Medigene AG: Positive final 2-year topline data in completed DC vaccine Phase I/II trial in AML patients

Martinsried/Munich (pta017/10.01.2020/14:25 UTC+1) * Final topline primary outcomes: DC vaccinations safe and feasible at 24 months of treatment
* Topline secondary outcomes: Overall survival rate (OS) of 80% (16 of 20 patients), progression-free survival rate (PFS) of 55% (11 of 20 patients)
* In the subgroup of patients at or over 60 years of age, OS of 80% (8 of 10 patients), PFS of 50% (5 of 10 patients)
* Successful manufacturing of DC vaccine from chemotherapy pre-treated AML patients
* Presentation of detailed medical data at upcoming scientific conferences

Martinsried/Munich, 10 January 2020. Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, today publishes topline results from its completed open-label Phase I/II clinical trial of Medigene's autologous dendritic cell (DC) vaccine in 20 patients with acute myeloid leukemia (AML). The study was conducted at the Oslo University Hospital, Norway. Data were collected shortly after completion of the clinical trial, i.e. after 24 months of vaccination and follow-up of all patients.

The trial's primary outcome measures assessing 1) the feasibility of DC vaccine manufacturing/administration, and 2) its safety/tolerability over 2 years, were successfully achieved. The DC vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment.

The secondary outcome measures evaluating key clinical parameters show that after 24 months of treatment overall survival rate (OS) was 80% (16 of 20 patients, 95% confidence interval (CI): 55 to 92%) and progression free survival rate (PFS) was 55% (11 of 20 patients, 95% CI: 31 to 74%).

In the current AML treatment paradigm, patients 60 years of age or older are often ineligible for hematopoietic stem cell transplantation and have poorer treatment outcomes. This group accounted for 50% of patients in this trial (risk groups good, intermediate, poor: 4, 4, 2) and an excellent OS of 80% (8 of 10 patients, 95% CI: 41 to 95%) and a PFS of 50% (5 of 10 patients, 95% CI: 18 to 75%) was observed at 24 months. In the patient group younger than 60 years of age (risk groups good, intermediate, poor: 9, 1, 0), also an excellent OS of 80% (8 of 10 patients, 95% CI: 41 to 95%) and a PFS of 60% (6 of 10 patients, 95% CI: 25 to 83%) was observed at 24 months.

As disclosed at the time of the 12-months interim analysis in December 2018, in patients where disease relapsed, most cases (5 out of 8) occurred within the first 80 days after the start of the vaccination. These early relapses were investigated by molecular mutational analysis which suggested that some relapses had already begun on a molecular level at the time of entry into the study.

Dr. Yngvar Floisand, Head Physician of the Department of Hematology at the Oslo University Hospital and Principal Investigator of the trial, comments: "New treatment options are desperately needed for patients with AML. The disease progresses rapidly and may be fatal within a few weeks or months, if untreated. Even despite having received a treatment, the majority of predominantly elderly patients continue to experience minimal residual disease burden that sooner or later leads to relapse of the disease. Medigene's DC vaccine trial was designed towards potentially making new treatments available for these patients, specifically aiming at reducing the risk of relapse in treated patients after completing conventional chemotherapy.

The now final topline results from this Phase I/II clinical trial with patient-derived DCs confirm the previously published promising 12-months interim analysis. The clinical outcome is encouraging, not only regarding the excellent safety and tolerability profile, but also for an overall survival when it comes to secondary endpoints."

Prof. Dolores Schendel, CEO and CSO of Medigene AG, comments: "We are pleased with these positive and promising results from the first clinical trial of our DC vaccine. We thank all the patients for participating in the trial and the study team for their efforts and contributions. In the future, this novel clinical approach could offer a treatment possibility for AML patients who have insufficient treatment options and face the risk of relapse. We are looking forward to providing further updates. More detailed data and analyses will be presented at upcoming scientific conferences."

