zorpocabtagene autoleucel (MB-CART 19.1) / Miltenyi Biotec, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology - LARVOL DELTA

Safety and preliminary efficacy of anti-CD19 CAR T cells zorpocabtagene-autoleucel in systemic autoimmune diseases: Final analysis of the castle trial (ASH 2025) - "The CASTLE study is the first phase I/II basket trial to demonstrate feasibility, favorablesafety, and high efficacy of zorpo-cel in three B-cell driven AIDs. These promising results provide strongrationale to further develop zorpo-cel in AID."

CAR T-Cell Therapy • Clinical • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Myositis • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Distinct inflammatory and immune recovery patterns after CD19-directed CAR T-cell therapy in SLE and B-cell lymphoma (ASH 2025) - "All patients received either commercial CAR T-cell products or theinvestigational medicinal product MB-CART19.1 (in-house manufactured 2nd generation anti-CD19 CAR T-cells with a 4.1BB co-stimulatory domain) in our center.To characterize inflammatory signatures, we performed serum proteomics using the Olink® Target 96Immuno-Oncology Panel across the CAR T-cell treatment course...Taken together, our data reveal a resolution of systemic inflammation specific to SLE patients followingCAR T-cell therapy, compared to patients with B-cell lymphoma. This resolution might be linked to theshorter persistence of CAR T-cells in SLE patients and thus benefit the reconstitution of the adaptiveimmune system."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Non-Hodgkin’s Lymphoma • Systemic Lupus Erythematosus • ANGPT1 • CXCL10 • CXCL12 • CXCL13 • CXCL5 • CXCL8 • IFNG • IL6 • IL7 • TGFB1

Study of CART Cell (MB-CART19.1) in Patients With Relapsed or Refractory CD19 Positive NHL (clinicaltrials.gov) - P2 | N=26 | Recruiting | Sponsor: King Hussein Cancer Center

New P2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"On-site manufactured anti-CD19 CAR-T cell therapy normalized platelet count in a case of refractory immune thrombocytopenia (ITP)" (DGHO 2025) - "Here we report the case of a 68-year-old woman with refractory severe primary ITP treated with anti-CD19 CAR-T cells. Leukapheresis and processing were performed on-site using the CliniMACS Prodigy platform® and MB-CART19.1 lentiviral vector (Miltenyi Biotec). The patient underwent conditioning with fludarabine and cyclophosphamide, followed by fresh CAR-T cell infusion (vein-to-vein time: 13 days). The patient presented with a 16-month history of ITP and severe gastrointestinal bleeding, requiring repeated transfusions and critical care due to hemorrhagic shock and was refractory to standard treatments including steroids, IVIg, TPO receptor agonists, fostamatinib, rituximab, azathioprine, cyclosporine and splenectomy...The patient developed cytokine release syndrome (CRS) grade 1 on day 7, which escalated to grade 2 on day 8 but resolved following administration of tocilizumab... Anti-CD19 CAR-T cell therapy is an effective treatment for refractory ITP, with..."

CAR T-Cell Therapy • Clinical • Gastroenterology • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Thrombocytopenia • Thrombocytopenic Purpura • CD4 • CD8

CD19-Targeted CAR-T Cells in Refractory Systemic Autoimmune Diseases: A Monocentric Experience from the First Fifteen Patients (ASH 2023) - "Autologous CD19 CAR T cells MB-CART19.1 were produced with the Miltenyi prodigy platform. After leukapheresis on day -13, manufacturing commenced in house and lymphodepletion was started with fludarabine 25 mg/m2/d intravenously (i.v.) on days -5 to -3 and cyclophosphamide 1000 mg/m2/d i.v. on day -3...6/15 patients received tocilizumab... CD19 CAR T cells induce persistent, drug-free remission in three distinct autoantibody dependent AID with very good tolerability. Though hypothetical cure appears possible, longer follow up is needed. This unprecedented drug-free remission is remarkable as B cells functionally reconstitute."

