Novavax, Inc. · NASDAQ:NVAX
Novavax — Investor Day (September 2015)
102 slides from Novavax's investor day presentation, Sep 29, 2015
Slide 1: Analyst & Investor Meeting September 2015
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 3 • Welcome and Corporate Overview 9:00 – 9:10 a.m. • Nanoparticle Technology: A New Paradigm 9:10 – 9:30 a.m. • Seasonal Influenza Clinical Update 9:30 – 9:40 a.m. • RSV Burden of Disease in Older Adults 9:40 – 9:55 a.m. • RSV Clinical Update • Older Adults • Maternal Phase II Results • Pedi
Slide 4: Breaking News
Breaking News NOVAVAX Novavax Announces 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, 2015—Novavax, Inc., (Nasdaq: NV
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 company
Slide 7: Investment Thesis
Investment Thesis 7 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
Slide 8: Respiratory Product Pipeline
Ebola + Matrix - M TM Combination Respiratory Product Pipeline Quadrivalent Seasonal Pandemic (H7N9 + Matrix - M TM ) Infants (Maternal Immunization ) Pediatrics (6 mos – 6 yrs) Older Adults (60+) Preclinical Phase 1 Phase 2 Phase 3 RSV Influenza New Product Opportunities Funding Support 8
Slide 9: Recent Accomplishments
Ebola + Matrix - M TM Recent Accomplishments Quadrivalent Seasonal Pandemic (H7N9 + Matrix - M TM ) Infants (Maternal Immunization ) Pediatrics (6 mos – 6 yrs) Older Adults (60 +) Q3 - 14 Q4 - 14 Q1 - 15 RSV Influenza New Product Opportunities Phase 1/2 Phase 1 Phase 1 Phase 2 Phase 2 Phase 2 9 Q2 -
Slide 10: Projected Highlights: 2016
Projected Highlights: 2016 10 Initiation of: Phase 3 pivotal RSV F Vaccine in Older Adults • D ata 4 th 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 •
Slide 11: Nanoparticle Platform Technology: A New Paradigm
Nanoparticle Platform Technology A New Paradigm 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 13 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
Slide 14: Novavax Nanoparticle Technology
HA trimers NA tetramers No genetic material M1 Matrix Protein Novavax Nanoparticle Technology Recombinant Nanoparticles : RSV F & Ebola GP Hydrophilic head of protein trimers Hydrophobic tail of protein trimers Virus - Like Particles (VLP) Seasonal & Pandemic Influenza Influenza VLPs • Correct 3D •
Slide 15: RSV F Hidden Neutralizing Epitopes
RSV F Hidden N eutralizing E pitopes 15 1 Beeler et al , Neutralization Epitopes of the F Glycoprotein of Respiratory Syncytial Virus: Effect of Mutation upon Fusion Function . J Virol , 1989 Competitive ELISA RSV F Epitope Sites I, II and IV Phase 2 Trial, Women of Childbearing Age, F 120µg + AlPO
Slide 16: Ebola GP Hidden Neutralizing Epitopes
Ebola GP Hidden N eutralizing E pitopes 16 • 13C6, KZ52 ( ZMapp ™) and other GP neutralizing epitopes are hidden • NVAX Ebola GP vaccine + Matrix - M induces antibodies against hidden epitopes • 100% protective in NHP 1 JE Lee, Erica Saphire et al. Nature 454: 177 - 182 (2008). 8 16 32 64 128 256 51
Slide 17: Matrix-M Adjuvant Enhances and Broadens Responses to Epitopes
Matrix - M™ Adjuvant Enhances and Broadens Responses to Epitopes 1 17 1 Novavax/FDA . Chung, et al. Vaccine 33 (2015) 3953 - 3962 Red: Exposed epitopes Green: Buried epitopes Non - adjuvanted H7N9 Vaccine Adjuvanted H7N9 Vaccine Matrix - M is a nanoparticle composed of saponins , cholesterol, and li
Slide 18: Novavax Nanoparticle Vaccines: Proving Effective
Ebola GP Vaccine – Non - human Primates Protective Efficacy = 100% Ebola lethal challenge RSV F Vaccine – Older Adults Protective Efficacy = 45% all RSV Protective Efficacy = 64% more severe RSV 18 Novavax Nanoparticle Vaccines : Proving Effective 5µg Ebola GP Vaccine (n=11) Placebo (n=5) Proportion
