The innovative approach of immunotherapy is regarded as crucial new-generation future technology for the treatment of cancer and other serious diseases. Immunotherapy specifically strenghens the immune system, using the body’s own defence mechanisms. Dedicated to advance these innovative approaches to help patients who are seriously ill, we are working at harnessing T-cells to combat serious diseases.

Medigene has positioned itself in the area of personalised immunotherapies. Through the acquisition of Trianta Immunotherapies (now Medigene Immunotherapies) in 2014, Medigene has secured excellent knowledge of the mechanisms of the immune system as well as innovative platforms within this ground-breaking field. This will offer opportunities for both scientific and economic development. 

Medigene Immunotherapies

Medigene is working on three complementary immunotherapy strategies for the treatment of different forms and stages of cancer with focus on T-cells. The role of these white blood cells is to identify and combat pathogens. However, they frequently fail to recognize cancer cells. Medigene’s immunotherapies activate, prepare and “train” patients’ own T-cells to detect and destroy tumour cells specifically. On the other hand, unwanted T-cells, such as in the case of autoimmune diseases, can be identified and removed. The aim is to combat diseases effectively and over longer periods.

DCs

Dendritic cell vaccines, in short DC vaccines, are therapeutic vaccines aiming to induce immune responses in cancer patients to treat low tumour burdens. Find out more about DCs

TCRs

Medigene develops a TCR-based therapy for the treatment of advanced cancers with high tumour burden. TCR stands for T cell receptor. 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. Find out more about TCRs

TABs

Medigene’s TABs therapy is aimed to treat T cell mediated diseases, such as T cell leukaemia and autoimmune diseases. TABs stands for T-cell-specific AntiBodies. Those help to identify and eleminate unwanted T cells. Find out more about TABs

PIPELINE

Medigene concentrates on the development of personalized T cell immunotherapies with focus on haematological malignancies. Medigene is the first German biotech company to have revenues from a marketed product, which is distributed by commercial partners companies. Medigene has advanced drug candidates which are licensed to partners and additional candidates in clinical development. The company is developing highly innovative treatment platforms concentrating on cancer and autoimmune diseases.

  • 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.

Each innovative drug starts with the search for a new active substance. If potential product candidates for new drugs have been defined, they must be tested for their quality, clinical safety and effectiveness in prescribed pre-clinical and clinical trials, before they can be approved by the drug authorities for marketing. This takes place in several phases.

Immunotherapy Platforms

Medigene is developing three complementary, personalized immunotherapy platforms for treating different forms and stages of cancer with programmes in clinical and preclinical development: Dendritic cell vaccines (DCs), T-cell receptor-based adoptive T-cell therapy (TCRs) and T-cell-specific monoclonal antibodies (TABs).

FOCUS IMMUNOTHERAPIES
  • 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

DCs

With Medigene’s most advanced platform the company develops new generation antigen-tailored dendritic cell (DC) vaccines.

Dendritic cells can take up antigens efficiently, process them and present them on their surface in a form that can induce antigen-specific T cells to proliferate and mature. This way T cells can recognisze and eliminate antigen-bearing tumour cells. Dendritic cells can also induce natural killer cells (NK cells) to become active and attack tumour cells. Scientists of Medigene Immunotherapies have developed new, fast and efficient methods for generating autologous (patient-specific) mature dendritic cells which have relevant characteristics to activate both T cells and NK cells. The dendritic cells can be loaded with various tumour antigens to treat different types of cancer. DC vaccines are being evaluated in two ongoing, externally funded investigator-initiated trials: a clinical phase I/II trial in acute myeloid leukaemia (AML) at the Ludwig-Maximilian University Hospital Großhadern, Munich, in cooperation with Prof. Marion Subklewe and Prof. Wolfgang Hiddemann, and a clinical phase II trial in prostate cancer at the Oslo University Hospital in cooperation with Prof. Gunnar Kvalheim. Moreover, a compassionate use programmeme  is being conducted at the Department of Cellular Therapy at the Oslo University Hospital, Norway, under the responsibility of Prof. Gunnar Kvalheim.