CAR T-Cell Therapy • Clinical • Immunology • Inflammatory Arthritis • Lupus • Myositis • Otorhinolaryngology • Renal Disease • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Vertigo • CD27

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | Phase classification: P1/2 ➔ P1

Phase classification • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • CD19

Distinct Safety and Toxicity Profile of CD19-Directed CAR T-Cell Therapy in Systemic Lupus Erythematosus Versus B-Cell Lymphoma – a Single-Center Experience (ASH 2024) - "All patients were treated in our center with either commercial CAR T-cell products or with the investigational medicinal product MB-CART19.1 (in-house manufactured 2nd generation anti-CD19 CAR T-cells with a 4.1BB co-stimulatory domain)...Consistent with reduced toxicity, SLE patients received less tocilizumab and glucocorticoid treatment...Despite comparable lymphodepletion with fludarabine/cyclophosphamide, SLE patients demonstrated on average a deeper nadir of neutrophils compared with lymphoma patients...Taken together, while both patient cohorts showed similar CAR T-cell expansion and dynamics, we observed less toxicity and less severe adverse events in SLE patients than in lymphoma patients. This is consistent with a lower base-line inflammation, a shorter CAR T-cell persistence, and a faster B-cell recovery in SLE patients, indicating an overall very good safety profile of CAR T-cell therapy in the treatment of SLE"

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Systemic Lupus Erythematosus

Update on Monocentric CD19-CAR T-Cell Therapy in 30 Patients with Autoimmune Disease (ASH 2024) - "Methods : Patients with treatment-refractory, progressive systemic SLE (18 patients), SSc (7) and IIM (5) were treated with 1x106 /kg autologous 2nd generation CD19 CAR-T cells MB-CART19.1 produced in-house in a closed system...Before CAR T-cell infusion, lymphodepletion was infused with fludarabine (25 mg/m², d-5 to d-3) and cyclophosphamide (1000 mg/m², d-3)...Tolerability has been high with no higher-grade acute toxicities and mild infectious complications in longer follow-up. Efficacy analysis showed long-standing drug-free remission (SLE and IIM) or no progression (SSc) with recurrence of disease in only one patient."

CAR T-Cell Therapy • Clinical • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Myositis • Neutropenia • Pediatrics • Pneumonia • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

CD19 CAR T Cell Therapy in refractory autoimmune hemolytic anemia (AIHA) with concurrent immunethrombopenia (ITP) – a case report (DGHO 2025) - "We offered lymphodepletion with cyclophosphamide/fludarabine and by expanded access, a single dose of 1 million MB-CART19.1 cells/kg, which is a fresh CD19-directed, 4-1BB CAR T cell product.AIHA-response was defined by independence of blood transfusions, level of hemoglobin (Hb), and hemolysis parameters and response of ITP by platelet counts...A pulse of steroids combined with a single dose of rituximab was not effective and was therefore extended to IVIG and steroids... This single case shows early efficacy of MB-CART19.1 in severe and refractory AIHA with partial remission at day 7 and complete remission at day 25 with virtually absent toxicity. To confirm this favorable course, a longer follow-up and clinical trials expanding on more patients are needed."

CAR T-Cell Therapy • Case report • Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Infectious Disease • Inflammation

Comparison of the safety profile of CD19-targeting CAR T-cell therapy in patients with refractory systemic lupus erythematosus and B-cell lymphoma (DGHO 2025) - "All patients were treated at the University Hospital of Erlangen with either commercial CAR T-cell products or with the investigational medicinal product MB-CART19.1 (in-house manufactured 2nd generation anti-CD19 CAR T-cells with a 4.1BB co-stimulatory domain). In contrast to similar peak and overall expansion of CAR T-cells, SLE patients showed lower incidence and severity of cytokine-release syndrome and immune-effector cell associated neurotoxicity syndrome than the B-NHL patients...Consistent with reduced toxicity, SLE patients received less tocilizumab and glucocorticoid treatment... Taken together, CAR T-cell treatment of SLE patients showed less toxicity and faster immune recovery than in the context of B-NHL, while CAR T-cell expansion and early kinetics were similar, indicating an overall excellent safety profile of CAR T-cell therapy in the treatment of SLE."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Non-Hodgkin’s Lymphoma • Systemic Lupus Erythematosus • CD4

