HARNESSING THE IMMUNE SYSTEM TO TREAT AND PREVENT DISEASE JANUARY 2014 CSE/OMX:BAVA, OTC:BVNRY BAVARIAN NORDIC CANCER IMMUNOTHERAPIES AND VACCINES FOR INFECTIOUS DISEASES BAVARIAN NORDIC IN BRIEF • • • • • • • • Vertically integrated multinational biotech company Revenue-generating Leader in vector-based active immunotherapy – two technology platforms First product approved in 2013 Two Phase 3 programs: Prostate cancer and smallpox Ebola vaccine license and supply agreement with Janssen Commercial scale cGMP manufacturing facility Long-term contracts with the US government REVENUES AND RESULTS, 5 YEARS 2009 1.000 500 0 -500 2 2010 2011 2012 2013 FACTS 2014E • Founded 1994, IPO 1998 • Headquartered in Denmark • Research centers in Mountain View, CA and Munich, Germany • Listed on NASDAQ OMX Copenhagen: BAVA PIPELINE Preclinical IMVANEX®/ IMVAMUNE® 1-4) Smallpox PROSTVAC® Prostate Cancer IMVAMUNE® freeze-dried 1) Smallpox CV-301 Colon 1) Colorectal Cancer CV-301 Bladder 1) Bladder Cancer CV-301 Breast 1) Breast Cancer MVA-BN® PRO Prostate Cancer MVA-BN® HER2 Breast Cancer MVA-BN® Brachyury MVA-BN® Filo 5) Metastatic Tumors Filoviruses (Ebola/Marburg) MVA-BN® RSV MVA-BN® FMDV 1) Respiratory Syncytial Virus 1) MVA-BN® Anthrax Foot-and-mouth Disease 1) Anthrax 1) Government funded programs 2) Sold to government stockpiles 3) Approved in the European Union under the trade name IMVANEX® and in Canada under the trade name IMVAMUNE® 4) Phase 3 registration studies are ongoing in the United States 5) Licensed to Janssen 3 Phase 1 Phase 1/2 Phase 2 Phase 3 Market THE MVA-BN® VACCINE PLATFORM MVA-BN (IMVAMUNE) Recombinant MVA-BN MVA-BN Antigen(s) + Vaccine Platform Approvals in EU and Canada Balanced Immune Response Strong IP Protection 4 Research & Development Construct Optimization Immune Enhancement Preclinical Analysis Manufacturing Research Drug Product Clinical Batch Production Commercial Manufacturing Immune Targets (Antigens) POXVIRUS TECHNOLOGY PLATFORM PROSTVAC CV-301 • Prostate cancer • Colorectal, Breast, Lung, Ovarian, Gastric, Bladder, Liver and Renal cancer PSA CEA TRICOM TRIad of CO-stimulatory Molecules Vectors LFA-3 ICAM-1 Vaccinia + Fowlpox (VF) (Prime) GM-CSF can be used as adjuvant in both PROSTVAC ® and CV-301 5 B7.1 (Boost) MUC-1 OUR INFECTIOUS DISEASES BUSINESS 6 IMVAMUNE® ADVANTAGES TRADITIONAL SMALLPOX VACCINES Traditional vaccines are based on a replicating vaccinia virus • Dryvax®, ACAM2000, LC16m8, Elstree-BN All have been shown to produce some/all of following serious side effects • Myocarditis, pericarditis, encephalitis, progressive or generalized vaccinia, eczema vaccinatum, inadvertent infection Significant population should not receive replicating vaccines • Congenital or acquired immunodeficiency, immunosuppresive medications, exfoliative skin disorders (e.g. eczema) IMVAMUNE®/IMVANEX® Based on a non-replicating virus Approved in EU and Canada More than 7,500 individuals have been vaccinated • Well tolerated – even in immune-compromised patients • No reports of the serious adverse events reported with the use of replicating vaccinia vaccines in the smallpox eradication campaign 7 SUCCESSFUL PARTNERSHIP WITH THE U.S. GOVERNMENT CONTRACTS AWARDED TO-DATE EXCEED US$ 1BN Developing freeze-dried vaccine 2003 2004 RFP-1 IMVAMUNE Smallpox Vaccine MVA-BN Marburg Vaccine MVA-BN Foot-andmouth disease MVA-BN Burkholderia US$ 55m US$ 18m US$ 1m US$ 500k BARDA NIH DHS DOD DTRA RFP Freeze Dried IMVAMUNE Smallpox Vaccine RFP Freeze Dried Expansion US$ 40m BARDA 2005 2006 RFP-2 IMVAMUNE Smallpox Vaccine US$ 14m US$ 100m NIH NIH 2007 2008 MVA-BN Ebola/Marburg Early research 2009 2010 2011 2012 2013 2014 Delivery contract IMVAMUNE Smallpox Vaccine RFP-3 IMVAMUNE Smallpox Vaccine RFP-2 Expansion IMVAMUNE Smallpox Vaccine