Meta10-19 / Leman Biotech - LARVOL DELTA

Ultralow-Dose Interleukin 10-Expressing Chimeric Antigen Receptor T Cells in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P1 | "Following lymphodepletion with fludarabine and cyclophosphamide, patients received META 10-19 at dose levels of 2 × 103, 5 × 103 or 2 × 104 CAR T cells/kg. Further investigation in larger cohorts is warranted. ClinicalTrials.gov Identifier: NCT06120166."

Clinical • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • IL10

1‰ Regular Dose of Metabolically Armored CD19 CAR-T Cells Induces Robust In Vivo Expansion and Complete Remission in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Patients (ASH 2024) - P1 | "The administration followed a standard lymphodepletion regimen involving 30 mg/m2/day fludarabine for 3 days, and 300 mg/m2/day cyclophosphamide for 3 days...Summary : This clinical trial of Meta10-19 has shown encouraging preliminary efficacy even at super tiny doses (1‰ doses of commercial products) with remarkable in vivo expansion ability. These low doses further reduced hematological toxicity in treated patients, significantly improving safety profiles. Ongoing investigations with larger patient cohorts and extended follow-up periods aim to provide further insight into the efficacy and safety parameters."

CAR T-Cell Therapy • Preclinical • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD19 • CD8 • IL10

META 10-19 in Patients With Relapsed/Refractory Autoimmune Hemolytic Anemia (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P1 trial • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Phase 1 study of META 10-19, an IL-10-expressing, anti-CD19 CAR T cell product in patients with high-risk DLBCL. (ASCO 2026) - P1 | "This first-in-human trial of META 10-19, an IL-10 expressing, anti-CD19 CAR T-cell product, for the treatment of relapsed/refractory DLBCL has exhibited manageable safety profile and durable efficacy at ultra-low doses in patients with high-risk features. Studies evaluating larger cohorts and longer follow-up are ongoing."

CAR T-Cell Therapy • Clinical • First-in-human • P1 data • B Cell Lymphoma • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Epilepsy • Hematological Disorders • Neutropenia • Thrombocytopenia • IL10

Metabolically armed CD19 CAR-T cells for safe and effective treatment of relapsed or refractory CD19+ B cell hematological malignancies at extremely low doses (AACR 2024) - P1 | "Patients in 3 dose cohorts (2.0 × 104, 5.0 × 104, or 1.0 × 105 CAR-T cells/kg, corresponding to 1%, 2.5%, or 5% doses of commercialized CAR-T infusion) underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine before Meta10-19 infusion. Preliminary findings suggest that Meta10-19 infusion exhibits promising breakthrough efficacy and safety profile, and active enrollment is ongoing to validate the initial results."

CAR T-Cell Therapy • Late-breaking abstract • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • IL10

Ultra-low-dose IL-10-expressing CAR-T cells achieve high efficacy in R/R DLBCL: An update analysis (ASH 2025) - P1 | "Followinglymphodepletion with fludarabine and cyclophosphamide, patients received Meta10-19 infusion at 3dose levels: 2×103, 5×103, or 2×104 CAR-T cells/kg (corresponding to 1‰ ~ 1% of conventional CAR-Tregimens). From November 16, 2023 to October 20, 2024, 12 patients were enrolled, of whom 11 receivedtreatment, and 10 evaluable for efficacy, with 1 succumbing before efficacy evaluation. Among theseevaluable patients, the objective responses rate was 100%, comprising 9 CR (90%) and 1 partial response(PR, 10%), suggesting a potent initial antitumor activity even at ultra-low doses. Cytokine releasesyndrome was observed in 10 patients (Grade 1: 6; Grade 2: 3; Grade 3: 1), while immune effector cell-associated neurotoxicity syndrome occurred in 2 patients (Grade 1: 1; Grade 2: 1)."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CD19 • IL10

IL-10 Expressing CD19 CAR-T Cells Induce Complete Remission and Improve Long-Term Protection in Relapsed or Refractory B-Cell Hematological Malignancies (ASH 2024) - P1 | "The administration followed a standard lymphodepletion regimen involving 30 mg/m2/day fludarabine for 3 days, and 300 mg/m2/day cyclophosphamide for 3 days...Notably, Meta10-19 exhibited a significantly higher CR rate compared to commercial products. Additionally, it provided substantial long-term survival benefits for infused cancer patients, especially at 6 months post-treatment. Ongoing investigations with larger patient cohorts and extended follow-up periods aim to provide further insight into the efficacy and safety parameters."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Anemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD19 • IL10

Leman Biopharma Meta10-19 Injection Completes Dosing of the First Systemic Lupus Erythematosus Subject [Google translation] (Sina Corp) - "...Leman Bio...recently announced that its metabolically enhanced CD19 CAR-T cell therapy product (Meta10-19 injection) has successfully completed the first systemic lupus erythematosus (SLE) subject administration in an investigator-initiated clinical trial (IIT) at the First Affiliated Hospital of Zhejiang University School of Medicine."