Safety and efficacy of autologous CD19-CAR T-cell therapy in patients with autoimmune disease - data from the CASTLE Phase I/II basket study (ACR Convergence 2025) - "Their results will provide further insights in the therapeutic role of CAR T-cells in these diseases. CASTLE is a phase I/II basket study (Miltenyi Biomedicine, EudraCT-Nr.2022-001366-35) assessing the safety (primary endpoint) and efficacy (secondary endpoint) of 1x106 autologous CD19 CAR T-cells (MB-CART19.1) /kg BW after lymphodepleting chemotherapy with Fludarabin/Cyclophosphamide in patients with SLE, IIM and SSc. The CASTLE study met its primary safety and secondary efficacy endpoint. The data confirm favorable safety and high efficacy of MB-CART19.1 in the setting of a controlled phase I/II study in patients with autoimmune disease."

CAR T-Cell Therapy • Clinical • P1/2 data • Pan tumor • Cytomegalovirus Infection • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Myositis • Neutropenia • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Thrombocytopenia

MB-CART19.1 in Refractory SLE (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial primary completion date: Aug 2025 ➔ Sep 2027

Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • CD19

A Study of MB-CART19.1 Cellular Therapy for People With Central Nervous System Lymphoma (CNSL) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma

TOWARDS ONE WEEK VEIN-TO-VEIN TIME OF PLACE-OF-CARE PRODUCED FRESH FORMULATION CAR-T CD19 THERAPY (ICML 2025) - "The 7-Day production of POC MB-CART19.1 cell fresh formulation products met the pre-defined quality criteria for clinical administration and resulted in a short vein-to-vein time of only 8 days."

IO biomarker • Leukemia • Lymphoma • IFNG

PLACE-OF-CARE PRODUCED FRESH FORMULATION MB-CART19.1 CELL THERAPY FOR RELAPSED OR REFRACTORY CD19+ HEMATOLOGICAL MALIGNANCIES WITH CENTRAL NERVOUS SYSTEM INVOLVEMENT (ICML 2025) - "From May 2022 to December 2024, nine ≥ 18-year-old patients (pts) with R/R CD19+ B-cell lymphoma or B acute lymphocytic leukaemia (B-ALL) with CNS involvement underwent leukapheresis followed by POC MB-CART19.1 production, fludarabine and cyclophosphamide lymphodepleting chemotherapy and subsequent administration of 1 × 106 cells/kg (fresh cells in 7 (78%) pts) as a single or split dose. Thiotepa was added as part of the lympodepletion regimen in 6 (67%) pts...One patient recovered after G-CSF and romiplostim, three after autologous, and one after allogeneic stem cell transplantation...However, a significant proportion of patients relapse, highlighting the need for additional therapeutic strategies. While acute toxicity was manageable, significant late immune effector cell-associated hematotoxicity required interventions including stem cell support."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Altered gut microbiota composition in autoimmune disease patients undergoing CD19-CAR T-cell therapy (EULAR 2025) - " Patients with severe SLE, SSc or IIM received a single infusion of 1x10 6 /kg body weight autologous CD19-CAR T-cells, manufactured by lentiviral-based transfection of T-cell with a vector encoding a second-generation CAR with a CD19 binder and a 4-1BB costimulation domain (MB-CART19.1; Miltenyi)... We show that CD19-CAR T-cell therapy changes gut microbiota composition in patients with AID. Prevalence of pathobionts associated with SLE, such as Enterococcus and Streptococcus species, decrease after CD19-CAR T-cell therapy. These changes may contribute to long-term remission in patients with AID."