Slide 19: Summary: New Nanoparticle Vaccine Paradigm
Summary: New Nanoparticle Vaccine Paradigm 19 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 criti
Slide 20: Nanoparticle Technology Applied to Emerging Threats
Nanoparticle Technology Applied to Emerging Threats H7N9 Influenza Ebola 20
Slide 21: H7N9 Vaccine Phase 2 Clinical Trial
H 7N9 Vaccine Phase 2 Clinical Trial Trial Overview • Phase 2 • 610 adults • Monovalent avian influenza vaccine: • H7N9 • Matrix - M adjuvant Objectives • Evaluate HAI and NAI antibody responses • Evaluate adjuvant effect of Matrix - M with H7N9 • Evaluate safety of Matrix - M formulation Outcomes •
Slide 22: Matrix-M Enables H7N9 HAI Responses
Matrix - M Enables H7N9 HAI Responses 22 • 4 to 5 - fold increase in HAI titer • Dose - sparing H7N9 HAI GMT (95% CI)
Slide 23: H7N9 NAI Responses
H7N9 NAI Responses 23 H7N9 NAI GMT (95% CI)
Slide 24: Ebola GP Vaccine Phase 1 Clinical Trial
Ebola GP Vaccine Phase 1 Clinical Trial 24 Trial Overview • Phase 1 • 230 adults • Makona strain glycoprotein : first vaccine candidate to 2014 Ebola strain • Matrix - M adjuvant Objectives • Evaluate antibody responses to GP and whole Zaire Ebola virus • Evaluate adjuvant effect of Matrix - M with
Slide 25: Ebola GP IgG ELISA
50 500 5000 50000 0 5 10 15 20 25 30 35 40 Geometric Mean ELISA Units Study Days Novavax Makona GP ELISA Ebola GP IgG ELISA ( Makona Strain) 25 • 2 doses of vaccine with adjuvant over 100 - fold more immunogenic • Dose - sparing at 6.5µg Placebo 6.5 µg, 2 doses, unadjuvanted 6.5 µg, 1 dose w/Matrix
Slide 26: Nanoparticle Technology for Emerging Viruses
Nanoparticle Technology for Emerging Viruses 26 • Demonstrated in H7N9, Ebola and MERS • Adaptable to new threats on a short timeline • Rapid manufacturing process • Thermostable at 2 - 8 º C • Matrix - M enables dose – sparing and protective responses: ▪ Enhanced immunogenicity for “difficult” anti
Slide 27: Quadrivalent Seasonal Influenza Vaccine Clinical Update
Quadrivalent Seasonal Influenza Vaccine Clinical Update 27
Slide 28: Quadrivalent Seasonal Influenza Phase 2 Clinical Trial
Trial Overview • Phase 2 • 400 adults • Quadrivalent seasonal vaccine; 4 strains: • A/California/04/09 • A/Victoria/361/11 • B/Massachusetts/2/12 • B/Brisbane/60/08 • Control: licensed trivalent vaccine • Serology: Days 0 and 21 Objectives • Evaluate immunogenicity • Demonstrate that immunogenicity
Slide 29: Quadrivalent Seasonal Influenza Vaccine - HAI
Quadrivalent Seasonal Influenza Vaccine - HAI 29 • At 15µg dose, all 4 strains met CBER criteria for seroprotection and seroconversion • Competitive with licensed trivalent seasonal influenza vaccine
Slide 30: Summary: Seasonal and Pandemic Influenza Programs
Summary: Seasonal and Pandemic Influenza Programs 30 Seasonal Influenza • Produced & tested every WHO/FDA recommended strain since 2009 • Demonstrated rapid adaptability to produce late - emerging strain • Demonstrated immunogenicity in the clinic that meets the CEBR criteria Pandemic Influenza • Ac
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 hom
Slide 34: RSV Disease Burden in the Elderly
RSV Disease Burden in the Elderly ( ≥ 65 yrs ) – U.S. 34 CDC , Falsey 2005 extrapolated to 2015 Census Population, Falsey 1995, Widmer , 2012 & 2014 Deaths 14,000 ER (151,801) + Hospital Admissions (203,612) = ˜355,400 (14.8% of RSV infections) Physician Office Visits ~497,280 (17% of RSV infections
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 35 Branche and Falsey . Drugs Aging, 2015. Sundaram et al. CID, 2014. Fals
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 36 Branche and Falsey . Drugs Aging, 2015. Mullooly et al.
