MOLOGEN AG. Company Presentation October 2015

Transcription

1 Company Presentation October 2015

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

3 Company Overview 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 Close network with scientific institutions & experts International network of excellence

4 Advanced Product Pipeline with 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 3 MGN1333 Hepatitis B MGN HIV MGN1601 Renal cancer MGN Malignant melanoma Oncology Infectious diseases Oncology & Infectious diseases 1 IND (Investigational New Drug) filed in US; safety trial in US completed in Collaboration with Max-Delbrueck-Center for Molecular Medicine and Charité Universitaetsmedizin, Berlin 3 Various diseases caused by parasites; mainly present in subtropical and tropical regions (major neglected disease) 4 Collaboration with University Hospital Aarhus, Denmark

5 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

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

7 Oncology Market: Leading Therapy Category 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

8 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

9 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)

10 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

11 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 time Source: "Immuno-oncology: The new weapon in the war against cancer, Alistair Campbell; Berenberg Equity Highlights, February

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

13 MGN1703: Best in Class TLR9 Agonist 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

14 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

15 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 April 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

16 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: MGN1703 maintenance therapy New PR * after 9 months Still ongoing PR (42 months as of April 2015) Good medical condition, mild local skin reactions, no further toxicities

17 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 around 120 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

18 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

19 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) Small Cell Lung Cancer (SCLC) IMPULSE (Randomized, controlled trial) First patient in, PEP: OS IMPULSE Recruitment completed IMPULSE Primary analyses (OS) HIV (Infectious Diseases) TEACH (Phase I trial) Activation of immune system Recruitment started and completed TEACH Primary analyses PEP: Change in proportions of activated NKT 2015 OS overall survival PEP primary endpoint NKT Natural Killer T cells 18

20 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 MGN1703 First time to evaluate MGN1703 in other disease than cancer Top-line results expected Q Potential expansion of applications

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

22 MGN1601 Unique Therapeutic Cancer Vaccination

23 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

24 Conclusion: Late-Stage Product MGN1703 with Unique Profile and Huge Market Potential 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 mcrc metastatic colorectal cancer SCLC small cell lung cancer

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

26 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

27 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

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

29 Key Financials H In million H H R&D expenses % EBIT % Cash flows from operating activities % Slight decrease of R&D costs due to phasing effects Monthly cash burn decreased accordingly Capital increase reflected in financing cash flows Cash flows from financing activities % Monthly cash burn In million June 30, 15 Dec 31, 14 Total assets % Main items impacted by capital increase of 28.3 m gross Cash & cash equivalents % Equity ratio 91% 88% 3%

30 Capital Increase Ensures Completion of Patient Recruitment for Ongoing Studies with MGN1703 Public offering to existing shareholders and private placement of new shares to international institutional investors Issuance of 5,657,875 new ordinary bearer shares Number of shares increased to now 22,631,501 shares ~ 28 m gross proceeds mainly to be used to finalize patient recruitment for ongoing IMPULSE and IMPALA studies with lead product MGN1703 Free float at approx. 54%

31 FY 2015: Unchanged Outlook 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

32 Corporate Calendar and Contact Details Nov 4-5, 2015 Citi Global Healthcare Conference New York City November 12, 2015 Quarterly Report as of Sep 30, 2015 Nov 20-21, 2015 ESMO IO, Geneva Nov 23-25, 2015 German Equity Forum, Frankfurt Claudia Nickolaus Head of Investor Relations & Corporate Communications Phone: Fax: MOLOGEN, MIDGE, dslim, and EnanDIM are registered trademarks of the 31

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

34 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

35 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

36 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

37 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

38 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

39 and Overall Survival (OS) 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

40 MGN1703 Established Mode of Action

41 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

42 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 Non-PP group (9 pts.): patients dropped out before finalizing the 12 weeks course of treatment Overall survival Trial inclusion DC PD ** PP non-pp ITT PD ** OS time [weeks]

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 MOLOGEN Shares ISIN DE Shares issued: 22,631,501 Max. 1.6 million share options (employee stock option plans) Frankfurt Stock Exchange (Prime Standard): MGN Reuters: MGNG.DE Distribution of shares (estimates)

45 Quarterly Key Financials [in million] 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

46 Company Presentation October