- end of press release -

Related News

10 December 2019, Interim 1-year clinical immune monitoring data from DC vaccine trial in AML presented at ASH 2019 Annual Meeting
17 June 2019, Interim analysis from ongoing Phase I/II clinical trial with DC vaccines in AML patients presented at EHA
8 January 2019, Additional European patent granted for Medigene's DC vaccine platform
19 December 2018, Medigene publishes topline interim data from ongoing Phase I/II clinical trial with DC vaccines in AML patients
19 April 2018, Medigene presents data on the successful production of AML DC vaccines at AACR conference

Further information

About Medigene's DC vaccines

In addition to Medigene's focus on T cell-receptor modified T cells (TCR-Ts), the Company has developed a new generation of antigen-tailored dendritic cell (DC) vaccines.
Dendritic cells (DC) are a specialized type of immune cells. They patrol throughout our body, take up antigens, process them and present short peptides on their cell surface. These peptides are recognized by other types of immune cells such as T cells or natural killer (NK) cells, which then become activated. In this way, the activated immune cells are enabled to recognize and eliminate tumor cells.
The scientific team of Medigene has developed new, fast and efficient methods for generating autologous (patient-specific) mature DCs which have the relevant characteristics to generate very strong T cell and NK cell immune responses. The DCs can be loaded with various tumor antigens to treat different forms of cancer. Since an immune response builds up over the total time of administration of the DC vaccine, this form of therapy is particularly designed for patients who suffer from a tumor disease which has been reduced by chemotherapy to such an extent that the prevention of the recurrence of the tumor disease is the main goal.

About acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) is a malignant disease of the hematopoietic system, affecting mainly adults above 60 years of age.
AML is a heterogeneous type of cancer affecting patients' blood and bone marrow. It is characterized by an overproduction of myeloid progenitor cells named myeloblasts or leukemic blasts. These cells prevent the generation of normal blood cells, causing a decrease in erythrocytes and platelets, for example. Typical symptoms of AML include anemia, fever, increased risk of infection, and bleeding. AML progresses rapidly and may be fatal within a few weeks or months, if untreated.
AML is typically treated initially with intensive induction chemotherapy in order to achieve remission. Some patients are eligible to receive additional chemotherapy or an allogeneic hematopoietic stem cell transplant (HSCT), which increases the potential for eradication of residual tumor cells. However, HSCT induces high morbidity and mortality and only less than half of the AML patients can be treated with HSCT.
Additionally, elderly patients may be unable to complete the full regimen of intensive chemotherapy due to its high toxic side effects. Thus, the majority of elderly patients remain undertreated and continue to experience minimal residual disease (MRD) burden that sooner or later will lead to leukemia relapse*.

*Webster JA, Pratz KW. "Acute myeloid leukemia in the elderly: therapeutic options and choice." Leuk Lymphoma. 2018 Feb;59(2):274-287. Epub 2017 Jun 2. Review.
Löwenberg B, Ossenkoppele GJ, van Putten W, et al. 2009: "High-dose daunorubicin in older patients with acute myeloid leukemia." N Engl J Med ;361:1235-48.
Röllig C, Thiede C, Gramatzki M, Aulitzky W, Bodenstein H, Bornhäuser M, Platzbecker U, Stuhlmann R, Schuler U, Soucek S, Kramer M, Mohr B, Oelschlaegel U, Stölzel F, von Bonin M, Wermke M, Wandt H, Ehninger G, Schaich M; Study Alliance Leukemia. "A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial." Blood. 2010 Aug 12;116(6):971-8. doi: 10.1182/blood-2010-01-267302. Epub 2010 May 4.
Wheatley K1, Brookes CL, Howman AJ, Goldstone AH, Milligan DW, Prentice AG, Moorman AV, Burnett AK; United Kingdom National Cancer Research Institute Haematological Oncology Clinical Studies Group and Acute Myeloid Leukaemia Subgroup. "Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials." Br J Haematol. 2009 Jun;145(5):598-605. doi: 10.1111/j.1365-2141.2009.07663.x. Epub 2009 Mar 26.

About the DC study design

The DC study (NCT02405338) was designed as an open-label trial at Oslo University Hospital, Norway. A total of 20 subjects (median age 59, range 24 to 73) with AML (risk groups good, intermediate, poor: 13, 5, 2), in morphologic complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction or consolidation therapy, not eligible for allogeneic hematopoietic stem cell transplantation, were enrolled into this safety and feasibility Phase I/II trial.
Patients participating in the trial had AML that was positive for Wilms Tumor-1 (WT-1) antigen with or without positivity for Preferentially Expressed Antigen in Melanoma (PRAME). Patients were vaccinated with their WT-1/PRAME DC vaccines monthly over a 24-month period (with a higher frequency within the first 6 weeks). AML diagnoses had been established with a median of 9.8 months before the first vaccination (range 4.5 to 17.5 months), and the last chemotherapy infusion had been performed at a median of 6.9 months (range 2 to 14.8 months).

About Medigene

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard) is a publicly listed, clinical-stage biotechnology company headquartered in Martinsried near Munich, Germany.
The Company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.
Read more about Medigene's company profile: www.medigene.com

This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.

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