Immunotherapies are being researched and developed worldwide as innovative methods for treating cancer. Medigene’s immunotherapies are based on targeted strengthening of the immune system, using the body’s own defence mechanisms, and are currently being tested in clinical trials for the benefit of critically ill patients. We are working on making the body’s own T cells usable in fighting serious diseases.

In spring 2015, Medigene made progress in terms of an important development stage and launched its first own clinical trial with its DC vaccines. Together with the current academically-led clinical trials, Medigene is set to obtain important findings and further data on the clinical application and safety of active immunotherapy. Additionally, the Company prepares the start of a clinical TCR study to be initiated in 2016 as part of a consortium with academic partners.

Medigene's Immunotherapies

Medigene is working on three complementary personalised immunotherapeutic strategies to treat various types of cancer in different stages. The focus is always on T cells. These white blood cells are tasked with identifying and attacking pathogens. However, they often fail to detect cancer cells. Medigene’s immunotherapies activate, prepare and “train” the patient’s own T cells in the targeted detection of tumour cells and their destruction. At the same time, any unwanted T cells, for example in several types of T cell leukaemia, can be identified and removed. This approach is aimed at facilitating effective, long-term treatment of diseases.

DCs

Medigene’s dendritic cell vaccines (DC vaccines) are therapeutic vaccines geared to treating types of cancer in patients with a low tumour burden. Dendritic cells activate the body’s own, specific T cells to treat disease. The use of DC vaccines in combination with other types of cancer treatment is also conceivable. 

With its most advanced immunotherapy platform, Medigene develops new generation antigen-tailored DC vaccines. Dendritic cells can take up and process antigens, and then present them on their surface in a form that can induce antigen-specific T cells to proliferate and mature. This enables T cells to recognise and eliminate antigen-bearing tumour cells. Dendritic cells can also induce natural killer cells to attack tumour cells.

The Medigene team has developed new, fast and efficient methods for generating autologous (patient-specific) mature dendritic cells which have the relevant characteristics to activate T cells. The dendritic cells can be loaded with various tumour antigens to treat different types of cancer.

DC vaccines which use Medigene’s technologies are being clinically evaluated. A clinical phase I/II investigator-initiated trial (IIT) to treat acute myeloid leukaemia (AML) is ongoing at the Ludwig-Maximilian University Hospital Großhadern, Munich, under the supervision of Prof. Marion Subklewe. Another phase II IIT to treat prostate cancer is in progress at Oslo University Hospital, led by Prof. Gunnar Kvalheim. He also treats patients there with DC vaccines in compassionate use1).

Initial positive clinical data from these programmes was presented by Medigene’s cooperation partners at several international conferences in 2015.

In April 2015, Prof. Gunnar Kvalheim gave a presentation at the Annual Meeting of the American Association for Cancer Research (AACR) in Philadelphia, PA, USA. The poster presentation showed data from patients with various solid tumours. All patients with solid tumours survived progression-free for longer than would normally be expected at their stage of the disease.

As part of the Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL, USA, clinical data on several AML patients was presented in December 2015, from both the ongoing IIT at University Hospital Munich and compassionate use patients at Oslo University Hospital. The safety profile of the DC vaccines used was very good. In addition, the vaccines generated a T-cell response in older AML patients who were not eligible for stem cell transplants.

In March 2015, Medigene announced the start of a clinical phase I/II trial with DC vaccines to treat acute myeloid leukaemia (AML). The trial is being conducted in cooperation with Oslo University Hospital in Norway and is Medigene’s first own clinical trial of personalised DC vaccines. This trial involves AML patients who have undergone chemotherapy and whose risk of relapse is to be reduced with the DC vaccines. Additional clinical data regarding the application and safety of active immunotherapy is also collected as part of the trial. Following an initial stage with six patients (phase I trial), Medigene plans to treat a further 14 patients in a subsequent phase II trial.

In March 2015, the European Patent Office granted a patent with a term until 2027 to protect the manufacturing process of mature dendritic cells, which was co-developed by Medigene scientists. In May 2015, Medigene announced that a different U.S. patent had been extended until 2031. The previous term was to end in 2028. Medigene has an exclusive licence to these patents that are central to the DC programme.

