CITI EUROPEAN HEALTHCARE CONFERENCE JUNE 2017

Transcription

1 CITI EUROPEAN HEALTHCARE CONFERENCE JUNE

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 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 3

4 THE BAVARIAN VACCINE PLATFORM Safe and effective, approved platform Applicable to cancer or infectious diseases Can stimulate broad and sustained immune responses Extremely 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 4

5 MAJOR PARTNERSHIPS VALIDATING OUR PLATFORM AND DEVELOPMENT ACTIVITIES 5

6 PIPELINE PRODUCT INFECTIOUS DISEASES INDICATION ONGOING STUDIES PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MARKET COMMERCIAL RIGHTS IMVAMUNE liquid-frozen 1) Smallpox 1 IMVAMUNE freeze-dried Smallpox - MVA-BN Filo Ebola/Marburg 10 MVA-BN RSV RSV 1 MVA-BN HPV Chronic HPV Infection - CANCER IMMUNOTHERAPY PROSTVAC mono Prostate Cancer 1 PROSTVAC mono/combo Prostate Cancer 10 CV301 + nivolumab Lung Cancer (NSCLC) 1 MVA-BN Brachyury Metastatic Tumors - 1) 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. 6

7 Studies from two decades of research have demonstrated our cancer vaccines to be safe and 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 7

8 PROSTVAC has extended overall survival 6-10 months on average in multiple studies 8 ADT (Xtandi) Chemotherapy Radiation Checkpoint Inhibition A 125pt Phase 2 placebo-controlled trial showed a 9.9 month improvement of overall survival A 1297pt global Phase 3 placebocontrolled trial expects final data in Q Option license agreement with BMS

9 survival (% of patients) PROSTVAC PHASE 2 RESULTS MOST PRONOUNCED SURVIVAL TO DATE IN PROSTATE CANCER months Significantly extended overall survival N Deaths Median OS Control PROSTVAC months Δ 9.9 months improvement in OS Hazard ratio 0.50 (95% CI ) p= 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 Revised in 2016 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 9

10 MOVING TOWARDS FINAL DATA FOR PROSTVAC ADDITIONAL COMBINATION STUDIES CONTINUES TO EXPAND POTENTIAL 4 new Phase 2 studies of PROSTVAC were initiated during 2016 and until today Now 11 ongoing trials and additional trials are in the planning Data from combination studies are expected from 2017 and onwards PROSPECT Phase 3 Trial A Randomized, Double-blind, Global Phase 3 Efficacy Trial of PROSTVAC in Metastatic Castration- Resistant Prostate Cancer (N=1,297) Primary endpoint: Overall survival Interim Analysis #1 214 events 40% Interim Analysis #2 321 events 60% Interim Analysis #3 427 events 80% Sep 2017 Final Analysis 534 events 100% Q Estimated timing of events 10

11 PROSTVAC STUDIES SPAN PROSTATE CANCER DISEASE LANDSCAPE Phase 3 study Monotherapy Combination study Completed study Non-metastatic Metastatic 8 completed 11 ongoing DOCETAXEL US$ 4.8B market JEVTANA PROSTVAC XTANDI XOFIGO Surgery LUPRON DOCETAXEL PROVENGE ZYTIGA XGEVA 11

12 PROSTVAC MARKET POSITIONING $4.8+ B USD market Long term Monotherapy in the late stage of the disease Combination with other approved drugs in the space AND earlier in the disease setting Combination with potentially curative agents, i.e. checkpoint inhibitors Medium term Monotherapy in the late stage of the disease Combination with other approved drugs in the space AND earlier in the disease setting Initial Application Monotherapy in the late stage of the disease 12

13 Cancer vaccine with potential in multiple solid tumors Combination treatment with checkpoint inhibitors 13

14 CV301 POTENTIAL IN MULTIPLE SOLID TUMORS Our platform is ideal for immunogenic intensification CV301 is engineered to create T-cells which target CEA and MUC1 Goal of becoming preferred treatment in combination with any checkpoint inhibitor Strong preclinical evidence of combination synergies Only approx. 1 in 5 patients respond to checkpoint inhibitors 14 How can we convert the non-responders? Carcinoma CEA MUC1 Colorectal >90% >90% Pancreatic >95% >95% Lung 1 70% >80% Breast 50% >90% Bladder 70% >90%