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 39 Falsey et al. NEJM, 2005 and Volling et al. BMC Infect Dis, 2014
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 in Adults 65+
Burden of Disease for RSV, Influenza, and Pneumococcal Pneumonia in Adults 65 and Older in U.S. 41 *Average of 3 past seasons, 2010 - 2013; includes vaccine averted cases CDC, Falsey et al. NEJM, 2005; Falsey et al. JID, 1995; MMWR 13 Dec 2013; Huang, et al. Vaccine, 2011; Jackson, et al. Clin Infec
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 43 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 immunogenic
Slide 44: RSV Vaccine Target Populations
RSV Vaccine Target Populations 44 Infants via Maternal Immunization Infants <6 months Older Adults Healthy individuals 60+ years and high risk adults Pediatrics Children >6 months - 5 years
Slide 45: RSV F-Protein Presents Multiple Conserved Sites
1 Beeler et al , Neutralization Epitopes of the F Glycoprotein of Respiratory Syncytial Virus: Effect of Mutation upon Fusion Function . J Virol , 1989 RSV F - Protein Presents Multiple Conserved Sites Site II Site IV Site I RSV Surface Proteins • G protein: Variable • F protein: Conserved Antigenic
Slide 46: Phase 2 RSV F Vaccine Clinical Trial in Older Adults
Phase 2 RSV F Vaccine Clinical Trial in Older Adults 46 One of the largest prospective epidemiologic RSV trials conducted older adults Trial Overview • Phase 2 trial randomized, observer - blinded • 10 trial sites in U.S. • 1,600 older adults, ages 60+ • 135 µg dose without adjuvant Goals • Evaluate
Slide 47: P2 Older Adults: Study Objectives
Primary • Epidemiology trial • Describe the incidence of all symptomatic respiratory illnesses due to RSV, medically attended illness, and hospitalization • Examine the amplitude and duration of anti - F IgG antibody responses • Evaluate safety and tolerability of the vaccine Secondary • Evaluate am
Slide 48: P2 Older Adults: Study Population and Demographics
P2 Older Adults: Study Population and Demographics 48 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
Slide 49: P2 Older Adults: RSV Epidemiology Trial Results
P2 Older Adults: RSV Epidemiology Trial Results 49 1 Interim analysis indicated 95%; 4 subjects recategorized as RSV + URI only 4.9% of placebo with symptomatic RSV infections • Pharyngitis , nasal congestion, cough, wheezing, shortness of breath or increased sputum production • Defines the RSV atta
Slide 50: P2 Older Adults: Anti-F Antibody Response
P2 Older Adults: Anti - F Antibody Response 50 • Durable, 4.8 - fold 1 increase in anti - F IgG response • Seroresponse in >93% of subjects 2 1 geometric mean rise relative to Day 0 2 % of group with EU >95 th percentile of the placebo group on that day 0 1000 2000 3000 4000 5000 6000 0 10 20 30 40
Slide 51: P2 Older Adults: PCA Response
P2 Older Adults: PCA Response 51 • Durable, 5.2 - fold 1 increase in PCA response • Seroresponse in >96% of subjects 2 1 geometric mean rise relative to Day 0 2 % of group with EU >95 th percentile of the placebo group on that day Days PCA GMC 1 (µg/mL) 0 20 40 60 80 100 120 0 10 20 30 40 50 60 135
Slide 52: P2 Older Adults: RSV A and B Microneutralizing Antibodies
P2 Older Adults: RSV A and B Microneutralizing Antibodies 52 0.9 1.1 1.3 1.5 1.7 1.9 2.1 RSV F Vaccine RSV/A Placebo RSV/A RSV F Vaccine RSV/A Placebo RSV/A RSV F Vaccine RSV/B Placebo RSV/B RSV F Vaccine RSV/B Placebo RSV/B Day 28 Day 56 Day 28 Day 56 Geometric Mean Rise in Neutralizing Titers (bas
