Medigene AG: Medigene announces dosing of first patient in Phase I/II trial with TCR therapy MDG1011 for various blood cancers

Martinsried/Munich (pta028/26.02.2019/12:36 UTC+1) Medigene AG (FSE: MDG1, Prime Standard, SDAX), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, announced today that it has dosed the first patient in its first-in-human clinical trial with its TCR therapy candidate MDG1011. The Phase I/II trial investigates the safety and feasibility of MDG1011 for the treatment of various types of blood cancer, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM). MDG1011 is a novel immunotherapy candidate using patient-derived, T cell receptor (TCR)-modified T cells targeting the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma) and was administered for the first time to a multiple myeloma patient in the Department of Medicine 5 (Director Prof. Dr. Andreas Mackensen) at the Universitätsklinikum Erlangen, Germany. MDG1011 is designed as a one-time treatment.

Dr. Kai Pinkernell, CMO/CDO of Medigene, comments: "Hematologic cancers such as AML, MDS and MM in advanced stages are difficult to treat and usually associated with a very poor prognosis for patients. With our TCR therapy, we hope to open new treatment options for seriously ill patients and the first-time use on patients is a very important step in the development of this new therapeutic candidate."

In the Phase I portion of the trial, approximately 12 patients who are suffering from advanced stage AML, MDS and MM and have previously undergone several cycles of standard therapies will be treated with MDG1011. PRAME expression on the tumor cells as well as the blood serotype HLA-A * 02:01 are further inclusion criteria for patients who can participate in this multicenter, open-label, dose escalation study using a 3 + 3 design. Three dose cohorts and an optional fourth dose cohort will test dose ranges from 100,000 to 10,000,000 transduced T cells per kg of body weight. Each dose cohort consists of 3 patients. At least one MM patient and at least one AML or MDS patient need to be included in each cohort. Patients will undergo preconditioning treatment with cyclophosphamide and fludarabine. After completing treatment of all patients in a dose cohort and a four-week safety follow-up period, dose escalation will be determined by an independent Data and Safety Monitoring Board (DSMB). The primary endpoint for the Phase I portion of this clinical trial will be safety and feasibility at three months with a total follow-up period of up to 12 months. Several secondary endpoints (i.e. overall response rate (ORR)) will be assessed as well.

In the Phase II portion of the trial, presumably two of the three indications will be carried forward after a positive DSMB assessment regarding the safety of MDG1011 and review by the competent authority and central ethics committee. In the Phase II portion, 40 HLA-A*02:01 and PRAME positive patients will be treated with MDG1011; another 40 patients, who are positive for PRAME but negative for HLA-A*02:01, will be included in the control groups (20 treated and 20 control patients per indication) and treated with investigator choice therapy. Co-primary endpoints of the Phase II portion are safety and preliminary efficacy, where efficacy is measured as ORR at 3 months. Several secondary endpoints will be assessed here as well.

The clinical trial is being conducted by the Department of Internal Medicine III of the University Hospital Regensburg (Director: Prof. Dr. Wolfgang Herr) under the leadership of the coordinating investigator PD Dr. Simone Thomas, as well as by the University Hospitals of Erlangen and Würzburg, Germany. Up to five additional clinical centers in Germany are currently being opened and are anticipated to open recruitment within the next three to five months and screen additional patients for their suitability to participate in the study.

About Medigene's TCR therapy: The TCR-T cell technology aims at arming the patient's own T cells with tumor-specific T cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient's tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient's T cells outside the body (ex vivo). TCR-T therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy. Medigene is establishing a pipeline of recombinant T cell receptors and has a collaboration with bluebird bio, Inc. for the development of six TCR-Ts.

About acute myeloid leukemia (AML): AML is a malignant disease of the hematopoietic system. The cause of the disease is the uncontrolled growth of nonfunctioning hematopoietic progenitor cells in the bone marrow. Typical symptoms of AML are anemia, fever, increased susceptibility to infection and bleeding. The disease develops rapidly and, if left untreated, can lead to death within a few weeks or months. AML therapy is usually started with intensive chemotherapy, often followed by consolidation therapy, with or without allogeneic hematopoietic stem cell transplantation. In a significant number of patients, relapse of the disease is expected.

About multiple myeloma (MM): Multiple myeloma (MM) is a malignant disease characterized by monoclonal plasma cell proliferation in the bone marrow, with increased production of complete or incomplete monoclonal immunoglobulins. These proteins are detectable in serum and / or urine. Every year around 3,000 men and about 2,700 women in Germany develop multiple myeloma. MM is thus the third most frequent hematological neoplasia after leukemia and non-Hodgkin's lymphoma and responsible for about 1% of all cancers in Germany.

About myelodysplastic syndrome (MDS): The term myelodysplastic syndrome is a group of diseases of the bone marrow, in which blood formation does not originate from healthy, but from mutated cells of origin (stem cells). The bone marrow of patients suffering from myelodysplastic syndromes is no longer able to produce fully mature and functional blood cells from these stem cells. In advanced stages of these diseases, more and more immature blood cells are produced. The blood formation process is therefore permanently disturbed and may also lead to acute myeloid leukemia (AML) in some patients at a later date.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, SDAX) 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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