BAVARIAN NORDIC BIO DEUTSCHLAND PRESENTATION OCTOBER 2014 CSE/OMX:BAVA, OTC:BVNRY
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.
PIPELINE CANCER IMMUNOTHERAPY Preclinical Phase 1 Phase 1/2 Phase 2 Phase 3 Market Prostate cancer PROSTVAC Colorectal cancer CV-301 Colon Bladder cancer CV-301 Bladder NEW Breast cancer CV-301 Breast Prostate cancer MVA-BN PRO Breast cancer MVA-BN HER2 Metastatic Tumors MVA-BN Brachyury NEW INFECTIOUS DISEASES Smallpox IMVANEX / IMVAMUNE * Smallpox Anthrax Filoviruses Foot-and-mouth disease RSV IMVAMUNE freeze-dried MVA-BN Anthrax MVA-BN Filo MVA-BN FMDV MVA-BN RSV * Approved in the EU under the trade name IMVANEX and in Canada under the trade name IMVAMUNE. Sold to government stockpiles under national emergency rules. Phase 3 registration studies ongoing in the U.S. 3
RECENT HIGHLIGHTS Cancer Immunotherapy: PROSPECT Phase 3 study on track with recruitment ongoing in all planned countries Construction of PROSTVAC manufacturing completed; test batches now in production Pipeline expanded through initiation of new NCI-sponsored Phase 2 study of CV-301 in bladder cancer and Phase 1 study of MVA-BN Brachyury New data combining BN s immunotherapy platform with checkpoint inhibitors Infectious Diseases: US Government exercised option valued at US$118M for continued delivery of IMVAMUNE smallpox vaccine Canada orders IMVAMUNE with option for a total of than 500,000 doses Acceleration for Ebola vaccine program with NIAID, including partnering with Johnson & Johnson s AdVac technology; clinical trial anticipated in 2015 4
KEY ADVANTAGES OF OUR ACTIVE IMMUNOTHERAPIES 1. Poxvirus-based vectors 2. Prime/boost dosing strategy 3. TRICOM immunostimulators 4. Antigen epitope optimization Intrinsic adjuvants, off-the-shelf subcutaneous administration Magnifies and focuses immune response away from vectors and toward antigen Set of three co-stimulatory molecules acting as Signal 2 for T cell activation One or more target tumor antigenic sequences with enhanced HLA haplotype binding TRICOM Antigen/s LFA-3 ICAM-1 B7.1 5
MULTIPLE TECHNOLOGY PLATFORMS OPTIMIZING TUMOR-SPECIFIC IMMUNE RESPONSES Boost doses Prime dose TAA(s) LFA-3 ICAM-1 B7.1 Selection of TAA gene(s) defines the cancer target TRICOM PROSTVAC PSA Prostate cancer CV-301 CEA MUC-1 Colorectal, breast, lung, ovarian, gastric, bladder, liver and renal cancers MVA-BN-HER2 HER2 Breast cancer MVA-BN-Brachyury Brachyury Colorectal, breast, lung, ovarian cancers 6
EBOLA AND MARBURG VACCINE IN DEVELOPMENT BN has ongoing collaboration with U.S. National Institutes of Health (NIH) to evaluate MVA-BN vaccine candidates for filoviruses (Ebola and Marburg viruses) Recent preclinical studies show 100% protection against Ebola in a setting with MVA-BN NIH is now planning to advance the vaccines into clinical studies, with the initiation of a Phase 1 study in humans, anticipated in 2015 Members of BN participated in the World Health Organization s (WHO) Consultation on potential Ebola therapies and vaccines in Geneva on September 4 and 5 7
PROSTVAC PHASE 2 RESULTS PRONOUNCED SURVIVAL EFFECT IN PROSTATE CANCER 100 Significantly extended overall survival survival (% of patients) 80 60 40 20 16.6 months 25.1 months N Deaths Median OS Control 40 37 16.6 PROSTVAC 82 65 25.1 Δ 8.5 months improvement in OS Hazard ratio 0.56 (95% CI 0.37 0.85) p=0.0061 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 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 8
