Medigene Corporate Presentation

Transcription

1 Medigene Corporate Presentation

2 This presentation contains forward-looking statements - that is, statements related to future, not past, events. These statements may be identified either orally or in writing by words as "expects", "anticipates", "intends", "plans", "believes", "seeks", "estimates", "will", "may" or words of similar meaning. Such statements are based on our current expectations and assumptions, and therefore are subject to various risks and uncertainties that could cause the actual results, performance or achievements to differ materially from any future results, performance or achievements that may be expressed or implied by such forward-looking statements. These factors include, without limitation, those discussed in our public reports filed with the Frankfurt Stock Exchange. The company does not assume any obligations to update or revise any of these forward-looking statements, even if new information becomes available in the future.

3 Medigene a strong player in immunotherapy 3

4 Medigene's immunotherapies are tailored to address different types and stages of cancer DCs TCRs TABs DC vaccines TCR-modified T cells T cellspecific mabs low tumour burden high tumour burden unwanted T cells Legend: tumour ; T cell ; DC Vaccine ; TCR-modified T cell ; pathogenic T cell 4

5 Platform 1: Therapeutic dendritic cell (DC) vaccines DC vaccines Monotherapy or Combination therapies As monotherapies, DC vaccines will likely be most effective for use in patients with minimal residual disease. They can be used in combination therapies for larger tumour burdens and to induce antitumour responses in patients where spontaneous responses have not occurred. Audio-visual DCs TCR-modified T cells Adoptive T cell therapy with TCRs: arms patient-derived T cells ex vivo with suitable T cell receptors that enable them to detect and efficiently kill cancer cells in vivo T cell-specific antibodies T cell-specific antibodies (TABs): deplete unwanted T cells 5

6 What are Medigene's now generation DC vaccines? maturation cocktail (2nd generation) GM-CSF + IL-4 IL-12 high IL-10 low maturation cocktail with TLR 7/8 agonist now generation mdc monocytes 1st generation immature DCs 2nd generation 7-9-day mature DCs Now generation 3-day polarized mdcs for optimal innate and adaptive immunotherapy 6

7 Medigene s DC vaccine phase I/II trial in AML Started on 24 March 2015 Trial design: Phase I/II multi-centre, open-label, prospective, non-randomized trial 20 AML patients (6 phase I + 14 phase II) with complete remission after chemotherapy who are not eligible for allo-transplantation Primary objectives: Feasibility and safety Secondary objectives: Induction of immune responses, Control of minimal residual disease (MRD), Clinical response: time to progression (TTP) Vaccinated for 50 weeks and a follow-up period of one year or until progression. 7

8 Medigene s DC vaccines display optimal properties Optimal biological properties for improved clinical efficacy Defined antigen loading replaces unknowns with peptides and lysates Use of full length antigen requires no need for HLA selection Positive co-stimulatory profile with young 3-day mature dendritic cells Optimal cytokine polarization to induce innate and adaptive responses High yields allow extended vaccination of patients Optimal product characteristics for commercialization 3-day production is cost effective and amenable to automation RNA as source of antigens is versatile, inexpensive and no need for tumour material Single-batch production reduces time, costs and is patient friendly (only one apheresis) Frozen vaccine formulation gives long shelf-life and simplified logistics 8

9 Platform 2: TCR-modified adoptive T cell therapy DC vaccines Dendritic cell (DC) vaccines: induce the maturation of own, cancer-specific dendritic cells and trigger both T cells and natural killer cells to attack the tumour TCR-modified T cells T cells Large advanced and bulky tumour loads Adoptive cell therapy with TCR-modified lymphocytes allows patients to be given ready-made immune responses with large numbers of activated T cells that are needed to eradicate large tumour burdens. Billions of TCR-modified T cells can be prepared in a matter of weeks. Audio-visual TCRs T cell-specific antibodies T cell- specific antibodies (TABs): deplete unwanted T cells 9

10 Platform 2: Adoptive T cell therapy with TCR-modified patient T cells for high tumour burden Patient T cells are isolated from blood samples and activated Patient T cells viral-vector mediated TCR transfer TCR-engineered patient T cells with antitumour specificity Appropriate TCR is selected from off-the-shelf library Anti-tumour TCR is introduced using a viral vector Modified T cells are expanded to large numbers in days Modified T cells are reinfused into patient 10