Slide 53: P2 Older Adults: Early and Durable Protection from RSV Infection
P2 Older Adults: Early and Durable Protection from RSV Infection 53 RT - PCR confirmed RSV Events Product - Limit Survival Estimate Log - Rank test or equality over strata; p=0.039 Proportion of Group With No RSV Infection Time to RSV Onset (days) 0.90 0.92 0.94 0.96 0.98 1.00 0 50 100 150 200 135 m
Slide 54: P2 Older Adults: Relative Risk and Efficacy Estimates
P2 Older Adults: Relative Risk and Efficacy Estimates 54 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
Slide 55: P2 Older Adults: Analysis of RSV LRTI and Difficulty Breathing
P2 Older Adults: Analysis of RSV LRTI and Difficulty Breathing 55 *LRTI: Symptoms include cough, increase or change in sputum, wheezing, shortness of breath; LRTI Signs: include increased respiratory rate Number of Symptoms and Signs Reported* Number of vaccine vs placebo subjects Vaccine Efficacy P
Slide 56: RSV Older Adults Data Results Analogous to Prevnar
RSV Older Adults Data Results Analogous to Prevnar 13 56 1 Primary endpoint 2 Secondary endpoint *Included in label claim Bonten , M.J.M. et al. Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults. NEJM , 2015; 372:1114 - 1125 Endpoint and Analysis Episodes PCV13 (N = 42,256) P
Slide 57: Efficacy of Licensed Influenza Vaccines
Efficacy of Licensed Influenza Vaccines 57 • Novavax RSV F Vaccine efficacy is similar to or better than a number of respiratory vaccines 1,2,3 • Vaccine effectiveness is lower in older adults Season Vaccine Effectiveness in All Ages Vaccine Effectiveness in Older Adults 2007 - 8 37% 37% 2009 - 10 5
Slide 58: RSV Older Adults: Lessons Learned
RSV Older Adults: Lessons Learned 58 • Well - conducted study • Attack rate in line with previously published data • MARI/hospitalizations logistics will be improved to enable data collection • F ollow - up with study nurse at - home visitations will be added to improve swabbing rates to capture ful
Slide 59: P2 Older Adults: Summary
P2 Older Adults: Summary 59 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 effectiv
Slide 60: RSV Older Adults: Next Steps
RSV Older Adults: Next Steps 60 *pending FDA approval Next Steps Manufacture and release product End of Phase 2 meeting Initiate Phase 2 Booster Study Initiate Phase 3 Phase 3 Trial Objectives Proposed endpoints* Primary: Prevent symptomatic RSV illness as indicated by patient reported outcomes Seco
Slide 61: Next Steps: Older Adults Phase 2 Booster Trial
Vaccine Vaccine Placebo Placebo Vaccine Placebo Next Steps: Older Adults Phase 2 Booster Trial 61 1,600 participants • Annual seasonal vaccine • Phase 2 older adult subjects provide a unique opportunity to demonstrate the need and desirability of a boost • Proposed trial endpoints will be similar to
Slide 62: RSV F Vaccine Phase 2 Clinical Trial to Protect Infants via Maternal Immunization
RSV F Vaccine Phase 2 Clinical Trial to Protect I nfants via Maternal I mmunization 62
Slide 63: RSV F Vaccine Maternal Immunization Highlights
RSV F Vaccine Maternal Immunization Highlights 63 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
Slide 64: P2 Maternal Immunization: Study Objectives
Primary • Mothers: Describe safety of the RSV F vaccine through delivery and 6 months post - delivery • Infants: Describe safety through their first year of life, including at least one RSV season Secondary • Mothers: Evaluate amplitude and duration of anti - F IgG, PCA and RSV A/B microneutralizing
Slide 65: P2 Maternal Immunization: Design and Protocol
