BRL-201 / BRL Medicine - LARVOL DELTA

Long term remission and survival in patients with relapsed or refractory non-Hodgkin lymphoma after treatment of brl-201, a CRISPR-based non-viral PD-1 locus specifically integrated anti-CD19 CAR-T cells: 4-year follow-up of a first-in-human phase I study (ASH 2025) - P=N/A, P1 | "The eligible participants underwent leukapheresis followed by lymphodepletion regimen withcyclophosphamide (500mg/m², D-3 to -2) and fludarabine (30mg/m², D-4 to -2) before BRL-201 infusion.Three dose levels (2.0, 4.0, and 6.0 × 10⁶ CAR-positive cells/kg) were designed with a single infusion usinga 3+3 dose-escalation schema...For all treated patients, mild cytokine release syndrome (CRS) (grade 1/2) occurred in66.7% (14/21) of patients, with one requiring tocilizumab...With a median 55.2 month follow-up, BRL-201 demonstrated durable and deep responses. One-third ofpatients remained long-term survival for more than 4 years with disease-free remission. The estimated 5-year OS rate with CR patients was 50.0%."

CAR T-Cell Therapy • Clinical • First-in-human • IO biomarker • P1 data • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • PD-1 • PD-L1

2022-BRL-201: The Safety and Efficacy of BRL-201 in the Treatment of r/r B Lymphocyte Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Bioray Laboratories | Trial completion date: Mar 2024 ➔ Jan 2027 | Trial primary completion date: Jan 2024 ➔ Nov 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Long Term Follow-up Results of Brl-201 Phase I Study, a Crispr-Based Non-Viral PD-1 Locus Specific Integrated Anti-CD19 CAR-T Cells in Treating Relapsed or Refractory Non-Hodgkin's Lymphoma (ASH 2023) - P=N/A, P1 | "Adult patients with r/r B-NHL underwent leukapheresis and a lymphodepletion chemotherapy with cyclophosphamide (500mg/m2, D -3 to -2) and fludarabine (30mg/m2, D -4 to -2) before BRL-201 infusion...14 patients (66.7%) experienced grade 1-2 cytokine release syndrome (CRS) and only one patient received tocilizumab... Over a median follow up of 29 months, BRL-201 was demonstrated durable response with a high median PFS of 20.8 months and 12-month OS rate of 76.2%. The median OS was not reached yet for responding patients, and the safety profile was manageable. More data will be collected to prove the value of clinical usage of BRL-201."

CAR T-Cell Therapy • IO biomarker • P1 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • PD-1 • PD-L1

LONG TERM FOLLOW-UP RESULTS OF BRL-201 PHASE I STUDY, A CRISPR-BASED NON-VIRAL PD-1 LOCUS SPECIFIC INTEGRATED ANTI-CD19 CAR-T CELLS IN TREATING RELAPSED OR REFRACTORY NON-HODGKIN'S LYMPHOMA (EHA 2024) - P=N/A, P1 | "Participantsunderwent leukapheresis followed by lymphodepletion chemotherapy with cyclophosphamide (500mg/m², D-3 to -2) and fludarabine (30mg/m², D-4 to -2) before BRL-201 infusion...7%(14/21) of patients, with onerequiring tocilizumab... With a median 38. 0 month follow-up, BRL-201 demonstrated durable responses, high median PFS (19. 5months), and a 12-month OS rate of 76."

CAR T-Cell Therapy • P1 data • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PD-1

Long term follow-up results of BRL-201 phase I study, a CRISPR-based non-viral PD-1 locus specific integrated anti-CD19 CAR-T cells in treating relapsed or refractory non-Hodgkin's lymphoma. (ASCO 2024) - P=N/A, P1 | "Participants underwent leukapheresis followed by lymphodepletion chemotherapy with cyclophosphamide (500mg/m², D-3 to -2) and fludarabine (30mg/m², D-4 to -2) before BRL-201 infusion...Mild CRS (grade 1-2) occurred in 66.7%(14/21) of patients, with one requiring tocilizumab... With a median 37.0 month follow-up, BRL-201 demonstrated durable responses, high median PFS (19.5 months), and a 12-month OS rate of 76.2%. The median OS for responders has not yet been reached. The safety profile was manageable, highlighting the clinical potential of BRL-201."

