Novavax, Inc. · NASDAQ:NVAX
Novavax — World Vaccine Congress 2019
40 slides from Novavax's conference presentation, Apr 18, 2019
Slide 1: Phase 3 and beyond: The RSV F nanoparticle vaccine for infants via maternal immunization
Phase 3 and beyond: The RSV F nanoparticle vaccine for infants via maternal immunization Presentation at World Vaccine Congress April 16, 2019
Slide 2: Agenda
• RSV disease burden in infants • ResVax - the RSV prefusogenic F nanoparticle v accine • Structure • Antigenicity • Immunogenicity • Prepare trial - A randomized b linded placebo controlled trial in the context of maternal immunization • Trial design and conduct • Efficacy • Safety • Immunogenicity
Slide 3: Maternal immunization for the prevention of RSV disease in infants: The thesis
3 Maternal immunization for the prevention of RSV disease in infants: The thesis 1. U.S. FDA. Vaccines for Use During Pregnancy to Protect Young Infants from Disease – FDA Update. Available at https://www.fda.gov /aboutfda/transparency/basics/ucm508553.htm. Immunization during pregnancy has emerged
Slide 4: Respiratory syncytial virus: largest unmet need for a vaccine-preventable disease
4 Respiratory syncytial virus Largest unmet need for a vaccine - preventable disease Leading cause of hospitalizations in infants in the U.S., especially in the first 6 months of life 1 Leading cause of death in children under one year of age worldwide 2 # 2 # 1 1. Leader S. J Pediatr . 2003;143:S12
Slide 5: Timing of RSV hospitalizations in infants
5 Timing of RSV hospitalizations in infants 1. Shi T/Nair H. Lancet. 2017/Sep2;390:946 69% of infants <1 year contract RSV 77% of these RSV infections occur before 6 months of age medical interventions 400,000 of infants < 6 months are admitted to the hospital 2 - 4% 1 Adapted from Hall Average Age
Slide 6: ResVax – the RSV prefusogenic F nanoparticle vaccine
ResVax – the RSV p refusogenic F nanoparticle vaccine Prefusogenic F in a s tructured nanoparticle
Slide 7: Structure and antigenicity of the fusion (F) protein evolves during infections
7 Structure and antigenicity of the fusion (F) protein , e volves during infections Site A Site B p27 F-Protein Prefusogenic F Postfusion FPrefusion F RSV Macropinocytes RSV F cleavage RSV F virus –cell membrane fusion RSV RNA FO Precursor Prefusogenic F F2=F1: P27 Prefusion F F2=F1 Post - fusion F
Slide 8: Novavax RSV F vaccine genetic modifications: Stable Prefusogenic F
Novavax RSV F v accine genetic modifications : Stable Prefusogenic F 1. Mutation furin site B • Stabilize RSV F as prefusogenic • Prevent formation of metastable prefusion F 2. Deletion 10aa fusion peptide • Increase yields • Minimize aggregation furin A furin B RSV Prefusogenic F NNR ARR -- p27 --
Slide 9: ResVax is a defined nanoparticle
9 ResVax is a defined nanoparticle • RSV F trimers are arranged around a core of PS80 • The nanoparticle forms in a stable colloidal system • On average there are 5 RSV prefusogenic F trimers per nanoparticle PS80
Slide 10: RSV prefusogenic F nanoparticle thermostability (DSC)
10 RSV prefusogenic F nanoparticle thermostability (DSC) RSV prefusion F (metastable) Prefusion F Tm = 52.5 ° C Prefusogenic sF Tm = 93.1 ° C Prefusogenic F Tm = 92.1 ° C Differential scanning colorimeter (DSC) 1. RSV prefusogenic F Tm = 92 – 100 ° C 2. RSV prefusogenic sF Tm = 93 – 100 ° C 3. RSV p
Slide 11: Binding of mAbs to RSV F prefusogenic, prefusion and postfusion epitopes
Binding of mAbs to RSV F p refusogenic , prefusion and postfusion epitopes 11 Graham BS, et al adapted from Current Opinion Virology 2017 Prefusogenic F p27 Ø VIII II IV Prefusion & Postfusion F Prefusion F only Antigenic Site Monoclonal Antibody Prefusogenic F Vaccine Prefusion F SCTM Postfusion F
Slide 12: M203: antibodies induced in women are efficiently adsorbed by RSV prefusion F
12 M203: RSV F nanoparticle v accine antibodies induced in women are efficiently adsorbed by RSV prefusion F