Trial status • Systemic Lupus Erythematosus

IL-10 expressing CD19 CAR-T cells induce complete remission and improve long-term protection in relapsed or refractory B-cell hematological malignancies (ESMO-IO 2024) - P1 | "Shenzhen, China Background Meta10-19, the innovative IL-10 expressing CD19 CAR-T cells, show significant potential in addressing T cell dysfunction, a major hurdle in current CAR-T therapies...The administration followed a standard lymphodepletion regimen involving 30 mg/m2/day fludarabine for 3 days, and 300 mg/m2/day cyclophosphamide for 3 days...Notably, 5 patients have been surviving over 12 months, with the longest observed remission duration to date being 17 months. Treatment-related AEs, predominantly neutropenia, thrombocytopenia, and anemia, were manageable and effectively resolved with standard and supportive care"

CAR T-Cell Therapy • Clinical • Late-breaking abstract • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology • CD19 • IL10

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r B-NHL Clinical Research (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Zhejiang University

CAR T-Cell Therapy • New P1 trial • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Leman Biotech Announces Oral Presentation of ITS IIT Clinical Trial Results for Metabolically Armed CD19 CAR-T Cells at ESMO Immuno-Oncology Congress 2024 [Google translation] (Leman Biotech Press Release) - "Leman Biotech...has been selected for an oral presentation at the ESMO Immuno-Oncology Congress 2024....At the congress, Leman Biotech will present clinical results from its investigator-initiated trials of metabolically armed CD19 CAR-T cell therapy for relapsed or refractory B-cell hematological malignancies. The co-founder and chair of Leman Biotech, Prof. Li Tang, who also serves as an associate professor at EPFL, will deliver the presentation."

Clinical data • Hematological Malignancies • Oncology

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Moderate to Severe Active SLE Clinical Research (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Zhejiang University

CAR T-Cell Therapy • New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Updated Clinical Progress of IL-10 expressing CD19 CAR-T Cells for Treatment of Relapsed or Refractory B-Cell Hematological Malignancies at Tiny Doses (SOHO 2024) - P1 | "As of March 18, 2024, Meta10-19 had been successfully infused into 18 eligible patients, who subsequently underwent comprehensive safety and preliminary efficacy evaluations. The median age of the cohort was 47 years (range 17-56). Notably, the complete response (CR) rate of all 18 patients reached 100% (18/18) and maintained at 100% 3 months (16/16) post treatment."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • IL10

Leman Biopharma’s metabolically enhanced CD19 CAR-T completed the first pediatric patient enrollment and dosing [Google translation] (bydrug.pharmcube.com) - "Recently, the metabolically enhanced CD19 CAR-T cell therapy (Meta10-19 injection) developed by Shenzhen Leman Biotechnology Co., Ltd...completed the first pediatric patient enrollment and administration at the Children's Hospital Affiliated to Zhejiang University School of Medicine...This marks an important step forward in the clinical research of this therapy in children with relapsed or refractory B- cell malignancies."

Trial status • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Tumor Immunotherapy Drug Developer Leman Biotech financing 50 Million RMB (EqualOcean) - "Leman Biotech recently completed a total of 50 million yuan in Angel+ and Angel++ financing rounds, accumulating about 150 million yuan in angel funding and grants. The funds will be used to develop metabolic enhancement CD19 CAR-T cell therapy drugs and accelerate the clinical development of therapies for solid tumors...The company also received approximately 20 million RMB in various grants....The funds raised will be used for the IND application of the company's 'ultra-low dose' metabolically enhanced CD19 CAR-T cell therapy drug and to accelerate the clinical development of metabolically enhanced cell therapy drugs targeting solid tumors."

Financing • Oncology • Solid Tumor

UPDATED CLINICAL RESULTS OF FIRST-IN-HUMAN STUDY OF IL-10-EXPRESSING CD19 CAR-T CELLS FOR RELAPSED/REFRACTORY B-CELL HEMATOLOGICAL MALIGNANCIES (EHA 2024) - P1 | "This first-in-human trial of Meta10-19, an IL-10 expressing CD19 CAR-T product, for the treatment of R/RDLBCL and B-ALL has exhibited promising breakthrough preliminary efficacy and manageable safety profile atultra-low doses. Studies with larger cohorts and longer follow-up is ongoing."

CAR T-Cell Therapy • Clinical • P1 data • Acute Lymphocytic Leukemia • Anemia • B Acute Lymphoblastic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD19 • IL10

Updated Clinical Results of Metabolically Armored CD19 CAR-T Cells for Safe and Effective Treatment of Relapsed or Refractory B-Cell Hematological Malignancies at Extremely Low Doses (ASGCT 2024) - P1 | "To further evaluate both efficacy and safety, we have initiated an open-label, single-arm, investigator-initiated phase I trial (NCT05715606; NCT05747157) of IL-10 expressing CD19 CAR-T cells, denoted as Meta10-19, targeting patients with R/R B-cell malignancies... This first-in-human trial of IL-10 expressing CD19 CAR-T product for the treatment of R/R DLBCL and B-ALL has demonstrated encouraging preliminary efficacy and manageable safety profile at ultra-low doses. Ongoing investigations with larger patient cohorts and extended follow-up periods aim to provide further insight into the efficacy and safety parameters."

CAR T-Cell Therapy • Clinical • Late-breaking abstract • Acute Lymphocytic Leukemia • Anemia • B Acute Lymphoblastic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • CD19 • IL10

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Relapsed and/or Refractory CD19-positive B Cell Hematological Malignancies Clinical Research (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: The Children's Hospital of Zhejiang University School of Medicine

CAR T-Cell Therapy • New P1 trial • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Relapsed and/or Refractory CD19-positive B Cell Hematological Malignancies Clinical Research (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Anhui Provincial Hospital

New P1 trial • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases. (PubMed, Nat Biotechnol) - "IL-10 CAR T cells also induced stem cell-like memory responses in lymphoid organs that imparted durable protection against tumor rechallenge. Our results establish a generalizable approach to counter CAR T cell dysfunction through metabolic armoring, leading to solid tumor eradication and long-lasting immune protection."

CAR T-Cell Therapy • Journal • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Hepatology • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • IL10

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical Research (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: He Huang

CAR T-Cell Therapy • New P1 trial • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD19 • IL6 • MYC

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10- 19) in the Treatment of r/r B-ALL Clinical Research (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Anhui Provincial Hospital

CAR T-Cell Therapy • New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD19

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical Research (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Anhui Provincial Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical Research (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Anhui Provincial Hospital

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