CAR T-Cell Therapy • P1 data • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PD-1

CRISPR-Based Anti-CD19 CAR T-Cell Therapy Is Safe and Effective in Relapsed/Refractory NHL (OncLive) - P1 | N=20 | NCT04213469 | Sponsor: Bioray Laboratories | "The CRISPR-based nonviral PD-1 locus-specific integrated CD19-directed CAR T-cell therapy BRL-201 was associated with a manageable safety profile and elicited early indications of efficacy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to findings from a first-in-human phase 1 trial (NCT04213469), which were presented during the 2023 SITC Annual Meeting. Furthermore, at a data cutoff of May 17, 2023, and a median follow-up of 29.0 months (range, 21.5-36.2), all patients responded to BRL-201 infusion, 85.7% of whom achieved a complete response (CR) and 14.3% of whom achieved a partial response (PR). Among the patients who achieved and maintained a CR, 7 had ongoing responses at the data cutoff."

P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The Safety and Efficacy of BRL-201 in the Treatment of r/r B Lymphocyte Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Bioray Laboratories | Not yet recruiting ➔ Recruiting | Phase classification: P1/2 ➔ P1

CAR T-Cell Therapy • Enrollment open • Phase classification • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

2019-CAR-00CH1: PD1-CD19-CART in Patients With r/r B-cell Lymphoma (clinicaltrials.gov) - P=N/A | N=20 | Completed | Sponsor: Bioray Laboratories | Active, not recruiting ➔ Completed | Trial completion date: Apr 2023 ➔ Nov 2023

Trial completion • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

High safety and efficacy of CRISPR-Based non-viral PD1 locus specific Integrated Anti-CD19 CAR-T cells (BRL-201) in treating relapsed or refractory non-Hodgkin’s lymphoma: first-in-human phase I study (SITC 2023) - P=N/A | "Methods Adult patients with r/r B-NHL underwent leukapheresis and a lymphodepletion chemotherapy with cyclophosphamide (500mg/m2, D -3 to -2) and fludarabine (30mg/m2, D -4 to -2) before BRL-201 infusion...7%) experienced grade 1–2 cytokine release syndrome (CRS) and only one patient received tocilizumab...2%, and a manageable safety profile. These data continues supporting the compelling clinical benefit-risk profile of BRL-201for r/r B-NHL patients."

CAR T-Cell Therapy • Clinical • P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PD-1

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

High Safety and Efficacy of CRISPR-Based Non-Viral PD-1 Locus Specific Integrated Anti-CD19 CAR-T Cells (BRL-201) in Treating Relapsed or Refractory Non-Hodgkin's Lymphoma: First-in-Human Phase I Study (ASH 2022) - P=N/A | "Adult patients with r/r B-NHL underwent leukapheresis and a lymphodepletion chemotherapy with cyclophosphamide (500mg/m2 , D -3 to -2) and fludarabine (30mg/m2, D -4 to -2) before BRL-201 infusion...Fourteen patients (66.7%) experienced low grade (1 or 2) cytokine release syndrome (CRS) and only one patient received tocilizumab... This is a first-in-human study of a novel type of non-viral genome specific targeted CAR-T cells in treating r/r B-NHL. As a two-in-one approach without using virus, the manufacturing procedure is simplified, with shortened preparation time, reduced production expenses. Low incidence and mild grade of CRS/ICANS preliminarily showed the high safety of BRL-201."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • PD-1 • PD-L1

The Safety and Efficacy of BRL-201 in the Treatment of r/r B Lymphocyte Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=18 | Not yet recruiting | Sponsor: Bioray Laboratories

CAR T-Cell Therapy • New P1/2 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

PD1-CD19-CART in Patients With r/r B-cell Lymphoma (clinicaltrials.gov) - P=N/A | N=20 | Active, not recruiting | Sponsor: Bioray Laboratories | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2022 ➔ Apr 2023

Enrollment closed • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19