Citi 12 th Annual Biotech Conference September 7, 2017

Transcription

1 Citi 12 th Annual Biotech Conference September 7, 2017

2 Safe harbor statement Certain information, particularly information relating to future performance and other business matters, including expectations regarding clinical development, market opportunities and anticipated milestones constitute forwardlooking statements within the meaning of the Private Securities Litigation Reform Act. Forward-looking statements may generally contain words such as believe, may, could, will, possible, can, estimate, continue, ongoing, consider, intend, plan, project, expect, should, would, or assume or variations of such words or other words with similar meanings. Novavax cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties that change over time and may cause actual results to differ materially from the results discussed in the forward-looking statements. Uncertainties include but are not limited to clinical trial results, dependence on third party contractors, competition for clinical resources and patient enrollment and risks that we may lack the financial resources to fund ongoing operations. Additional information on Risk Factors are contained in Novavax filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which are available at Forward-looking statements are based on current expectations and assumptions and currently available data and are neither predictions nor guarantees of future events or performance. Current results may not be predictive of future results. You should not place undue reliance on forward-looking statements which speak only as of the date hereof. The Company does not undertake to update or revise any forward-looking statements after they are made, whether as a result of new information, future events, or otherwise, except as required by applicable law. 2

3 Novavax Targets: Influenza and RSV, the leading causes of respiratory tract infection RSV RSV remains a major unmet medical need in both children and older adults and a vaccine is an ideal solution Novavax is the leader in RSV vaccine development Novavax RSV F Vaccine is a multi-billion dollar revenue opportunity Influenza (Flu) Efficacy of seasonal flu vaccines is inconsistent and rarely better than 50% 1 Annual flu vaccination is universally recommended due to large burden of disease Novavax is targeting a better, differentiated flu vaccine Flu vaccine market was approximately $3.1B in 2015 in the 7 major markets 2, major markets: USA, Japan, Italy, Spain, UK, Germany and France 3 PharmaPoint Seasonal Influenza Vaccines Global Drug Forecast and Market Analysis to 2025, October

4 ` RSV F Vaccine Phase 3 Trial Infants via Maternal Immunization

5 Novavax Phase 3 RSV F Vaccine For Infants Via Maternal Immunization Addresses Significant Unmet Medical Need RSV is the most common cause of lower respiratory tract infections among young children RSV is the leading cause of hospitalization among children <1 year old in the United States 2,3 Globally, RSV is second only to malaria as a cause of death in children <1 year old 4 $89 million Bill and Melinda Gates Foundation grant supports the Prepare trial, addresses Foundation mission of childhood mortality RSV is largely a disease of healthy, full-term infants The smaller airways and immature immune systems of infants make them more susceptible to severe disease Natural immunity, derived from the mother, is relatively ineffective, and would benefit from a maternal vaccine 1. Nair H et al. Lancet. 2010;375: Munoz FM. Curr Opin Infect Dis. 2015;28: Leader SL, Kohlhase K. Pediatr Infect Dis J. 2002;21(7): Oxford Vaccine Group. Vaccine Knowledge Project. Respiratory syncytial virus (RSV). May 11, Accessed July 23,

6 Maternal Immunization: Building on a Proven Strategy Building on Proven Strategy Growing acceptance of maternal vaccination for flu and pertussis among HCPs and mothers American College of Obstetrics and Gynecology conducts CME-accredited webinar: Respiratory Syncytial Virus: The Need for a Maternal Immunization Strategy Vaccine Injury Compensation Program (VICP) Amendment in 21st Century Cures Act: As of December 13, 2016, program covers both a woman who received a covered vaccine while pregnant and any child who was in utero under government no-fault insurance program ACIP RSV Working Group CDC Advisory Committee on Immunization Practices (ACIP) established RSV Working Group, May 2016 First step towards ACIP consideration for recommendation RESCEU (REspiratory Syncytial virus Consortium in EUrope) EU consortium of global leaders in RSV research (academia, public policy, industry) Epidemiology, surveillance and economic burden research 6

