Novavax, Inc. · NASDAQ:NVAX
Novavax — Investor Day (September 2015)
102 slides from Novavax's investor day presentation, September 2015
Slide 1: Analyst & Investor Meeting
Analyst & Investor Meeting September 2015
Slide 2: Safe Harbor Statement
Safe Harbor Statement Certain information contained herein, particularly information relating to future financial or business performance, conditions or strategies and other financial and business matters, including expectations regarding clinical development, product sales, operating expenses, our
Slide 3: Agenda
Agenda 9:00 – 9:10 a.m. • Welcome and Corporate Overview 9:10 – 9:30 a.m. • Nanoparticle Technology: A New Paradigm 9:30 – 9:40 a.m. • Seasonal Influenza Clinical Update 9:40 – 9:55 a.m. • RSV Burden of Disease in Older Adults • RSV Clinical Update • Older Adults 9:55 – 10:15 a.m. • Maternal Phase I
Slide 4: Breaking News
Breaking News NOVAV, BILL@MELINDA GATES foundation Novavax Amnounces Grant of up to $89 Million to Support Development of RSV F Vaccine to Protect Infants via Maternal Immunization Bill & Melinda Gates Foundation to support development of the RSV F Vaccine Program Gaithersburg, Md., September 29, 20
Slide 5: Breaking News
Breaking News NOVAVAX Novavax Announces Positive Top-Line Data from Phase 2 Clinical Trial of RSV F Vaccine to Protect Infants via Maternal Immunization RSV F Vaccine was safe and well-tolerated Significant anti-F, PCA and microneutralizing antibody responses elicited in mothers Efficient antibody t
Slide 6: Breaking News
Breaking News NOVAVAX Novavax Announces Positive Top-Line Data from RSV F Vaccine Phase 1 Clinical Trial in Pediatrics Novavax’ fifth positive top-line clinical trial announcement of the 3"¢ quarter Gaithersburg, Md., September 29, 2015 — Novavax, Inc., (Nasdaq: NVAX) a clinical-stage vaccine compan
Slide 7: Investment Thesis
Investment Thesis Novavax Vaccine Platform • Recombinant nanoparticle technology induces robust immunity • Matrix‐M™ adjuvant increases magnitude and quality of immune response Clinical Development Programs • RSV: Older adults, infants via maternal immunization, pediatrics • Seasonal & Pandemic Infl
Slide 8: Product Pipeline
Product Pipeline Funding Preclinical Phase 1 Phase 2 Phase 3 Support RSV Older Adults (60+) Infants (Maternal Immunization) Pediatrics (6 mos – 6 yrs) Influenza Quadrivalent Seasonal Pandemic (H7N9 + Matrix‐MTM) New Product Opportunities Ebola + Matrix‐MTM Combination Respiratory 8
Slide 9: Recent Accomplishments
Recent Accomplishments Q3‐14 Q4‐14 Q1‐15 Q2‐15 Q3‐15 Q4‐15 RSV Older Adults (60+) Phase 2 Infants (Maternal Immunization) Phase 2 Pediatrics (6 mos – 6 yrs) Phase 1 Influenza Quadrivalent Seasonal Phase 2 Pandemic (H7N9 + Matrix‐MTM) Phase 1/2 New Product Opportunities Ebola + Matrix‐MTM Phase 1 Dat
Slide 10: Projected Highlights: 2016
Projected Highlights: 2016 Initiation of: Phase 3 pivotal RSV F Vaccine in Older Adults • Data 4th quarter, 2016 Phase 3 pivotal RSV F Vaccine to Protect Infants via Maternal Immunization • Trials initiated in U.S., S. Africa, Argentina…more Phase 2 RSV F Vaccine Booster Trial in Older Adults • Data
Slide 11: Nanoparticle Platform Technology: A New Paradigm
Nanoparticle Platform A New Paradigm Technology 11
Slide 12: Novavax Platform Technology
Novavax Platform Technology Click here to view video 12
Slide 13: Novavax Nanoparticle Vaccines: New Paradigm
Novavax Nanoparticle Vaccines: New Paradigm Traditional vaccines “mimic” pathogens Edward Jenner, vaccinating a baby in 1796, coined term 'vaccination' to describe inoculation of cowpox from milk maids to induce immunity to smallpox Viruses escape immune surveillance by hiding conserved epitopes req
Slide 14: Novavax Nanoparticle Technology
Novavax Nanoparticle Technology Recombinant Nanoparticles: Virus‐Like Particles (VLP) RSV F & Ebola GP Seasonal & Pandemic Influenza HA trimers Hydrophilic NA tetramers head of protein trimers M1 Matrix Protein Hydrophobic tail of protein No genetic trimers material Nanoparticles Influenza VLPs • Co
