MOLOGEN AG. Company Presentation February 2016

Transcription

1 Company Presentation February 2016

2 Agenda Business Overview Market Lefitolimod (MGN1703) Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

3 MOLOGEN Snapshot Based in Berlin, Germany; founded 1998 ~ 60 employees Management Board Dr. Mariola Soehngen, CEO (since Nov 2015) Extensive expertise and experience in the biotechnological and pharmaceutical industry Co-founder of biopharmaceutical company PAION AG, Germany Dr. Alfredo Zurlo, CMO (since Apr 2013) Long-standing and extensive expertise in the pharmaceutical industry (e.g. Roche) Worked as Medical Advisor at the European Organization for Research and Treatment of Cancer (EORTC) in Brussels, Belgium

4 MOLOGEN Shares ISIN DE Shares issued: 22,631,501 Market capitalization ~ 106m (30 Dec 2015) Frankfurt Stock Exchange (Prime Standard): MGN Reuters: MGNG.DE Global Derivative Trading GmbH 24% Baloise Holding 54% 6% 6% 5% 5% Deutscher Ring Krankenversicherungsverein a.g. Salvator Vermoegensverwaltungs GmbH Deutsche Balaton Aktiengesellschaft Freefloat

5 Company Overview Biotechnology company with focus on immunotherapies One of the pioneers in immunotherapies Advanced products / promising pipeline Lead product lefitolimod (MGN1703) in registration study Three proprietary immunotherapy platforms Highly attractive markets Immunotherapies: A new megatrend Cancer treatments: A multi-billion US-$ market Highly qualified & dedicated team Long-term experience, in particular in R&D of DNA- and cell-based products Close network with scientific institutions & experts

6 MOLOGEN s Proprietary Immunotherapy Platforms Lefitolimod (MGN1703) TLR9 agonist In registration study Applicable in various indications: Suitable for monoand combinationtherapies SCLC small cell lung cancer MIDGE Vector System DNA-based, non-viral vector system: gene ferries Three products in development: MGN1404 (malignant melanoma) MGN1331 (leishmaniasis) MGN1333 (hepatitis B) Cell-based therapeutic vaccination (MGN1601) Genetically modified human renal cancer cell line - using MIDGE platform combined with lowdose lefitolimod as adjuvant Phase I/II data available Orphan drug status

7 Advanced Product Pipeline with Strong Focus on Cancer Immunotherapies Preclinical Phase I Phase II Phase III EnanDIM 1 Oncology & Anti-infectives Lefitolimod (MGN1703) 1 Other solid tumors Lefitolimod (MGN1703) 1 SCLC Lefitolimod (MGN1703) 1 Colorectal cancer MGN Leishmaniasis 5 MGN Hepatitis B Lefitolimod (MGN1703) 1,6 HIV Lefitolimod (MGN1703) 1 + ipilimumab (Yervoy ) 7 Advanced solid malignancies Oncology Infectious diseases Oncology & Infectious diseases Oncology combination trials SCLC small cell lung cancer MGN Renal cancer MGN1404 2,4 Malignant melanoma 1 TLR9 agonist 2 MIDGE vector system 3 Cell line modified using MIDGE technology with adjuvant low-dose Lefitolimod 4 Collaboration with Max-Delbrueck-Center for Molecular Medicine and Charité Universitaetsmedizin, Berlin 5 Various diseases caused by parasites; mainly present in subtropical and tropical regions (major neglected disease) 6 Collaboration with University Hospital Aarhus, Denmark 7 Collaboration with MD Anderson Cancer Center, Texas, US; study is expected to start in H

8 Strategic Focus: Outlicensing of Products to Generate High Returns Partnering agreement for lefitolimod (MGN1703) High returns in the mid- and long-term Ensure funding of lefitolimod (MGN1703) until filing/approval High market potential Continue clinical development of MGN1601 Unique proprietary technology Develop vaccine candidates Support to treat diseases with high unmet medical need: Leishmaniasis & hepatitis B Initiate new projects Initiate combi trials; extend and advance product pipeline: ensure long-term growth

9 Agenda Business Overview Market Lefitolimod (MGN1703) Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

10 Oncology Market: Leading Therapy Category Worldwide Prescription Drugs in US$ billion Business Overview Worldwide Oncology Drugs in US$ billion Market CAGR +5.1% 1,017 CAGR +11.2% lefitolimod 717 (MGN1703) Cancer Immunotherapy 153 MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Pharmaceutical Industry struggled with weak economic growth in recent years Appendix Patent cliff overcome Source: EvaluatePharma 2014 CAGR Compound Annual Growth Rate Major therapy category Highest growth rate & strongest sales increase worldwide in the long-term Immunotherapies represent emerging field => new mega-trend with US$ 35 billion market potential