RFP-3 Expansions IMVAMUNE Smallpox Vaccine US$ 500m US$ 16m US$ 49m US$ 228m BARDA NIH BARDA BARDA Developing, producing, supplying liquid-frozen IMVAMUNE® 8 Expanding MVA-BN® platform GROWING THE IMVAMUNE BUSINESS WITH FREEZE-DRIED Ongoing US$ 95m contract with BARDA to develop a freeze-dried IMVAMUNE BENEFITS • • Anticipated shelf life of greater than 10 years Easier logistics and storage TIMELINES • • Ongoing transfer of FD process to commercial scale facility Phase 2 ongoing; anticipated EUA in 2016, which allows for federal stockpiling POTENTIAL • • 9 First wave of replenishment could replace 20M expiring doses in stockpile Long term stated goal of US Government calls for non-replicating vaccine for 66M US citizens EBOLA/MARBURG VACCINE AGREEMENT WITH JANSSEN Supply agreement US$ 99m BN to manufacture and supply ~2 million vaccine doses • US$ 70m upfront • US$ 29m pro rata with deliveries in 2015 License agreement US$ 45m BN grants exclusive license to Janssen for its MVA-BN Filovirus vaccine (Ebola Zaire, Ebola Sudan and Marburg) Janssen will cover development costs • US$ 25m upfront • US$ 20m in development and regulatory milestones Equity investment Johnson & Johnson Development Corporation has subscribed for 1.3 million new BN shares through private placement 10 US$ 43m EBOLA - CLINICAL TRIALS • Ongoing safety and immunogenicity trials of MVA-BN Filo in prime-boost regimen with Janssen and GSK • MVA-BN Filo/AdVac (Janssen) • Phase 1 (n=72) initiated January 2015 in UK • Full recruitment anticipated by end of January • Additional trials starting soon in US and Africa • MVA-BN/cAd EBO Z (GSK) • Phase 1 (n=60) - 30 subjects will receive a booster of MVA-BN Filo 11 JANSSEN COLLABORATION ADDITIONAL COMMERCIAL INFECTIOUS DISEASE TARGETS • Subsequent to the Ebola collaboration, BN and Janssen have agreed to collaborate on three additional infectious disease targets • Bavarian Nordic will develop MVA-BN constructs for scientific evaluation • Janssen will have an exclusive window to decide if they wish to enter into licensing agreements MVA/ADVAC – PRIME-BOOST RATIONALE • All adenoviruses require a separate boost to be an effective vaccination regime. • One of the best boost platforms that has been used in combination with adenoviruses (of all species, human or chimp) is MVA. • As it relates to Ebola, the combination of adenovirus and MVA improves the induction of strong immune responses in the short term (due to the highly immunogenic adenovirus), and provides long-term protection, due to the properties of MVA-BN. 12 RSV: RESPIRATORY SYNCYTIAL VIRUS RSV • Major cause of upper & lower respiratory tract infections in adults and children • No approved vaccine; high unmet medical need • Immunity wanes and recurrent infections are common, particularly in individuals with respiratory & circulatory diseases Mortality Rate Per 100,000 person by years LARGE UNMET MEDICAL NEED: CHILDREN & ELDERLY 40 35 30 25 20 15 10 5 0 <1 1-4 5-49 50-64 ≥65 Age Bracket SERIOUS HEALTH RISK FOR ELDERLY LEADING CAUSE OF INFANT HOSPITALIZATION • 177,000 hospitalizations and 14,000 deaths annually among US adults older than 65 years • Up to 176,000 hospitalizations in the US annually in children under 5 • Infection rate in adults ranges between 5-10% per year, 70-80% get respiratory symptoms, 10-20% are hospitalized, and 2-5% die • 1.5 million outpatient visits in the US annually in children under 5 • High levels of transmission in nursing homes increase disease burden in these facilities • 90% of infants contract RSV infection by 2 years of age, infants < 6 months of age are most at risk for severe disease • Major risk factor for adults with chronic pulmonary conditions • Children are major source of disease transmission 13 MVA-BN RSV VACCINE