MOLOGEN AG. Company Presentation April 2016

Transcription

1 Company Presentation April 2016

2 Agenda Business Overview Market Lefitolimod (MGN1703) MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2016 Appendix

3 MOLOGEN Snapshot Based in Berlin, Germany; founded 1998 ~ 65 employees Management Board Dr. Mariola Soehngen, CEO (since Nov 2015) Extensive expertise and experience in the biotechnological and pharmaceutical industry Co-founder of the biopharmaceutical company PAION AG, Germany Walter Miller, CFO (since Apr 2016) Extensive expertise in the biotechnological and pharmaceutical industry (Nuvisan GmbH, Santhera Pharmaceuticals Group) Long-standing experience in finance and management Ad interim Dr. Ronald Carter, Senior Medical Officer acting CMO (since Apr 2016) Long-standing and extensive expertise in the pharmaceutical industry Previous experience at MOLOGEN as a Medical Director

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 DNA-based TLR9 agonists MIDGE Vector System Cell-based therapeutic vaccination (MGN1601) Bind to TLR9 receptors Several products in development: Immune Surveillance Reactivator ISR Lefitolimod (MGN1703): Four trials EnanDIM: New class of linear TLR9 agonists Suitable for mono- and combination therapies DNA-based, non-viral vector system: gene ferries Three products in development: MGN1404 (malignant melanoma) MGN1331 (leishmaniasis) MGN1333 (hepatitis B) Genetically modified human renal cancer cell line using MIDGE platform combined with low-dose 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 Achievements 2015 Until Today, Successful capital increase Significant progress in patient recruitment for pivotal study IMPALA TEACH Completion first phase; start of prolonged treatment phase in Q Randomized study IMPULSE (SCLC) Patient recruitment finalized Continued partnering discussions Initiated agreement with MD Anderson Cancer Center, US to conduct combination study with lefitolimod (MGN1703) + ipilimumab (Yervoy ) Presented positive clinical data at scientific congresses 2016 mcrc metastatic colorectal cancer SCLC small cell lung cancer 8

10 Agenda Business Overview Market Lefitolimod (MGN1703) MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2016 Appendix

11 Oncology Market: Leading Therapy Category Worldwide Prescription Drugs in US$ billion Business Overview Worldwide Oncology Drugs in US$ billion Market CAGR +4.8% 987 CAGR +11.6% lefitolimod 743 (MGN1703) Cancer Immunotherapy 153 MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Pharmaceutical Industry and prescription drug sales return to growth Appendix Patent cliff overcome Source: EvaluatePharma 2015 CAGR Compound Annual Growth Rate Oncology remains the largest segment vs. outlook 2013 Highest growth rate & strongest sales increase worldwide in the long-term Immunotherapies represent emerging field => new mega-trend with US$ 35 billion market potential

12 Colorectal Cancer & Lung Cancer: High Growth Expected Colorectal Cancer Sales in US$ billion 1 Lung Cancer Sales in $US billion 2 SCLC Sales in $US billion 3 CAGR +1.8% CAGR +12.5% 13 4 CAGR +27.7% Launch of premium-priced adjuvant / maintenance therapies will extend first-line 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 Main drivers for growth: novel immunotherapies 1 5EU, US, Japan & Canada; Source: ResearchandMarkets Jan G7 Countries; Source: MarketsandMarkets Nov EU, US, Japan; Source: GlobalData, Jan 2016 CAGR Compound Annual Growth Rate I SCLC small cell lung cancer

13 Combination Therapies: The Next Opportunity Combination therapies are expected to be launched in increasing numbers in the coming years Treatment options will increase with launch of new immunotherapeutic agents Combination of immunotherapy with chemotherapy offer new potential for breaktrough outcomes New partnering opportunities Source: IMS Institute for Healthcare Informatics: Global Oncology Trend Report

14 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)

15 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

16 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

17 Agenda Business Overview Market Lefitolimod (MGN1703) MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2016 Appendix

