Company Presentation October 2015
Agenda Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix 2015 1
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 2015 2
Advanced Product Pipeline with Strong Focus on Cancer Immunotherapies Preclinical Phase I Phase II Phase III / Approval EnanDIM Oncology & Anti-infectives MGN1703 1 Other solid tumors MGN1703 1 Small cell lung cancer MGN1703 1 Colorectal cancer MGN1331 Leishmaniasis 3 MGN1333 Hepatitis B MGN1703 4 HIV MGN1601 Renal cancer MGN1404 2 Malignant melanoma Oncology Infectious diseases Oncology & Infectious diseases 1 IND (Investigational New Drug) filed in US; safety trial in US completed in 2014 2 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 2015 3
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 2015 4
Agenda Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix 2015 5
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% 153 73 2013 2020 Pharmaceutical Industry struggled with weak economic growth in recent years Patent cliff overcome Source: EvaluatePharma 2014 CAGR Compound Annual Growth Rate 2013 2020 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 2015 6
Colorectal and Lung Cancer: High Growth Expected Colorectal Cancer Sales in US$ billion 1 Lung Cancer Sales in $US billion 2 CAGR +4.9% 5 8 CAGR +12.5% 4 13 2013 2023 Launch of premium-priced adjuvant / maintenance therapies will extend firstline treatment 2010 2020 Most common cancer worldwide in terms of incidence and death High income countries have more than double the lung cancer incidence of low income countries 1 5EU, US, Japan & China; Source: GlobalData Nov 2014 2 G7 Countries; Source: MarketsandMarkets Nov 2011 CAGR Compound Annual Growth Rate 2015 7
Oncology Market: Sharp Increase of Incidences Incidences Oncology 1 Incidences by Oncology indication 2012 2 +40% 20m 1.8m Lung 14m 9.2m 1.7m 1.4m Breast Colorectum Other 2012 2025 Aging populations will increase incident case rates in all markets covered Cancer rates for all cancers combined rise with increasing levels of country income Total number of estimated cancer cases: 14.1 million 1 World, Source: IARC World Cancer Report 2014 2 World, Source: WHO GLOBOCAN 2012 (IARC) 2015 8
Cancer Immunotherapies: New Megatrend Science Magazine: Breakthrough of the Year 2013 US$ 35,000,000,000 market potential* *Source: Citi-Bank 2013 estimated peak sales 2015 9
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 2014 2015 10
Agenda Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix 2015 11
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 2015 12
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 2015 13
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. 15.1 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 44-51 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 2015 14
IMPACT Sustained Efficacy April 2010: Patient 049 Initial diagnosis Colon carcinoma with multiple liver metastases December 2010: After induction chemotherapy 06/2010-11/2010: 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 2015 15
IMPALA mcrc Pivotal Phase III Study Started in Sep 2014 Trial Treatment Period Maintenance Re-Induction Induction CT 12 30 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 2015 16
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 2015 17
MGN1703 Milestones for Various Clinical Trials 2014 2015 2016 2017 / 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
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 Q2 2016 Potential expansion of applications 2015 19
Agenda Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix 2015 20
MGN1601 Unique Therapeutic Cancer Vaccination 2015 21
ASET Trial with MGN1601: Promising Data Phase I/II study (12/2010 08/2013): 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 2015 22
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 2015 23
Agenda Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix 2015 24
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 2015 25
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 2015 26
Agenda Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix 2015 27
Key Financials H1 2015 In million H1 2015 H1 2014 R&D expenses 5.2 5.9-12% EBIT -6.9-7.9-13% Cash flows from operating activities -4.7-6.5-28% 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 26.1 14.7 78% Monthly cash burn 1.2 1.3 In million June 30, 15 Dec 31, 14 Total assets 36.0 15.1 139% Main items impacted by capital increase of 28.3 m gross Cash & cash equivalents 34.9 13.6 157% Equity ratio 91% 88% 3% 2015 28
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% 2015 29
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 2015 30
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: +49-30-841788-38 Fax: +49-30-841788-50 investor@mologen.com www.mologen.com 2015 MOLOGEN, MIDGE, dslim, and EnanDIM are registered trademarks of the 31
Agenda Business Overview Market MGN1703 Cancer Immunotherapy MGN1601 Therapeutic Vaccination against Cancer EnanDIM New Generation of Immunomodulators Key Financials and Outlook 2015 Appendix 2015 32
IMPACT Phase II Study Design and Results Trial Treatment Period Maintenance Induction CT 4.5-6 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 2015 33
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 [2.8-4.1] Placebo (n=16) 2.6 months [2.5-2.8] HR=0.55 [95% CI: 0.3-1.0] Log-rank p=0.04 4 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 2015 34
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 [14.9-..] Placebo (n=16) 15.1 months [10.6- ] HR=0.63 [95% CI: 0.3-1.5] Log-rank test p=0.2886 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 2015 35
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 2015 36
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 MDX010-20 with Ipilimumab in melanoma (Yervoy ) 1 IMPACT trial with MGN1703 in colorectal cancer Median PFS HR = 0.64 p < 0.001 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; 363:711-723 (modified); Yervoy is a registered trademark of Bristol-Myers Squibb 2015 37
and Overall Survival (OS) Kaplan-Meier curves open before median Subgroup of patients (20%) shows huge benefit in terms of OS Clinical trial MDX010-20 with Ipilimumab in melanoma (Yervoy ) 1 IMPACT trial with MGN1703 in colorectal cancer (OS not mature yet) Median OS HR = 0.66 p = 0.003 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; 363:711-723 (modified); Yervoy is a registered trademark of Bristol-Myers Squibb 2015 38
MGN1703 Established Mode of Action 2015 39
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 2015 40
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 1.0 0.8 Overall survival Trial inclusion DC PD ** PP non-pp ITT PD ** 0.6 0.4 0.2 0.0 0 20 40 60 80 100 120 OS time [weeks] 2015 41
MGN1601 ASET Study Results Median OS: 24.8 weeks (ITT group): 115.3 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 2015 42
MOLOGEN Shares ISIN DE0006637200 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) 2015 43
Quarterly Key Financials [in million] Q2 2015 Q1 2015 Q4 2014 Q3 2014 Q2 2014 Q1 2014 Q4 2013 Q3 2013 Q2 2013 Q1 2013 2014 2013 R&D expenses 2.8 2.4 2.8 4.6 3.0 2.9 3.4 1.7 1.4 1.4 13.3 7.9 EBIT -3.7-3.2-3.8-5.4-3.8-4.1-4.2-2.5-2.0-2.2-17.1-10.9 Cash flow from operating activities Cash flow from financing activities -2.5-2.2-4.1-5.0-3.3-3.2-2.8-2.3-1.8-2.0-15.6-8.9 25.4-0.7-0.2 - -0.1 14.8 - - - - 14.5 - Monthly cash burn 1.4 1.0 1.4 1.7 1.1 1.4 0.9 0.8 0.6 0.7 1.4 0.8 2015 44
Company Presentation October 2015 2015 45