COMPANY PRESENTATION JUNE 2016

Transcription

1 COMPANY PRESENTATION JUNE 2016

2 Agenda Business Overview and Next Level Strategy Market TLR9 Agonist Product Family: Lefitolimod (MGN1703) EnanDIM New Generation of Immunomodulators MGN1601 Therapeutic Vaccination against Cancer Key Financials and Outlook 2016 Appendix 2

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 3

4 MOLOGEN Shares ISIN DE Shares issued: 22,631,501 Market capitalization ~ 87m (31 March 2016) Frankfurt Stock Exchange (Prime Standard): MGN Reuters: MGNG.DE Global Derivative Trading GmbH 54% 24% 6% 6% 5% 5% Baloise Holding Deutscher Ring Krankenversicherungsverein a.g. Salvator Vermoegensverwaltungs GmbH Deutsche Balaton Aktiengesellschaft 4

5 Company Overview Biotechnology company with focus on immunotherapies One of the pioneers in immunotherapies Close-to-market compounds Focus on family of TLR9 agonists: Lefitolimod (MGN1703) EnanDIM 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 MOLOGEN AG Close network with scientific institutions & experts 5

6 New Strategy,,Next Level Shift from Research- to Product- and Market-Oriented Company Strong market- and product-oriented strategy program Focus on close-to-market compounds: Lead product immunomodulator lefitolimod (MGN1703) EnanDIM : Lefitolimod successor molecules and next-generation technology MGN1601: Shelve clinical development backup compound MIDGE technology: Divestment or spin-off Streamline company s organizational structure Accelerate commercialization of products via out-licensing Create added value 6

7 Target Portfolio: Focus on Lead Product Lefitolimod and Its Next-Generation Compound EnanDIM DNA-based TLR9 agonists (ISRs) Bind to TLR9 receptors Several Immune Surveillance Reactivators (ISR) in development: Lefitolimod (MGN1703): Four trials EnanDIM: New class of linear TLR9 agonists Suitable for mono- and combination therapies 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 low-dose lefitolimod as adjuvant Phase I/II data available Orphan drug status Focus Divestment/Spin-off Backup 7

8 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 Lefitolimod (MGN1703) 1,2 HIV Lefitolimod (MGN1703) 1 + ipilimumab (Yervoy ) 3 Advanced solid malignancies MGN1601 Renal cancer Oncology Infectious diseases Oncology & Infectious diseases Oncology combination trials 1 Immune Surveillance Reactivator and TLR9 agonist 2 Collaboration with University Hospital Aarhus, Denmark 3 Collaboration with MD Anderson Cancer Center, Texas, US; study is expected to start in Q SCLC small cell lung cancer 8

9 Target Product Portfolio Focus on TLR9 Product Family: Lefitolimod and EnanDIM Platform Compound Indications PC PH I PH II PH III Study Cooperation partners Metastatic colorectal cancer (mcrc) IMPALA - DNAbased TLR9 agonists (ISR) Lefitolimod (MGN1703) Small cell lung cancer (SCLC) HIV IMPULSE - TEACH Aarhus University Hospital Advanced solid malignancies Lefitolimod & ipilimumab MD Anderson Cancer Center EnanDIM Cancer / antiinfective therapies Therapeutic Vaccine (cell-line) MGN 1601 Renal cancer On hold: backup compound ISR Immune Surveillance Reactivator I PC pre-clinical 9

10 Strategic Focus: Outlicensing of Products to Generate High Returns Focus on Lefitolimod Partnering agreement for lefitolimod (MGN1703) Ensure funding of lefitolimod (MGN1703) until filing/approval Shelve clinical development of MGN1601 Initiate new projects High returns in the mid- and long-term High market potential Backup compound Initiate combi trials; extend and advance product pipeline: ensure long-term growth 10

11 Agenda Business Overview and Next Level Strategy Market TLR9 Agonist Product Family: Lefitolimod (MGN1703) EnanDIM New Generation of Immunomodulators MGN1601 Therapeutic Vaccination against Cancer Key Financials and Outlook 2016 Appendix 11

12 Oncology Market: Leading Therapy Category Worldwide Prescription Drugs in US$ billion Business Overview Market CAGR +4.8% lefitolimod (MGN1703) Cancer Immunotherapy Worldwide Oncology Drugs in US$ billion MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators CAGR +11.6% 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 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

13 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 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 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

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 1 World, Source: IARC World Cancer Report World, Source: WHO GLOBOCAN 2012 (IARC) Cancer rates for all cancers combined rise with increasing levels of country income Total number of estimated cancer cases: 14.1 million 14

15 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 breakthrough outcomes New partnering opportunities Source: IMS Institute for Healthcare Informatics: Global Oncology Trend Report

16 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

17 Cancer Immunotherapy: Superior Treatment - How to Increase Overall Survival? Chemotherapy Fast effect in many patients Effect not lasting Patients alive in % Chemotherapy Immunotherapy Needs time to be effective Long-lasting effect in a subgroup of patients Patients alive in % Immunotherapy Combi-therapy Control group time Control group Ca. 10% time 17

