DALY 2-EU study demonstrate a statistically significant and clinically meaningful increase in event free survival in relapsed/refractory diffuse large B-cell lymphoma.

Bergisch Gladbach, November 3, 2025, Miltenyi Biomedicine is closer to its goal of providing a new therapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) and will present new data at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition, 6-9 December 2025. DALY 2-EU, is a multinational, randomized study, evaluating the safety and efficacy of zamtocabtagene autoleucel (zamto-cel), a tandem CD20-CD19 directed non-cryopreserved chimeric antigen receptor T (CAR-T) cell product, compared to chemoimmunotherapy (CIT) as a second-line therapy in r/r DLBCL.¹

Dr. Toon Overstijns, Managing Director of Miltenyi Biomedicine, said: “The presentation of the DALY 2-EU study results at ASH marks a milestone in our 35-year commitment to pioneering cell and gene therapies, showcasing promising efficacy and safety for zamto-cel, our tandem CD20-CD19 directed non-cryopreserved CAR-T cell product. These encouraging findings bring us closer to providing an additional option for this vulnerable patient population and underscore our dedication to addressing unmet medical needs through innovative therapies.”

Prof. Dr. Peter Borchmann, Lead investigator of the DALY 2-EU trial and Assistant Medical Director in the Department of Hematology and Oncology at the University Hospital of Cologne, Germany, said: “I look forward to presenting these data which show the potential of zamto-cel to meet the very real needs of people living with relapsed/refractory diffuse large B-cell lymphoma, who are at high risk of treatment failure.”

Presentation details:

About DALY 2-EU²
DALY 2-EU (NCT04844866) is a pivotal, randomized, multi-center, open-label Phase II study conducted in 12 countries within the EU, evaluating the safety and efficacy of genetically engineered autologous T-cells expressing anti-CD20 and anti-CD19 specific chimeric antigen receptor, zamtocabtagene autoleucel (zamto-cel), compared to CIT, rituximab, gemcitabine, and oxaliplatin (R.GemOx) or polatuzumab vedotin plus bendamustine/rituximab (Pola-BR), as a second-line therapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). It is the only CAR-T randomized study in this patient population.

Eligible patients were adults with r/r DLBCL who were refractory or relapsed within 24 months of their first-line treatment, had received at least an anthracycline and a rituximab-containing regimen and were ineligible for a stem-cell transplant.

Participants were randomized 1:1 to receive either zamto-cel or CIT (R-GemOx/Pola-BR). Zamto-cel was administered as a single non-cryopreserved infusion at a dose of 2.5 x 10^6 CAR- transduced T cells per kg body weight after lymphodepletion with fludarabine and cyclophosphamide. Patients randomized to the comparator arm received either R-GemOx or Pola-BR.

The primary endpoint of the study is event-free survival (EFS) assessed by a blinded independent review committee (BIRC), defined as the time from randomization to objective disease progression, failure to achieve a partial response (PR) or complete response (CR) at or beyond Week 8, leading to a new anti-lymphoma therapy or death from any cause. Secondary endpoints include progression-free survival (PFS), best complete response rate (CRR), duration of complete response (DOR), and overall survival (OS).

These data will be reported as part of a pre-planned EFS interim analysis after a median follow- up of 17 months. Additional analyses are planned with longer follow-up periods and will be presented at future meetings.

About zamtocabtagene autoleucel (zamto-cel)
Zamto-cel is an investigational autologous chimeric antigen receptor (CAR) T-cell therapy designed to target both CD20 and CD19. It is being studied in clinical trials for the treatment of relapsed or refractory B-cell malignancies, including large B-cell lymphoma (LBCL), diffuse large B-cell lymphoma (DLBCL), primary and secondary central nervous system (CNS) lymphoma, mantle cell lymphoma (MCL), Richter’s transformation (RT), and other B-cell neoplasms.³

Zamto-cel is manufactured utilizing the CliniMACS Prodigy® (Miltenyi Biotec), a closed, automated system. Manufacturing has a fixed 12-day production processes and a 14-16 day vein- to-vein time with zamto-cel administered as a non-cryopreserved formulation.

About Miltenyi Biomedicine
Miltenyi Biomedicine is committed to making innovative cancer treatments and regenerative therapies accessible to patients with serious diseases. Leveraging cutting-edge technology, the company is investigating various cell therapy assets to address unmet needs in hematological- oncological and autoimmune diseases in order to transform patient care.

About Miltenyi Biotec
Miltenyi Biotec is a global leader in innovating technologies and services for patient-specific cell and gene therapies, transforming scientific discoveries into practical treatments for personalized medicine. With over 35 years of expertise, it supports biomedical discoveries and translates them into clinical applications, enhancing patient access to new therapies. Miltenyi Biotec, with its integrated solutions, including GMP-certified CliniMACS® Cell Factories, provides expert guidance to therapy developers efficiently from process development to commercialization through its Miltenyi Bioindustry global CDMO division.

Contact
Miltenyi Biomedicine
Friedrich-Ebert-Strasse 68
51429 Bergisch Gladbach, Germany
[email protected]

References

1. Borchmann P, et al. 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. Presented at American Society of Hematology (ASH) Annual Meeting. Abstract #abs25-738.
2. Cheson BD, et al. J Clin Oncol 2014; 32(27): 3059–68.
3. ClinicalTrials.Gov. Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients (DALY 2-EU). Available at:
   https://clinicaltrials.gov/study/NCT04844866. Accessed September 2025
4. ClinicalTrials.Gov. DALY II USA/MB-CART2019.1 for DLBCL. Available at:
   https://clinicaltrials.gov/study/NCT04792489. Accessed September 2025.

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