Outlook: in 2016, Medigene will continue the phase I/II trial to treat acute myeloid leukaemia (AML) as planned, which was originally launched in March 2015. Further studies utilising Medigene’s DC vaccine technologies include investigator-initiated trials (IITs) at Oslo University Hospital (a phase II trial in prostate cancer) and at Ludwig-Maximilians University Hospital Grosshadern, Munich (a phase I/II trial in AML). Moreover, compassionate use patients care currently treated with DC vaccines at the Department of Cellular Therapy at Oslo University Hospital.

1) Compassionate use: Prescription of as-yet unapproved drugs in particularly severe cases where there are no treatment alternatives

  • DC vaccines activate T cells to attack cancer cells.

    DC vaccines are therapeutic vaccines aiming to induce immune responses in cancer patients to treat low tumour burdens.

    tumour
    T cell
    DC vaccine
  • DC vaccines activate T cells to attack cancer cells.

    Dendritic cells activate the body’s own T cells, which can then attack cancer cells.

    tumour
    T cell
    DC vaccine
  • DC vaccines activate T cells to attack cancer cells.

    Some of the activated T cells remain in the body after treatment. These cells have a memory and can independently trigger an immune response on the reappearance of cancer cells.

    tumour
    T cell
    DC vaccine

TCRs

Medigene develops TCR-based T-cell therapy to treat cancer in advanced stages where there is a high tumour burden. TCR stands for T-cell receptors. The aim is to modify the body’s own T cells so that they detect tumours with the help of specific T cells and attack them on a targeted basis.

This form of immunotherapy aims to overcome the patient’s tolerance to cancer cells, and the tumour-induced immunosuppression in the patient, by activating and modifying the patient’s T cells outside the body (ex vivo). This makes it possible to give patients a large number of specific T cells to fight the tumour within a short period of time.

Medigene is developing a growing library of recombinant TCRs on this platform. Moreover, a good manufacturing practice (GMP) compliant process for their combination with patient-derived T cells is currently being established.

In March 2015, the highly regarded journal Nature Biotechnology published a scientific article on positive TCR research results. The findings were collected as part of a research alliance between Prof. Thomas Blankenstein, Director of the Institute for Medical Immunology of Charité – Universitätsmedizin Berlin hospital and leader of a working group at the Max Delbrück Center for Molecular Medicine (MDC), Berlin, in close cooperation with Prof. Dolores Schendel. The alliance has been supported by German Research Foundation (Deutsche Forschungsgemeinschaft; DFG) since 2006; Medigene is a DFG member.

In September 2015, the Helmholtz Centre in Munich, a Medigene cooperation partner, presented data at the European Congress of Immunology in Vienna, which was collected as part of the transregional Collaborative Research Centre “Principles and Applications of Adoptive T-cell Therapy” of the DFG (Deutschen Forschungsgemeinschaft). In the same month, Medigene presented a poster with the title “Expitope: A webserver for TCR candidate validation” at the Inaugural International Cancer Immunotherapy Conference in New York.

In January 2016, Medigene reported on its cooperation with the University of Lausanne in researching new technologies for the characterisation of TCRs. The goal is to establish a faster and better method for selecting tumour-specific T cells characterised by expression of suitable TCRs. They will then be transferred to Medigene’s expanding TCR library.

Outlook: the development of a GMP compliant manufacturing process for adoptive T-cell therapy using TCR-modified T cells will be continued. Medigene is preparing the clinical development of the first product candidates. In addition, novel TCRs with specificities for promising tumour-associated antigens will be isolated and further characterised. In the coming years, Medigene aims to initiate up to three clinical trials based on this therapeutic approach. The first is to be started in 2016 (IIT phase I study with the participation of Medigene, subject to grant funding). Medigene sponsored trials are scheduled to start in 2017 and 2018 respectively.

  • Adoptive T cell therapy for treating advanced stages of cancer.