CAR T-Cell Therapy • Clinical • Gut Microbiota • Gene Therapies • Immunology • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Safety and preliminary efficacy of CD19 CAR T-Cell Treatment in Rheumatic Disease – Data from the Phase I/II CASTLE Basket Study (EULAR 2025) - "Standard cyclophosphamide/fludarabine conditioning therapy was followed by a single infusion of an advanced therapy medicinal product (MB-CART19.1) containing 1x10 6 CD19-CAR T-cells/kg body weight. These data underline the safety of CD19-CAR T-cell therapy in the treatment of autoimmune disease. No higher-grade CRS or ICANS and no sustained myelotoxicity were observed. Also, the preliminary efficacy data met the expectations in SLE, IIM and SSc."

CAR T-Cell Therapy • Clinical • P1/2 data • Pan tumor • Hematological Disorders • Infectious Disease • Inflammatory Arthritis • Leukopenia • Lupus • Myositis • Neutropenia • Pneumonia • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM) (clinicaltrials.gov) - P1/2 | N=48 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial completion date: Dec 2024 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Mar 2026

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

Decentralized Point-of-Care Manufacturing of CD19 Chimeric Antigen Receptor T Cells in Mexico. (PubMed, JCO Glob Oncol) - "Our study demonstrates an effective methodology with satisfactory and comparable performance to international reports. Point-of-care manufacturing is a feasible alternative to increase access to CAR-T cells in academic centers."

Journal

Safety and Preliminary Efficacy of CD19 CAR-T Cell Treatment in Rheumatic Disease – Data from the First Part of the Phase I/II CASTLE Basket Study (ACR Convergence 2024) - "Standard cyclophosphamide/fludarabine conditioning therapy was followed by a single infusion of an advanced therapy medicinal product (MB-CART19.1) containing 1×106 CD19-CAR-T cells/kg body weight. These data underline the safety of CD19-CAR-T therapy in the treatment of autoimmune disease. No higher-grade CRS or ICANS and no myelotoxicity was observed. Also, the preliminary efficacy data met the expectations in SLE, IIM and SSc."

CAR T-Cell Therapy • Clinical • P1/2 data • Pan tumor • Hematological Disorders • Immunology • Inflammation • Inflammatory Arthritis • Leukopenia • Lupus • Myositis • Neutropenia • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Safety of CD19-targeted CAR T-cell therapy in refractory systemic lupus erythematosus versus B-cell lymphoma – experiences of a center (DGHO 2024) - "All patients were treated in our center with either commercial CAR T-cell products or with the investigational medicinal product MB-CART19.1 (in-house manufactured 2 nd generation anti-CD19 CAR T-cells with a 4.1BB co-stimulatory domain)...Consistent with reduced toxicity, SLE patients received less tocilizumab and glucocorticoid treatment... Taken together, we observed less toxicities and severe adverse events in SLE patients than in lymphoma patients despite similar CAR T-cell expansion and dynamics."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Systemic Lupus Erythematosus • CRP

Interim analysis of the phase I safety run in the cohort of the monocentric study "CD19-CAR-T cells in systemic B-cell-mediated autoimmune disease" (CASTLE) (DGHO 2024) - "Following lymphodepletion a single dose of 1 mio MB-CART19.1 CD19 CAR T cells/kg BW was infused... Our data emphasize the safety of CD19 CAR-T therapy in autoimmune diseases without a higher degree of CRS, ICANS or bone marrow toxicity."

CAR T-Cell Therapy • Clinical • P1 data • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Lupus • Myositis • Neutropenia • Pneumonia • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

MB-CART19.1 in Refractory SLE (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2027 ➔ Aug 2027 | Initiation date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2025 ➔ Aug 2025

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

CAR T cell therapy for CD19-positive cancer - phase I clinical trial (ANZCTR) - P1 | N=25 | Recruiting | Sponsor: Metro North Hospital and Health Service | N=15 ➔ 25

CAR T-Cell Therapy • Enrollment change • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CD19