Slide 13: Poly-epitopic immune responses: competitive antibodies transferred mother to infant
S c r e e n i n g M o t h e r D 1 4 - M o t h e r D e l i v e r y M o t h e r I n f a n t C o r d D 1 4 - I n f a n t D 6 0 - I n f a n t 0 50 100 150 200 250 300 C A E ( g / m l ) S c r e e n i n g M o t h e r D 1 4 - M o t h e r D e l i v e r y M o t h e r I n f a n t C o r d D 1 4 - I n f a n t
Slide 14: The Prepare trial
The Prepare trial - A r andomized blinded placebo controlled trial in the context of maternal immunization
Slide 15: Gratitude to the 4,636 pregnant women who volunteered
15 The investigators are grateful to the 4,636 pregnant women across the globe who volunteered for this study Prevention of RSV disease in infants via maternal immunization
Slide 16: Prepare trial design and objective
Determine the efficacy of maternal immunization with the RSV F vaccine against medically significant symptomatic RSV lower respiratory tract infection (LRTI) through 90, 120, 150 and 180 days of life in infants. 16 Design Randomized, Observer - Blind, Placebo - Controlled Number of Participants • 4,
Slide 17: Participating countries
Participating countries Multi - year global trial Enrollment occurred at 87 sites in 11 countries 4,636 women volunteers in their third trimester of pregnancy enrolled 17
Slide 18: Endpoints
• Primary endpoint (site only data) • Medically - significant RSV LRTI • RSV detected by RT - PCR and • At least one manifestation of LRTI , and • At least one of the following: • SpO2 <95 or, • Tachypnea respiratory rate ≥70 bpm in infants 0 to 59 d or ≥60 bpm in infants ≥60 d • Secondary endpoints
Slide 19: Expected hierarchy of attack rates by severity
19 We observed the expected hierarchy of attack rates by severity 15.5% 13.6% 6.1% 3.9% 3.8% 2.2% Infections LRTI LRTI w/ hypoxemia or tachypnea Primary endpoint LRTI Hospitalization Severe hypoxemia RSV attack rates 1 1. Expanded data from sites and hospitalizations, through 90 days, * LB 95%CI >0
Slide 20: Expectation for relative efficacy against RSV endpoints
20 What was our expectation for relative efficacy against the RSV infections/endpoints ? 15.5% 13.6% 6.1% 2.2% HIGH LOW Infections LRTI Primary endpoint LRTI Hospitalization Severe hypoxemia 3.9% 3.8% RSV attack rates 1 Expected vaccine efficacy rates 1. Expanded data from sites and hospitalizations
Slide 21: A hierarchy of efficacy by severity of disease
21 A hierarchy of efficacy by severity of disease 15.5% 13.6% 6.1% 3.9% 3.8% 2.2% 59.6%* 11% Observed vaccine efficacy rates Infections LRTI Primary endpoint LRTI Hospitalization Severe hypoxemia 15% 19% 40.9%* 41.7%* RSV attack rates 1 1. Expanded data from sites and hospitalizations, through 90 da
Slide 22: Consistent patterns of RSV disease and efficacy in M301
22 Consistent patterns of RSV disease and efficacy in M301 15.5% 13.6% 6.1% 3.9% 3.8% 2.2% 59.6%* 11% Observed vaccine efficacy rates Infections LRTI Primary endpoint LRTI Hospitalization Severe hypoxemia 15% 19% 40.9%* 41.7%* 27.8%* 46.0%* Vaccine efficacy for all - cause respiratory events RSV att
Slide 23: Summary of key efficacy findings: per protocol population
Summary of key efficacy findings: Per protocol population Efficacy (%) (97.52%CI and 95%CI for MS RSV LRTI primary endpoint, all others 95%CI) Placebo, Vaccine cases MS LRTI LRTI hospitalizations LRTI w/ severe hypoxemia Primary and secondary RSV + w/ Site data through 90 days 39.4 ( - 1, 63.7) 1 (5
Slide 24: Summary of key efficacy findings: per protocol population
Summary of key efficacy findings: Per protocol population Efficacy (%) (97.52%CI and 95%CI for MS RSV LRTI primary endpoint, all others 95%CI) Placebo, Vaccine cases MS LRTI LRTI hospitalizations LRTI w/ severe hypoxemia Primary and secondary RSV + w/ Site data through 90 days 39.4 ( - 1, 63.7) 1 (5
Slide 25: Summary of key efficacy findings: per protocol population