18 Agenda Business Overview and Next Level Strategy Market TLR9 Agonist Product Family: Lefitolimod (MGN1703) EnanDIM New Generation of Immunomodulators MGN1601 Therapeutic Vaccination against Cancer Key Financials and Outlook 2016 Appendix 18

19 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

20 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

21 IMPACT Phase II Study in Colorectal Cancer Generated Sustained Long-Term Responses Primary endpoint met: Progression free survival (HR 0.55, p=0.04) Secondary endpoint Overall Survival : Median OS 22.6 months (lefitolimod (MGN1703)) vs months (p=ns), and in subgroup (relevant pts for phase III): Median OS 24.5 months (lefitolimod (MGN1703)) vs months (p=0.069) Predictive biomarkers identified: Tumor reduction by induction therapy, normalized 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: 3 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 HR Hazard Ratio NKT Natural Killer T cells ns not significant 21

22 IMPACT Primary Endpoint Provides Proof of Efficacy AS OF MARCH 2013 PFS from start of maintenance (local assessment) ~10% long-term responders MGN1703 (n=43) Placebo (n=16) mpfs [95% CI] 2.8 months [ ] 2.6 months [ ] HR=0.55 [95% CI: ] 4 progression-free patients still on treatment at end of study CI confidence interval HR hazard ratio mpfs median progression-free survival 22

23 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 23

24 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 Currently Recruiting Small Cell Lung Cancer (SCLC) Randomized study 100 patients 4 European countries: Austria, Belgium, Germany, Spain Recruitment completed (Oct 2015) HIV (Infectious Disease) Early Stage Study (phase I) 15 patients (first phase); 15 patients in extension phase Denmark Extension phase to start shortly Combination trial Advanced Solid Malignancies Lefitolimod (MGN1703) + ipilimumab (Yervoy ) Early Stage Study (phase I) patients Texas, US Study expected to start shortly 24

25 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 25

26 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 26

27 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 27

28 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 28

29 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) * Start primary endpoint analysis (OS) Results Final results End of recruitment 2019 Results Start of primary analyses mcrc metastatic colorectal cancer SCLC small cell lung cancer I * Study expected to start in Q

30 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 30

31 Agenda Business Overview and Next Level Strategy Market TLR9 Agonist Product Family: Lefitolimod (MGN1703) EnanDIM New Generation of Immunomodulators MGN1601 Therapeutic Vaccination against Cancer Key Financials and Outlook 2016 Appendix 31

32 EnanDIM Next Generation TLR9 Agonists 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

33 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

34 Agenda Business Overview and Next Level Strategy Market TLR9 Product Family: Lefitolimod (MGN1703) EnanDIM New Generation of Immunomodulators MGN1601 Therapeutic Vaccination against Cancer Key Financials and Outlook 2016 Appendix 34

35 MGN1601 Unique Therapeutic Cancer Vaccination 35

36 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 36

37 Agenda Business Overview and Next Level Strategy Market TLR9 Agonist Product Family: Lefitolimod (MGN1703) EnanDIM New Generation of Immunomodulators MGN1601 Therapeutic Vaccination against Cancer Key Financials and Outlook 2016 Appendix 37

38 Key Financials Q In million Q Q R&D expenses % EBIT % Cash flows from operating activities % R&D expenses increased due to advanced study program Accordingly increase of cash burn Cash flows from financing activities Monthly cash burn % In million 31 Mar Dec 2015 Total assets % Main items impacted by study progress; cash outflows accordingly Cash & cash equivalents % Equity ratio 70% 74% -5% 38

39 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 Continue partnering discussions R&D expenses increased due to study progress; results accordingly below FY

40 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% 40

41 Financial Calendar and Contact Details 12 May 2016 Quarterly Statement as of 31 March August 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 MOLOGEN AG 41

42 Agenda Business Overview and Next Level Strategy Market TLR9 Agonist Product Family: Lefitolimod (MGN1703) EnanDIM New Generation of Immunomodulators MGN1601 Therapeutic Vaccination against Cancer Key Financials and Outlook 2016 Appendix 42

43 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 43

44 Lefitolimod (MGN1703) Mode of Action ISR by Lefitolimod 44

45 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 45

46 OS rate MGN1601 ASET Study Results ITT group (19 pts) : all patients who received at least one vaccination PP group (10 pts.): patients received eight vaccinations within twelve weeks as planned Trial inclusion DC PD ** Non-PP group (9 pts.): patients dropped out before finalizing the 12 weeks course of treatment Overall survival PP non-pp ITT PD ** OS time [weeks] 46

47 MGN1601 ASET Study Results Median OS: 24.8 weeks (ITT group): weeks (PP group) Potential biomarker identified MSKCC Score & NLR may have predictive value for longer OS Trial inclusion DC PD ** 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 47

48 COMPANY PRESENTATION JUNE 2016