Positive clinical data of these programmes were presented by Medigene’s cooperation partners at several international conferences in 2014. The abstracts of these presentations are available at Medigene’s company website.

In September 2014, the Oslo University Hospital presented initial clinical data on their investigator-initiated clinical phase II trial for the treatment of prostate cancer-patients at the 14th International Conference on Progress in Vaccination Against Cancer (PIVAC) in Rome, Italy.

In November 2014, initial clinical data on Medigene’s DC vaccine for the treatment of AML were presented at the SITC (Society for Immunotherapy of Cancer) 29th Annual Meeting in National Harbor/Washington D.C., USA showing clinical data collected in the current investigator-initiated phase I/II clinical trial conducted at the Ludwig-Maximilians University Hospital Großhadern, Munich, Germany.

Additionally, the Oslo University Hospital presented early clinical data from patients with various types of tumours  collected in its compassionate use programmeme at the 56th American Society of Hematology (ASH) Annual Meeting in San Francisco, USA, in December 2014.

Preclinical data on its DC vaccine programmeme were presented by Medigene at the 13th International Dendritic Cell Symposium (DC 2014) in Tours, France, and at the 14th International Conference on Progress in Vaccination Against Cancer (PIVAC) in Rome, Italy, in September 2014 as well as in the October 2014 volume of the scientific journal “Cancer Immunology, Immunotherapy.”

In March 2014, the US Patent Office issued a patent relating to the manufacturing of mature, polarised dendritic cells. The patent has a term until 2028 and is licenced exclusively to Medigene Immunotherapies (formerly Trianta) by Helmholtz Zentrum München - German Research Center for Environmental Health (HMGU).

Moreover, Medigene announced that the development team for dendritic cell (DC) vaccines has successfully concluded a project for the development of an optimised formulation of a DC vaccine for the specific treatment of prostate cancer. The project was carried out at the HMGU, and was supported by the Bavarian Ministry of Economic Affairs as part of the m4 Award. This optimised vaccine formulation will form the basis of discussions that Medigene will have with potential partners on the continued clinical development of DC vaccines for prostate cancer.

End of December the Norwegian Medicines Agency (NoMA) and the relevant Ethic Committee have granted Medigene the approval to conduct a phase I/II clinical trial with its dendritic cell (DC) vaccine. Thereby, all regulatory prerequisites for the study start are fulfilled and the trial was started in March 2015. The study for the treatment of acute myeloid leukaemia (AML) will enable Medigene to prove its personalized DC vaccines in a company-sponsored trial the first time and additionally generate further clinical feasibility and safety data. It will enroll AML-patients after chemotherapy to reduce their risk of relapse by using Medigene's DC vaccines.

Outlook: The current investigator-initiated trials (IITs) being conducted at the University Hospital in Oslo (phase II trial in prostate cancer) and at the University Hospital in Munich (phase I/II trial in acute myeloid leukaemia, AML) will be continued. Additionally, a compassionate use programme, including patients with different types of tumour is currently ongoing at the Oslo University Hospital in order to test Medigene’s DC vaccine. Medigene recently started its own clinical trial in AML which will generate further clinical feasibility and safety data for Medigene’s personalised DC vaccines. The study will enrol AML patients after chemotherapy to reduce their risk of relapse by using Medigene’s DC vaccines.

  • 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

TCRs

Medigene’s second platform in the field of immunotherapy aims to arm the patient's own T cells with tumour-specific T cell receptors.

The receptor-modified T cells are then able to detect and efficiently kill tumour cells. 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). A large army of specific T cells to fight the tumour is made available to patients within a short period of time.

Medigene is developing a comprehensive library of recombinant T cell receptors. Moreover and a good manufacturing practice (GMP)-compliant process for their combination with patient-derived T cells is currently being established. First discussions with regulatory authorities for the preparation of first clinical trials with defined drug candidates have already taken place.

In April 2014, the US Patent Office issued a patent relating to a T cell receptor against the tumour-associated antigen tyrosinase. In October 2014, Medigene announced that the Australian Patent Office had issued a similar patent. The patents have a term until 2030 in the US and 2029 in Australia and have been licenced exclusively to Medigene Immunotherapies by Helmholtz Zentrum München (HMGU).

