FORWARD-LOOKING STATEMENTS

Transcription

1 DECEMBER

2 FORWARD-LOOKING STATEMENTS 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 regarding our short-term objectives and opportunities, financial expectations for the full year and financial preparedness as of year end, as well as statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. 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. 2

3 BAVARIAN NORDIC: A COMPELLING PROFILE Revenue generating; strong cash position Fully integrated R&D & manufacturing Approved discovery platform Differentiated pipeline in infectious diseases and oncology Excellent track history in government and pharma collaborations 3

4 BAVARIAN NORDIC S GOAL To develop innovative and safe therapies against cancer and infectious diseases; to improve the health and quality of life for children and adults. CANCER INFECTIOUS DISEASES PROSTVAC improving survival HPV preventing cancer before it starts RSV protecting the broader population against diseases with no approved therapies CV301 & Brachyury in combination therapies potentially curing cancer Smallpox / Ebola preparation and protection against global pandemic threats HIV / HBV seeking a functional cure 4

5 OUR VACCINE PLATFORM Approved platform Applicable to cancer or infectious diseases Can stimulate broad and sustained immune responses Well tolerated Based on large viruses which allows for larger payloads Ability to encode multiple targets for specific diseases Other platforms are much more limited Validated and approved manufacturing facility Multi-purpose facility capable of producing all clinical materials Over 28m doses of IMVAMUNE and 2m doses of MVA-Ebola, to date. Highly customizable approach to curing diseases 5

6 THE STRATEGY..a busy Maintain the global leadership of our smallpox vaccine franchise Awarded freeze-dried contract from BARDA Investing in fill/finish line securing future manufacturing requirements 2 Rapidly advance our pipeline of infectious disease programs Completed Phase 2 and outlined development strategy for RSV Expanded collaboration with Janssen on HIV & HBV 3 Establishing a broad and deep cancer immunotherapy franchise Industry and sponsor collaborations for combination studies of CV301 in multiple indications Advancing BN-Brachyury into Phase 2 Initiated two combination studies of PROSTVAC with checkpoint inhibitors from Bristol-Myers Squibb PROSTVAC Phase 3 monotherapy discontinued Strong financial position enables executing on strategy going forward 6

7 CLINICAL PIPELINE PRODUCT INFECTIOUS DISEASES INDICATION ONGOING STUDIES PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MARKET COMMERCIAL RIGHTS IMVAMUNE liquid-frozen 1) Smallpox 2 IMVAMUNE freeze-dried Smallpox - MVA-BN Filo Ebola/Marburg 13 MVA-BN RSV RSV 1 CANCER IMMUNOTHERAPY PROSTVAC mono/combo Prostate Cancer 10 CV301 + anti-pd-1 Lung Cancer (NSCLC) 1 CV301 + anti-pd-l1 Bladder Cancer - Planned 2018 BN-Brachyury Metastatic Tumors 1 BN-Brachyury Chordoma - Planned ) Approved in the European Union under the trade name IMVANEX and in Canada under the trade name IMVAMUNE. Phase 3 registration studies are ongoing in the United States. 7

8 PRECLINICAL COLLABORATIONS PRODUCT INDICATION PRECLINICAL COLLABORATION COMMERCIAL RIGHTS INFECTIOUS DISEASES MVA-BN HPV + AdVac Chronic HPV infection MVA-BN HBV + AdVac Hepatitis B MVA-BN HIV + AdVac HIV-1 8

9 OUR VACCINE PLATFORM Unprepared, weakened, or failing immunity Upgraded Immunity allows body to identify and attack specific diseases 9

10 CV301 PRIME/BOOST CEA & MUC-1 TARGETED OFF THE SHELF CANCER VACCINE TRICOM CEA MUC-1 LFA-3 ICAM-1 B7.1 M F Heterologous prime/boost regimen MVA-BN (M) + Fowlpox (F) Subcutaneous administration CEA & MUC-1 Tumor antigens overexpressed in the majority of solid tumors Lung, bladder, colorectal, breast, ovarian, pancreatic, renal and head & neck indications TRICOM (TRIad of COstimulatory Molecules) Enhance T-Cell activation in synergistic manner Strengthen the anticancer immune response Safe and well tolerated (9 completed & ongoing clinical trials) Injection site reactions and flulike symptoms 10

11 BROAD PARTNERSHIPS IN THERAPEUTIC VACCINES Development of IMVAMUNE and procurement for national stockpile Research and development agreement on PROSTVAC, CV301 and Brachyury Ebola license and production agreement HPV, HIV & HBV license agreements Option license agreement on PROSTVAC, including clinical collaboration - still to be decided by partner 11

