BRL-101 / BRL Medicine - LARVOL DELTA

Efficacy and Safety of Brl-101, CRISPR-Cas9-Mediated Gene Editing of the BCL11A Enhancer in Transfusion-Dependent β-Thalassemia (ASH 2023) - P=N/A, P1, P1/2 | "These cells were edited with CRISPR-Cas9 RNP at the +58 erythroid specific enhancer region of the BCL11A gene and then reinfused after the patients had undergone myeloablative busulfan conditioning. Whether genotype was β0/β0 or non-β0/β0, BRL-101 demonstrated clinically meaningful increases in total Hb and HbF which occurred early and have been maintained over time, the safety profile of BRL-101 is generally consistent with that of myeloablative conditioning and autologous hematopoietic stem cell transplant. The updated data with 10 patients reported here are consistent with previous reports and support continued investigation of BRL-101 as a potential functional cure for patients with TDT."

Clinical • Anemia • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Hepatology • Infectious Disease • Transplantation • BCL11A • CD34 • HBB

EFFICACY AND SAFETY OF BRL-101 IN TDT AND SCD (EHA 2025) - P=N/A, P1, P1/2 | "Before BRL-101 infusion, all patients underwent myeloablative conditioning with busulfan. Subsequently, we monitored adverse events (AEs), neutrophil and platelet engraftment, transfusion independence (TI, defined as 60-Day washout period after last red-cell transfusion, no routine transfusions, total Hb continued ≥ 9.0 g/dL) for TDT patients and hemoglobin response (defined as having met the following criteria for at least 6 months: no transfusion and no hydroxyurea use, HbF ≥ 30% Hb with a concurrent Hb increase from baseline ≥ 3.0 g/dL or Hb ≥ 10.0 g/dL without transfusion) for SCD patient.As of February 10, 2025, the median follow-up was 24.1 (range: 17.6-57.4) months for TDT patients,the SCD patient was followed for 95 days... Whether TDT or SCD, one-time infusion of BRL-101 provided clinically meaningful increases in total Hb and HbF, the safety profile of BRL-101 was manageable, resulted in durable efficacy and improved quality of life for TDT..."

Clinical • Genetic Disorders • Hematological Disorders • Hepatology • Infectious Disease • Sickle Cell Disease • BCL11A • CD34 • GATA1

Efficacy and Safety of BRL-101, CRISPR-Cas9-mediated Gene Editing of The BCL11A Enhancer in Transfusion-dependent β-thalassemia and Severe Sickle Cell Disease (ASGCT 2025) - P=N/A, P1, P1/2 | "Before BRL-101 infusion, all patients underwent myeloablative conditioning with busulfan. Subsequently, we monitored adverse events (AEs), neutrophil and platelet engraftment, transfusion independence (TI, defined as 60-Day washout period after last red-cell transfusion, no routine transfusions, total Hb continued ≥ 9.0 g/dL) for TDT patients and hemoglobin response (defined as having met the following criteria for at least 6 months: no transfusion and no hydroxyurea use, HbF ≥ 30% Hb with a concurrent Hb increase from baseline ≥ 3.0 g/dL or Hb ≥ 10.0 g/dL without transfusion) for SCD patient... Whether TDT patients or SCD patient, one-time infusion of BRL-101 provided clinically meaningful increases in total Hb and HbF, the safety profile of BRL-101 was manageable, resulted in durable efficacy and improved quality of life for patients with TDT."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hepatology • Infectious Disease • Sickle Cell Disease • BCL11A • CD34 • GATA1

Clinical Study of BRL-101 in Severe SCD (clinicaltrials.gov) - P=N/A | N=3 | Enrolling by invitation | Sponsor: Bioray Laboratories | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

EFFICACY AND SAFETY OF BRL-101, CRISPR-CAS9-MEDIATED GENE EDITING OF THE BCL11A ENHANCER IN TRANSFUSION-DEPENDENT ΒETA-THALASSEMIA (EHA 2024) - P=N/A, P1, P1/2 | "These cells were edited with CRISPR-Cas9 RNP at the +58 erythroid specificenhancer region of the BCL11A gene and then reinfused after the patients had undergone myeloablativebusulfan conditioning. Whether genotype was β0/β0 or non-β0/β0, BRL-101 demonstrated clinically meaningful increases in total Hband HbF which occurred early and have been maintained over time, the safety profile of BRL-101 is generallyconsistent with that of myeloablative conditioning and autologous hematopoietic stem cell transplant. Theupdated data with 15 patients reported here are consistent with previous reports and support continuedinvestigation of BRL-101 as a potential functional cure for patients with TDT."