Slide 15: RSV F Hidden Neutralizing Epitopes
RSV F Hidden Neutralizing Epitopes Competitive ELISA RSV F Epitope Sites I, II and IV Phase 2 Trial, Women of Childbearing Age, F 120µg + AlPO4 0.4mg Site I Site II (PCA) Site IV LLOQ 1Beeler et al, Neutralization Epitopes of the F Glycoprotein of Respiratory Syncytial Virus: Effect of Mutation upon
Slide 16: Ebola GP Hidden Neutralizing Epitopes
Ebola GP Hidden Neutralizing Epitopes • 13C6, KZ52 (ZMapp™) and Ebola GP Phase 1 Trial other GP neutralizing epitopes mAb 13C6 Competitive ELISA are hidden Competative ELISA Titer (Log2) • NVAX Ebola GP vaccine + Matrix‐M induces antibodies against hidden epitopes • 100% protective in NHP Day 0 Day
Slide 17: Matrix-M Adjuvant Enhances and Broadens Responses to Epitopes
Matrix‐M™ Adjuvant Enhances and Broadens Responses to Epitopes1 Matrix‐M is a nanoparticle composed of saponins, cholesterol, and lipids Nano‐particulate (~40 nm) formulation of saponin with cholesterol and phospholipid Green: Buried Red: Exposed epitopes epitopes Non‐adjuvanted Adjuvanted H7N9 Vacc
Slide 18: Novavax Nanoparticle Vaccines: Proving Effective
Novavax Nanoparticle Vaccines: Proving Effective RSV F Vaccine – Older Adults Ebola GP Vaccine – Non‐human Primates 1.00 135 g RSV F Vaccine 5µg Ebola GP Vaccine Proportion of Group With 0.98 (n=11) No RSV Infection 0.96 0.94 Placebo 0.92 Placebo (n=5) 0.90 0 50 100 150 200 Time to RSV Onset (days)
Slide 19: Summary: New Nanoparticle Vaccine Paradigm
Summary: New Nanoparticle Vaccine Paradigm Nanoparticle technology platform based on antigens with conserved, hidden epitopes essential for virus replication • RSV F, Ebola GP, Rabies G, Influenza HA Unlike traditional vaccines that ‘mimic’ viruses, nanoparticles expose amino acid sequences critical
Slide 20: Nanoparticle Technology Applied to Emerging Threats
Nanoparticle H7N9 Influenza Technology Applied to Ebola Emerging Threats 20
Slide 21: H7N9 Vaccine Phase 2 Clinical Trial
H7N9 Vaccine Phase 2 Clinical Trial H7N9: Initial GMP vaccine released for human use in 81 days from project inception Data published in New England Journal of Medicine Trial Overview Objectives Outcomes • Phase 2 • Evaluate HAI and NAI • Strong adjuvant effect • 610 adults antibody responses of Mat
Slide 22: Matrix-M Enables H7N9 HAI Responses
Matrix‐M Enables H7N9 HAI Responses • 4 to 5‐fold increase in HAI titer • Dose‐sparing H7N9 HAI GMT (95% CI) 22
Slide 23: H7N9 NAI Responses
H7N9 NAI GMT (95% CI) H7N9 NAI Responses 23
Slide 24: Ebola GP Vaccine Phase 1 Clinical Trial
Ebola GP Vaccine Phase 1 Clinical Trial Ebola: GMP vaccine released for human use in 94 days from project inception Trial Overview Objectives Outcomes • Phase 1 • Evaluate antibody • Strong adjuvant effect • 230 adults responses to GP and of Matrix‐M • Makona strain whole Zaire Ebola virus • Robust
Slide 25: Ebola GP IgG ELISA (Makona Strain)
Ebola GP IgG ELISA (Makona Strain) Novavax Makona GP ELISA • 2 doses of vaccine with 6.5 µg, 2 doses w/Matrix‐M 50000 adjuvant over 100‐fold more immunogenic Geometric Mean ELISA Units • Dose‐sparing at 6.5µg 5000 6.5 µg, 1 dose w/Matrix‐M 500 6.5 µg, 2 doses, unadjuvanted Placebo 50 0 5 10 15 20 25
Slide 26: Nanoparticle Technology for Emerging Viruses
Nanoparticle Technology for Emerging Viruses • Demonstrated in H7N9, Ebola and MERS • Adaptable to new threats on a short timeline • Rapid manufacturing process • Thermostable at 2‐8º C • Matrix‐M enables dose–sparing and protective responses: Enhanced immunogenicity for “difficult” antigens Pro
Slide 27: Quadrivalent Seasonal Influenza Vaccine Clinical Update
Quadrivalent Seasonal Clinical Update Influenza Vaccine 27
Slide 28: Quadrivalent Seasonal Influenza Phase 2 Clinical Trial
Quadrivalent Seasonal Influenza Phase 2 Clinical Trial Trial Overview Objectives Outcomes • Phase 2 • Evaluate • Improved HAI and NAI • 400 adults immunogenicity responses • Quadrivalent seasonal • Demonstrate that • Fullfills CEBR vaccine; 4 strains: immunogenicity can seroconversion and • A/Califo