In July 2014, Medigene announced that Medigene Immunotherapies will be an active project partner in the transregional Collaborative Research Centre (SFB-TR36) “Principles and Applications of Adoptive T Cell Therapy” of the German Research Foundation (DFG). The DFG has continued the funding period of the SFB-TR36, started in 2006, for another four years. The project of the former Trianta is an integral part of the consortium that includes other projects of acclaimed scientists from Charité Universitätsmedizin Berlin, the Max Delbrück Center for Molecular Medicine (MDC), Humboldt University of Berlin (HU), Ludwig Maximilian University of Munich (LMU), Munich University of Technology (TUM) and the HMGU. The scientists’ aim is to develop effective approaches to treat tumours using adoptive T cell transfer. Medigene’s participation in SFB-TR36 secures established scientific and project-related cooperation with these leading German research institutions in the field of cancer immunotherapy. In particular, the promotion of technology transfer in a joint project with the HMGU facilitates access for Medigene to highly innovative preclinical tumour models for testing the efficacy of its own therapeutic concepts.

Moreover, at the Annual Meeting of Society for Immunotherapy of Cancer (SITC Conference) in November 2014 Medigene presented parts of Medigene’s immunotherapeutic TCR programmeme, particularly the isolation and identification of tumour-specific T cells.

Outlook: The development of a GMP-compliant manufacturing process for adoptive T cell therapy using TCR-modified T cells will be continued. Medigene prepares the clinical development of the first drug candidates. First preparatory talks with the authorities have already taken place. In addition, novel TCRs with specificities for promising tumour-associated antigens will be isolated and further characterised.

  • 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

TABs

T cell-specific monoclonal antibodies (TABs) The third product platform serves to generate monoclonal antibodies which are able to recognise different T cells (TABs = T cell-specific AntiBodies).

These TABs are intended to remove unwanted T cells from the body in order to treat T cell-induced diseases such as T cell leukaemia or various autoimmune diseases. This platform is used to produce and characterise monoclonal antibodies which are able to distinguish between different T cells.

Proof of technology was established in preclinical experiments. In June 2014, it was announced that Medigene Immunotherapies received public funding for the development of its TABs immunotherapy platform for the treatment of various types of cancer and autoimmune diseases. The grant was awarded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) within the scope of the “m4 – Personalized Medicine and Targeted Therapies: a new Dimension of Drug Development” Munich Leading-Edge Cluster initiative. The sponsored project intends to provide evidence of the elimination of pathogenic T cells in T cell leukaemia and autoimmune diseases, applying in vivo and in vitro methods with T cell-specific monoclonal antibodies. The project is financed by Medigene (60%) as well as the BMBF grant (40%). In September 2014, Medigene announced an increase of this public funding support.

Moreover, in September 2014 Medigene announced that Medigene Immunotherapies has entered into two new research collaborations in the field of TABs. In the future, scientists of the Max Delbrück Center for Molecular Medicine (MDC) and Helmholtz Zentrum München - German Research Center for Environmental Health, Munich (HMGU) will undertake certain research and development tasks in this specialised field. In the context of this collaboration, monoclonal antibodies for the treatment of autoimmune diseases and T cell leukaemia will be tested. The in vivo data generated during the granted period will be of great value for further clinical development of this immunotherapy platform. Overall, the collaboration with both research institutions offers Medigene extended scientific synergies regarding technology transfer, infrastructure and exchange of knowledge.

Outlook: Preclinical development of the T cell specific monoclonal antibodies (TABs) continues with the aim of achieving proof of principle.

  • Antigens on the surface of the AAVLP trigger the production of specific antibodies.

    The AAVLP is injected into the body. A specific antigen is presented on its surface. B-cell receptors recognize this antigen and activate the immune system.

    AAVLP
    Receptor
    Antibody
    Antigen
  • Antigens on the surface of the AAVLP trigger the production of specific antibodies.

    Upon infection and availability of antigens in the body, B cells increasingly proliferate and higher amounts of specific antibodies against the antigens will be produced.