P2 Maternal Immunization: Design and Protocol Treatments 65 • 120µg RSV F + 0.4mg aluminum phosphate • Randomization was stratified by age: • 18 to < 29 years and 29 to ≤40 years *Small difference in randomization is due to block randomization and low numbers per site Treatment Group Label RSV F Ant
Slide 66: P2 Maternal Immunization: Safety Follow-up
P2 Maternal Immunization: Safety Follow - up 66 *Passive and active follow - up for RSV disease began day 14 **An infant blood draw may have been obtained within 24 hours of birth if cord blood was not collected at delivery or the integrit y o f the sample was compromised . Infant participants were
Slide 67: P2 Maternal Immunization: Maternal Population and Demographics
P2 Maternal Immunization: Maternal Population and Demographics 67 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/m 2 ) 30 30
Slide 68: P2 Maternal Immunization: Safety Summary
P2 Maternal Immunization: Safety Summary 68 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 • T
Slide 69: P2 Maternal Participants: Anti-F IgG
Anti - F IgG GMEU 1 ( 95% CI ) Days 0 2000 4000 6000 8000 10000 12000 14000 0 14 Delivery Delivery + 35 P2 Maternal Participants: Anti - F IgG 69 1 geometric mean rise relative to Day 0 120 mg RSV F Vaccine + 0.4 mg AlPO 4 adjuvant Placebo
Slide 70: P2 Maternal Participants: PCA
P2 Maternal Participants: PCA 70 1 geometric mean rise relative to Day 0 0 50 100 150 200 250 300 350 0 14 Delivery Delivery + 35 120 mg RSV F Vaccine + 0.4 mg AlPO 4 adjuvant Placebo PCA GMC 1 ( 95% CI ) Days
Slide 71: P2 Maternal Participants: RSV A and B Microneutralizing Antibodies
P2 Maternal participants: RSV A and B Microneutralizing Antibodies 71 1 2 4 Active Placebo Active Placebo Active Placebo Active Placebo Active Placebo Active Placebo Day 14 post- vaccine Delivery Day 35 post- delivery Day 14 post- vaccine Delivery Day 35 post- delivery RSV/A RSV/B Geometric Mean Ris
Slide 72: P2 Infants: Time from Vaccination to Delivery Impacts Placental Antibody Transfer
P2 Infants: Time from Vaccination to Delivery (Days) Impacts Placental Antibody Transfer 72 Ad hoc analysis Excludes 1 mother/infant pair with delivery 5 days post - immunization, late pre - term delivery Cord Blood Titer/ Maternal Serum Titer Delivery < 30 days Post Vaccination Delivery > 30 days P
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 73 GA = gestational age Ad hoc analysis *Excludes 1 mother/infant pair with delivery 5 days post - immunization, late pre - term delivery Important Findings: • Maternal antibody peaks 14d after vaccination • Per
Slide 74: P2 Infants: Estimated RSV Antibody Half-life
P2 Infants: Estimated RSV Antibody Half - life 74 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)
Slide 75: P2 Maternal Immunization: RSV F Vaccine Elicits Additional Known Neutralizing Antibodies
P2 Maternal Immunization: RSV F Vaccine Elicits Additional Known Neutralizing Antibodies 75 1 maternal baseline GMTs were < 20 for all assays Beeler et al , Neutralization Epitopes of the F Glycoprotein of Respiratory Syncytial Virus: Effect of Mutation upon Fusion Function . J Virol , 1989 Delivery
Slide 76: P2 Maternal Immunization: Primary Objective Outcomes
P2 Maternal Immunization: Primary Objective Outcomes 76 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 - bein
Slide 77: P2 Maternal Immunization: Secondary Objective Outcomes
P2 Maternal Immunization: Secondary O bjective Outcomes 77 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
Slide 78: P2 Maternal Immunization: Next Steps
