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

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

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 Disorders • 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

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

New P2 trial • Oncology • Pediatrics

DALY 2-EU: Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients (clinicaltrials.gov) - P2 | N=168 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | Trial completion date: Dec 2024 ➔ Jul 2027 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • 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 | Not yet recruiting | Sponsor: Miltenyi Biomedicine GmbH | Initiation date: Nov 2023 ➔ Feb 2024

Gene therapy • Trial initiation date • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

BISPECIFIC ANTI-CD20/19 CAR-T – ZAMTOCABTAGENE AUTOLEUCEL FOR RELAPSED/REFRACTORY DLBCL – INTERIM ANALYSIS RESULTS OF DALY-II-USA STUDY (EHA 2023) - "Prespecified efficacy threshold of zamto-cel was exceeded in the interim analysis Treatment demonstrated a favorable safety profile, with promising ORR and PFS in advanced DLBCL population often pre-treated with agents not available in the previous similar studies. We also demonstrate the feasibility of a rapid manufacturing process with 100% fresh infusion in eligible pts."

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

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

Gene therapy • New trial • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

DALY II USA: DALY 2.0 USA/ MB-CART2019.1 for DLBCL (clinicaltrials.gov) - P2 | N=110 | Recruiting | Sponsor: Miltenyi Biomedicine GmbH | N=65 ➔ 110 | Trial completion date: Jun 2025 ➔ Dec 2026 | Trial primary completion date: Jul 2023 ➔ Dec 2024

Enrollment change • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

A RANDOMIZED PHASE II STUDY OF MB-CART2019.1 COMPARED TO STANDARD OF CARE IN PATIENTS WITH RELAPSED/REFRACTORY DLBCL INELIGIBLE FOR ASCT – DALY 2-EU TRIAL (ICML 2023) - P1/2, P2 | "The comparator treatment consists of R-GemOx (rituximab, gemcitabine and oxaliplatin) or Pola-BR (polatuzumab vedotin, bendamustine and rituximab). In addition, a separate pivotal Phase II trial in the USA is currently enrolling patients with r/r DLBCL who have failed at least two lines of prior systemic therapy (NCT04792489). The study is sponsored by Miltenyi Biomedicine"

Clinical • P2 data • Diffuse Large B Cell Lymphoma • Oncology

BISPECIFIC ANTI-CD20/19 CAR-T—ZAMTOCABTAGENE AUTOLEUCEL FOR RELAPSED/REFRACTORY DLBCL—INTERIM ANALYSIS RESULTS OF DALY-II-USA STUDY (ICML 2023) - "The prespecified efficacy threshold of zamto-cel was exceeded in the interim analysis Treatment demonstrated a favorable safety profile, with promising ORR and PFS in advanced DLBCL population often pre-treated with agents not available in previous similar studies. We also demonstrate the feasibility of a rapid manufacturing process with 100% fresh infusion in eligible pts. Encore Abstract—previously submitted to EHA 2023"

Diffuse Large B Cell Lymphoma • Oncology