18 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

19 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

20 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

21 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

22 Lefitolimod (MGN1703) Ongoing Clinical Trials IMPALA IMPULSE TEACH Metastatic Colorectal Cancer (mcrc) Pivotal trial (phase III) 540 patients 8 European countries: Austria, Belgium, Estonia, France, Germany, Italy, Spain, UK Small Cell Lung Cancer (SCLC) Randomized study 100 patients 4 European countries: Austria, Belgium, Germany, Spain HIV (Infectious Disease) Early Stage Study (phase I) 15 patients (first phase); additional patients (extension) Denmark Combination trial Advanced solid malignancies Lefitolimod (MGN1703) + ipilimumab (Yervoy ) Early Stage Study (phase I) patients Texas, US Currently Recruiting Recruitment completed (Oct 2015) Extension phase to start in Q Study expected to start in Q

23 IMPALA Pivotal Phase III Study in mcrc 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

24 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

25 TEACH Phase I Study in HIV Collaboration agreement with Aarhus University Hospital, DK conducting the study; funding received from the American Foundation for AIDS research (amfar) MOLOGEN provides lefitolimod (MGN1703) More patients to be treated for 6 months in extension phase based on broad activation of immune system induced by lefitolimod as shown in first phase: Activation of plasmacytoid dendritic cells (pdc), natural killer cells (NK) and T cells in HIV patients during the antiretroviral therapy (ART) Final results expected in Q Potential expansion of applications

26 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, mainly melanoma Potential expansion of applications

27 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 Start/end of first phase 2016 Recruitment completed Start of primary analyses Initial results of first phase; start extension First patient in (FPI) * Primary endpoint analysis (OS) Results Final results End of recruitment 2019 mcrc metastatic colorectal cancer SCLC small cell lung cancer I * Study expected to start in Q

28 Conclusion: Late-Stage Product Lefitolimod (MGN1703) with Unique Profile and Huge Market Potential Best in Best class in and class most TLR9 advanced agonist in and mcrc most (pivotal advanced in mcrc trial) (pivotal 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

29 Agenda Business Overview Market Lefitolimod (MGN1703) MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2016 Appendix

30 MGN1601 Unique Therapeutic Cancer Vaccination

31 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

32 Agenda Business Overview Market Lefitolimod (MGN1703) MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2016 Appendix

33 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

34 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

35 Agenda Business Overview Market Lefitolimod (MGN1703) MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2016 Appendix

36 Key Financials FY 2015 In million FY 2015 FY 2014 R&D expenses % EBIT % R&D expenses increased due to positive study progress Capital increase reflected in financing cash flows Cash flows from operating activities Cash flows from financing activities % % Monthly cash burn % In million 31 Dec Dec 2014 Main items impacted by capital increase Total assets % Cash & cash equivalents % Equity ratio 74% 88% -16%

37 Outlook 2016 Intensify product development Focus on lefitolimod (MGN1703) IMPULSE study: start of analyses towards end of 2016 IMPALA study: finalize patient recruitment in H Continue TEACH study with extension phase Start combination study with ipilimumab (Yervoy ) in patients with solid cancers in cooperation with the MD Anderson Evaluation of additional combination studies Evaluate and prioritize pipeline Continue partnering discussions R&D increase due to study progress; results accordingly below FY

38 Financial Calendar and Contact Details 12 May 2016 Quarterly Statement as of 31 March May 2016 Annual General Meeting 11 August 2016 Half-Yearly Financial Report as of 30 June November 2016 Quarterly Statement 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 37

39 Agenda Business Overview Market Lefitolimod (MGN1703) MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2016 Appendix

40 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

41 Lefitolimod (MGN1703) Established Mode of Action

42 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

43 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

44 Quarterly Key Financials [in million] 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

45 Main Events TEACH Topline results IMPULSE Start Primary analyses (OS) ODDO Lyon JPM HCC SanFran, US ASCO GI, SanFran ODDO Frankfurt HIV 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 44

46 Company Presentation April 2016