P2 Maternal Immunization: Next Steps 78 * Pending FDA approval Next Steps Manufacture and release product End of Phase 2 meeting Initiate Phase 3 trial 1Q16 Proposed endpoints* Primary: Prevention of RSV bronchiolitis with hypoxia Secondary : Prevention of severe RSV bronchiolitis with hypoxia Explo
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 80 Trial Overview • Phase 1 trial randomized, observer - blinded, dose - ranging study to evaluate safety and immunogenicity • Healthy participants >24 to < 72 months of age Status • Trial completed with smaller cohort due to onset of RSV season • Safety in
Slide 81: P1 Pediatrics: Study Objectives
P1 Pediatrics: Study Objectives 81 Primary • Accumulate safety data for the candidate vaccine formulations and regimens • Determine adjuvant effect of aluminum phosphate • Describe effect of formulations and regimens on serum anti - F IgG antibody responses Secondary • Describe immune responses to f
Slide 82: RSV Pediatrics: Phase 1 Recruited Subjects
RSV Pediatrics : Phase 1 Recruited Subjects 82 ++: 2 doses, with adjuvant; +: 1 dose, with adjuvant -- : 2 doses, without adjuvant, - : 1 dose, without adjuvant Population Placebo N =7 60µg ++ N=6 60µg + N=6 60µg - - N=6 60µg – N =7 ITT 7 (100%) 5 (83.3%) 6 (100%) 6 (100%) 7 (100%) Per protocol 3 (4
Slide 83: P1 Pediatrics: Safety Summary
P1 Pediatrics: Safety Summary 83 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
Slide 84: P1 Pediatrics: Anti-F IgG, Per Protocol
P1 Pediatrics: Anti - F IgG, Per Protocol 84 ++: 2 doses, with adjuvant; +: 1 dose, with adjuvant -- : 2 doses, without adjuvant, - : 1 dose, without adjuvant Anti - F IgG 60µg ++ N=4 60µg + N=5 60µg - - N=2 60µg – N=4 Placebo N=3 Baseline 689 1,236 1,789 1,853 1,318 Day 14 GMEU 21,563 15,417 14,039
Slide 85: P1 Pediatrics: PCA, Per Protocol
P1 Pediatrics : PCA, Per Protocol 85 ++: 2 doses, with adjuvant; +: 1 dose, with adjuvant -- : 2 doses, without adjuvant, - : 1 dose, without adjuvant PCA 60µg ++ N=4 60µg + N=5 60µg - - N=2 60µg – N=4 Placebo 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 - ris
Slide 86: P1 Pediatrics: RSV A Microneutralizing Antibodies Per Protocol
P1 Pediatrics : RSV A Microneutralizing Antibodies Per Protocol 86 1 2 4 8 16 32 60µg + Al x 2 60µg + Al x 1 60µg w/o Al x 2 60µg w/o Al x 1 Placebo 60µg + Al x 2 60µg + Al x 1 60µg w/o Al x 2 60µg w/o Al x 1 Placebo 60µg + Al x 2 60µg + Al x 1 60µg w/o Al x 2 60µg w/o Al x 1 Placebo Geometric Mean
Slide 87: P1 Pediatrics: RSV B Microneutralizing Antibodies Per Protocol
P1 Pediatrics : RSV B Microneutralizing Antibodies Per Protocol 87 1 2 4 8 16 32 60µg + Al x 2 60µg + Al x 1 60µg w/o Al x 2 60µg w/o Al x 1 Placebo 60µg + Al x 2 60µg + Al x 1 60µg w/o Al x 2 60µg w/o Al x 1 Placebo 60µg + Al x 2 60µg + Al x 1 60µg w/o Al x 2 60µg w/o Al x 1 Placebo Geometric Mean
Slide 88: RSV Pediatrics: Preliminary Conclusions
RSV Pediatrics: Preliminary Conclusions 88 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
Slide 89: Commercial Landscape
Slide 90: RSV F Vaccine Franchise
RSV F Vaccine Franchise Infants (Maternal Immunization ) Pediatrics (6 mos – 6 yrs) Older Adults (60+) Preclinical Phase 1 Phase 2 Phase 3 RSV Funding Support 90 TBD 2016 Activity
Slide 91: RSV Incidence and Burden in Major Markets
RSV Incidence and Burden in Major Markets 91 * Estimated value of life lost, future health implications and lost earnings; all estimates based on available epidemiology a nd health outcomes data US ~15 M Infections/Year ~$5 B Direct Cost Burden ~$32 B * Indirect Cost Burden EU5 (UK, Italy, France, S
