Martinsried / Munich, Germany (Press Release) – 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

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

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.

About Medigene

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

Forward-Looking Statements

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.

Source: Medigene.