    AAVLP
    Receptor
    Antibody
    Antigen

AAVLPs

The AAVLP (adeno-associated virus-like particles) programmeme is an innovative technology platform for the generation of new prophylactic and therapeutic vaccines.

For this purpose, non-infectious virus-like particles derived from adeno-associated viruses (AAV) are used as epitope carriers. Epitopes delivered to the immune system in this way result in the production of specific antibodies. These antibodies in turn recognise the relevant epitope, e.g. on pathogens or mutant cancer cells, and consequently fight and/or protect against the relevant disease.

Research into the use of the AAVLP technology to treat infectious diseases and cancer is being conducted by pursuing two different approaches. One is the direct integration of known epitopes. The second approach is based on the use of AAV libraries. Rather than defined epitopes, AAV libraries contain random sequences. Appropriate screening strategies enable the targeted selection of novel vaccine candidates from these libraries. The key benefit of this technology is the possibility of directly transferring the mode of action of existing therapeutically effective antibodies into an active vaccine.

A preclinical long-term study completed in cooperation with Pennsylvania State University with the aim of demonstrating long-term cross-protection against various human papilloma virus (HPV) infections has recorded positive results.

Outlook: The final results of the preclinical trial conducted in cooperation with Pennsylvania State University to demonstrate long-term protection against infection and cross-reactivity to various types of HPV are available. The data is positive and is expected to be published as part of a scientific publication as soon as possible.

Marketed and partnered Products

Medigene is the first Germany biotechnology company, to receive income from a marketed drug: Veregen® is distributed by partners throughout the world. Medigene has outlicenced the advanced drug candidates EndoTAG®-1 and RhuDex® to partners, who will assume the costs and responsibility for developing the drug candidates further. 

  • Changes in a wart induced by Veregen®

    Human papillomaviruses (HPV) infection of skin cells induces warts formation
    Veregen® penetrates the skin, acts directly on infected cells, and unfolds its presumed immune-modulatory and antiviral effect
  • Changes in a wart induced by Veregen®

    Messengers (cytokines, interferons) are released
    Cells of the immune system invade and destroy infected cells

VEREGEN®

Worldwide partners: Veregen®
Veregen®, a drug for the treatment of genital warts, was developed by Medigene AG and is currently available in the US and Canada, in 15 European countries and Taiwan and has been approved in additional countries.

Veregen® is an innovative drug formulation based on a defined extract from green tea leaves, which is obtained in a complex and specifically developed production process. In several clinical studies, Veregen® showed complete clearance of genital warts in more than 60% of the patients, and was very well tolerated. In its current treatment guidelines for sexually transmitted diseases, the US Center for Disease Control and Prevention recommends Sinecatechins 15% ointment (Veregen®) as a possible option for treating genital warts. In addition, Sinecatechins 10% and 15% ointment (Veregen®) were included in the current European guideline ("2012 European Guideline for the Management of Anogenital Warts”) as a recommended treatment option for genital warts. Medigene has marketing agreements for Veregen® in place with numerous partners worldwide. Medigene receives one-time upfront payments, revenues from milestone payments and from the supply of the finished product, as well as royalties on the sales of Veregen® in these countries.

In April 2014, Medigene and the pharmaceutical company Kora Healthcare concluded an exclusive agreement for the supply and commercialisation of Veregen® in the United Kingdom and Ireland. In October 2014, Medigene’s US licensee, Fougera Pharmaceuticals Inc, a Sandoz company, signed a promotion agreement with Women’s Choice Pharmaceuticals LLC (WCP), a US specialty pharmaceutical company to expand product sales within the obstetrics, gynaecology and urology medical specialties.

In the third quarter of 2014 Medigene filed marketing authorisation applications in eight additional European countries (UK, Ireland, Italy, Portugal, Croatia, Latvia, Lithuania and Estonia) using the mutual recognition procedure. These marketing authorisation applications were positively assessed in February 2015.  In November 2014, a marketing authorisation application for Veregen® was submitted in Russia.

Outlook: Medigene’s partners anticipate the successive market launches of Veregen® in the UK, Ireland, Italy, Portugal, Croatia, Latvia, Lithuania and Estonia to start in the second half of 2015.

