zamtocabtagene autoleucel (MB-CART2019.1) / Miltenyi Biotec - LARVOL DELTA

Zamtocabtagene autoleucel, a tandem CD20-CD19 directed CAR-T cell therapy as second-line treatment for Relapsed/Refractory large B-cell lymphoma: primary analysis of the randomized, pivotal DALY 2-EU study. (ASH 2025) - P2 | "Key inclusion criteria were LBCL, ECOG PS ≤ 2, age ≥ 18 years (y) and one NTE criterion,age ≥ 65 y and impaired organ function or age ≥70 y. Pts in the zamto-cel arm started lymphodepletion(fludarabine and cyclophosphamide) during manufacturing, followed by infusion of a non-cryopreservedzamto-cel product, target dose 2.5 × 106 CAR-T cells/kg body weight...For CRS 29 (38%) pts received tocilizumab and 14 (18%) corticosteroids... Zamto-cel demonstrated highly significant and clinically meaningful superiority over R-GemOx in NTE patients at high risk for treatment failure. Moreover, zamto-cel was well tolerated in thisvulnerable elderly patient population with low rates of severe CRS and ICANS. This favorable risk/benefitprofile suggests the use of zamto-cel as preferred treatment option in 2L for NTE patients with r/r LBCL."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • CD20

MB-CART2019.1 in Refractory Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=26 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH | Initiation date: Oct 2025 ➔ Jan 2026

Trial initiation date • CNS Disorders • Multiple Sclerosis

Miltenyi Biomedicine presents primary analysis of the pivotal DALY 2-EU trial for second-line relapsed/refractory large B-cell lymphoma at the 67th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "At the data cutoff, patients were randomly assigned to receive zamto-cel (n=82) or R-GemOx/ PolaBR (n=86)....The median event-free survival (EFS) for zamto-cel was 6.2 months (95% CI 3.8-13.8) compared to 2.5 months (95% CI 2.0-3.3) for R-GemOx (HR 0.39; 95% CI 0.27-0.58; p<0.0001). The median progression-free survival (PFS) was significantly longer with zamto-cel at 8.5 months (95% CI 3.8-16.8) versus 3.3 months (95% CI 2.0-3.8) for R-GemOx (HR 0.43 [95% CI 0.28-0.65]; p<0.0001). In the intent-to-treat (ITT) population, the overall response rate (ORR) was 72% with a 54% complete response rate (CRR) for zamto-cel compared to 45% ORR and 14% CRR for R-GemOx."

P2 data • Large B Cell Lymphoma

Interim Results from a Phase 2 Pivotal Study (DALY II USA) of Tandem CD20-CD19-Directed Non-Cryopreserved CAR-T Cells - Zamtocabtagene Autoleucel (Zamto-Cel) in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma (ASH 2024) - P2 | "Lymphodepletion chemotherapy was initiated during the manufacturing process (either cyclophosphamide/ fludarabine or bendamustine) prior to receiving a single dose of zamto-cel at a dose of 2.5x106 CAR T cells/kg on Day 0. Unlike currently registered CAR-T cell products, zamto-cel is administered as a fresh product with a short vein-to-vein time of 14 days with lymphodepletion initiated during the manufacturing process. With a manufacturing success rate of 91% we have demonstrated the feasibility of this process among high-risk patients with r/r DLBCL."

CAR T-Cell Therapy • Clinical • IO biomarker • P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • CD20

A Phase I safety, dose finding and feasibility clinical trial of zamtocabtagene autoleucel (zamto-cel) in patients with relapsed or refractory B-NHL: 5-year follow up report (DGHO 2025) - "Lymphodepletion consisted of cyclophosphamide and fludarabine and holding therapy besides steroids was not permitted. No DLT and no severe (grade ≥3) CRS or ICANS were observed. MTD was not reached. 42% of pts are in ongoing remission at the last time point of FU."

Clinical • IO biomarker • P1 data • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CD20 • CD27 • IL7R

CNS infiltration by zamtocabtagene autoleucel tandem CD20/CD19 CAR T cells leading to complete remission in a patient with primary CNS lymphoma. (PubMed, Haematologica) - "Not available."

