MOLOGEN AG. Dr. Matthias Schroff Chief Executive Officer Dr. Alfredo Zurlo Chief Medical Officer. Roadshow Abu Dhabi, Dubai April 2015

Transcription

1 Dr. Matthias Schroff Chief Executive Officer Dr. Alfredo Zurlo Chief Medical Officer Roadshow Abu Dhabi, Dubai April 2015

2 Disclaimer Certain statements in this presentation contain formulations or terms referring to the future or future developments, as well as negations of such formulations or terms, or similar terminology. These are described as forward-looking statements. In addition, all information in this presentation regarding planned or future results of business segments, financial classification numbers, developments of the financial situation, or other financial or statistical data contains such forward-looking statements. The company cautions prospective investors not to rely on such forwardlooking statements as certain prognoses of actual future events and developments. The company is neither responsible nor liable for these forward-looking statements. It is not responsible for updating such information, which only represents the state of affairs on the day of publication. V

3 Agenda MOLOGEN AG Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

4 Snapshot MOLOGEN AG Biotechnology company with focus on immunotherapies One of the pioneers in immunotherapies Advanced products / Promising pipeline Lead product MGN1703 in registration study MGN1601: Unique therapeutic cancer vaccination 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 International network of excellence

5 Pipeline: Strong Focus on Cancer Immunotherapies Preclinical Phase I Phase II Phase III / Approval EnanDIM Oncology & Anti-infectives MGN Other solid tumors MGN Small cell lung cancer MGN Colorectal cancer MGN1331 Leishmaniasis MGN1601 Renal cancer MGN1333 Hepatitis B MGN Malignant melanoma Oncology Infectious diseases Oncology & Infectious diseases 1 IND (Investigational New Drug) filed in U.S.; safety trial in U.S. completed 2 Collaboration with Max-Delbrueck-Center for Molecular Medicine and Charité Universitaetsmedizin, Berlin

6 Strategic Focus: Outlicensing of Products to Generate High Returns License agreements with pharma companies High returns in the mid- and long-term Prioritize development of lead product MGN1703 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 Extend and advance product pipeline to ensure long-term growth

7 Achievements 2014 MOLOGEN AG Capital increase to start IMPALA study Start IMPALA Registration study Start IMPULSE Randomized study EnanDim New generation of immunomodulators Present positive clinical data at scientific congresses

8 Agenda MOLOGEN AG Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

9 Oncology Market: Leading Therapy Category MOLOGEN AG Worldwide Prescription Drugs in US$ billion Worldwide Oncology Drugs in US$ billion CAGR +5.1% 717 1,017 CAGR +11.2% Pharmaceutical Industry struggled with weak economic growth in recent years 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

10 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

11 Oncology Market: Sharp Increase of Incidences MOLOGEN AG 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 comb. 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)

12 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

13 Immunotherapy: Superior Treatment MOLOGEN AG 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 time Source: "Immuno-oncology: The new weapon in the war against cancer, Alistair Campbell; Berenberg Equity Highlights, February

14 Agenda MOLOGEN AG Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

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

16 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

17 IMPACT Phase II Study in Colorectal Cancer Generated Outstanding Long-Term Responses Primary endpoint met: Progression free survival Secondary endpoint Overall Survival : Results are not yet mature (too many patients alive), median OS 22.6 (MGN1703) vs months 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 September 2014 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

18 IMPACT Sustained Efficacy MOLOGEN AG Patient 049 At initial diagnosis (04/2010) Colon carcinoma with multiple liver metastases After induction chemotherapy (12/2010) 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 During MGN1703 maintenance (04/2012) Since 12/2010: MGN1703 maintenance therapy New PR * after 9 months Still ongoing PR (40 months as of Jan 2015) Good medical condition, mild local skin reactions, no further toxicities

19 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 MGN1703 Control group PD PD 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 more than 100 sites in eight European countries, including Top 5 European pharma markets Biomarkers used as stratification factors: CEA level and NKT activation CR complete response CEA carcinoembryonic antigen - a tumor marker for colorectal cancer CT chemotherapy mcrc metastatic colorectal cancer NKT Natural Killer T cells PR partial response PD progressive disease

20 IMPULSE SCLC Randomized Study Started in Mar 2014 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 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 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

21 MGN1703 Milestones for Various Clinical Trials / 2018 Metastatic Colorectal Cancer (mcrc) IMPALA (Phase III trial) First patient in, PEP: OS IMPACT (Phase II trial) OS data expected IMPALA Recruitment completed IMPALA Primary analyses (OS), Filing/Approval Small Cell Lung Cancer (SCLC) IMPULSE (randomized, controlled trial) First patient in, PEP: OS IMPULSE Recruitment completed IMPULSE Primary analyses (OS) OS overall survival PEP primary endpoint

22 Summary MGN1703: Most Advanced Product Phase II study IMPACT colorectal cancer: Outstanding long-term responses Pivotal phase III study IMPALA in colorectal cancer Patient enrolment started in September 2014 Switch maintenance therapy to prolong overall survival Study design is based on findings of the phase II IMPACT study Randomized study IMPULSE in small cell lung cancer Patient enrolment started in March 2014 Switch maintenance therapy to prolong overall survival Indication with high unmet medical need Investigational New Drug (IND) application approved in the US Prerequisite for US application for marketing authorization Safety and tolerability study in the US; completed in

23 Agenda MOLOGEN AG Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

24 MGN1601 Unique Therapeutic Cancer Vaccination

25 ASET Trial with MGN1601: Promising Data ASET 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

26 Conclusion: Late-Stage Products with Unique Profile and Huge Market Potential MGN1703 First-line maintenance 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 MGN1601 Promising phase I/II data in renal cancer EMA: Orphan Drug Status; 10 yrs. market exclusivity Attractive market potential mcrc metastatic colorectal cancer SCLC small cell lung cancer EMA European Medicines Agency