Slide 29: Quadrivalent Seasonal Influenza Vaccine - HAI
Quadrivalent Seasonal Influenza Vaccine ‐ HAI • At 15µg dose, all 4 strains met CBER criteria for seroprotection and seroconversion • Competitive with licensed trivalent seasonal influenza vaccine 29
Slide 30: Summary: Seasonal and Pandemic Influenza Programs
Summary: Seasonal and Pandemic Influenza Programs Seasonal Influenza Pandemic Influenza • Produced & tested every WHO/FDA • Achieved threat strain sequence to recommended strain since 2009 GMP production & release in <90 • Demonstrated rapid adaptability to days produce late‐emerging strain • Delive
Slide 31: RSV F Vaccine Burden of Disease in Older Adults
RSV F Vaccine Burden of Disease in Older Adults 31
Slide 32: The Burden of RSV Disease in Older Adults
The Burden of RSV Disease in Older Adults William Schaffner, MD Professor of Preventive Medicine, Department of Health Policy Professor of Medicine, Division of Infectious Diseases Vanderbilt University School of Medicine 32
Slide 33: Respiratory Syncytial Virus - RSV
Respiratory Syncytial Virus ‐ RSV • Originally reported as a cause of severe respiratory infections in young children • Now recognized as causing severe disease in older adults: Community – dwelling Those with chronic obstructive pulmonary disease cardiopulmonary disease long‐term care nursing homes
Slide 34: RSV Disease Burden in the Elderly (≥65 yrs) - U.S.
RSV Disease Burden in the Elderly (≥ 65 yrs) – U.S. Deaths 14,000 ER (151,801) + Hospital ˜852,680 Medical Admissions (203,612) Interventions = ˜355,400 (14.8% of RSV (35.5% of infections) RSV infections) Physician Office Visits ~497,280 (17% of RSV infections – healthy) (29% of RSV infections ‐ hig
Slide 35: RSV - Clinical Manifestations
RSV – Clinical Manifestations RSV(%) Influenza(%) Nasal congestion 22‐78 64 Cough 90+ 89 Sore throat 16‐64 64 Shortness of breath 51‐93 32 Wheezing 33‐90 30 Muscle pain 10‐64 70 Fever 48‐56 72 Onset Gradual Sudden Branche and Falsey. Drugs Aging, 2015. Sundaram et al. CID, 2014. Falsey et al. JID, 2
Slide 36: RSV - Complications
RSV ‐ Complications • Patients with COPD, cardiopulmonary disease • Pneumonia: 30‐50% of hospitalized patients RSV viral Bacterial co‐infection • Respiratory failure requiring intensive care admission: • 8‐13% of hospitalized patients Branche and Falsey. Drugs Aging, 2015. Mullooly et al. Vaccine, 2
Slide 37: RSV - Epidemiology
RSV ‐ Epidemiology Community‐dwelling older adults (65+) studied over 4 years Healthy: 3‐7%/year High‐risk: 4‐10%/year Falsey, N Engl J Med, 2005 37
Slide 38: Annual RSV Morbidity and Mortality
Annual RSV Morbidity and Mortality 177,500 Hospital admissions with respiratory symptoms 11,000‐17,000 Older adults die Walsh, Infect Disorder Drug Targets, 2012 38
Slide 39: Comparability of RSV and Influenza
Comparability of RSV and Influenza Falsey et al. NEJM, 2005 and Volling et al. BMC Infect Dis, 2014 39
Slide 40: RSV and Influenza are Comparably Severe
RSV and Influenza are Comparably Severe 4‐years (1989‐1992) Hospitalized patients age 65+ with influenza‐like or cardiopulmonary illness Diagnosis Deaths Influenza 11% 6% RSV 10% 10% Falsey, J Infect Dis, 1995 40
Slide 41: Burden of Disease for RSV, Influenza, and Pneumococcal Pneumonia
Burden of Disease for RSV, Influenza, and Pneumococcal Pneumonia in Adults 65 and Older in U.S. RSV Influenza* Pneumonia Number of Infections 2,400,000 2,883,052 1,286,556 Hospitalization 203,600 262,095 339,853 Deaths 14,000 14,607 22,449 *Average of 3 past seasons, 2010‐2013; includes vaccine aver
Slide 42: RSV F Vaccine Phase 2 Clinical Trial in Older Adults
RSV F Vaccine Phase 2 Clinical Trial in Older Adults 42
Slide 43: Novel RSV F Vaccine
Novel RSV F Vaccine Novel RSV Fusion‐protein vaccine (RSV F Vaccine) developed using recombinant nanoparticle technology Elicits palivizumab competing antibodies (PCA) Palivizumab levels correlate to protection Six clinical trials completed or initiated, demonstrating safety and immunogenicity in ov