15 CV301 ENHANCING THE CURES WE SEE TODAY BIVALENT VACCINE FOR MULTIPLE CANCERS Exploring synergies in combination with checkpoint inhibitors Non-small cell lung cancer BN sponsored Ongoing proof-of-concept study of CV301 plus OPDIVO Collaboration with BMS to supply OPDIVO at no cost Bladder cancer BN sponsored Collaboration with Roche to supply TECENTRIQ at no cost for planned Phase 2 study Other indications Bavarian Nordic retains all commercial rights in lung, bladder, colorectal, breast, ovarian, gastric, liver and renal cancer Exploring combinations in company collaborations or with NCI 15

16 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 M V A -B N -H E R 2 a n ti-p D -1 + a n ti-p D -1 C o n tr o l + a n ti-l A G -3 M V A -B N -H E R 2 + a n ti-l A G D a y D a y D a y D a y CT26-HER2 solid tumor model: MVA-BN-HER2 immunotherapy (s.c.) and/or anti-pd1 + anti-lag3 antibody (i.p.) Durable response after mice were rechallenged Q2wks x2 (d1 and 15) 16

17 RSV represents a high unmet medical need; similar disease burden and death rate in the elderly population as influenza Phase 1 data demonstrated safety and tolerability Data from 400 patient Phase 2 trial anticipated summer

18 RSV A LARGE, UNSERVED PATIENT POPULATION 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) 18

19 BUILDING A UNIVERSAL RSV VACCINE WHY ARE WE DIFFERENT? Historical vaccine development provided incomplete protection Possibly related to: Lack of T cell production Lack of mucosal protection Poor duration of protection (i.e. not lasting a full season) Our platform allows for broad protection against multiple targets Boosting the natural immunity we all possess Promising Phase 1 data highlights our extensive protection MVA-BN RSV a highly differentiated approach By encoding 5 distinct targets of RSV, we have built our vaccine to equip the immune system with enough information to protect against a potential infection, regardless of serotype (A or B) F (A) G (A) G (B) N M2 19

20 PREVENTING THE NEXT PANDEMIC Bioterrorism is a much larger risk - Bill Gates With nuclear weapons, you d think you would probably stop after killing 100 million. Smallpox won t stop. Because the population is naïve, and there are no real preparations. That, if it got out and spread, would be a larger number. It doesn t take much biology expertise nowadays to assemble a smallpox virus. Biology is making it way easier to create these things. 20

21 SUCCESSFUL PARTNERSHIP WITH THE U.S. GOVERNMENT MORE THAN $1.2 BILLION IN R&D AND SUPPLY CONTRACTS TO-DATE US strategic long-term stockpiling goal, as outlined by BARDA. 132 million doses IMVAMUNE freeze-dried R&D Contract $95m Bulk Supply $233m Stockpile Re-supply 20 million doses IMVAMUNE liquid-frozen R&D & Supply Contracts 20 million doses $679m Supply Contract 8 million doses $228m

22 OUR COLLABORATION WITH JANSSEN Janssen completed a submission for Emergency Use Assessment and Listing for the Ebola vaccine to the WHO MVA-BN Filo (Ebola) License & Supply Agreement US$ 187m Phase 1, 2 and 3 studies ongoing HPV vaccine to start clinical trials in 2017 Janssen retains option to license two additional disease targets MVA-BN HPV License Agreement US$ 171m MVA-BN Undisclosed target Potential license agreement MVA-BN Undisclosed target Potential license agreement 22

23 ANTICIPATED SELECTED MILESTONES IMVAMUNE Expected award for freeze-dried IMVAMUNE Top-line data for Phase 3 non-inferiority study Approval and Priority Review Voucher RSV MVA-BN RSV Phase 2 dosing study read out Select ideal dosing regimen and carry forward into second RSV season Establish meeting with FDA to determine appropriate registration pathway JANSSEN Initiate HPV Phase 1 study in cervical cancer Potential expanded collaboration on two additional infectious disease targets Data from Ebola prime-boost vaccine regimen PROSTVAC Phase 3 top-line data including interim analyses Data from NCI-sponsored Phase 2 trials CV301 Initiate Phase 2 study with Roche in bladder cancer CV301 + checkpoint inhibitor proof-ofconcept studies in additional indications BRACHYURY MVA-BN Brachyury Phase 2 initiation 23

24 Our efficient and cost effective business model allows for significant investment in R&D 24 $150M in annual revenues 5th straight year with breakeven result Cash position tripled in past 3 years ~$75M invested in R&D annually

