Bioray Biotech Announces CDE Approval of IND for BRL-101, a Gene Therapy for Transfusion-Dependent β-Thalassemia

On August 16, 2022, BRL Medicine Inc. (hereinafter referred to as "BRL Medicine"), a company focused on gene and cell therapy, announced,The IND application for BRL Medicine's gene therapy product "BRL-101 Autologous Hematopoietic Stem and Progenitor Cell Injection," intended for transfusion-dependent β-thalassemia, has officially received approval from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration!

CDE Official Website Public Information

For the approval of this β-thalassemia gene therapy product IND application,Professor Mingyao Liu, founder and chairman of BRL Medicine, stated,"We are very pleased that the clinical trial application for BRL-101 has been approved by the CDE. The smooth approval of the IND is inseparable from the hard work of all departments of the company. We also want to express our special thanks to the CDE for their high recognition of our efforts, as well as for their continuous dedication to protecting and promoting public health and supporting new drug development. The approval of this IND not only marks the formal entry of the company into the clinical stage but also signifies that BRL Medicine has successfully joined the international first-tier team in gene and cell therapy. As a company committed to becoming a global leader in cell and gene therapy, we will continue to focus on the high-quality transformation of gene-editing technology applications in cell and gene therapy in the future. We will always put patients at the center and continuously advance the progress of various pipeline R&D products, bringing more breakthrough therapies to patients with genetic diseases and malignant tumors in China and even around the world."

BRL Medicine's BRL-101 is primarily indicated for β-thalassemia, based on BRL Medicine's self-developed hematopoietic stem cell platform (ModiHSC).^®) Gene therapy product developed by BRL Medicine Inc.

β-Thalassemia is a hereditary hemolytic disease that is prevalent worldwide and is one of the most common monogenic disorders. Due to a severe deficiency of functional β-globin, a significant number of patients require regular blood transfusions to survive, leading to transfusion-dependent thalassemia (TDT). With limited blood resources and the high cost of iron chelators, only a portion of TDT patients in China can maintain standardized transfusion and iron chelation therapy, resulting in a concerning survival status. The survival rate of TDT patients is significantly lower than in developed countries.

According to the latest data from the "China Thalassemia Blue Book (2020)" published in May 2021, thalassemia gene carriers account for approximately 345 million people globally, with about 30 million carriers in mainland China. The number of patients with severe and intermediate thalassemia is around 300,000, increasing at an annual rate of about 10%. Currently, in traditional therapies for thalassemia, hematopoietic stem cell transplantation is the only method that can completely cure β-thalassemia, but it is expensive, and matching is extremely difficult, with only a small number of patients able to receive transplants. If autologous hematopoietic stem cells can be genetically corrected and then reinfused into the patient's body, it would address the issues of insufficient sources of hematopoietic stem cells and the difficulty of matching. Advances in CRISPR gene editing technology provide the possibility for this treatment strategy.

BRL Medicine ModiHSC^®Mainly using gene editing systems to genetically modify patients' hematopoietic stem cells, the modified hematopoietic stem cells are reinfused into the patient’s body. Through self-renewal and differentiation, the modified cell population is rebuilt, thereby achieving the goal of treating hematological diseases. Currently, BRL Medicine utilizes its self-developed hematopoietic stem cell platform based on gene editing technology (ModiHSC).^®) has achieved good results in the treatment of β0/β0 type severe thalassemia patients in investigator-initiated clinical trials, and has successfully helped multiple β-thalassemia patients across China摆脱输血依赖.

Since July 2020, BRL Medicine has collaborated with Dr. Bin Fu, Deputy Chief Physician of the Hematology Department at Xiangya Hospital of Central South University, and Director Xinhua Zhang from the 923rd Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army to treat multiple patients with β-thalassemia through gene therapy. These patients have been cured and discharged, no longer dependent on blood transfusions, and are now living a healthy life. Among them, two patients from Xiangya Hospital have been free from blood transfusions for over two years. This marks the first time in Asia that gene editing technology has been used to treat thalassemia and the world’s first successful case of treating severe β0/β0 type thalassemia using CRISPR gene editing technology.On August 4, 2022, the results of this investigator-initiated clinical trial were published in a top international medical academic journal.Nature Medicine(Impact Factor: 87.241). This event also represents a breakthrough achievement in clinical research for gene editing therapy in China.

It is also worth mentioning that the outstanding achievements of BRL Medicine in the field of thalassemia have been selected for inclusion in the treatment section of the second edition of the *Blue Book of Thalassemia Prevention and Control in China* (2020). Moreover, compared to other β-thalassemia gene therapies that often cost tens of millions, BRL Medicine's hematopoietic stem cell gene therapy is more efficient, convenient, and safer. It boasts advantages such as excellent targeting, high safety, broad scope of action, and significant therapeutic effects, achieving lifelong cure with a single treatment. Additionally, the cost can be significantly reduced, making it a potentially more accessible therapy for the general public.

Focusing on β-thalassemia gene therapy, BRL Medicine will further expand the age of study subjects for this project to 35 years old in the future, which is expected to benefit the "long-standing difficult group" in the thalassemia transplantation field—elderly patients and those without matching donors.

Moreover, BRL Medicine, a cell and gene therapy company with the mission of "leading innovation through gene editing, developing breakthrough therapies, and benefiting all humanity," has established a pipeline layout logic centered on gene editing technology. It has created five proprietary technology platforms: a gene editing technology innovation platform, a hematopoietic stem cell platform, a non-viral targeted integration CAR-T platform, a universal cell platform, and an enhanced T-cell platform. Among these, BRL Medicine utilizes its proprietary non-viral targeted integration CAR-T platform (Quikin CART).^®), breakthrough results have been achieved in the investigator-initiated clinical trial using this platform product to treat relapsed/refractory non-Hodgkin lymphoma.

It can be said that BRL Medicine has been adhering to technological innovation, not only continuously overcoming industry barriers for multi-target strategic layout but also committing to the development of internationally leading gene-editing tools to acquire core technologies with independent intellectual property rights. Currently, the research achievements have been published in internationally renowned academic journals.Nature Biotechnology、Nature Cell Biology、Cell ResearchPublished multiple academic papers, while BRL Medicine has applied for and obtained several invention patents, and has carried out global layout. In the future, it aims to solve core issues and bottleneck technical problems encountered in gene and cell therapy, thereby actively promoting the development of the CGT industry, hoping to bring good news to more patients with genetic diseases and cancer, benefiting humanity!

BRL Medicine Inc. is committed to becoming a global leading cell and gene pharmaceutical company in the era of new commercial civilization. With the mission of "leading innovation through gene editing, developing breakthrough therapies, and benefiting all humanity," BRL Medicine has relied on its self-developed research center and the "Shanghai Gene Editing and Cell Therapy Research Center" co-built with universities. Over the past five years, it has generated more than 100 patent achievements. Five projects are currently undergoing investigator-initiated clinical trials at eight renowned hospitals, with multiple projects entering the IND application stage. Among these, projects such as gene-editing therapy for β-thalassemia, non-viral PD1 targeted integration CAR-T, and UCART have achieved excellent clinical outcomes, demonstrating global leadership.Nature、Nature Medicine、Nature biotechnology...published multiple academic papers in well-known academic journals. 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. It also owns a 7,000-square-meter GMP pilot production base and a nearly 200-person operations team, effectively 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. With an open, sharing, and win-win attitude, BRL Medicine is working with global innovative biopharmaceutical ecosystem companies to accelerate the transformation and implementation of innovative drugs for the benefit of patients with genetic diseases and malignant tumors worldwide!