Slide 44: RSV Vaccine Target Populations
RSV Vaccine Target Populations Infants Older Adults Pediatrics via Maternal Immunization Healthy individuals Children Infants <6 months 60+ years and high >6 months ‐ 5 years risk adults 44
Slide 45: RSV F-Protein Presents Multiple Conserved Sites
RSV F‐Protein Presents Multiple Conserved Sites RSV Surface Proteins Site I • G protein: Variable • F protein: Conserved Site IV Antigenic site II • Targeted by palivizumab (Synagis®) and motavizumab Site II • Antibodies shown to prevent RSV disease in infants in 5 randomized clinical trials • Crypt
Slide 46: Phase 2 RSV F Vaccine Clinical Trial in Older Adults
Phase 2 RSV F Vaccine Clinical Trial in Older Adults Trial Overview Goals Method Trial Overview Goals Method • Phase 2 trial • Evaluate the • All subjects with randomized, incidence of symptomatic observer‐blinded symptomatic RSV respiratory illness • 10 trial sites in U.S. illness in 60+ were teste
Slide 47: P2 Older Adults: Study Objectives
P2 Older Adults: Study Objectives Primary Secondary Exploratory • Epidemiology trial • Estimate efficacy of • Evaluate amplitude of vaccine on all • Describe the PCA and incidence of all symptomatic RSV microneutralizing respiratory illnesses symptomatic antibody responses respiratory illnesses • Ex
Slide 48: P2 Older Adults: Study Population and Demographics
P2 Older Adults: Study Population and Demographics RSV F Vaccine Placebo Study Populations Safety 798 801 Intent‐to‐Treat 798 798 Per‐Protocol 759 771 Percent Male 42.0 41.7 Mean Age, yrs (SD) 69.4 (6.5) 69.5 (6.4) Percent 60‐75 yrs 82.7 82.1 Percent >75 yrs 17 17.9 Race (%) White 90.4 90.9 Black 7.
Slide 49: P2 Older Adults: RSV Epidemiology Trial Results
P2 Older Adults: RSV Epidemiology Trial Results 4.9% of placebo with symptomatic RSV infections • Pharyngitis, nasal congestion, cough, wheezing, shortness of breath or increased sputum production • Defines the RSV attack rate in this population 88% of RSV infected subjects with LRTI symptoms1 • Cou
Slide 50: P2 Older Adults: Anti-F Antibody Response
P2 Older Adults: Anti‐F Antibody Response • Durable, 4.8‐fold1 increase in anti‐F IgG response • Seroresponse in >93% of subjects2 6000 Anti‐F IgG GMEU1 (95% CI) 5000 135 g RSV F Vaccine 4000 3000 2000 Placebo 1000 0 0 10 20 30 40 50 60 Days 1 geometric mean rise relative to Day 0 2% of group with
Slide 51: P2 Older Adults: PCA Response
P2 Older Adults: PCA Response • Durable, 5.2‐fold1 increase in PCA response • Seroresponse in >96% of subjects2 120 100 135 g RSV F Vaccine PCA GMC 1 (µg/mL) 80 60 40 Placebo 20 0 0 10 20 30 40 50 60 Days 1 geometric mean rise relative to Day 0 2 % of group with EU >95th percentile of the placebo g
Slide 52: P2 Older Adults: RSV A and B Microneutralizing Antibodies
P2 Older Adults: RSV A and B Microneutralizing Antibodies 2.1 Geometric Mean Rise in Neutralizing Titers 1.9 (baseline adjusted) 1.7 1.5 1.3 1.1 0.9 RSV F Placebo RSV F Placebo RSV F Placebo RSV F Placebo Vaccine RSV/A Vaccine RSV/A Vaccine RSV/B Vaccine RSV/B RSV/A RSV/A RSV/B RSV/B Day 28 Day 56 D
Slide 53: P2 Older Adults: Early and Durable Protection from RSV Infection
P2 Older Adults: Early and Durable Protection from RSV Infection 1.00 Proportion of Group With No RSV Infection 0.98 135 g RSV F Vaccine 0.96 Placebo 0.94 p=0.039 0.92 October 31, 2014 April, 15, 2015 0.90 0 50 100 150 200 Time to RSV Onset (days) RT‐PCR confirmed RSV Events Product‐Limit Survival
Slide 54: P2 Older Adults: Relative Risk and Efficacy Estimates
P2 Older Adults: Relative Risk and Efficacy Estimates Population Endpoint Placebo Vaccine Efficacy P‐value ITT Total N 798 798 All symptomatic RSV 39 23 41% 0.041 Per protocol Total N 771 759 All symptomatic RSV 38 21 44% 0.031 RSV LRTI (ad hoc) 33 18 45%1 0.041 60 to <75 yrs Total N 636 630 All sym
