On May 16, 2023, Shanghai BRL Medicine Inc. (hereinafter referred to as "BRL Medicine") announced that the gene therapy product for transfusion-dependent β-thalassemia developed based on the self-developed hematopoietic stem cell platform (ModiHSC®) The research on "BRL-101 Autologous Hematopoietic Stem and Progenitor Cell Injection" (pipeline code: BRL-101) was successfully selected for the 26th ASGCT Annual Meeting and the 28th EHA Annual Meeting, will present its latest clinical progress data in an oral presentation. It is worth mentioning that this is the first time that BRL Medicine has disclosed the results of early clinical research on BRL-101 update at an international conference .

Significant clinical efficacy of BRL-101: once treatment, life-long cure

BRL-101 is a gene therapy product developed based on the hematopoietic stem cell platform (ModiHSC^®) independently developed by BRL Medicine, and its indication is transfusion-dependent β-thalassemia. ModiHSC® mainly uses the gene editing system to genetically modify the patient's hematopoietic stem cells, and the modified hematopoietic stem cells are reinfused into the patient's body, and the modified cell population is rebuilt through self-renewal and differentiation, so as to achieve the purpose of treating blood system diseases.

To be presented at the 26th ASGCT Annual Meeting and the 28th EHA Annual Meeting will be the results of an early clinical study of BRL-101, a study conducted in China to evaluate "autologous hematopoietic stem cells reactivated by gamma globin Safety and effectiveness of transplantation in the treatment of β-thalassemia major (thalassemia)" was an IIT clinical study initiated by the investigator. Thalassemia is an inherited hemolytic disease that is prevalent worldwide and is the largest single-gene mutation genetic disease. Thalassemia patients are mainly due to the fragment deletion or mutation of the HBB gene, resulting in a severe lack of functional β-globin, causing severe anemia and related complications. The genetically sustained expression of fetal hemoglobin (HbF) can relieve the symptoms of anemia. Therefore, in this clinical study, the reduction of BCL11A expression through CRISPR/Cas9-mediated mutation of the BCL11A erythrocyte enhancer can induce the expression of fetal γ-hemoglobin. It is a feasible therapeutic strategy for the treatment of transfusion-dependent β-thalassemia (TDT).

In this IIT clinical study jointly conducted by BRL Medicine, Xiangya Hospital Central South University and The 923 Hospital of the Chinese People's Liberation Army, a total of 6 patients aged 5-15 were enrolled, and all of them were cured. , including four thalassemia major patients with the β0/β0 phenotype. The results of clinical treatment showed that after all patients received gene-edited HSC transplantation, the number of red blood cells and the overall HbF level began to increase significantly, and two-thirds of the patients got rid of blood transfusion dependence within 2 months, and HbF reached the normal range. And during the whole course of treatment, myeloablative pretreatment-related toxicity was mild, and no adverse events such as severe infection related to drugs occurred. In addition, CRISPR/Cas9-edited autologous hematopoietic stem and progenitor cells (HSPCs) were transplanted and differentiated into multiple gene-editing cell lines. During the follow-up period, the editing efficiency of the patients' peripheral blood mononuclear cells (PBMCs) increased to more than 60%. This study shows that BRL Medicine BRL-101 gene therapy is more efficient, convenient and safe. It has the advantages of good targeting, high safety, wide range of action, and significant therapeutic effect. It can be cured for life with one treatment, and it is expected to become a more accessible therapy for the masses. At present, BRL-101 has been approved by the Center for Drug Evaluation (CDE) of the State Drug Administration of China in August 2022. In October of the same year, the multi-center phase 1/2 registration clinical trial of BRL-101 was officially launched.