CANDIDATE MVA-BN RSV • Highly immunogenic – inducing strong mucosal and serological immunity (antibodies & T cells) • No enhanced disease in animal models • Protection against both RSV subtypes (A&B) in animal models • Flexible administration options: intranasal or intramuscular • Received NIH support (animal efficacy) • Favorable pre-IND – Phase 1 planned Q1 2015 MVA-BN: IDEAL RSV VACCINE PLATFORM • Licensed platform • Extraordinary safety profile • Vector tested safely in elderly and children DEVELOPMENT STRATEGY Elderly + Adults at risk Children >5yrs 14 Phase 1 2015 Second indication OUR CANCER IMMUNOTHERAPY BUSINESS 15 PROSTVAC CLINICAL DEVELOPMENT PROGRAM PROSTVAC has a robust clinical data package providing rationale for: • Phase 3 trial as monotherapy in late-stage prostate cancer • Combination and sequencing studies • PROSTVAC plus anti-androgens • PROSTVAC plus immune checkpoint inhibitors • Early prostate cancer indications 12 ongoing or completed PROSTVAC clinical trials Completed Ongoing Phase 1 4 - Phase 2 4 4 Phase 3 - 1 Total 8 5 300+ 1,400+ Total patients 16 PROSTVAC PHASE 2 RESULTS MOST PRONOUNCED SURVIVAL TO DATE IN PROSTATE CANCER Significantly extended overall survival 100 N Deaths Median OS Control 40 37 16.6 PROSTVAC 82 65 25.1 80 survival (% of patients) 25.1 months 60 40 Δ 8.5 months improvement in OS 16.6 months Hazard ratio 0.56 (95% CI 0.37–0.85) p=0.0061 20 0 0 12 24 36 48 60 months Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer Kantoff et al., Journal of Clinical Oncology, January 2010 17 Pivotal data of approved agents: Provenge®: ΔOS = 4.1 mo (AS/MS mCRPC) Zytiga®: ΔOS = 5.2 mo (pre-chemo mCRPC) Xtandi®: ΔOS = 2.2 mo (pre-chemo mCRPC) Reference Package insert Sipuleucel-T, enzalutamide and abiraterone PROSTVAC PHASE 3: FULLY ENROLLED DECEMBER 2014 • Primary endpoint is overall survival • Either one of the treatment arms must be superior to placebo PROSPECT A Randomized, Double-blind, Global Phase 3 Efficacy Trial of PROSTVAC in Metastatic Castration-Resistant Prostate Cancer 1,200 patients • Each comparison requires 534 deaths for the final analysis • Interim analysis plan • Pre-specified interim data analyses will evaluate whether the trial should continue as planned or potentially be stopped early for efficacy or futility Phase 2 results: Demonstrated hazard ratio 0.56 = 44% reduction in risk of death 18 SPA terms for Phase 3: Required hazard ratio 0.82 or less = 18% reduction in risk of death Enrolled at 214 sites in 15 countries Australia, Belgium, Canada, Denmark, Estonia, France, Germany, Iceland, Israel, Netherlands, Poland, Russia, Spain, UK & US 3 study arms PROSTVAC + GM-CSF PROSTVAC Placebo PROSTVAC - PATIENT CASE HISTORY (“FRANK”) PUBLISHED 2013 CASE REPORT IN CLINICAL GENITOURINARY CANCER PSA 1.000,0 Radical Prostatectomy External Beam Radiation Vaccine Treatment Second Vaccine Treatment 100,0 10,0 1,0 0,1 61 62 63 64 65 66 67 68 69 70 71 72 73 74 Gleason grade: 4 + 3 = 7 Trend before radical prostatectomy ( ) Trend after radical prostatectomy. External beam radiation Trend after first vaccine trial ( ) Trend after second vaccine trial ( ) 19 ( ) 5.8 months DT (doubling time) 9.6 months DT 28.6 months DT 75 76 77 78 79 80 81 82 Age COMBINATION RATIONALE POXVIRUS-BASED IMMUNOTHERAPY Other Anti-cancer Therapy Combination Benefits • Enhance tumor immunogenicity • Significant synergy of therapeutic benefit Targeted Therapies BN Poxvirus-Based Immunotherapy Immune Checkpoint Inhibitors Radiation Therapy 20 • Accelerate timing to anticancer immune response • Long duration of anticancer response post-therapy • Minimal-to-no added side effects from immunotherapy • Potential for dose reduction of systemic anticancer therapy EARLY RESULTS COMBINING PROSTVAC WITH IPILIMUMAB APPEAR