Slide 55: P2 Older Adults: Analysis of RSV LRTI and Difficulty Breathing
P2 Older Adults: Analysis of RSV LRTI and Difficulty Breathing Measures of more severe illness: Number of Symptoms Number of vaccine vs Vaccine and Signs Reported* placebo subjects P‐value Efficacy Any symptomatic RSV 21 vs 38 44% 0.031 At least 3 LRTI signs and 5 vs 14 64% 0.047 symptoms (ad hoc) A
Slide 56: RSV Older Adults Data Results Analogous to Prevnar 13
RSV Older Adults Data Results Analogous to Prevnar 13 Endpoint and Analysis Episodes PCV13 Placebo % Vaccine P Value (N = 42,256) (N = 42,256) Efficacy Infection with vaccine‐type strain Confirmed community‐acquired pneumonia1* 139 49 90 46% <0.001 Per‐protocol analysis Invasive pneumococcal disease
Slide 57: Efficacy of Licensed Influenza Vaccines
Efficacy of Licensed Influenza Vaccines • Novavax RSV F Vaccine efficacy is similar to or better than a number of respiratory vaccines1,2,3 • Vaccine effectiveness is lower in older adults Season Vaccine Effectiveness Vaccine Effectiveness in in All Ages Older Adults 2007‐8 37% 37% 2009‐10 56% ‐6%*
Slide 58: RSV Older Adults: Lessons Learned
RSV Older Adults: Lessons Learned • Well‐conducted study • Attack rate in line with previously published data • MARI/hospitalizations logistics will be improved to enable data collection • Follow‐up with study nurse at‐home visitations will be added to improve swabbing rates to capture full incidenc
Slide 59: P2 Older Adults: Summary
P2 Older Adults: Summary 4.9% of older adults had symptomatic RSV disease 88% of these illnesses were associated with LRTI 44% reduction in symptomatic RSV in vaccinees 64% reduction in LRTI with difficulty breathing Durable protection for the entire RSV season First study to demonstrate effective R
Slide 60: RSV Older Adults: Next Steps
RSV Older Adults: Next Steps Next Steps Manufacture and release Phase 3 Trial Objectives product Proposed endpoints* Phase 3 Trial Design End of Phase 2 meeting Primary: Prevent Initiate Phase 2 Booster symptomatic RSV illness as Older adults, ages 60+ Study indicated by patient 8,000‐10,000 partici
Slide 61: Next Steps: Older Adults Phase 2 Booster Trial
Next Steps: Older Adults Phase 2 Booster Trial • Annual seasonal vaccine • Phase 2 older adult subjects provide a unique opportunity to demonstrate the need and desirability of a boost Vaccine 1,600 participants Placebo Vaccine Placebo Vaccine Placebo • Proposed trial endpoints will be similar to Ph
Slide 62: RSV F Vaccine Phase 2 Clinical Trial to Protect Infants via Maternal Immunization
RSV F Vaccine Phase 2 Clinical Trial to Protect Infants via Maternal Immunization 62
Slide 63: RSV F Vaccine Maternal Immunization Highlights
RSV F Vaccine Maternal Immunization Highlights Today announced a grant of up to $89 million from the Bill & Melinda Gates Foundation to support development of the RSV F Vaccine Phase 3 clinical trial in pregnant women • P3 trial planned to initiate during the first quarter of 2016 • Will support reg
Slide 64: P2 Maternal Immunization: Study Objectives
P2 Maternal Immunization: Study Objectives Primary Secondary • Mothers: Describe safety of the RSV F • Mothers: Evaluate amplitude and vaccine through delivery and 6 months duration of anti‐F IgG, PCA and RSV A/B post‐delivery microneutralizing antibody responses in • Infants: Describe safety throug
Slide 65: P2 Maternal Immunization: Design and Protocol
P2 Maternal Immunization: Design and Protocol Treatments • 120µg RSV F + 0.4mg aluminum phosphate • Randomization was stratified by age: • 18 to < 29 years and 29 to ≤40 years Design: Maternal Treatment RSV F Antigen Aluminum Dosing Subjects per Group Label Content Adjuvant Content Volume Group, N A
Slide 66: P2 Maternal Immunization: Safety Follow-up
P2 Maternal Immunization: Safety Follow‐up Infant participants were assigned to one of two postpartum phlebotomy cohorts: Mothers: Infant cohort 1*: Infant cohort 2**: Day 14* Delivery +14 days +35 days +60 days +180 days *Passive and active follow‐up for RSV disease began day 14 **An infant blood d