11 Colorectal and Lung Cancer: High Growth Expected Colorectal Cancer Sales in US$ billion 1 Lung Cancer Sales in $US billion 2 CAGR +4.9% 5 8 CAGR +12.5% Launch of premium-priced adjuvant / maintenance therapies will extend firstline treatment Most common cancer worldwide in terms of incidence and death High income countries have more than double the lung cancer incidence of low income countries 1 5EU, US, Japan & China; Source: GlobalData Nov G7 Countries; Source: MarketsandMarkets Nov 2011 CAGR Compound Annual Growth Rate

12 Oncology Market: Sharp Increase of Incidences Incidences Oncology 1 Incidences by Oncology indication % 20m 1.8m Lung 14m 9.2m 1.7m 1.4m Breast Colorectum Other Aging populations will increase incident case rates in all markets covered Cancer rates for all cancers combined rise with increasing levels of country income Total number of estimated cancer cases: 14.1 million 1 World, Source: IARC World Cancer Report World, Source: WHO GLOBOCAN 2012 (IARC)

13 Cancer Immunotherapies: New Megatrend Science Magazine: Breakthrough of the Year 2013 US$ 35,000,000,000 market potential* *Source: Citi-Bank 2013 estimated peak sales

14 Immunotherapy: Superior Treatment Chemotherapy Fast effect in many patients Effect not lasting Patients alive in % Immunotherapy Needs time to be effective Long-lasting effect in a minority of patients Patients alive in % Chemotherapy Immunotherapy Control group time Control group 10% time Source: "Immuno-oncology: The new weapon in the war against cancer, Alistair Campbell; Berenberg Equity Highlights, February

15 Agenda Business Overview Market Lefitolimod (MGN1703) Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

16 Lefitolimod (MGN1703): Best in Class TLR9 Agonist Activation profile and chemical structure supports application in cancer therapy High dosing over long periods of time without major toxic effects Clinical strategy optimized for lefitolimod (MGN1703) TLR9 activation pattern Maximized probability of success compared to other TLR9 agonists Light blue area: recognized by TLR9 receptor

17 Activating the Immune System to Fight Cancer Cancer patient mdc myeloid dendritic cell NK cell natural killer cell NKT cell natural killer T cell pdc plasmacytoid dendritic cell

18 IMPACT Phase II Study in Colorectal Cancer Generated Sustained Long-Term Responses Primary endpoint met: Progression free survival Secondary endpoint Overall Survival : Median OS 22.6 (lefitolimod (MGN1703)) vs months (p=ns) Predictive biomarkers identified: Tumor reduction by induction therapy, CEA level, presence of activated NKTs Follow-up of four patients who continued MGN1703 treatment in compassionate use programs since no relapse at end of study: Three patients progression-free in excess of months as of August 2015 Excellent safety and tolerability, also when treated long-term Findings from subgroup analyses were used to optimize the phase III study design CEA carcinoembryonic antigen - a tumor marker for colorectal cancer NKT Natural Killer T cells ns not significant

19 IMPACT Sustained Efficacy April 2010: Patient 049 Initial diagnosis Colon carcinoma with multiple liver metastases December 2010: After induction chemotherapy 06/ /2010: 9 courses of CT (FOLFIRI) + bevacizumab (biologic) 12/2010: Response to induction CT: PR * CT chemotherapy PR partial response *confirmed by two independent radiologists March 2015: Under maintenance therapy Since 12/2010: Lefitolimod (MGN1703) maintenance therapy New PR * after 9 months Still ongoing PR (46 months as of August 2015) Good medical condition, mild local skin reactions, no further toxicities

20 Lefitolimod (MGN1703) Ongoing Clinical Trials IMPALA IMPULSE TEACH Metastatic Colorectal Cancer (mcrc) Pivotal trial (phase III) 540 patients Small Cell Lung Cancer (SCLC) Randomized study 100 patients HIV (Infectious Disease) Early Stage Study (phase I) 16 patients Combination trial Advanced solid malignancies Lefitolimod (MGN1703) + ipilimumab (Yervoy ) 8 European countries: Austria, Belgium, Estonia, France, Germany, Italy, Spain, UK 4 European countries: Austria, Belgium, Germany, Spain Denmark Early Stage Study (phase I) patients Texas, US Currently Recruiting Recruitment completed (Oct 2015) Recruitment completed (Sep 2015) Study expected to start in H

21 IMPALA mcrc Pivotal Phase III Study Started in Sep 2014 Trial Treatment Period Maintenance Re-Induction Induction CT weeks Standard first-line CT for mcrc PR/CR Responder Screening/ Randomization 1:1 Lefitolimod (MGN1703) Control group PD PD Lefitolimod (MGN1703) with induction CT Induction CT PD PD Start of 2 nd line Primary endpoint: Overall survival Open-label, randomized, controlled, two-arm, multinational phase III trial 540 patients in around 120 sites in eight European countries, including Top 5 European pharma markets Biomarkers used as stratification factors: CEA level and NKT activation CT chemotherapy CR complete response PR partial response PD progressive disease mcrc metastatic colorectal cancer CEA carcinoembryonic antigen - a tumor marker for colorectal cancer NKT Natural Killer T cells