12 OUR COLLABORATION WITH JANSSEN A LONG-TERM VALUE DRIVER MVA-BN Filo (Ebola) License & Supply Agreement US$ 119m + Upfront US$ 25m Equity investment US$ 43m 2014 MVA-BN HPV License Agreement US$ 162m MVA-BN HIV Upfront US$ 9m Potential milestone payments of more than US $1BN + royalties License Agreement US$ 606m MVA-BN HBV 2017 License Agreement US$ 230m + Upfront US$10m Equity investment US$ 33m

13 Non-replicating smallpox vaccine for national stockpiles Indicated for persons with compromised immune systems (but also healthy individuals) 28 million doses produced and delivered to the U.S. Approved in EU and Canada Phase 3 ongoing in the U.S. 13

14 IMVAMUNE PARTNERSHIP WITH THE U.S. GOVERNMENT Freeze-dried Bulk supply $333m Fill-finish Clinical/Reg & Prod support $439m Additional bulk &/or IMVAMUNE doses Approval CDC procurement 132 million doses Representing ~ 13 million doses of FD IMVAMUNE 2018 and beyond US strategic long-term stockpiling goal, as outlined by BARDA. Liquid-frozen Delivered 28M IMVAMUNE doses Positive Phase 3 (POX-MVA-006) FDA approval and award of a PRV

15 ESTABLISHMENT OF FILL-FINISH CAPACITY Taking full control of value chain in manufacturing BN will invest approx. USD 75 million in a fill-finish line at its existing facility in Denmark BARDA invests approx. USD 33 million in process transfer and validation of the new manufacturing line Secures deliverables for future supply orders and pipeline assets Capacity for handling both liquidfrozen and freeze-dried products 15

16 RSV represents a high unmet medical need; similar disease burden and death rate in the elderly population as influenza 16 Phase 1 data demonstrated safety and tolerability Positive data from 421 subject Phase 2 trial show durable response

17 RSV A LARGE UNMET MEDICAL NEED DEATH RATE OF RSV SIMILAR TO THAT OF INFLUENZA RSV Influenza Pneumonia Deaths # of infections Hospitalizations No approved prophylactic vaccine $5.4B USD global market ~$6B USD global annual sales (Prevnar) 17

18 Geometric Mean Fold Increase (GMFI) RSV IgG ELISA [GMT] AT THE FOREFRONT OF RSV VACCINE DEVELOPMENT Competitive advantages Designed to mimic natural RSV infection: Induction of T-cells and antibodies against RSV Induction of mucosal immunity Balanced vaccine construct Encodes 5 distinct targets of RSV to provide protection against multiple antigens providing a balanced T-cell and antibody response Durable immune response lasting an RSV season F (A) G (A) G (B) N M2 Robust T-cell and antibody responses demonstrated in Phase 1 and 2 studies 17,0 15,0 13,0 11,0 9,0 7,0 5,0 3,0 1,0 RSV-specific T cell response RSV RSV F RSV N RSV G(A) RSV G(B) RSV M2 Antibody responses demonstrated over a full RSV season (Phase 2) RSV-specific total IgG Antibody Titers High / Placebo (N=80) Placebo (N=83) Week 18

19 MVA-BN RSV DEVELOPMENT STRATEGY FOR ELDERLY INDICATION Generate 12 months FU and booster data in ongoing Ph2 Conduct a human challenge trial (HCT) Agree on Ph3 field efficacy design during EoP2 with FDA Evaluate HCT topline data in 2018 Initiate Ph3 field efficacy Enroll number of subjects needed for futility testing Follow-up for symptomatic RSV cases through the 2019/2020 RSV season Continue Ph3 field efficacy into 2 nd season Follow-up for symptomatic RSV cases through the 2020/2021 RSV season 19

20 Studies from two decades of research have demonstrated our cancer vaccines to be well tolerated and have shown promise in extending overall survival Our vaccine platform has been found to be a potent stimulator of T-cells directed at particular tumor targets, breaking tolerance and inflaming tumors 20

21 Survival (% of patients) DEMONSTRATED POTENTIAL AS A COMBINATION THERAPY WITH CHECKPOINT INHIBITORS PROSTVAC + ipilimumab Phase 1 Trial PSA Waterfall Plot: ipi/prostvac PROSTVAC + Ipi (all Ipi dose cohorts) 31.6 months Madan Schlom, Gulley, Lancet Oncology, Months Ongoing Phase 2 (n=29) 30 mcrpc Patients: Predicted survival average: 18.5 months 2 Phase 3 studies of Ipilimumab in prostate cancer did not show significant OS benefit Gulley J, NCI. Madan RA, et al. Lancet Oncol. 2012;3: Lead-in mcrpc Cohort Neoadjuvant Cohort Sponsor: NCI NCT PROSTVAC + nivo PROSTVAC + nivo