Slide 67: P2 Maternal Immunization: Maternal Population and Demographics
P2 Maternal Immunization: Maternal Population and Demographics Active Placebo Safety 22 28 ITT 22 28 Per‐protocol 22 28 Mean Age +/‐ SD (yrs) 27.8 +/‐ 4.53 27.7 +/‐4.91 18 to <29 yrs 59% 57% 29 to ≤40 yrs 41% 43% White 82% 79% Black 14% 14% Asian 7% 5% BMI (kg/m2) 30 30 67
Slide 68: P2 Maternal Immunization: Safety Summary
P2 Maternal Immunization: Safety Summary The vaccine was safe for both mothers and infants • Increase in local AEs (placebo, 4%; vaccine, 59%) • Predominantly mild‐moderate, transient injection site pain No Severe Respiratory Events • No hospitalizations • No enhanced disease RSV Infections • Two RS
Slide 69: P2 Maternal Participants: Anti-F IgG
P2 Maternal Participants: Anti‐F IgG 14000 120 mg RSV F Vaccine + 0.4 mg AlPO4 adjuvant Anti‐F IgG GMEU1 (95% CI) 12000 10000 8000 6000 4000 Placebo 2000 0 0 14 Delivery Delivery + 35 Days 1geometric mean rise relative to Day 0 69
Slide 70: P2 Maternal Participants: PCA
P2 Maternal Participants: PCA 350 120 mg RSV F Vaccine 300 + 0.4 mg AlPO4 adjuvant PCA GMC1 (95% CI) 250 200 150 100 50 Placebo 0 0 14 Delivery Delivery + 35 Days 1geometric mean rise relative to Day 0 70
Slide 71: P2 Maternal Participants: RSV A and B Microneutralizing Antibodies
P2 Maternal participants: RSV A and B Microneutralizing Antibodies 4 Geometric Mean Rise in Neutralizing Titers (baseline adjusted) 2 1 Active Placebo Active Placebo Active Placebo Active Placebo Active Placebo Active Placebo Day 14 post‐ Delivery Day 35 post‐ Day 14 post‐ Delivery Day 35 post‐ vacc
Slide 72: Infant/Maternal Anti-F Antibody Ratio
P2 Infants: Time from Vaccination to Delivery (Days) Impacts Placental Antibody Transfer Cord Blood Titer/ Maternal Serum Titer Delivery < 30 days Post Vaccination Delivery > 30 days Post Vaccination Infant/Maternal Anti‐F Antibody Ratio Time from Vaccination to Delivery Ad hoc analysis Excludes 1 m
Slide 73: P2 Infants: Time from Vaccination to Delivery Impacts Placental Antibody Transfer
P2 Infants: Time from Vaccination to Delivery (Days) Impacts Placental Antibody Transfer Del. < 30d Del. > 30d Assay Source post vacc., post vacc., All n=7 * n=14 n=21* Anti F IgG Cord 7,227 8,659 8,153 Mothers 12,979 6,993 8,594 Important Findings: Ratio 0.6 1.2 0.9 • Maternal antibody peaks 14d af
Slide 74: P2 Infants: Estimated RSV Antibody Half-life
P2 Infants: Estimated RSV Antibody Half‐life Vaccine Anti‐F IgG Cord Blood, GMEU (95% CI) 7307 (5113‐10443) Half Life 30 days PCA Cord Blood, GMC (95% CI) 189 (151‐236) Half Life 41 days RSV/A MN Cord Blood, GMT (95% CI) 691 (452‐1056) Half Life 36 days RSV/B MN Cord Blood, GMT (95% CI) 496 (310‐793
Slide 75: P2 Maternal Immunization: RSV F Vaccine Elicits Additional Known Neutralizing Antibodies
P2 Maternal Immunization: RSV F Vaccine Elicits Additional Known Neutralizing Antibodies Site I Delivery GMT (95% CI) Placebo Vaccine Site IV Mother <20 (<20‐25.2) 161 (119‐217) Site I Site II Cord Blood 25 (<20‐35) 135 (99‐184) Mother <20 (<20‐<20) 96 (71‐129) Site IV Cord Blood 20 (<20‐<20) 86 (64
Slide 76: P2 Maternal Immunization: Primary Objective Outcomes
P2 Maternal Immunization: Primary Objective Outcomes No observed prenatal, labor, delivery or immediate postpartum safety issues • Short‐term local reactogenicity is low • No meaningful imbalance in unsolicited AEs • No vaccine related SAEs No observed safety issues related to fetal well‐being and i
Slide 77: P2 Maternal Immunization: Secondary Objective Outcomes
P2 Maternal Immunization: Secondary Objective Outcomes Robust immune response to vaccine in mothers • Anti‐F IgG, PCA, and microneutralizing antibody responses are similar to prior trials in women of child‐bearing age All antibody measures show transient dilution at delivery, rebound at day 35 post‐
Slide 78: P2 Maternal Immunization: Next Steps