22 IMPULSE - SCLC Randomized Study Trial Treatment Period Maintenance Induction CT 4 cycles of platinum-based therapy Standard first-line CT for extensive disease SCLC PR/CR Responder Screening/ Randomization 3:2 Experimental Group: 5 th cycle of platinum based CT followed by lefitolimod (MGN1703) maintenance Control Group: 5 th cycle of platinum based CT followed by local practice PD PD Start of 2 nd line Primary endpoint: Overall survival Randomized, controlled, two-arm, multinational trial with 100 patients in Belgium, Austria, Germany and Spain Biomarkers used as stratification factors: NSE level and NKT activation Patient enrollment completed: end of October 2015 CR complete response CT chemotherapy NKT Natural Killer T cells NSE neuron specific enolase - a tumor marker for lung cancer PD progressive disease PR partial response SCLC small cell lung cancer

23 TEACH Early Stage Study in HIV Completed Recruitment in September 2015 Collaboration agreement with Aarhus University Hospital, DK Aarhus University Hospital conducts the study funding received from the American Foundation for AIDS research (amfar) MOLOGEN provides lefitolimod (MGN1703) First time to evaluate lefitolimod (MGN1703) in other disease than cancer Top-line results expected Q Potential expansion of applications

24 Combination Trial with Lefitolimod (MGN1703) and Ipilimumab (Yervoy ) Collaboration with MD Anderson Cancer Center, US, Texas First combination study of lefitolimod (MGN1703) with checkpoint inhibitor, commercially available ipilimumab (Yervoy ), manufactured by Bristol-Myers Squibb Co. MD Anderson Cancer Center conducts the trial; MOLOGEN provides lefitolimod (MGN1703) and funding for the trial Phase I trial in patients with advanced solid malignancies Potential expansion of applications

25 Lefitolimod (MGN1703) Milestones Clinical Trials IMPALA (mcrc) Pivotal study IMPULSE (SCLC) Randomized study TEACH (HIV) Phase I Combination trial Phase I 2014 First patient in (FPI) First patient in (FPI) 2015 Recruitment completed Recruitment started and completed 2016 Recruitment completed Start of primary analyses Start of primary analyses; results (H1) First patient in (FPI) * Primary endpoint analysis (OS) Results End of recruitment 2019 mcrc metastatic colorectal cancer SCLC small cell lung cancer I * Study expected to start in H

26 Conclusion: Late-Stage Product Lefitolimod (MGN1703) with Unique Profile and Huge Market Potential Best in in class and TLR9 most agonist advanced and most in mcrc advanced (pivotal in mcrc (pivotal trial) trial) Long-term treatment Usable for various indications (mcrc, SCLC, ) Superior safety and tolerability Blockbuster potential Suitable for mono- and combination therapy Patient selection via biomarker mcrc metastatic colorectal cancer SCLC small cell lung cancer

27 Agenda Business Overview Market Lefitolimod (MGN1703) Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

28 MGN1601 Unique Therapeutic Cancer Vaccination

29 ASET Trial with MGN1601: Promising Data Phase I/II study (12/ /2013): Open-label, proof-of-principle, multi-center phase I/II trial 19 patients with advanced renal cell carcinoma who failed prior systemic therapies Primary endpoint met: Favorable safety and tolerability profile Promising overall survival data in subgroup of patients Identification of potential biomarkers

30 Agenda Business Overview Market Lefitolimod (MGN1703) Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

31 EnanDIM New Generation of Immunomodulators New class of linear TLR9 agonists Combines advantages of molecules containing only natural DNA components with benefits from linear molecules Specific structure protects against degradation - no chemical modifications needed Broad immune activation shown in pre-clinical models Potential application in the fields of cancer and anti-infective therapies

32 Combining Advantages of Two Types of Agonists: Linear and Not Chemically Modified Structure lefitolimod (MGN1703) Linear DNA-structure Closed, dumbbell-shaped structure Only natural DNA components Good safety and tolerability profile One additional production step Linear molecules Easy and cost-effective production Chemically modified structure ( ) EnanDIM = Enantiomeric DNA-based ImmunoModulator Linear molecules No chemical modifications Good safety and tolerability profile expected Easy and cost-effective production DNA sequence essential for function (so-called CG motifs ) New structural feature Protection against degradation