7 Novavax Has Conducted a Number of Successful Phase 2 Trials with RSV F Vaccine Women of child-bearing age Safety and immunogenicity confirmed in dose selection trials Demonstration of ~50% reduction of RSV infections in vaccine groups in two trials in two separate seasons Pregnant women Vaccine was well-tolerated Response to RSV F Vaccine in pregnant women replicated immune response in non-pregnant women Anti-F, PCA, and neutralizing transplacental antibody transfer confirmed Observed half-life of ~40 days for MN and PCA through first 60 days post delivery Suggests protection of infants for up to 180 days 7

8 Phase 3 RSV F Vaccine for Infants via Maternal Immunization Trial: Goals and Design Primary Objective Design Determine the efficacy of maternal immunization with the RSV F Vaccine against symptomatic RSV lower respiratory tract infection (LRTI) with objective measures of medical significance of LRTI through the first 90 days of life in infants. Randomized, Observer-Blind, Placebo-Controlled, Group Sequential Number of participants Global Sites Length of Participation Minimum 4,600 women Year 3: US, Mexico, Chile, Argentina, UK, Spain, South Africa, Australia, New Zealand, Philippines, India Maternal Participants: 9 months Infant Participants: 1 year 1 IM Injection (RSV F Vaccine or Placebo), weeks EGA 8

9 The Phase 3 Prepare Trial has Entered its Third Year Global infrastructure has been established to drive enrollment and surveillance Recruitment and surveillance are going well and indicate trial feasibility Global Season 1: 16 sites in 5 countries Global Season 2: 46 sites in 7 countries Global Season 3: 80 sites in 11 countries Argentina Australia Chile India Mexico New Zealand Philippines South Africa Spain United Kingdom United States 9

10 Protecting Infants from RSV via Maternal Immunization Global footprint has grown from 16 sites in 5 countries in first season of enrollment to 80 sites in 11 countries in third season Interim analysis occurs at 4,600 vaccinees Requires a minimum of 3,000 vaccinees Expect to trigger unblinding in 2018 Novavax has the only vaccine in clinical trials for maternal immunization 10

11 Annual burden of RSV disease in infants 0-6 months of 1.9m infections affects those most at risk Potential U.S. market: ~4 million pregnancies/year ~34,000 Hospital Admissions 2 ~109,000 ER Visits 2 1.9M Infections 1 ~263,000 Outpatient Visits 2 ~31 Deaths 3 Values represent estimated annual rates. 1 CDC National Vital Statistics Birth Cohort Data; 2 Hall et al., NEJM 2009; 3 McLaurin et al., J Perinatol

12 ` Nanoparticle influenza vaccine with Matrix-M (NanoFlu) 12

13 Influenza (Flu) Market is Large, and Growing, with Little Product Differentiation Effectiveness of current licensed flu vaccines is inconsistent, and in some years, not effective at all Pricing is generally commodity-like, the exception being Fluzone HD and, recently, FluAd, both for the older adult market Novavax is targeting a high-value, differentiable product Product timelines create very near-term value: Phase 1/2 immunogenicity data in 330 older adults against market leader FDA End Of Phase 2 meeting Potential for accelerated approval (precedent: Fluzone HD, FluAd, Flulaval) Dec 2017 Jan 2018 Initiate pivotal phase 3 trial Sep 2018 Phase 3 data readout Dec 2018 BLA filing 4Q

14 NanoFlu Target Product Profile Point of Market Entry Immunogenicity Profile Broadly Neutralizing Capability Older Adults (65 years and older) HAI and Microneutralization titers equal to (or better than) the best-selling vaccine in older adults (Fluzone High Dose) Better neutralization against drifted strains Effectiveness Superior protection over Fluzone High Dose Manufacturing High yields High purity Stable Recombinant, egg-free 14