P2 Maternal Immunization: Next Steps Next Steps Manufacture and 1Q16 release product Proposed endpoints* Adaptive trial design End of Phase 2 meeting Primary: Prevention of Anticipated subjects: Initiate Phase 3 trial RSV bronchiolitis with 4,500 to 9,000 hypoxia Expect to initiate Phase 3 Secondary
Slide 79: RSV F Vaccine Pediatrics
RSV F Vaccine Pediatrics 79
Slide 80: RSV F Vaccine Phase 1 Trial in Pediatrics
RSV F Vaccine Phase 1 Trial in Pediatrics Trial Overview Status Method • Phase 1 trial • Trial completed with • 60 µg dose with or randomized, observer‐ smaller cohort due to without aluminum blinded, dose‐ranging onset of RSV season adjuvant study to evaluate safety • Safety in 32 subjects was • Im
Slide 81: P1 Pediatrics: Study Objectives
P1 Pediatrics: Study Objectives Primary Secondary Exploratory • Accumulate safety • Describe immune • Describe immune data for the responses to responses to candidate vaccine formulations and formulations and formulations and regimens in terms regimens in terms regimens of serum of serum IgG • Deter
Slide 82: RSV Pediatrics: Phase 1 Recruited Subjects
RSV Pediatrics: Phase 1 Recruited Subjects Placebo 60µg ++ 60µg + 60µg ‐ ‐ 60µg – Population N=7 N=6 N=6 N=6 N=7 ITT 7 (100%) 5 (83.3%) 6 (100%) 6 (100%) 7 (100%) Per protocol 3 (42.9%) 4 (66.7%) 5 (83.3%) 2 (33.3%) 4 (57.1%) Age >24 ‐ <36 mos. 2 (28.6%) 1 (16.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) >36 ‐ <7
Slide 83: P1 Pediatrics: Safety Summary
P1 Pediatrics: Safety Summary All RSV F Vaccine formulations were well‐tolerated No significant differences in adverse events between RSV F Vaccine and placebo Solicited systemic adverse events were highest in the placebo group No severe unsolicited events reported 83
Slide 84: P1 Pediatrics: Anti-F IgG, Per Protocol
P1 Pediatrics: Anti‐F IgG, Per Protocol Anti‐F IgG 60µg ++ 60µg + 60µg ‐ ‐ 60µg – Placebo N=4 N=5 N=2 N=4 N=3 Baseline 689 1,236 1,789 1,853 1,318 Day 14 GMEU 21,563 15,417 14,039 16,103 1,385 Day 14 fold‐rise (95% CI) 23.8 12.4 9.2 10.4 1.1 (11.4‐49.9) (6.7‐23.0) (3.4‐24.8) (5.1‐21.2) (0.5‐2.4) Day
Slide 85: P1 Pediatrics: PCA, Per Protocol
P1 Pediatrics: PCA, Per Protocol PCA 60µg ++ 60µg + 60µg ‐ ‐ 60µg – Placebo N=4 N=5 N=2 N=4 N=3 Baseline <14 22.1 31.3 42.0 16.9 Day 14 421.6 363.3 339.4 422.6 17.9 Day 14 fold‐rise (95% CI) 33.3 25.4 15.7 19.5 1.0 (15.1‐73.5) (12.1‐53.2) (5.5‐45.2) (6.6‐57.2) (0.4‐2.4) Day 28 442.6 385.4 302.3 356.
Slide 86: P1 Pediatrics: RSV A Microneutralizing Antibodies
P1 Pediatrics: RSV A Microneutralizing Antibodies Per Protocol 32 DAY 28 Geometric Mean Rise in Neutralizing Titers DAY 56 16 DAY 14 (baseline adjusted) 8 4 2 1 60µg + 60µg + 60µg 60µg Placebo 60µg + 60µg + 60µg 60µg Placebo 60µg + 60µg + 60µg 60µg Placebo Al x 2 Al x 1 w/o Al x w/o Al x Al x 2 Al x
Slide 87: P1 Pediatrics: RSV B Microneutralizing Antibodies
P1 Pediatrics: RSV B Microneutralizing Antibodies Per Protocol 32 Geometric Mean Rise in Neutralizing Titers DAY 28 DAY 56 DAY 14 16 (baseline adjusted) 8 4 2 1 60µg + 60µg + 60µg 60µg Placebo 60µg + 60µg + 60µg 60µg Placebo 60µg + 60µg + 60µg 60µg Placebo Al x 2 Al x 1 w/o Al x w/o Al x Al x 2 Al x
Slide 88: RSV Pediatrics: Preliminary Conclusions
RSV Pediatrics: Preliminary Conclusions The vaccine was well‐tolerated The vaccine was highly immunogenic • Limited benefit to second dose • Findings similar to prior study in women of childbearing age Data support advancement to Phase 2 88
Slide 89: Af ae
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Slide 90: RSV F Vaccine Franchise 2016 Activity
RSV F Vaccine Franchise 2016 Activity Funding Preclinical Phase 1 Phase 2 Phase 3 Support RSV Older Adults (60+) Infants (Maternal Immunization) Pediatrics (6 mos – 6 yrs) TBD 90
Slide 91: RSV Incidence and Burden in Major Markets
RSV Incidence and Burden in Major Markets Infections/Year: ~37 M Total Cost Burden: ~$88 B US EU5 ASIA (UK, Italy, France, Spain, Germany) (Japan, South Korea, Taiwan) ~15 M ~14 M ~8 M Infections/Year Infections/ Year Infections/Year ~$5 B ~$3 B ~$1.4 B Direct Cost Burden Direct Cost Burden Direct C