25 FINANCIAL PERFORMANCE AND GUIDANCE Consistent with previous years we have generated revenues above DKK 1 billion and recorded a break-even result Cash preparedness was significantly strengthened and has more than tripled over the last three years mdkk mdkk E E Revenue EBIT Cash preparedness 25

26 SAVE THE DATE SEPTEMBER 21, 2017 BAVARIAN NORDIC CAPITAL MARKETS DAY LE PARKER MERIDIEN HOTEL NEW YORK CITY 26

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28 MULTIVALENT VACCINE PLATFORM SAFE, APPROVED, HIGHLY CUSTOMIZABLE APPROACH EMPLOYING POXVIRUSES Antigenic Complexity Low Recombinant Poxviruses Customized Immunogenicity Simple Wide Variety of Target Diseases Target Multiple Antigens for a Single Disease High + Complex Vectors Antigens Promoters Co-Stimulatory Molecules (TRICOM) Widely Applicable Technology for Infectious Disease and Cancer Immunotherapy 28

29 PROSTVAC PRIME/BOOST PSA TARGETED OFF THE SHELF CANCER VACCINE TRICOM TAA LFA-3 ICAM-1 B7.1 V F Heterologous prime/boost regimen Vaccinia or MVA + Fowlpox Subcutaneous administration PSA CEA, MUC-1 HER-2 Brachyury Tumor antigens with epitopes enhanced for HLA binding Prostate, lung, head & neck, bladder, colorectal, breast, ovarian and renal cancers TRICOM (TRIad of COstimulatory Molecules) Enhance T-Cell activation in synergistic manner Strengthen the anticancer immune response Safe and well tolerated (11 clinical trials) Injection site reactions and flulike symptoms 29

30 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) 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:

31 COMBINATION TREATMENT RATIONALE: ANDROGEN DEPRIVATION THERAPY ADT increases thymus size, cell number and regeneration ADT increases T cell trafficking to the prostate gland ADT treated tumor cells become more sensitive to T cell killing Aragon-Ching e tal: Frontiers in Bioscience 2007 Mercader M et al.: Proc Natl Acad Sci USA

32 Survival (% of patients) DEMONSTRATED POTENTIAL AS A COMBINATION THERAPY WITH BMS IPILIMUMAB PROSTVAC + ipilimumab Phase 1 Trial 100 Additional Phase 2 Combination Studies Neoadjuvant Prostate cancer PROSTVAC + Ipi (all Ipi dose cohorts) 31.6 months Phase 2 (n=75) PROSTVAC ipilimumab PROSTVAC + ipi Ongoing Sponsor: UCSF NCT PROSTVAC + ipi 30 mcrpc Patients: Months Predicted survival average: 18.5 months 2 Phase 3 studies of Ipilimumab in prostate cancer did not show significant OS benefit Phase 2 (n=65) PROSTVAC + nivo PROSTVAC + ipi + nivo Ongoing Sponsor: NCI NCT Gulley J, NCI. Madan RA, et al. Lancet Oncol. 2012;3:

33 PSA WATERFALL PLOT: IPI/PROSTVAC Madan Schlom, Gulley, Lancet Oncology,

34 PROSTVAC - PATIENT CASE HISTORY ( FRANK ) PUBLISHED 2013 CASE REPORT IN CLINICAL GENITOURINARY CANCER PSA 1.000,0 100,0 Radical Prostatectomy External Beam Radiation Vaccine Treatment Second Vaccine Treatment 10,0 1,0 0, Gleason grade: = 7 Age Trend before radical prostatectomy ( ) Trend after radical prostatectomy. External beam radiation ( ) Trend after first vaccine trial ( ) Trend after second vaccine trial ( ) 5.8 months DT (doubling time) 9.6 months DT 28.6 months DT 34

35 PROSTVAC OPTION LICENSE AGREEMENT WITH BMS Total deal terms $60M upfront with up to $975M in total milestones Precommercial Up to $480M* total prior to approval Commercial Sales milestones up to $495M Tiered royalties on sales from high teens to midtwenties 35 * Based on Phase 2 data

36 Non-vaccinated RSV MVA-BN G MVA-BN F MVA-BN FG MVA-BN-RSV RSV in the lungs (L gene copies) MORE TRANSGENES INCREASE THE PROTECTIVE EFFICACY OF RSV VACCINES Improved efficacy by multi-antigen vaccine in the sensitive RT-qPCR MVA-BN-RSV encodes F, G (a), G (b), N and M2 36 Business Proprietary