15 Percent Effectiveness A Significant Percentage of Older Adults get Vaccinated for Influenza Current influenza immunization rates in North America: Vaccination rate Year USA (U.S. CDC) 66.7% 2014/15 Canada (Statistics Canada) % 2014 Total (pop. wt. avg.) 66.4% CDC aims to have at least 90% of adults aged 65 or older receive an annual flu shot by Effectiveness of Licensed Flu Vaccines All Ages Older Adults * ** Source: 1 Statistics Canada: x/ /article/14218-eng.htm; Bonten, M.J.M. et al. Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults. NEJM, 2015; 372: * Pandemic H1N1 season ** 14% for dominant H3N2 15

16 Influenza Vaccine Market Landscape Approximately $3.1B in 2015 in the 7 major markets 1,2 Growing to $4.3B by EU5 market is expected to grow by 70% and reaching almost $1B in sales by Current average influenza vaccination rate of older adults in EU5 is 57% Strong growth since 2005/ ACIP recommendation for universal vaccination in U.S. 3 US remains the largest market with ~59% of major market sales 2 Source: 1 7 major markets: USA, Japan, Italy, Spain, UK, Germany and France 2 PharmaPoint Seasonal Influenza Vaccines Global Drug Forecast and Market Analysis to 2025, October ECDC 2012/3 Survey: 16

17 Novavax Nanoparticle Influenza Vaccine candidate (NanoFlu) Novavax NanoFlu preclinical data demonstrate a superior, differentiated immunogenicity and efficacy profile based on those established models and markers, potentially addressing deficiencies of current flu vaccines Flu has established preclinical models and surrogate immunogenicity markers that are reasonably likely to predict clinical benefit We expect to have Phase 1/2 human safety and immunogenicity data by year-end which will drive discussions with BARDA and potential partners Plan for 1Q 2018 end of phase 2 FDA meeting, could lead to near-term pivotal Phase 3 immunogenicity trial 17

18 Influenza Virus - Primary Vaccine Target: Hemagglutinin Receptor binding region is the target for antibodies that prevent virus binding to cells. These antibodies are highly strainspecific and dominate the immune response. HA Protein Structure Antibodies to receptor binding site can be detected by hemagglutination inhibition (HAI) Hemagglutination inhibiting antibodies are established surrogate markers of protection from influenza that could be the basis for licensure 18

19 Flu Program Data Published in Vaccine Full publication is available on Novavax website or at: 19

20 Preclinical Study Design - Ferret Immunogenicity & Challenge Study Group Immunization Blood Draw Virus Challenge Influenza A/H3N2 Placebo NanoFlu 15µg/HA + 50µg Matrix Fluzone HD 60µg/HA Fluzone 15µg/HA Days 0 and 21 Days 21 and 42 Day 49 Challenge Virus in Ferret Model A H3N2: current strain, matched to vaccine A H3N2: 10-yr. old strain, unmatched to vaccine 20

21 Ferret Immunogenicity & Challenge Study Novavax NanoFlu Fluzone HD Fluzone Quadrivalent A/Michigan (H1N1) A/California (H1N1) A/HongKong (H3N2) B/Brisbane B/Phuket 21

22 H A I T i t e r H A I T i t e r s H A I T i t e r H A I T i t e r Immunogenicity: NanoFlu Induced Superior Hemagglutination Inhibition (HAI) Day 42 Antibody Responses A/Michigan (H1N1) A / M i c h i g a n / 4 5 / A/California (H1N1) A / C a l i f o r n i a / 0 7 / L O D L O D 2 P l a c e b o NanoFlu N I V + Matrix M + M a t r i x - M 1 F l u z o n e H D F l u z o n e 2 P l a c e b o NanoFlu N I V + + M a t r i x Matrix M F l u z o n e H D F l u z o n e A / H o n g K o n g / / A/Hong Kong (H3N2) B/Brisbane B / B r i s b a n e / 6 0 / L O D L O D 2 4 P l a c e b o N I V NanoFlu + Matrix M + M a t r i x M F l u z o n e H D F l u z o n e 2 P l a c e b o NanoFlu N I V + Matrix + M a t r i x M F l u z o n e H D F l u z o n e 22