Journal • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • CD20

DALY PED: Safety and Efficacy Study of Zamtocabtagene Autoleucel (MB-CART2019.1) in Pediatric Patients With Relapsed or Refractory B-Cell Neoplasms (clinicaltrials.gov) - P2 | N=31 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pediatrics

MB-CART2019.1 in Refractory Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=26 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH

New P1/2 trial • CNS Disorders • Multiple Sclerosis

Best of Cell Therapy for Lymphoma: What We Learned in 2024 and 2025 (SOHO 2025) - P1/2, P2 | "Autologous CAR-T Therapy CD19 CAR-T New Regulatory Approvals In March 2024, the United States Food and Drug Administration (FDA) granted accelerated approval to lisocabtagene maraleucel (lisocel) for relapsed/refractory (R/R) chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) after Bruton tyrosine kinase inhibitors (BTKis) and B-cell lymphoma 2 (BCL2) inhibitors, making it the first CAR-T approval in this disease...Long-Term Follow-up of Pivotal CD19 CAR-T Trials TRIAL (PRODUCT) LYMPHOMA SUBTYPE MEDIAN FU (MONTHS) ORR (%) CR (%) MEDIAN PFS (MONTHS) PFS (%) OS (%) NOTABLE SAFETY FINDINGS 64.6 90 75 (79% in FL cohort, 65% in MZL cohort) 62.2 53 (5 yr) 69 (5 yr) No new late signals ZUMA-5 (AXICEL) FL/MZL ( ≥ 3L) ELARA (TISA-CEL) FL ( ≥ 3L) 53 – * 69.1 53.3 50.2 (4 yr) 79.3 (4 yr) No new late signals; 6.2% secondary primary malignancies TRANSCEND FL (LISO-CEL) FL (2L+ high-risk/3L+) 29.5 – 30 95.7 – 97.1 94.2 – 95.7 NR 72.5 – 82.6 (2 yr) 88.2 –..."

IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hodgkin Lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Oncology • Peripheral T-cell Lymphoma • Small Lymphocytic Lymphoma • T Cell Non-Hodgkin Lymphoma • CD22 • CD5 • IL15 • TNFRSF8

TANDEM CD20-19-DIRECTED NON-CRYOPRESERVED CAR-T CELLS–ZAMTOCABTAGENE AUTOLEUCEL (ZAMTO-CEL)—IN PATIENTS WITH RELAPSED/REFRACTORY CNS LYMPHOMA IN DALY II US STUDY (ICML 2025) - P2 | "Lymphodepletion chemotherapy with cyclophosphamide/fludarabine was initiated during the manufacturing process prior to a single infusion of zamto-cel at a dose of 2.5 × 106 CAR-T cells/kg. Zamto-cel exhibited a favorable safety profile and was well tolerated in patients with r/r CNSL with encouraging efficacy in the majority of treated patients. Longer follow-up time is needed to evaluate the duration of response. Dual targeting and the very short vein-to-vein time may be beneficial in this rapidly growing disease."

CAR T-Cell Therapy • Clinical • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma • CD20

INTERIM RESULTS OF TANDEM CD20-CD19-DIRECTED NON-CRYOPRESERVED CAR-T CELLS—ZAMTOCABTAGENE AUTOLEUCEL IN RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA (ICML 2025) - P2 | "This pre-planned interim analysis represents the first pivotal trial of a tandem CD20-CD19 directed non-cryopreserved CAR-T cell product for patients with third-line r/r DLBCL. The results show encouraging activity and a favorable safety profile. Unlike currently registered CAR-T cell products, zamto-cel is a dual-targeting, freshly administered product with lymphodepletion started during manufacturing resulting in a short vein-to-vein time with a high manufacturing success rate."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

DALY 1: A PHASE I SAFETY, DOSE FINDING AND FEASIBILITY TRIAL OF ZAMTOCABTAGENE AUTOLEUCEL (MB-CART2019.1) IN PATIENTS WITH R/R B-NHL: 5Y FOLLOW-UP REPORT (ICML 2025) - "Zamto-cel showed no DLT and no severe (grade ≥ 3) CRS or neurotoxicity was observed. Feasibility and safety were promising in this cohort of r/r B-NHL patients. All 5 patients with CR are in ongoing remission at least 2 years after treatment."

Clinical • P1 data • B Cell Non-Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • CD20

Safety of MB-CART2019.1 in Lymphoma Patients (MB-CART2019.1 Lymphoma / DALY 1) (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Miltenyi Biomedicine GmbH | Phase classification: P1/2 ➔ P1

Phase classification • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

DALY PED: Safety and Efficacy Study of Zamtocabtagene Autoleucel (MB-CART2019.1) in Pediatric Patients With Relapsed or Refractory B-Cell Neoplasms (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial completion date: Oct 2029 ➔ Dec 2029 | Initiation date: Apr 2025 ➔ Jul 2025 | Trial primary completion date: Sep 2029 ➔ Dec 2029

Trial completion date • Trial initiation date • Trial primary completion date • Oncology • Pediatrics

DALY II USA/ MB-CART2019.1 for DLBCL (clinicaltrials.gov) - P2 | N=248 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | N=110 ➔ 248 | Trial completion date: Dec 2026 ➔ Dec 2028 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Enrollment change • Trial completion date • Trial primary completion date • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Mantle Cell Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • Secondary Central Nervous System Lymphoma