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

28 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 trials Potential application in the fields of cancer and anti-infective therapies

29 Combining Advantages of Two Types of Agonists: Linear and Not Chemically Modified Structure 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

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

31 Key Financials FY 2014: Ongoing High R&D Expenses Due to Advanced Study Programs [in million] Dec Dec Cash & cash equiv % Balance sheet total Equity ratio 88% 94% -6% Balance sheet almost unchanged: high cash consumption due to extended R&D compensated by cash inflow from capital increase [in million] R&D expenses % EBIT % Cash flow from operating activities % Cash flow from financing activities Monthly cash burn % IMPALA and IMPULSE studies main drivers of increased R&D costs Monthly cash burn increased accordingly Cash flow from financing activities includes capital increase

32 FY 2015: Qualitative Outlook MOLOGEN AG Development of product pipeline well on track Intensify clinical development of 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 MGN1703, mainly IMPALA

33 Corporate Calendar and Contact Details MOLOGEN AG May 12, 2015 Quarterly Report as of March 31, 2015 August 13, 2015 Quarterly Report as of June 30, 2015 November 12, 2015 Quarterly Report as of Sep 30, 2015 Claudia Nickolaus Head of Investor Relations & Corporate Communications Phone: Fax: MOLOGEN, MIDGE, dslim, and EnanDIM are registered trademarks of the MOLOGEN AG 32

34 Agenda MOLOGEN AG Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix

35 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 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

36 IMPACT Primary Endpoint Provides Proof of Efficacy PFS from start of maintenance (local assessment) 10% long-term responders mpfs [95% CI] MGN1703 (n=43) 2.8 months [ ] Placebo (n=16) 2.6 months [ ] HR=0.55 [95% CI: ] Log-rank p= progression-free patients still on treatment at end of study Further information on IMPACT: Journal of Cancer Research and Clinical Oncology (J Cancer Res Clin Oncol) CI confidence interval HR hazard ratio mpfs median progression-free survival

37 IMPACT Secondary Endpoint: Promising Trend in OS After a median follow-up in excess of 17 months: approx. 65% of patients in the MGN1703 arm still alive vs. 50% of patients in the placebo arm OS from start of maintenance mos [95% CI] MGN1703 (n=43) 22.6 months [ ] Placebo (n=16) 15.1 months [10.6- ] HR=0.63 [95% CI: ] Log-rank test p= Further information on IMPACT: Journal of Cancer Research and Clinical Oncology (J Cancer Res Clin Oncol) CI confidence interval HR hazard ratio mos median overall survival OS overall survival

38 IMPACT PFS and OS Benefit in Patients Relevant for Phase III Responders to prior induction therapy show encouraging PFS and OS benefit (shown from start of maintenance therapy, time of induction therapy is not included) Data on OS still preliminary due to lack of events [patients alive] MGN1703 n=29 Placebo n=14 HR=0.40; p=0.009 MGN1703 (n=29) Placebo (n=14) mos 24.5 months 15.1 months HR=0.40; p=0.069 (cut-off date: March 2013) HR hazard ratio mos median overall survival PFS progression-free survival

39 IMPACT Comparable Immunotherapies Show Similar Effects on Progression-Free Survival (PFS) Kaplan-Meier curves only separate with respect to survival after median Subgroup of patients (10%) shows huge benefit in terms of PFS Clinical trial MDX with Ipilimumab in melanoma (Yervoy ) 1 IMPACT trial with MGN1703 in colorectal cancer Median PFS HR = 0.64 p < Ipilimumab (137 patients) Median PFS MGN1703 HR = 0.55 p = 0.04 Control group (gp100, 136 patients) Control group (placebo) 1 Hodi et al., N Engl J Med 2010; 363: (modified); Yervoy is a registered trademark of Bristol-Myers Squibb

40 and Overall Survival (OS) MOLOGEN AG Kaplan-Meier curves open before median Subgroup of patients (20%) shows huge benefit in terms of OS Clinical trial MDX with Ipilimumab in melanoma (Yervoy ) 1 IMPACT trial with MGN1703 in colorectal cancer (OS not mature yet) Median OS HR = 0.66 p = Median OS HR = 0.63 p = 0.29 Ipilimumab MGN1703 Control group (gp100) Control group (Placebo) 1 Hodi et al., N Engl J Med 2010; 363: (modified); Yervoy is a registered trademark of Bristol-Myers Squibb

41 MGN1703 Established Mode of Action MOLOGEN AG

42 MGN1601 ASET Study Design MOLOGEN AG Trial Treatment Period Patients with advanced renal cell cancer No standard therapy available Trial inclusion TPP 8 applications of MGN1601 in 12 weeks i.d. 8 applications of MGN1601 in 12 weeks i.d. Extension phase 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 MOLOGEN Shares MOLOGEN AG ISIN DE Shares issued: 16,973,626 (before capital increase April 2015) Max. 1.6 million share options (employee stock option plans) Frankfurt Stock Exchange (Prime Standard): MGN Reuters: MGNG.DE Distribution of shares (estimates) Free float 53% Private investor, Germany 24% Deutscher Ring Krankenversicherungsverein a.g., Germany 8% Baloise Holding, Switzerland 8% Salvator Vermoegensverwaltungs GmbH, Germany 7%

44 Dr. Matthias Schroff Chief Executive Officer Dr. Alfredo Zurlo Chief Medical Officer Roadshow Abu Dhabi, Dubai April 2015