23 H A I T i t e r H A I T i t e r s H A I T i t e r H A I T i t e r Immunogenicity: NanoFlu Induced Superior Hemagglutination Inhibition (HAI) Day 42 Antibody Responses A/Michigan (H1N1) A / M i c h i g a n / 4 5 / A/California (H1N1) A / C a l i f o r n i a / 0 7 / L O D L O D 2 P l a c e b o NanoFlu N I V + Matrix M + M a t r i x - M 1 F l u z o n e H D F l u z o n e 2 P l a c e b o NanoFlu N I V + + M a t r i x Matrix M F l u z o n e H D F l u z o n e A/Hong Kong (H3N2) A / H o n g K o n g / / B/Brisbane B / B r i s b a n e / 6 0 / L O D 8 4 L O D 2 P l a c e b o NanoFlu N I V + Matrix M + M a t r i x M F l u z o n e H D F l u z o n e 2 P l a c e b o NanoFlu N I V + + M a t r i x Matrix M F l u z o n e H D F l u z o n e 23

24 50% MN Titers (Log 2 ) 50% MN Titers (Log 2 ) 50% MN Titers (Log 2 ) 50% MN Titers (Log 2 ) Immunogenicity: NanoFlu Induced Superior Microneutralizing (MN) Day 42 Antibody Responses A/Michigan (H1N1) A/California (H1N1) NanoFlu + Matrix M NanoFlu + Matrix M A/Hong Kong (H3N2) B/Brisbane NanoFlu + Matrix M NanoFlu + Matrix M 24

25 50% MN Titers (Log 2 ) 50% MN Titers (Log 2 ) 50% MN Titers (Log 2 ) 50% MN Titers (Log 2 ) Immunogenicity: NanoFlu Induced Superior Microneutralizing (MN) Day 42 Antibody Responses A/Michigan (H1N1) A/California (H1N1) NanoFlu + Matrix M NanoFlu + Matrix M A/Hong Kong (H3N2) B/Brisbane NanoFlu + Matrix M NanoFlu + Matrix M 25

26 Immunogenicity: NanoFlu Vaccine Induced Broadly Neutralizing Antibodies against Drifted A(H3N2) Influenza Viruses 5 0 % M N T i t e r s ( L o g 2 ) NNanoFlu I V + M + a Matrix t r i x M M FFluzone l u z o n e HD H D Fluzone F l u z o n e Q I V A / H o n g K o n g / / 1 4 A / S w i t z e r l a n d / / 1 3 A / T e x a s / 5 0 / 1 2 A / V i c t o r i a / / 1 1 A / P e r t h / 1 6 / 0 9 A / B r i s b a n e / 1 0 / 0 7 A / W i s c o n s i n / 6 7 / 0 5 A / N e w Y o r k / 5 5 / 0 4 A / F u j i a n / / 0 2 A / P a n a m a / 0 7 /

27 N a s a l W a s h V ir u s T ite r (L o g 1 0 p fu /m L ) N a s a l W a s h V ir u s T ite r (L o g 1 0 p fu /m L ) NanoFlu Vaccine was Superior in Protecting Ferrets Challenged with Matched and 10-year Drifted H3N2 (unmatched) Strain A/Hong Kong/4801/2014 (H3N2) like A /H o n g K o n g / / (H 3 N 2 ) A/Alaska/140/2015 (matched) A /A la s k a /1 4 0 / A/Brisbane/10/2007 (H3N2)-like A/Texas/71/2007 (unmatched) A /B ris b a n e /1 0 / )H 3 N 2 )-lik e A /T e x a s /7 1 / NanoFlu vs placebo p < NanoFlu vs placebo p < NanoFlu vs Fluzone HD p < NanoFlu vs Fluzone p < NanoFlu vs Fluzone HD p < NanoFlu vs Fluzone p < LO Q LO Q D a y P o s t-c h a lle n g e D a y P o s t-c h a lle n g e NanoFlu + Matrix M Placebo c e b o N IV + M a trix -M FFluzone z o n e HHD D FFluzone z o n e n=5 for each group Statistics were longitudinal (repeat measure) analysis performed by including Days 2, 4 and 6. Day 8 was excluded because all animals came back down to baseline 27