ENDOTAG®-1

  • EndoTAG®-1 attacking tumour-activated endothelial cells.

    Tumour cells
    Tumour releases signals inducing growth of new blood vessels.
  • EndoTAG®-1 attacking tumour-activated endothelial cells.

    Endothelial cells divide, the blood vessel grows towards tumour.
  • EndoTAG®-1 attacking tumour-activated endothelial cells.

    EndoTAG® attacks the activated dividing endothelial cells, preventing formation of new blood vessels. In this way, blood supply to the tumour is interrupted.

ENDOTAG®-1

EndoTag®-1 is a cancer drug candidate outlicenced and further developed by Medigene’s partner SynCore Biotechnology Co., Ltd.

The clinical drug candidate EndoTAG®-1 is an innovative composition of the established cytostatic drug paclitaxel combined with neutral and positively charged lipids. Due to the positive charge, EndoTAG®-1 interacts with newly formed, negatively charged endothelial cells, which are specifically required for the growth of tumour blood vessels. The EndoTAG®-1 paclitaxel component attacks the activated endothelial cells as they divide, thus targeting the blood supply to tumours without affecting endothelial cells of healthy tissues. By doing this, EndoTAG®-1 is expected to prevent the formation of new tumour blood vessels and to inhibit tumour growth.

Medigene successfully completed two clinical phase II trials with EndoTAG®-1 in the indications of pancreatic cancer and triple-negative breast cancer (TNBC). Furthermore, Medigene published positive results from an investigator-initiated trial (IIT) with EndoTAG®-1 in HER2-negative high-risk breast cancer at the ASCO 2013 Annual Meeting.

As part of the licence agreement with the partner SynCore Biotechnology Co., Ltd., SynCore is fully responsible for the development and financing of the planned phase III clinical trial with EndoTAG®-1 in the indication of TNBC, and has in turn received the global marketing rights for EndoTAG®-1. Medigene received an upfront payment from SynCore and is entitled to payments upon certain development and approval milestones as well as royalties after market approval of EndoTAG®-1.

Outlook: SynCore is preparing a pivotal international phase III trial with EndoTAG®-1 in the indication of triple-negative breast cancer (TNBC) and assumes full responsibility and the entire financing for this trial.

RHUDEX®

  • RhuDex® inhibits autoimmune mediated inflammation processes.

    T cell activation by certain immune cells is an important process in the onset of tissue destruction in autoimmune diseases.

    T cell activation requires interaction between the surface proteins CD80 and CD28.

  • RhuDex® inhibits autoimmune mediated inflammation processes.

    RhuDex® prevents the interaction between CD80 and CD28, therefore acting as an anti-inflammatory agent.

RhuDex® is a drug candidate outlicenced and further developed by Medigene’s partner Dr. Falk Pharma GmbH in the indications hepatology and gastroenterology.

The drug candidate RhuDex® is an oral, disease modifying agent to treat autoimmune diseases. It serves as a CD80 antagonist that blocks undesired T-cell activation and production and therefore has an immune modulating and anti-inflammatory effect.

The safety and tolerability of RhuDex® was demonstrated in a number of phase I clinical trials. Medigene successfully completed a pilot phase IIa trial in the indication rheumatoid arthritis. In March 2014, a licence agreement was concluded with the pharmaceutical company Dr. Falk Pharma GmbH, Freiburg, for the development and marketing rights to RhuDex® in the indications hepatology and gastroenterology. Falk Pharma will assume responsibility and all costs relating to the clinical development and marketing of RhuDex® in these therapeutic areas. Medigene receives an upfront payment and is entiteled to receive future milestone payments from Falk Pharma, plus double-digit royalties on sales of RhuDex®. Falk Pharma initially concentrates on development in primary biliary cirrhosis (PBC). Medigene retains the rights for RhuDex® in rheumatoid arthritis, psoriasis and other autoimmune diseases.

Outlook: Falk Pharma is conducting a comprehensive development programmeme with the aim of developing RhuDex® optimally in the indication primary biliary cirrhosis (PBC). The start of clinical trials will be announced at the start of each trial.

Top