PROMISING Median Halabi Predicted Survival* (months) % Chemo Naïve Median Overall Survival (months) Δ OS (months) Alive at 24 months PROSTVAC alone (n=32)1 17.2 100% 26.3 + 9.1 53% Ipilimumab alone (n=71)2 – 56.3% 17.1 – – PROSTVAC + Ipilimumab (n=30)3 18.5 80% 34.4 +15.9 73% Phase 1 dose escalation trial; subjects with metastatic castration resistant prostate cancer (mCRPC) *Halabi et al., JCO 2003; 1Gulley et al, Cancer Immunol Immunother, 2010 2Madan et al, Lancet Oncology, 2012; 3Slovin et al, Annals Onc, 2013 21 MVA-BN BRACHYURY NOVEL IMMUNOTHERAPY CANDIDATE WITH BROAD POTENTIAL- NCI FUNDED • Brachyury is a tumor-associated antigen which is overexpressed in major solid tumor indications • Brachyury is reported to play a key role in the metastasis and progression of tumors • Tumors which overexpress Brachyury are believed to be highly resistant to current therapies and are associated with decreased survival rates • Brachyury highly expressed in ultra-orphan Chordoma indication • A Phase 1 study of MVA-BN Brachyury TRICOM initiated in patients with advanced cancer • Open label trial enrolling patients with advanced cancer into three cohorts (6 patients per dose cohort) with dose escalation of MVA-BN Brachyury • The objective is to determine the safety and tolerability of escalating doses of MVA-BN Brachyury and to evaluate immunologic responses as measured by an increase in Brachyury-specific T cells 22 COMPANY SUMMARY & FINANCIALS 23 SELECTED MILESTONES • Manufacture and deliver MVA-BN Filo (Ebola/Marburg) vaccine; targeting 2 million doses (2015) • Investigational New Drug submission for MVA-BN RSV followed by initiation of Phase 1 study (2015) • Complete Phase 2 study of freeze-dried IMVAMUNE to support a pre-EUA submission (requirement for stockpiling) (2015) • Secure IMVANEX/IMVAMUNE orders from rest of world • Advance clinical studies exploring the therapeutic potential of PROSTVAC in combination with checkpoint inhibitors • Interim analyses of PROSTVAC 24 FINANCIAL OUTLOOK 2014 Revenue EBIT Cash preparedness at year-end $215m $0m $175m Assumptions: Deliver and revenue recognize 6.5 million doses of IMVAMUNE to the U.S. Strategic National Stockpile R&D costs - GROUP Infectious Disease Division, EBIT Cancer Immunotherapy Division, EBIT All numbers are approximate * R&D costs include approximately USD $17.5 million in contract expenses (stated under production costs in the P&L statement) as well as USD $8 million capitalized in the balance sheet 25 * $105m $70m ($70m) SUMMARY AND CONTACTS INVESTOR RELATIONS CONTACTS Rolf Sass Sørensen/EU +45 3326 8383 / [email protected] Seth Lewis/USA +1 978 298 5654 / [email protected] BAVARIAN NORDIC (CSE/OMX:BAVA) • Approved product; validated platform • Two Phase 3 programs: • Prostate cancer and smallpox • • • • 26 Diversified pipeline drawing from distinct technologies Commercial manufacturing capability Long-term R&D and delivery contracts with the US government Revenue-generating SHAREHOLDER INFORMATION SHARE INFORMATION Share price (Jan 8, 2015) High/low 52 weeks Market cap Volume (3m, daily average) No. of shares, 100% free-float No. of registered shareholders DKK 213 91/ 220 USD $940M 225,000 27.7m 22,000 Largest shareholders ATP (> 10%) A.J. Aamund A/S (> 5%) 220 12% 10% 200 15% 180 63% Denmark US UK RoW 9% Institutional 28% 63% Private Non-registered 160 FINANCIAL CALENDAR 140 120 100 80 Dec-13 27 Jan-14 Feb-14 Mar-14 Apr-14 May-14 Jun-14 Jul-14 Aug-14 Sep-14 Oct-14 Nov-14 Dec-14 2014 Annual Report Annual General Meeting 2015 First Quarterly Report (Q1) 2015 Half-year Report (Q2) 2015 Third Quarterly Report (Q3) 11-Mar-15 23-Apr-15 05-May-15 25-Aug-15 03-Nov-15 This presentation includes "forward-looking statements" that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.