Miltenyi Biomedicine will share positive interim results from DALY II USA, a pivotal Phase II trial investigating the tandem CD20-CD19 (directed) non- cryopreserved CAR-T cell product, zamtocabtagene autoleucel (zamto-cel) in patients with third line, relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) at the American Society of Hematology (ASH) Annual Meeting

Bergisch Gladbach, December 7, 2024 – Miltenyi Biomedicine presented interim results from the DALY II USA trial evaluating the efficacy, safety and pharmacokinetics of zamtocabtagene autoleucel (zamto-cel) in patients with third line, relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) at the American Society of Hematology (ASH) Annual Meeting on December 7, 2024. The pre-planned interim analysis showed that zamto-cel has a favorable safety profile and promising overall response rate (ORR) and complete response rate (CRR) in patients with R/R DLBCL.¹

Dr. Nirav Shah, Associate Professor of Medicine at the Medical College of Wisconsin, said: “These data represent the largest prospective clinical trial of a dual targeted CAR-T cell treatment for DLBCL, the most common type of lymphoma. More so, it is the first CAR-T trial to incorporate a rapid manufacturing process and a fresh infusion, which will improve accessibility to these novel treatments.”

Dr. Toon Overstijns, Chief Executive Officer of Miltenyi Biomedicine, said: “For 35 years, the Miltenyi Group has been a leading pioneer in exploring and enabling cell and gene therapies and we are excited to receive interim data from one of our potential CAR-T treatments. We look forward to further developing this investigational medicine and making it affordable and accessible for patients in need, across the world.”

ASH Annual Meeting 2024 – Interim data presentation
The interim results from DALY II USA were presented at the 66^thAmerican Society of Hematology (ASH) Annual Meeting on December 7, 2024, in San Diego, California by Dr. Nirav Shah at the 9.30 am (PT) session 628: Aggressive Lymphomas: Cellular Therapies: Novel Strategies for Cell Therapies in Aggressive Lymphomas.

DALY II USA interim results¹
Interim analysis data (cutoff: March 29, 2024), showed that investigational zamtocabtagene autoleucel (zamto-cel) has a favorable safety profile and promising overall response rate (ORR) and complete response rate (CRR) in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).

At the data cutoff, 59 of all treated patients (N=69) had received fresh, conforming zamto-cel and completed ≥3 months of follow-up. Efficacy endpoints were assessed in the evaluable population (n=59), and safety endpoints were assessed in the safety population (N=69).

• The overall response rate (ORR) as assessed by an Independent Radiology Committee (IRC) was 72.8% (95% CI, 59.7–83.6). The complete response rate (CRR) was 50.8% (95% CI, 35.9–62.5).
• The median duration of response (DOR) was 11.4 months.
• At 6-months and 12-months, progression free survival (PFS) was 55% (95% CI, 41.0–67.0) and 42% (95% CI, 28.0–56.0), respectively. At 12-months, overall survival (OS) was 72% (95% CI, 57.0–83.0).
• Grade 1–2 cytokine release syndrome (CRS) occurred in 46.4% patients (n=32).
• Immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 1–2 occurred in 13% (n=9) patients and grade 3 in 4.3% (n=3) patients, respectively.
• Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), occurred in 1 patient, which resolved after 2 days.

About DALY II USA¹
DALY II USA (NCT04792489) is a multi-center, single arm Phase II trial evaluating the safety and efficacy of genetically engineered autologous cells expressing anti-CD20 and anti-CD19 specific chimeric antigen receptor, zamtocabtagene autoleucel (zamto-cel), administered fresh in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

Eligible patients were adults with R/R DLBCL after at least 2 prior lines of treatment, including anti- CD20 monoclonal antibody and anthracycline-containing regimen, and had measurable disease at baseline (Lugano 2014 classification).² Zamto-cel was administered as a fresh, non-cryopreserved formulation in a single dose (at 2.5 x 10⁶ CAR+ cells/kg body weight on Day 0, per trial protocol) after lymphodepletion chemotherapy with cyclophosphamide/fludarabine or bendamustine.

The primary endpoint is overall response rate (ORR) defined as best overall response (BOR) of either complete response (CR) or partial response (PR). Secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and CD19 and CD20 antigen expression at relapse.

These data were reported as part of a pre-planned interim analysis, and the trial plans to enroll 100 evaluable patients and final data will be present upon trial completion.

About zamtocabtagene autoleucel (zamto-cel)¹
Zamto-cel is an investigational autologous tandem CD20/CD19 directed non-cryopreserved chimeric antigen receptor (CAR) T cell product, administered to patients with third-line relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) in the DALY II USA clinical trial. Zamto-cel is manufactured utilizing the CliniMACS Prodigy® (Miltenyi Biotec), a closed, automated system with a 14-day vein-to- vein time and administered as a fresh formulation.

About Miltenyi Biomedicine³
Miltenyi Biomedicine is committed to making innovative cancer treatments and regenerative therapies accessible to patients with serious diseases. Leveraging cutting-edge technology, the company innovates independently to address hard-to-treat blood cancers and harness the potential of CAR technology to transform patient care. Miltenyi Biomedicine is currently investigating its first cell therapy asset.

About Miltenyi Biotec⁴
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. Shah NN, et al. In 66th American Society of Hematology Annual Meeting. San Diego, California. Online abstract. Available at: https://ash.confex.com/ash/2024/webprogram/Paper208539.html[Accessed November 2024].
2. Cheson BD, et al. J Clin Oncol 2014; 32(27):3059–68.
3. Miltenyi Biomedicine. About us. Available at: https://www.miltenyibiomedicine.com/about/[Accessed November 2024].
4. Miltenyi Biotec. About us. Available at https://www.miltenyibiotec.com/about-us [Accessed November 2024].

MAT-GL-ASH24-20.1
Date of Preparation: December 2024