22 PROSTVAC STUDIES Monotherapy Combination study Completed study Non-metastatic Metastatic 8 completed 10 ongoing DOCETAXEL JEVTANA XTANDI XOFIGO Surgery LUPRON DOCETAXEL PROVENGE ZYTIGA XGEVA 22

23 CV301 IMMUNOTHERAPY PLATFORM WITH POTENTIAL IN MULTIPLE SOLID TUMORS Our goal is to become preferred treatment in combination with multiple checkpoint inhibitors (CPI) Strong preclinical evidence of combination synergies Opportunity to convert the CPI non-responders Exploring combinations in company collaborations or with NCI Multiple near and long-term data points (ORR, DoR, PFS, OS) Non-small cell lung cancer (NSCLC) Proof-of-concept study of CV301 plus KEYTRUDA (pembrolizumab) as firstline maintenance therapy (n=176) Bladder cancer Phase 2 single-arm study of CV301 plus TECENTRIQ (atezolizumab) (n=60) Other potential indications In addition to NSCLC and bladder, Bavarian Nordic retains all commercial rights in colorectal, pancreatic, breast, ovarian, gastric, liver and renal cancer 23

24 COMPLETE TUMOR REGRESSION FROM POXVIRUS-BASED IMMUNOTHERAPY COMBINED WITH PD-1 & LAG-3 BLOCKADE MVA-BN-HER2 20/20 + anti-pd1 + anti-lag3 anti-pd1 + 14/20 anti-lag3 CT26-HER2 solid tumor model: MVA-BN-HER2 immunotherapy (s.c.) and/or anti-pd1 + anti- LAG3 antibody (i.p.) Q2wks x2 (d1 and 15) Control MVA-BN-HER2 2/20 Durable response after mice were rechallenged 24

25 BN-BRACHYURY NOVEL IMMUNOTHERAPY TARGETING THE METASTATIC PROCESS Brachyury expression is highly correlated with metastatic disease, and multi-drug resistance Brachyury is not expressed in most normal tissue Brachyury is responsible for epithelial to mesenchymal transition (EMT), which is a major driver of metastasis A Phase 1 study of 38 patients receiving MVA-BN Brachyury showed presence of brachyury specific T-cells in vast majority of patients, post-treatment. Potential indications: Triple negative breast cancer Other breast cancer Small cell lung cancer Neuroendocrine tumors Merkel Cell Carcinoma Non-small cell lung cancer Hepatocellular carcinoma Colorectal cancer Head and neck/oral 25

26 BN-BRACHYURY CLINICAL TRIAL PLANS Transitioning to prime-boost regimen Phase 1 planned to initiate by end 2017 Adding fowlpox (FPV) booster to construct Safety evaluation expected Q Immune response data Q Goal demonstrate persistent brachyury-specific T-cell activation with boost Phase 2 with prime-boost vaccine planned to initiate Q Combination with radiation in advanced chordoma Primary endpoint: Objective response rate (radiation alone <5% ORR at 6 months) Potential for Breakthrough Designation Expect to initiate enrollment Q Combination with PD-1/L1 in various indications planned 26

27 27

28 FINANCIALS AND SHAREHOLDER INFORMATION mdkk E mdkk Revenue EBIT Stock exchange Ticker symbol Nasdaq Copenhagen BAVA Share price (Dec 13, 2017) DKK 231 High/low 52 weeks 444/183 Market cap DKK 7.2bn Volume (3m, daily average) 350,000 No. of shares, 100% free-float 32m No. of registered shareholders 48, E Cash preparedness 17% Denmark 8% 59% 16% EU North America Non-registered 28

29 ANTICIPATED SELECTED MILESTONES H H H RSV Data: booster study Initiate challenge study EOP2 FDA to determine registration pathway for elderly Top-line efficacy data from challenge study Ongoing preparations to initiate phase 3 IMVAMUNE Top-line data for Phase 3 non-inferiority study Approval and Priority Review Voucher CV301 Phase 2 initiation of CV301 and KEYTRUDA in first-line NSCLC Phase 1 data of CV301 and OPDIVO Phase 2 initiation of CV301 and TECENTRIQ Phase 2 data (ORR) for CV301 and KEYTRUDA Phase 2 data (PFS) for CV301 and KEYTRUDA Phase 2 data (ORR) for CV301 and TECENTRIQ Brachyury Initiate fowlpox booster study Data from fowlpox booster study Initiate study in Chordoma Initiate study in 2 nd indication PROSTVAC Emerging data from NCIsponsored Phase 2 29

30 30