37 MVA-BN RSV - PHASE 1 FOLLOW-UP DATA RSV antibody response by IgA ELISA (GMT) RSV antibody responses by PRNT (A strain) 37 vaccinations given at week 0 and week 4

38 MVA-BN RSV ADDITIONAL T-CELL DATA RSV-specific T cell response (ELISPOT) ES = Elderly Standard Dose group; vaccinations given at week 0 and week 4 38

39 MVA-BN RSV PHASE 2 PROOF OF CONCEPT STUDY Randomized, blinded, placebo-controlled study 400 healthy subjects ( 55 years old) Study expected confirm results seen in phase 1 and help identify optimal dose and schedule Optimal group will be carried forward into 2017 RSV season with a booster dose Groups N Vaccine Dose Schedule (Day) 0 28 Route 1 80 Low MVA-BN RSV Placebo IM 2 80 Low MVA-BN RSV MVA-BN RSV IM 3 80 High MVA-BN RSV Placebo IM 4 80 High MVA-BN RSV MVA-BN RSV IM Placebo Placebo IM Total

40 PROOF-OF-CONCEPT STUDY OF CV301 & NIVOLUMAB IN NSCLC Phase 1 Safety CV301 single agent (n=18) Single dose combination with nivolumab (n=22) Phase 2 Multi-center trial Up to 20 sites in USA Randomization CV301 + nivo (n=60) nivo (mono) (n=60) Endpoints Safety, tolerability Primary endpoint: OS Secondary endpoints: ORR, DOR, PFS, Immune effects 40

41 CV301 + ATEZOLIZUMAB (ANTI PD-L1) IN 2ND LINE METASTATIC BLADDER CANCER Single-arm, combination of standard therapy (atezolizumab) + CV301 Primary Endpoint: Improve OS compared with historical control (7.9 months) Secondary Endpoints = Early indicators possible: objective response rate (control = 19%), progression free survival (control median = 2.1 months) Exploratory = biomarker discovery Inform future trial design and other indications Bx Bx CT CT CT q9 weeks, thereafter Week 1 Week 4 Week 7 Week 10 Week 13 Week 16 Week 19 Week 22 Week 25 Week 28 MVABN CV301 MVABN CV301 FPV CV301 FPV CV301 FPV CV301 FPV CV301 FPV CV301 FPV CV301 FPV CV weeks until progression Atezo Atezo Atezo Atezo Atezo Atezo Atezo Atezo Atezo Atezo Q2 weeks until progression 41

42 MVA-BN BRACHYURY PHASE 1 NOVEL IMMUNOTHERAPY CANDIDATE WITH BROAD POTENTIAL 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. Indications Chordoma (ultra-orphan disease) Triple negative breast cancer Merkel Cell Carcinoma NSCLC SCLC Multiple solid tumors Development Strategy NCI Phase 1 and Phase 2 trials Initiation of both monotherapy and combination trials 42

43 MVA-BN BRACHYURY: PHASE 1 DATA 38 patients with advanced cancer (N=25) or chordoma (N=13) Advanced cancers included Colorectal, Breast (ER+) NSCLC (EGFR mutated), Prostate, Pancreatic, Ovarian and Cholangiocarcinoma Dose escalation, safety and immunogenicity study No SAE s associated with vaccine At DL2 and DL3, ~80% of the patients that demonstrated brachyury-specific T-cells demonstrated responses in both CD4 and CD8 T-lymphocytes Dose Level Dose and Schedule 1 (N=3) 1 site of injection at 2 x 108 IU given every 28 days for 3 doses 2 (N=17) 2 sites of injection at 2 x 108 IU given every 28 days for 3 doses 3 (N=18) 4 sites of injection at 2 x 108 IU given every 28 days for 3 doses These findings show for the first time that advanced cancer patients can be safely immunized with an MVA-based vaccine targeting brachyury, and can develop brachyury-specific T-cell immune responses. 1 1 Heery, Donahue, et al. 43

44 EBOLA PHASE 1 DATA, 1-YEAR FOLLOW-UP The longest duration follow-up for any heterologous primary and booster Ebola vaccine schedule JAMA, March 14, 2017: Immune Responses to Novel Adenovirus Type 26 and Modified Vaccinia Ankara-Vectores Ebola Vaccines at 1 Year 44