Slide 92: Target U.S. Segment for RSV Immunization
Target U.S. Segment for RSV Immunization ~98M Individuals U.S. population by target RSV patient segment (2014) 64.8 97.9 90 80 70 Millions of people 60 50 The 40 11.5 30 12.0 20 5.9 10 3.7 0 Pregnancies Infant Toddler High risk Older Addressable ≥34 wks >6 ‐ ≤24 mos >24 ‐ ≤60 mos 50 ‐ 59 yrs adults
Slide 93: Annual Burden of RSV Disease in Older Adults
Annual Burden of RSV Disease in Older Adults, 65 Years of Age and Older ~14,000 (0.5%) Deaths3 ~157,000 ~531,000 (20.9%) (6.2%) Physician Visits1 ER Visits2 2.5M (5.5%) Infections1 Note on percentages: • Infection percentage is relative to target U.S. segment ~177,000 (7%) • Burden percentages relat
Slide 94: Annual Economic Burden of RSV in Older Adults Exceeds $24 Billion
Annual Economic Burden of RSV in Older Adults Exceeds $24 Billion USD $87 M ER Visits2,5 $110 M Physician Visits1,6,7 2.5M Infections1 $2,800 M Hospital Visits1,4,8 $21,500 M Deaths3,9 Values represent estimated US dollars in 2015. Based on currently available literature, additional economic evaluat
Slide 95: Annual Burden of RSV Disease in Infants 0-6 Months of Age
Annual Burden of RSV Disease in Infants 0‐6 Months of Age ~140 (0.01%) Deaths3 ~109,000 (8%) ~260,000 (19.1%) Physician Visits2 ER Visits2 1.36M (69%) Infections1 Note on percentages: • Infection percentage is relative to ~33,400 (2.5%) target U.S. segment Hospital Admissions2 • Burden percentages r
Slide 96: Annual Economic Burden of RSV in Infants Exceeds $770 Million
Annual Economic Burden of RSV in Infants 0‐6 Months of Age Exceeds $770 Million USD $ 60 M ER Visits2,4 $ 36 M Physician Visits2,4,6 1.36M Infections1 $ 315 M Hospital Visits2,4,5 $ 360 M Deaths3,7 Values represent estimated US dollars in 2015. Based on currently available literature, additional eco
Slide 97: US Vaccine Comparator Prices Range from ~$30 to $750
US Vaccine Comparator Prices Range from ~$30 to $750 Indicating Market Support for Pricing in this Range Average non‐discounted price for course† of comparator vaccines by patient segment 400 $345 AWP* ($) for full course – 2015 300 $38/dose $187 200 $176 $750/course $137 100 0 Maternal Pediatric Ol
Slide 98: The Commercial Strategy Relies on Reaching Across Key Stakeholders
The Commercial Strategy Relies on Reaching Across Key Stakeholders Who Influence Treatment Decisions U.S. Launch Campaign Policy Support timely, evidence‐based policy recommendations and guidelines encouraging appropriate patient access Product The first and only RSV vaccine, with demonstrated effic
Slide 99: Building Towards Commercialization
Building Towards Commercialization P2 Data P3 P3 Data BLA License ACIP Launch Disease awareness Marketing Provider target market Brand strategy KOL development Publication planning Medical Affairs Data generation strategy Provider education Payer research Align advocates and medical associations Mar
Slide 100: Looking at RSV in Our Patient Segments
Looking at RSV in Our Patient Segments Adults with compromised immune systems and Infants have immature immune systems those 60 and older are also at increased risk of and are vulnerable to infection severe disease There are 2.5 million RSV infections in older There are 1.4 million RSV infections in
Slide 101: Summary
Summary RSV is a significant disease, comparable to influenza and pneumonia The first and only RSV vaccine, with demonstrated efficacy and safety, that reduces symptomatic RSV and RSV associated with difficulty breathing Worldwide RSV F Vaccine revenue opportunity estimated to be $6‐8B per year 101
Slide 102: Investment Thesis
Investment Thesis Novavax Vaccine Platform • Recombinant nanoparticle technology induces robust immunity • Matrix‐M™ adjuvant increases magnitude and quality of immune response Clinical Development Programs • RSV: Older adults, infants via maternal immunization, pediatrics • Seasonal & Pandemic Infl