11 Patient T cells are tailored to tumour type using library of therapeutic TCRs Library of therapeutic TCRs (as recombinant vectors) TCR-modified patient T cells AML TCR-1 TCR-2 TCR-3 TCR-4 TCR-5 TCR-6 NSCLC TCR-7 TCR-8 TCR-9 Prostate cancer 11

12 Medigene's technology delivers high versatility to build library of therapeutic TCRs The Process: T cells to acquire therapeutic TCRs mdc No need for patient blood In vitro system using healthy donors TCRs specific for any HLA and antigen The Product: Therapeutic TCRs to modify patient T cells High affinity without mutation Specific for well selected target antigens Extensively screened for safety Transfer of desired functional activities 12

13 TCRs allow many more antigens to be targeted compared to CARs TCR/CD3 complex Chimeric antigen receptor (CAR) Vα Vβ ε CD3 δ CD3 Cα Cβ γ CD3 ε CD3 ITAM chain CM I: CD28 ITAM chain CM I: CD28 CM II: CD134/CD137 TCRs: Recognize intracellular targets, with many thousands of options Recognition is MHC-restricted CARs: ITAM chain Limited to cell surface antigens, only tens of options Recognition is MHC-independent Adapted from Cartellieri et al,

14 Medigene s threefold value creation along the TCR development chain TCR generation module TCRs GMP production module TCR clinical development programme TCR therapies Value creation through: TCR R&D collaborations with external academic/commercial partners TCR product development collaborations with commercial partners Medigene Immunotherapies own TCR product development programme 14

15 Medigene s TCR-based therapy displays optimal properties Optimal biological properties for improved clinical efficacy TCRs are easily isolated for diverse MHC allotypes and antigens from healthy donors Wide range of affinities allow selection of lead TCRs with optimal sensitivity Natural sequences of lead TCRs with no need for mutation to improve sensitivity Optimal product characteristics for commercialization TCR library allows patients with different MHCs to be included in treatment High safety profile established through extensive in silico, in vitro and in vivo assays TCR-modified T cells display optimal functional characteristics 15

16 Platform 3: T cell-specific monoclonal antibodies DC vaccines Dendritic cell (DC) vaccines: induce the maturation of own, cancer-specific dendritic cells and trigger both T cells and natural killer cells to attack the tumour TCR-modified T cells T cells Adoptive T cell therapy (TCR): arms patient-derived T cells ex vivo with suitable T cell receptors that enable them to detect and efficiently kill cancer cells in vivo T cell-specific antibodies T cell leukemia and autoimmunity TABs can be used to eliminate unwanted T cells without causing deleterious cytokine storm. Elimination of unwanted T cells can be made while leaving normal T cell immunity intact for pathogen defense. Audio-visual TABs 16

17 Platform 3: TABs - TCR-specific monoclonal antibodies for removal of misguided or unwanted T cells Full-scope platform for antibody isolation Unique animal models to assess MoA and clinical efficacy Proof-of-principle of technology is established Ongoing studies establish proof-of-concept in pre-clinical models Unwanted T cells: T cell leukemia T cell drivers of autoimmunity TCR-modified T cells: T cell tracking ex vivo T cell removal in vivo 17

18 Characteristics of Medigene's TAB technology Selective depletion of unwanted T cells with low toxicity by TABs Vector libraries available to make cellular screening reagents HT cellular screening systems have been established and validated Prototype antibodies have been isolated using standard hybridoma methods Unique humanized T cell-bearing mice are available to study effects of TABs in vivo 18

19 Medigene s immunotherapy pipeline PROJECT INDICATION PRECLINICAL PHASE I PHASE II PHASE III APPROVAL MARKET DC vaccine Prostate cancer* DC vaccine AML** Acute myeloid leukemia DC vaccine AML Acute myeloid leukemia TCRs Cancer TABs Leukaemia and autoimmune d. * investigator initiated trial (IIT) Oslo University Hospital ** investigator initiated trial (IIT) Ludwig-Maximilians University Hospital 19

20 Marketed/partnered pipeline (non-core) Numerous marketing partnerships for Veregen in place Currently marketed in the US, Canada, 17 European countries and Taiwan Exclusive global license and development agreement for EndoTAG with SynCore Biotechnology Complete financing for phase III trial in return for EndoTAG global marketing rights Licence agreement with Falk Pharma for RhuDex in hepatology and gastroenterology Falk Pharma will fully fund all costs for development and commercialisation of RhuDex in PBC Medigene retains RhuDex rights for rheumatoid arthritis and other autoimmune diseases * for hepatology & gastroenterology 20

