievements have been published in internationally renowned academic journals.Nature、Nature Medicine、Nature Biotechnology、Nature Cell Biology、Cell Research Published multiple academic papers, while BRL Medicine has applied for and obtained several invention patents, and has carried out a global layout. In the future, it aims to solve core issues and bottleneck technical problems in gene and cell therapy, thereby bringing good news to more patients with genetic and tumor diseases, benefiting humanity.。