Zamto-Cel Delivers Responses in R/R Diffuse Large B-Cell Lymphoma (OncLive) - P2 | N=110 | DALY II USA (NCT04792489) | Sponsor: Miltenyi Biomedicine GmbH | "Treatment with the tandem CD19- and CD20-directed CAR T-cell therapy zamtocabtagene autoleucel (zamto-cel; MB-CART2019.1) led to responses, including durable complete responses (CRs), in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to data from the phase 2 DALY II USA trial (NCT04792489) presented at the 2025 Transplant and Cellular Therapy Meetings. Findings showed that evaluable patients in the modified intention-to-treat (mITT) population (n = 59) achieved an overall response rate (ORR) of 72.8% comprising a CR rate of 50.8% and a partial response rate of 22.0%. Additionally, 5.1% of patients experienced stable disease, 20.3% had progressive disease, and 1.7% were not evaluable. The median duration of response (DOR) was 11.4 months, and the median duration of CR was not reached."

P2 data • Diffuse Large B Cell Lymphoma

Tandem CD20-CD19-Directed Non-Cryopreserved CAR T Cells - Zamtocabtagene Autoleucel (Zamto-Cel) in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma - Interim Results from a Phase 2 Pivotal Study (DALY II USA) (TCT-ASTCT-CIBMTR 2025) - P2 | "This pre-planned interim analysis represents the first pivotal trial of a tandem CD20-CD19 directed non-cryopreserved CAR-T cell product for patients with third-line r/r DLBCL. The results show encouraging activity and a favorable safety profile. Unlike currently registered CAR-T cell products, zamto-cel is administered as a fresh product with a short vein-to-vein time with a high manufacturing success rate."

CAR T-Cell Therapy • Clinical • IO biomarker • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • CD20

Tandem CD20/CD19 CAR Zamto-Cel Shows Promise in DLBCL (CGTLive) - P2 | N=110 | DALY II USA (NCT04792489) | Sponsor: Miltenyi Biomedicine GmbH | "The tandem CD20/CD19 targeted non-cryopreserved CAR T-cell therapy zamtocabtagene autoleucel (zamto-cel) showed promising early complete response (CR) rates and survival outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to interim findings from the pivotal phase 2 DALY II USA study (NCT04792489) presented at the 2024 ASH Annual Meeting....In the preplanned interim findings from phase 2 study, the overall response rate (ORR) was 72.8% and the complete remission (CR) rate was 50.8%. The median duration of response was 11.4 months for those with an ORR and was not yet reached for those with a CR. The median progression-free survival (PFS) was 9.0 months and the PFS rate was 55% (95% CI, 41%-67%). The median overall survival was not reached at the interim analysis."

P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

DALY 2-EU: Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients (clinicaltrials.gov) - P2 | N=168 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial completion date: Jul 2027 ➔ Jul 2029

Trial completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD19

Lentiviral Gene Therapy (Zamtocabtagene Autoleucel) LTFU (clinicaltrials.gov) - P=N/A | N=150 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

US Zamto-cel Autoimmune Diseases (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH

New P1 trial • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Sustained drug-free remission in rheumatoid arthritis associated with diffuse large B-cell lymphoma following tandem CD20-CD19-directed non-cryopreserved CAR-T cell therapy using zamtocabtagene autoleucel. (PubMed, RMD Open) - "We report the case of long-term persisting rheumatoid arthritis (RA), treated with CD20-CD19 CAR-T when it became associated with diffuse large B cell lymphoma (DLBCL), resulting in a sustained drug-free remission of the preceding RA, as well as of the subsequent DLBCL that formed the indication of the CAR-T therapy using zamtocabtagene autoleucel, with a 1-year follow-up. According to our best knowledge, this is the first published clinical case report of long-term persisting RA treated with CAR-T cell therapy."

CAR T-Cell Therapy • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rheumatoid Arthritis • Rheumatology • CD20

DALY 2-EU: Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients (clinicaltrials.gov) - P2 | N=168 | Active, not recruiting | Sponsor: Miltenyi Biomedicine GmbH | Recruiting ➔ Active, not recruiting

Enrollment closed • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD19

LONGSAFE: Long-Term Follow-up of Patients Treated With Miltenyi Cell and Gene Therapies (clinicaltrials.gov) - P=N/A | N=40 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH

Gene therapy • New trial • Chronic Lymphocytic Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Solid Tumor

Safety of MB-CART2019.1 in Lymphoma Patients (MB-CART2019.1 Lymphoma / DALY 1) (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: Miltenyi Biomedicine GmbH | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ May 2024

Trial completion • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6