33 Agenda Business Overview Market Lefitolimod (MGN1703) Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

34 Key Financials 9M 2015 In million 9M M 2014 R&D expenses % EBIT % R&D costs almost unchanged Monthly cash burn accordingly Capital increase reflected in financing cash flows Cash flows from operating activities Cash flows from financing activities % % Monthly cash burn % In million 30 Sep Dec 2014 Total assets % Main items impacted by capital increase of 28.3 m gross Cash & cash equivalents % Equity ratio 81% 88% -8%

35 FY 2015: Outlook Confirmed Development of product pipeline well on track Intensify clinical development of lefitolimod (MGN1703): Registration study IMPALA: Continue patient recruitment Randomized study IMPULSE: Finalize patient recruitment MGN1601: Plan and prepare continuative study in renal cancer Continue partnering discussions Increase of R&D expenses due to studies with lefitolimod (MGN1703), mainly IMPALA

36 Financial Calendar and Contact Details 22 March 2016 Annual Financial Statements and Annual Report May 2016 Quarterly Report as of 31 March May 2016 Annual General Meeting 11 August 2016 Half-Year Report as of 30 June November 2016 Quarterly Report as of 30 September 2016 Claudia Nickolaus Head of Investor Relations & Corporate Communications Phone: Fax: MOLOGEN, MIDGE, dslim, and EnanDIM are registered trademarks of the 35

37 Agenda Business Overview Market Lefitolimod (MGN1703) Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

38 IMPACT Phase II Study Design and Results Trial Treatment Period Maintenance Induction CT months mcrc patients treated first-line with FOLFOX / XELOX or FOLFIRI +/- bevacizumab * At least SD Screening / Randomization 2:1 Experimental Group: 60mg lefitolimod (MGN1703) twice weekly s.c. No maintenance Placebo Twice weekly s.c. PD ** PD ** ** Treatment after PD at investigators discretion * at investigators discretion Primary endpoint: Progression-free survival Double-blind, randomized, placebo-controlled, two-arm, multinational phase II trial with 59 mcrc patients Predictive biomarkers identified: Tumor reduction by induction therapy, CEA level, NKT activation Start: June 2010 primary completion date: February 2013 CEA carcinoembryonic antigen - a tumor marker for colorectal cancer CT chemotherapy mcrc metastatic colorectal cancer NKT Natural Killer T cells PD progressive disease s.c. subcutaneous injection SD stable disease

39 Lefitolimod (MGN1703) Established Mode of Action

40 MGN1601 ASET Study Design Trial Treatment Period TPP Extension phase Patients with advanced renal cell cancer No standard therapy available Trial inclusion 8 applications of MGN1601 in 12 weeks i.d. 8 applications of MGN1601 in 12 weeks i.d. Max. 5 applications in DC PD ** week 24, 36, 48, 72 and 120 PD ** ** Treatment after PD at investigators discretion Primary endpoints met: safety and tolerability Open-label, proof-of-principle, multi-center phase I/II trial 19 patients with advanced renal cell carcinoma who failed prior systemic therapies Orphan drug designation from EMA Start: December 2010 primary completion date: August 2013 DC Disease Control EMA European Medicines Agency i.d. intradermal injection PD progressive disease TPP Treatment per protocol

41 MGN1601 ASET Study Results Median OS: 24.8 weeks (ITT group): weeks (PP group) Potential biomarker identified MSKCC Score & NLR may have predictive DC value for longer PD ** OS Trial inclusion First evidence of cytotoxic antitumor immune response after MGN1601 vaccination (in patient subgroup) Significant improvement of cellular immune function during treatment (in patient subgroup) PD ** MSKCC Memorial Sloan Kettering Cancer Center NLR Neutrophil-Lymphocyte Ratios

42 Quarterly Key Financials [in million] Q Q Q Q Q Q Q Q Q Q Q R&D expenses EBIT Cash flow from operating activities Cash flow from financing activities Monthly cash burn

43 Main Events TEACH Topline results IMPULSE Start Primary analyses (OS) ODDO Lyon JPM HCC SanFran, US ASCO GI, SanFran ODDO Frankfurt CROI Conf Boston, US Keystone CA, US DE Krebskongress Berlin AACR New Orleans, US ASGCT Washington, US CIMT Mainz ASCO Chicago, US Quirin Champ. Frankfurt BioEquity, DK Q1 ESMO WCGIC Barcelona EACR UK Q2 Berenberg GS Conf. MUC ESMO IO Copenhagen SITC US New Harbour HSBC HCC Frankfurt IMPALA Recruitment completed WCLC Vienna EKF FFM FY 2014 AGM Q3 Q1 Q2 Q3 Q4 Scientific Conferences Financial Reporting Investor Conferences Clinical Trials CROI Conference on Retroviruses and Opportunistic Infections ASGCT American Society of Gene Cell Therapy CIMT Cancer Immunotherapy 2016 EACR European Association of Cancer Research WCLC World Conference on Lung Cancer SITC Society for Immunotherapy of Cancer 42

44 Company Presentation February 2016