Clinical • Anemia • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Hepatology • Infectious Disease • Transplantation • BCL11A • CD34

Clinical Study of BRL-101 in Severe SCD (clinicaltrials.gov) - P=N/A | N=1 | Not yet recruiting | Sponsor: Bioray Laboratories | Initiation date: Apr 2024 ➔ Sep 2024

Trial initiation date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Efficacy and Safety of BRL-101, CRISPR-Cas9-Mediated Gene Editing of The BCL11A Enhancer in Transfusion-Dependent β-Thalassemia (ASGCT 2024) - P=N/A, P1, P1/2 | "These cells were edited with CRISPR-Cas9 RNP at the +58 erythroid specific enhancer region of the BCL11A gene and then reinfused after the patients had undergone myeloablative busulfan conditioning. Whether genotype was β0/β0 or non-β0/β0, BRL-101 demonstrated clinically meaningful increases in total Hb and HbF which occurred early and have been maintained over time, the safety profile of BRL-101 is generally consistent with that of myeloablative conditioning and autologous hematopoietic stem cell transplant. The updated data with 15 patients reported here are consistent with previous reports and support continued investigation of BRL-101 as a potential functional cure for patients with TDT."

Clinical • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hepatology • Infectious Disease • Transplantation • BCL11A • CD34 • HBB

Clinical Study of BRL-101 in Severe SCD (clinicaltrials.gov) - P=N/A | N=5 | Not yet recruiting | Sponsor: Bioray Laboratories

New trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Long-term Follow-up Study of BRL-101 for TDT (clinicaltrials.gov) - P=N/A | N=45 | Not yet recruiting | Sponsor: Bioray Laboratories

New trial • Beta-Thalassemia • Genetic Disorders

Clinical Study on the Safety and Efficacy of BRL-101 in the Treatment of Sickle Cell Disease (clinicaltrials.gov) - P=N/A | N=5 | Not yet recruiting | Sponsor: Bioray Laboratories

New trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Clinical Study of BRL-101 in the Treatment of Sickle Cell Disease (clinicaltrials.gov) - P=N/A | N=5 | Not yet recruiting | Sponsor: Bioray Laboratories

New trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Safety and Efficacy Evaluation of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia (clinicaltrials.gov) - P1 | N=9 | Enrolling by invitation | Sponsor: Bioray Laboratories | Recruiting ➔ Enrolling by invitation | Phase classification: P1/2 ➔ P1

Enrollment status • Phase classification • Beta-Thalassemia • Genetic Disorders

Porton Advanced and BRL Medicine Build Strategic Partnership to Accelerate Commercialization of Gene and Cell Therapies (PRNewswire) - "...Porton Advanced Solutions (Porton Advanced) announced a strategic partnership with BRL Medicine Inc. (BRL Medicine). This collaboration will enhance the cell and gene therapy pipelines from BRL Medicine from clinical trials to further expedite the commercialization of innovative therapies...Through this strategic partnership, the two companies will work together to accelerate the commercialization of gene and cell therapy drugs, making innovative treatments accessible to a wider range of patients....Dr. Zheng hopes that this diversified collaboration will expedite the clinical translation and implementation of multiple innovative drugs benefiting patients worldwide who suffer from genetic diseases, malignant tumors, and autoimmune disorders."

Licensing / partnership • Genetic Disorders • Immunology • Oncology

AN UPDATED FOLLOW-UP OF BRL-101, CRISPR-CAS9-MEDIATED GENE EDITING OF THE BCL11A ENHANCER FOR TRANSFUSION-DEPENDENT BETA-THALASSE (EHA 2023) - P=N/A | "All 6 patients with different genotypes achieved transfusion independence, including the patients with the most severe β0/β0 phenotype. After BRL-101 infusion, the levels of total Hb and HbF increased significantly, and gene editing is retained in multiple lineages of HSPCs. The safety profile of BRL-101 is generally consistent with mobilization, apheresis, myeloablation and autologous hematopoietic stem cell transplantation."

Anemia • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Infectious Disease • Pediatrics • Respiratory Diseases • Thrombocytopenia • Transplantation • BCL11A • CD34 • HBB

An Updated Follow-Up of BRL-101, CRISPR-Cas9-Mediated Gene Editing of the BCL11A Enhancer for Transfusion-Dependent β-thalassemia (ASGCT 2023) - P=N/A | "All 6 patients with different genotypes achieved transfusion independence, including the patients with the most severe β0/β0 phenotype. After BRL-101 infusion, the levels of total Hb and HbF increased significantly, and gene editing is retained in multiple lineages of HSPCs. The safety profile of BRL-101 is generally consistent with mobilization, apheresis, myeloablation and autologous hematopoietic stem cell transplantation."

Anemia • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Infectious Disease • Pediatrics • Respiratory Diseases • Thrombocytopenia • Transplantation • BCL11A • CD34 • HBB

Safety and Efficacy Evaluation of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia (clinicaltrials.gov) - P1/2 | N=9 | Recruiting | Sponsor: Bioray Laboratories | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders

Safety and Efficacy Evaluation of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia (clinicaltrials.gov) - P1/2 | N=9 | Not yet recruiting | Sponsor: Bioray Laboratories

New P1/2 trial • Beta-Thalassemia • Genetic Disorders