21 Outlook for immunotherapy platforms DCs Deliver therapeutic data in patients vaccinated for more than 1.5 years Conduct the company-sponsored phase I/II study in AML Continue investigator-initiated trials and compassionate use programme TCRs Isolate TCRs with optimal affinities for lead candidate targets Develop up to 10 lead TCR candidates Implement process for good manufacturing practice (GMP) Initiate clinical development Start IIT phase I trial in H (subject to grant funding) Commence two Medigene clinical trials in H2 2017/ H TABs Advance pre-clinical studies with the aim of achieving proof of principle 21

22 Anticipated and completed milestones (summary) Expand pipeline with three immunotherapy programs (DC/TCR/TABs) acquisition of Trianta Integrate Trianta (now Medigene Immunotherapies) and establish R&D team Raise capital and expand lab capabilities Present data at ASH and AACR Start own clinical DC trial in AML Secure mid-term financing Develop up to 10 lead candidates in TCR platform IND/IMPD for IIT Phase I TCR trial IND/IMPD for 2 Medigene TCR trials Q1/Q Q2/Q Q3/Q Q / Q Q Q ff H / 2018

23 Financial guidance 2015 confirmed 2014 Guidance 2015 Veregen royalties 2.4 m double digit percentage increase Veregen total revenue 5.2 m stable R&D expenses Immunotherapies 2.9 m 7-9 m EBITDA loss 2.1 m m 23

24 Funding for immunotherapy platforms through capital measure successfully completed Raising of 46.4 m by issuance of 5,594,178 new shares Placement of all offered new shares for a subscription price of EUR 8.30 Participation of new renowned institutional investors from USA and Europe, including QVT, a leading US-based sector specialist as cornerstone investor Enables Medigene to achieve important milestones in clinical validation of the immunotherapy platforms Continuation of DC vaccine & acceleration of TCR clinical development programmes Cash reach at least until H

25 Capital measure added new institutional investors * Current shareholder structure 15,6% Before capital measure 9,7% QVT Aviva SynCore Ridgeback 10,1% 5,5% 5,0% 4,4% 3,9% Aviva SynCore Ridgeback DJS Montana RTW Master Fund 54,3% 3,3% 4,0% 6,2% 3,9% ~3,0% Morgan Stanley DJS Montana RTW Master Fund Freefloat ** 71,1% Freefloat ** Key share information Current number of shares outstanding: 19,678,055 Current market cap of ~ 140 m *Capital increase July 2015/ based on last voting right notifications **Shareholding below 3% 25

26 A fully established biopharmaceutical company Complete infrastructure with expertise in Medical Affairs, CMC (QM, GMP, GLP, GCLP), Quality Control, Regulator Affairs, Business Development, Alliance Management, IP, IR/PR and Administration 26

27 Management team: Track record from pre-clinical development to marketed products Frank Mathias Ph.D. CEO Pharmaceutical marketing experience at general management level with international companies To 2008 corporate VP and General Manager Germany of Amgen Responsible for Commercial Operations & Alliance Management, Supply Chain Management, CMC/Quality Control, Quality Assurance and Regulatory Affairs Prof. Dolores Schendel Ph.D. CSO Served as Member of the German Cancer Aid Grants Review Panel and Chair of a Life Science Study Panel of the European Research Council To 2014 Director of the Institute of Molecular Immunology of German Research Center for Environmental Health Professorship in immunology at the Ludwig Maximilians University of Munich Founder of Trianta Immunotherapies GmbH (now Medigene Immunotherapies GmbH) Responsible for Research / Immunotherapies, Preclinical Development, Clinical Development and Medical & Scientific Affairs Peter Llewellyn-Davies CFO Commercial and financial experience at C level in international companies To 2012 CFO of Wilex AG Responsible for Administration, Business Development, Finance, Purchasing, Corporate Communications, Human Resources, IT, Intellectual Property and Legal Affairs 27

28 Medigene AG Lochhamer Straße Strasse Planegg / Martinsried Germany T F investor@medigene.com Listed on Frankfurt Stock Exchange (MDG, (MDG1, Prime Standard)