Summary of key efficacy findings: Per protocol population Efficacy (%) (97.52%CI and 95%CI for MS RSV LRTI primary endpoint, all others 95%CI) Placebo, Vaccine cases MS LRTI LRTI hospitalizations LRTI w/ severe hypoxemia Primary and secondary RSV + w/ Site data through 90 days 39.4 ( - 1, 63.7) 1 (5
Slide 26: All-cause exploratory endpoints: Durable effect
All - cause exploratory endpoints: Durable effect Endpoints using the same definitions, LRTI with severe hypoxemia, and LRTI hospitalization, but without a requirement for RSV o Benefit of the vaccine on high impact outcomes present at day 90, through 6 months after vaccination. o Additional increme
Slide 27: Framing the all-cause findings
• The effect of the pneumococcal vaccine against all - cause LRTI hospitalization was 7 - 9% 1 , or against all - cause ‘clinical pneumonia’ was 4 - 7% 2,3 • By contrast , ResVax showed a 25% 5 reduction in all hospitalizations with LRTI signs or symptoms constitutes a major benefit of a vaccine • S
Slide 28: Top-line safety
Top - line s afety
Slide 29: Safety summary: maternal subjects
Safety summary • Solicited reactogenicity reported in 57% of vaccinees vs. 41.3% in placebo group • Primary driver are injection site pain and swelling, but <1% severe and <1% persists beyond 7 days • Minimal difference in systemic reactogenicity , no increase in fever in the 7 days post - treatment
Slide 30: Safety summary: infants
Safety Summary • 98.7% placebo recipients and 98.8% vaccinees delivered live infants: • 6.1% of placebo infants and 5.8% of vaccine group infants delivered at < 37 weeks • 1 and 5 minute APGARS are essentially identical between treatment groups • No significant difference in rates of any peri - part
Slide 31: Immune responses
Immune responses 31
Slide 32: Palivizumab-competitive antibodies: mothers and infants
Palivizumab - competitive antibodies (PCA) through Day 180 : Mothers and infants Cord serum/maternal serum 1.04 (1.06, 1.02) T 1/2 = 49.1 days in active vaccine infants Seroresponse rates in vaccinees = 99.4% 4 - fold rise in vaccines = 88.1% 32
Slide 33: Anti-F IgG antibodies: mothers and infants
Anti - F IgG antibodies through Day 180 : Mothers and infants Cord serum/maternal serum 1.17 (1.19, 1.14) T 1/2 = 38.3 days in active vaccine infants Seroresponse rates in vaccinees = 98.3% 4 - fold rise in vaccinees = 91.8% 33
Slide 34: RSV A and RSV B microneutralization: mothers and infants
RSVA and RSV/B microneutralization * (Seasons 1 and 2 only): Mothers and infants *MN data are normalized to international RSV/A standard. Day 14 values and resultant fold - rise are based on a subset, baseline and delivery are a full population. 34
Slide 35: Potential public health benefit of ResVax
Potential public health benefit of ResVax
Slide 36: Vaccine preventable disease incidence per 100,000 child months
Vaccine preventable disease incidence (VPDI) per 100,000 child months 36
Slide 37: Conclusions / next steps
• The RSV F prefusogenic vaccine is a discrete, stable, well - characterized nanoparticle • Induces poly - epitopic responses characterized by high affinity, neutralizing antibodies • Although based on an RSV A virus sequence, the vaccine protects against RSV A and B infections, likely driven by res
Slide 38: Conclusions / next steps
• The consistency of effect and totality of the data indicate that the vaccine has potential to protect infants against the most severe manifestations of RSV infection with major effects on infant health • Geographic inhomogeneity in efficacy was noted in the trial due to small subject numbers/event
Slide 39: Thanks to
Thanks to: • Our conscientious advisors and investigators and clinical site staff around the world; and of course the subjects themselves • The Novavax manufacturing, QA, regulatory, clinical operations, biostatistics, pharmacovigilance and clinical immunology teams • The DSMB members • Baylor Colle
Slide 40: Creating Tomo REE
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