PROSTVAC ACTIVATES PSA-SPECIFIC T CELLS p = 0.039 p = 0.98 n = 46 n = 20 IFNγ ELISPOT assay Samples from RDBPC Phase 2 PROSTVAC study 9
PROSPECT A RANDOMIZED, DOUBLE-BLIND, GLOBAL PHASE 3 EFFICACY TRIAL OF PROSTVAC IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER Recruitment on track - full enrollment anticipated in 2014 1,200 patients All (15) countries active, 200 sites recruiting Australia, Belgium, Canada, Denmark, Estonia, France, Germany, Iceland, Israel, Netherlands, Poland, Russia, Spain, UK & US 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 Potential for early data read-out 3 study arms PROSTVAC + GM-CSF PROSTVAC Placebo Primary endpoint is overall survival Either one of the treatment arms must be superior to placebo Each comparison requires 534 deaths for the final analysis Phase 2 results: Demonstrated hazard ratio 0.56 = 44% reduction in risk of death SPA terms for Phase 3: Required hazard ratio 0.82 or less = 18% reduction in risk of death 10
MVA-BN BRACHYURY NOVEL IMMUNOTHERAPY CANDIDATE WITH BROAD POTENTIAL Exciting new pipeline opportunity funded by NCI 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 A Phase 1 study of MVA-BN Brachyury TRICOM initiated in patients with advanced cancer Open label trial that will enroll 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 11
COMBINATION TREATMENT RATIONALE: IMMUNE CHECKPOINT INHIBITORS Immune Checkpoint Inhibitors Foot off the brakes BN Active Immunotherapy Foot on the gas Combination Monotherapy Monotherapy Remarkable efficacy, but only in fraction of subjects treated Unfocused immune activation Dose-related toxicity concerns Long-term clinical outcome differences but limited short-term response Immune activation may be modulated by checkpoint system 12
PROSTVAC + IPILIMUMAB COMBINATION IMPACT ON MEDIAN OVERALL SURVIVAL PROSTVAC Phase 2 study NCI Phase 1 PROSTVAC + Ipilimumab 100 80 survival (% of patients) 60 40 16.6 months 25.1 months 20 0 0 12 24 36 48 60 months Kantoff et al (2010) J Clin Oncology Madan et al (2012) Lancet Oncol 13, 501-508 13
POXVIRUS IMMUNOTHERAPIES WITH CHECKPOINTS SYNERGY WITH ANTI-PD1 BLOCKADE **** p<0.0001 MVA-BN-HER2 + anti-pd1 Control MVA-BN-HER2 Anti-PD1 CT26-HER2 tumors endogenously express PD-L1 Mice challenged with CT26-HER2 tumors i.d. were subsequently administered MVA-BN-HER2 immunotherapy and/or anti-pd1 antibody 14
POXVIRUS IMMUNOTHERAPIES WITH CHECKPOINTS COMPLETE TUMOR REGRESSION WITH PD-1 AND LAG3 BLOCKADE MVA-BN-HER2 + anti-pd1 + anti-lag3 anti-pd1 + anti-lag3 Control MVA-BN-HER2 Mice challenged with CT26-HER2 tumors i.d. were subsequently administered MVA-BN- HER2 immunotherapy and/or anti-pd1 + anti-lag3 antibody 15
POXVIRUS IMMUNOTHERAPIES WITH CHECKPOINTS RETENTION OF EFFICACY WITH CHECKPOINT DOSE REDUCTION Mice challenged i.v. with metastatic CT26-HER2 tumors were subsequently administered MVA-BN-HER2 immunotherapy and/or anti-pd1 plus anti-ctla4 antibodies Statistical significance was determined against untreated controls by Log-Rank with Bonferroni correction **p<0.01; ***p<0.001 16
17 THANK YOU