Slide 92: The Target U.S. Segment for RSV Immunization
The Target U.S. Segment for RSV Immunization ~98M Individuals 92 Older adults ≥ 60 yrs U.S. population by target RSV patient segment (2014) Pregnancies ≥34 wks 90 80 70 60 50 40 30 20 10 0 3.7 5.9 12.0 11.5 64.8 Infant >6 - ≤24 mos Toddler >24 - ≤ 60 mos High risk 50 - 59 yrs Addressable population
Slide 93: Annual Burden of RSV Disease in Older Adults
Annual Burden of RSV Disease in Older Adults, 65 Years of Age and Older 93 Values represent estimated annual rates. 1 Falsey et al., NEJM 2005; 2 Widmer et al., Influ . Oth . Respir . Viruses 2014; 3 Thompson et al., JAMA 2003. ~177,000 (7%) Hospital Admissions 1 ~157,000 (6.2%) ER Visits 2 ~531,000
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 94 Values represent estimated US dollars in 2015. Based on currently available literature, additional economic evaluations ongoing. 1 Falsey et al., NEJM 2005; 2 Widmer et al., Influ . Oth . Respir . Viruses 2014; 3 Thompson et al
Slide 95: Annual Burden of RSV Disease in Infants
Annual Burden of RSV Disease in Infants 0 - 6 Months of Age 95 Values represent estimated annual rates. 1 Glezen et al., AJDC 1986; 2 Hall et al., NEJM 2009; 3 Thompson et al., JAMA 2003. ~33,400 (2.5%) Hospital Admissions 2 ~109,000 (8%) ER Visits 2 ~260,000 (19.1%) Physician Visits 2 1.36M (69%) I
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 96 Values represent estimated US dollars in 2015. Based on currently available literature, additional economic evaluations ongoing. 1 Glezen et al., AJDC 1986; 2 Hall et al., NEJM 2009; 3 Thompson et al., JAMA 2003
Slide 97: US Vaccine Comparator Prices Range from ~$30 to $750
$38/dose AWP* ($) for full course – 2015 400 300 200 100 0 Maternal Pediatric Older adult Average Recently launched ‡ $176 $137 $187 $345 US Vaccine C omparator P rices R ange from ~$30 to $750 Indicating Market Support for Pricing in this Range 97 Note: *AWP – average wholesale price. † Analogue ra
Slide 98: The Commercial Strategy Relies on Reaching Across Key Stakeholders
The Commercial Strategy Relies on Reaching Across Key Stakeholders Who Influence Treatment Decisions 98 U.S. Launch Campaign Policy Support timely, evidence - based policy recommendations and guidelines encouraging appropriate patient access Payer Proactive education to public and private payers dem
Slide 99: Building Towards Commercialization
Building Towards Commercialization 99 Develop training tool for Medical Affairs Training & Education Develop sales training materials Execute training Market Access Payer research Advocate for Medicare coverage Align advocates and medical associations Define provider strategy Medical Affairs Data ge
Slide 100: Looking at RSV in Our Patient Segments
Looking at RSV in Our Patient Segments 100 Adults with compromised immune systems and those 60 and older are also at increased risk of severe disease In the US, there are nearly 900,000 medical interventions every year for older adults with RSV disease Total cost burden in US older adults related to
Slide 101: Summary
The first and only RSV vaccine, with demonstrated efficacy and safety, that reduces symptomatic RSV and RSV associated with difficulty breathing Summary 101 Worldwide RSV F Vaccine revenue opportunity estimated to be $ 6 - 8B per year RSV is a significant disease, comparable to influenza and pneumon
Slide 102: Investment Thesis
Investment Thesis 102 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 & Pandemi