FORWARD-LOOKING STATEMENTS

Transcription

1 NOVEMBER

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 THE BN VACCINE PLATFORM DISCOVERY DEVELOPMENT LARGE-SCALE MANUFACTURING Virus target Tumor cell New poxvirus based vaccine Validated Sustainable Innovation 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 CV301, Brachyury & PROSTVAC in combination studies HPV improving survival preventing cancer before it starts RSV Smallpox / Ebola protecting the broader population against diseases with no approved therapies preparation and protection against global pandemic threats HIV / HBV seeking a functional cure 4

5 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. 5

6 EXTERNAL COLLABORATORS BN VACCINE PLATFORM Validated Sustainable Innovation SAFETY VECTOR Collaborators 5 MAJOR PARTNERSHIPS validating our platform and development activities in infectious disease and oncology Development and procurement of IMVAMUNE smallpox vaccine Multiple NCI-sponsored Phase 2 clinical studies (incl. PROSTVAC + ipi + nivo) ongoing PAYLOAD PROSTVAC (mono & combos) 4 infectious disease targets CV301 + Tecentriq 6

7 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

8 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. 8

9 IMVAMUNE FREEZE-DRIED CONTRACT Base contract for additional IMVAMUNE bulk valued at USD 100 million Will be recognized as revenue evenly in 2018 and 2019 Bulk orders for freeze-dried IMVAMUNE to date now total USD 333 million Contract includes initial options valued at USD 439 million USD 299 million for fill/finish of bulk stockpile USD 140 million for clinical development, regulatory commitments, and contributions toward the establishment and validation of fill/finish activities Additional options can potentially increase total contract value Options to purchase additional IMVAMUNE bulk or freeze dried doses in the future 9

10 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

11 RSV represents a high unmet medical need; similar disease burden and death rate in the elderly population as influenza 11 Phase 1 data demonstrated safety and tolerability Positive data from 421 subject Phase 2 trial show durable response

12 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 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 12

13 PHASE 2 BOOSTER STUDY Key Objectives of Booster Study Get clarity on long-term durability of immune response (12 months following primary vaccination) Evaluate effect of a single booster dose after primary vaccination with a single shot using same dose as in the main study (N=86) Adult population 55 years of age; N=80 per group IM administration of vaccine or placebo on Day 0 and Day 28 1 x 10 8 Day 0 Placebo Day 28 1 x 10 8 Day 0 1 x 10 8 Day 28 Randomization 5 x 10 8 Day 0 Placebo Day 28 5 x 10 8 Day 0 5 x 10 8 Day 28 Placebo Day 0 Placebo Day 28 Main Study Primary vaccination Booster 1 x 10 8 Booster 5 x 10 8 N=43 N=43 Booster study 1-year durability and booster 13

14 DEVELOPING A HUMAN CHALLENGE TRIAL FOR RSV PREPARATION FOR PHASE 3 Strategy Collaboration to develop a human challenge model Prior success in the development of a flu challenge model Healthy volunteers will be intranasally infected with a strain of RSV Monitored for viral load, immune markers and clinical symptoms Key advantages compared to field trials Well-defined viral infectivity, independent of RSV season Close monitoring of onset, severity and duration of disease symptoms Intensive sampling of immune responses Rapid, small sample size, cost-effective Benefits Provides important learnings for Phase 3 design Mitigates the risk in progressing to large, costly field efficacy trials Potential for accelerated approval 14

15 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 15

16 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 16

17 PROSTVAC PRIME/BOOST PSA TARGETED OFF THE SHELF CANCER VACCINE TRICOM PSA LFA-3 ICAM-1 B7.1 V F Heterologous prime/boost regimen Vaccinia (V) + Fowlpox (F) Subcutaneous administration PSA Tumor antigen with epitopes enhanced for HLA binding Prostate indication TRICOM (TRIad of COstimulatory Molecules) Enhance T-Cell activation in synergistic manner Strengthen the anticancer immune response Safe and well tolerated (8 completed & 11 ongoing clinical trials) Injection site reactions and flulike symptoms 17

18 PROSPECT - BLINDED OVERALL SURVIVAL (ALL GROUPS) Reference OS in mcrpc (pre-chemo) Abiraterone NR (>27.2 months) Placebo 27.2 months COU-AA-302 Ryan et al. NEJM 2013 Median Survival = 33.9 months Enzalutamide 32.4 months Placebo 30.2 months PREVAIL Beer et al., NEJM 2014 Ipilimumab 28.7 months Placebo 29.8 months CA Beer et al., JCO 2016 Sipuleucel-T 25.8 months Placebo 21.7 months IMPACT Kantoff et al., NEJM

19 PROSTVAC INDUCES AN ANTIGEN CASCADE AGAINST PROSTATE CANCER CELLS Summary of T-cell responses from six PROSTVAC clinical trials Test Result Comment PSA-Specific Immune response 56.7% (59/104) 28 days after last vaccine Median fold increase in PSAspecific immune response 5X PSA response 30 / 10 6 cells flu response 33 / 10 6 cells Antigen Cascade 67.9% (19/28) New T cells generated against new tumor antigens (non-psa) Anti-PSA Ab 0.57% (2/349) Gulley et al., Immune impact by PROSTVAC (PSA-TRICOM), a therapeutic vaccine for prostate cancer. Cancer Immunol Res. 2:

20 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

21 Vaccines targeting multiple solid tumour indications Aligning combination treatments to reflect the commercial landscape 21

22 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 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=30) 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 T u m o r V o lu m e (m m 3 ) T u m o r V o lu m e (m m 3 ) T u m o r V o lu m e (m m 3 ) T u m o r V o lu m e (m m 3 ) 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 M V A -B N -H E R 2 C o n tr o l a n ti-p D -1 + a n ti-l A G -3 M V A -B N -H E R 2 + a n ti-p D -1 + a n ti-l A G Durable response after mice were rechallenged D a y D a y D a y D a y 24

25 BRACHYURY PRIME/BOOST BRACHYURY TARGETED OFF THE SHELF CANCER VACCINE TRICOM Brachyury LFA-3 ICAM-1 B7.1 M F Heterologous prime/boost regimen MVA-BN (M) + Fowlpox (F) Subcutaneous administration Brachyury 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 (Phase I completed) Injection site reactions and flulike symptoms 25

26 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 26

27 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 27

28 FINANCIAL SUMMARY AND OUTLOOK On target for the year FY revenue target met; only minor revenues expected in Q4 PROSTVAC upfront of ~400 mdkk was recognized in Q3 (expected Q4) Slightly higher IMVAMUNE revenues than expected FY guidance maintained Revenue 9m IMVAMUNE US + RoW PROSTVAC Upfront R&D Contracts mdkk 9m m 2016 FY2017E Revenue 1, ,300 EBIT 531 (82) 350 Cash preparedness, period-end 2,808 1,647 2,600 musd 9m m 2016 FY2017E (13) Cash preparedness includes cash, cash equivalents, investments in securities and the aggregate amount of undrawn credit lines. USD/DKK = 6.30 (as of September 30, 2017) 28

29 THE STRATEGY 1 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 PROSTVAC Phase 3 monotherapy discontinued Initiated two combination studies of PROSTVAC with checkpoint inhibitors from Bristol-Myers Squibb Strong financial position enables executing on strategy going forward 29

30 ANTICIPATED SELECTED MILESTONES H H H RSV Initiate booster-study in subjects that received a single shot 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 30

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