28 NanoFlu Product Development Strategy Seasonal, older adult vaccine candidate in head-to-head trial 4Q 2017: Data from Phase 1/2 trial designed to show product differences from current market leader 1Q 2018: End of Phase 2 meeting expected, potential for accelerated approval 4Q 2018: Pivotal immunogenicity data 2019: Followed by lot consistency trials and BLA filing Potential for funding with an industry partner and/or HHS-BARDA NanoFlu platform meets goals targeted by HHS-BARDA Potential for funding of seasonal and pandemic vaccines BARDA: Biomedical Advanced Research and Development Authority 28

29 ` RSV F Vaccine in Older Adults (E205)

30 Recently Announced E-205 Vaccine/Adjuvant Study Conclusions Adjuvant effects The adjuvants meaningfully increased immunity in measures generally associated with effective immunity Anti-F and PCA MN titers Avidity of antibodies to neutralizing epitopes Memory B cell and CD4+ T cells specific for F protein Durability of the responses are important and are improved with 2 doses The totality of the immune effects makes use of the adjuvants desirable and likely to de-risk the next steps Both classic and new immune measures build our confidence that these are better formulations to use in the next steps With respect to safety: All adjuvanted formulations were clinically tolerable 30

31 Path Forward for Older Adult Vaccine Building on E-205 data, RSV F Vaccine will be formulated with adjuvant for older adults Two pathways to licensure: 1. Conduct a Phase 2 efficacy trial in a highly susceptible population A profound vaccine effect was demonstrated in both our Phase 2 and Phase 3 trial in older adults w/ COPD, and/or, 2. Conduct a pivotal trial in all older adults Trial design to mimic Phase 3 maternal immunization, event-driven, multiple season trial with adjuvant formulation Initiation dependent upon status of NanoFlu development 31

32 Impact of Vaccine on COPD Exacerbations Post-hoc Analyses of Hospitalizations for All Cause COPD Exacerbations in E-201 and E-301 Data from the Safety Database E301 Day Placebo Vaccine VE% 95% CI p value COPD hospitalization rate in all subjects COPD hospitalization rate in subjects with baseline COPD E 201 Day COPD hospitalization rate in all subjects COPD hospitalization rate in subjects with baseline COPD 23/5935 (0.39%) 9/5921 (0.15%) 60.8% /362 (4.1%) 9/403 (2.2%) 46.1% /801 (0.50%) 0/798 (0%) 100% NC NC 2/62 (3.2%) 0/58 (0%) 100% NC NC After Day 182 (i.e., after the winter-spring RSV season) the effect on COPD exacerbation essentially disappears in E-301 After Day 182, an effect appears to continue in E

33 Proportion of Population Free of COPD Exacerbation COPD Hospitalizations in E All-Cause COPD Exacerbation Hospitalization-Free Survival in E Active Placebo Days From Treatment 33

34 Summary of COPD Opportunity A significant market opportunity exists with COPD, ~ $1.5 billion globally Prevention of acute exacerbations of COPD with the RSV F Vaccine would have a significant impact on the clinical and economic burden of COPD in the United States 1. Centers for Disease Control and Prevention. MMWR. Employment and Activity Limitations Among Adults with Chronic Obstructive Pulmonary Disease United States, March 27, Accessed July 21, Wilkinson TMA et al. Thorax. Published Online first 2017 Apr 21; doi: /thoraxjnl Qureshi H et al. Ther Adv Chronic Dis. 2014;5(5):

35 Upcoming Flu and RSV Milestones Novavax is the leader in RSV vaccine development Phase 3 program for RSV maternal immunization supported by Bill & Melinda Gates Foundation grant of $89 million Interim data analysis in 2018 Differentiated NanoFlu program Data from Phase 1/2 trial in 4Q 2017 End Of Phase 2 FDA meeting 1Q 2018 NanoFlu pivotal Phase 3 data 4Q