    Medigene develops a TCR-based therapy for the treatment of advanced cancers with high tumour burden.

    tumour
    T cells
    TCR-modified T cell
    Viral-vector mediated TCR transfer
  • Adoptive T cell therapy for treating advanced stages of cancer.

    The aim is to modify the body’s own T cells with tumour-specific T cell receptors so that they can recognise and target the tumour.

    tumour
    T cells
    TCR-modified T cell
    Viral-vector mediated TCR transfer
  • Adoptive T cell therapy for treating advanced stages of cancer.

    Those modified T cells lead to the destruction of tumour cells in a targeted way.

    tumour
    T cells
    TCR-modified T cell
    Viral-vector mediated TCR transfer

TABs

Medigene’s TABs therapy is aimed at treating T-cell-induced diseases such as T-cell leukaemias. TABs stands for T-cell-specific AntiBodies.

Medigene is working on generating monoclonal antibodies which are able to recognise and distinguish different T cells. These TABs identify and mark T cells in the body and can also remove unwanted T cells, for example in T-cell leukaemias. Medigene intends to produce and characterise monoclonal antibodies which are able to distinguish between different T cells. Proof of technology was established in preclinical studies.

Outlook: preclinical development of T-cell-specific-monoclonal antibodies (TABs) will continue with the aim of achieving proof of principle.

  • T cell specific antibody therapy to remove unwanted T cells.

    Under some circumstances the body's own T cells can attack own healthy cells as in many autoimmune diseases, instead of protecting the organism.

    T cell
    Pathogenic T cell
    T cell specific antibody
  • T cell specific antibody therapy to remove unwanted T cells.

    TABs immunotherapy aims to target and fight those “pathogenic” T cells that are causing these diseases.
    Medigene develops monoclonal antibodies, which are able to recognize and distinguish between healthy and pathogenic T cells.

    T cell
    Pathogenic T cell
    T cell specific antibody
  • T cell specific antibody therapy to remove unwanted T cells.

    As a result of therapeutic treatment, the unwanted T cells will be eliminated and a full immunological defence is provided by all the remaining untouched healthy T cells. This has been proven by preclinical studies.

    T cell
    Pathogenic T cell
    T cell specific antibody

PIPELINE

 

At Medigene, the focus is on developing personalised immunotherapies centred on different types of leukaemia. Following the Company’s first own clinical DC vaccines trial, further product candidates are to be included in trials. 

Chart: Medigene Pipeline Chart: Medigene Pipeline

Every innovative drug starts with the search for a new active pharmaceutical ingredient. Once potential product candidates for new drugs have been defined, they must be tested in mandatory preclinical and clinical studies for quality, safety and efficacy before they are approved for marketing by the medicines agencies. This process is completed in several stages.

  • PRECLINICAL:

     

    In the preclinical phase of drug development, a new active substance is tested outside human beings in safety and effectiveness trials.

  • CLINICAL PHASE I:

     

    In the clinical phase I, the new potential active substance is tested for the first time on healthy human beings (on patients in oncology) to test the toxicity and the dosage of the substance.

  • CLINICAL PHASE II:

     

    In the clinical phase II, the first trial of the effectiveness of the new drug candidate are carried out on patients.

  • CLINICAL PHASE III:

     

    In clinical phase III, trials of the potential product candidate are carried out on a substantial number of patients for statistically significant safety and effectiveness data.

  • APPROVAL:

     

    During the approval process, the competent authority decides whether the drug candidate can be approved for marketing. The decision is based on an application, which contains summarised and evaluated data on manufacturing and the results of preclinical and clinical trials.

NON-CORE PRODUCTS (marketed and partnered products)

As part of its non-core business, Medigene achieves sales with the drug Veregen®, which is marketed globally by partner distributor companies. In December 2015, Medigene sold EndoTAG®, an advanced drug candidate, to its existing licence partner SynCore. Medigene licensed another advanced drug candidate in 2014, RhuDex®, to the partner company Falk Pharma, which assumes the cost and responsibility for its further development.

Read more about drugs and drug candidates that are non-core business for Medigene:
Group Management's Discussion and Analysis 2015

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