Medigene AG: Interim analysis from ongoing Phase I/II clinical trial with DC vaccines in AML patients presented at EHA

Martinsried/Munich (pta009/17.06.2019/07:30 UTC+2) -
- Very good feasibility for manufacture of vaccines from patient-derived cells
- Excellent safety and tolerability profile
- Encouraging data on overall survival and progression-free survival
- Mutational load analysis may allow patients to be stratified in future clinical trials.

Medigene AG (FWB: MDG1, Prime Standard) announced today that clinical data from the interim analysis of the ongoing Phase I / II clinical trial with Medigene's DC vaccine for the treatment of acute myeloid leukemia was presented during the annual congress of the European Hematology Association (EHA) taking place from 13 - 16 June in Amsterdam.

The poster presented was entitled "Interim Analysis of a WT-1 and PRAME `Fast-DC´ vaccine shows safety as active immunotherapy for the prevention of AML relapse". The primary objectives of the study enrolling 20 AML patients are the safety and feasibility of this active immunotherapy with patient-derived DCs produced according to Medigene's proprietary technology.

The data presented was generated over a period of one year of vaccination of all patients representing an interim dataset after half of the treatment period. Topline data of this interim analysis was already published on 19 December 2018, demonstrating a very good feasibility for manufacture of the vaccines as well as an excellent safety profile and encouraging data on overall survival and progression-free survival (Link to press release: http://tiny.cc/f2377y).

In addition, the data presented at EHA included details about the mutational load status of patients who relapsed.

Clinical trial outline: 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, vaccinated and followed up for 12 months at the interim analysis timepoint. Subjects in this trial had AML that was positive for Wilms Tumor-1 (WT-1) antigen with or without positivity for Preferentially Expressed Antigen in Melanoma (PRAME). Vaccination with dendritic cells, presenting the antigens WT-1 and PRAME, was carried out monthly, 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).

Interim results: The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and mild in nature (Grade 1). The feasibility of the manufacture of the dendritic cell vaccine in these chemotherapy-pretreated subjects was already presented at AACR in 2018 (Link to poster: https://www.medigene.de/fileadmin/download/ab-stracts/180414_AACR_2018_Poster_DC_vaccine_Medigene.pdf).

After a 12-months treatment period, the overall survival was 89% (18 of 20 patients, 95% confi-dence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after initiation of vaccination, suggesting a possible molecular relapse upon entering the study.

The presence of common mutations was analyzed in all patients via next generation sequencing and two of the five early relapses showed mutational load upon entering the study (IDH2 and DNMT3A mutation in one patient and multiple mutations in the second (RUNX1, KRAS, ETV6, BCOR, DNMT3A). Two of the later relapses also showed mutational load before vaccination, one patient with a KRAS and TET2 mutation and one patient with multiple mutations (RUNX1, IDH2, SRSF2 and DNMT3A).

Dr. Kai Pinkernell, CMO and CDO of Medigene AG, comments: " We are pleased that the interim results after one year of treatment show an excellent safety profile, a very good manufacturability and encouraging overall and progression free survival data. In addition, the mutational load analysis may also allow patients to be stratified in future clinical trials."

The completion of the ongoing trial is scheduled for the end of 2019, following a two-year treatment period.

About acute myeloid leukaemia (AML): Acute myeloid leukaemia is a malignant disease of the hematopoietic system, affecting mainly adults above 60 years of age. In Germany, about 3,600 cases are registered annually.

AML is caused by uncontrolled growth of dysfunctional hematopoietic precursor cells in the bone marrow. 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 treatment is often started with intensive chemotherapy, followed by consolidation with or without allogeneic hematopoietic stem cell transplantation. Unfortunately, a significant proportion of patients suffer a relapse of the original disease. Depending on the biologic risk profile of the disease, age and co-morbidity the long-term survival is highly variable.

About Medigene's DC vaccines: In addition to Medigene's development 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) can take up antigens, process them and present peptides on their surface in a form that can induce antigen-specific T cells to mature and proliferate. In this way, T cells recognize and eliminate tumor cells which bear the same antigen peptide on their surface. Dendritic cells can also induce natural killer cells (NK cells) to attack tumor cells. The scientific team of Medigene has developed new, fast and efficient methods for generating autologous (patient-specific) mature dendritic cells which have the relevant characteristics to generate very strong T cell and NK cell immune responses. The dendritic cells 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 to such an extent by chemotherapy that the prevention of the recurrence of the tumor disease is the main goal.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard) is a publicly listed 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 the focus on T cell-receptor modified T cells (TCR-Ts) and has associated projects currently in pre-clinical and clinical development.

For more information, please visit http://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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