Novavax, Inc. · NASDAQ:NVAX
Novavax — RSV Vaccines for the World (October 2013)
33 slides from Novavax's conference presentation, October 2013
Slide 1: Maternal Immunization with the RSV F Nanoparticle Vaccine On Behalf of Young Infants
Maternal Immunization with the RSV F Nanoparticle Vaccine On Behalf of Young Infants Gregory M. Glenn M.D. RSV Vaccines for the World Porto, Portugal October 2013 1 www.novavax.com
Slide 2: Pediatric Respiratory Syncytial Virus (RSV)
Pediatric Respiratory Syncytial Virus (RSV) Who is the addressable population? What are the clinical plans/TPP for these populations? What is the most rational approach? 2
Slide 3: US RSV Hospitalization Rates in Children <2 years of age
US RSV Hospitalization Rates in Children <2years of age Age in Months Figure 1. Numbers of hospitalizations by years (left) and by months (right). Data from the National Hospital Discharge Survey, 2005-9. 3
Slide 4: Maternal Transfer of Antibodies
Maternal Transfer of Antibodies • Active transport of mother’s antibodies into baby’s circulation ‒ Mother’s antibodies from past infections or immunization are actively concentrated ‒ Begins at 20th week of gestation. ‒ At full term baby has >100% of mother’s antibody levels. Antibody Mother’s Bloo
Slide 5: Peak Antibody Concentration/Gestational Age
Peak Antibody Concentration/Gestational Age 5
Slide 6: Correlation of Maternal Antibodies with Cord Blood Antibodies
Correlation of Maternal Antibodies with Cord Blood Antibodies 6
Slide 7: RSV is a Constantly Changing Virus
RSV is a Constantly Changing Virus Budding RSV Virus Changes mostly occur in one of the key surface glycoproteins: the G protein The Fusion protein is highly Frequency of Amino Acid Changes conserved Site II on the Fusion protein is the target of palivizumab 7
Slide 8: F Protein Nanoparticle Vaccine Displays an Antibody Target Associated with Protective Efficacy
F Protein Nanoparticle Vaccine Displays an Antibody Target Associated with Protective Efficacy • The F protein Site II is targeted by palivizumab (Synagis) and motavizumab (Numax) • These monoclonal antibodies have been shown clinically to prevent RSV disease in multiple randomized clinical trials •
Slide 9: Serum Palivizumab Levels After Injection
Serum Palivizumab Levels After Injection Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia SÁEZ-LLORENS, XAVIER; CASTAÑO, ELIZABETH; NULL, DONALD; STEICHEN, JEAN; SÁNCHEZ, PABL
Slide 10: Efficacy in Term Infants: Effects of Site II Binding by Monoclonal Antibodies (Motavizumab)
Efficacy in Term Infants: Effects of Site II Binding by Monoclonal Antibodies (Motavizumab) 10
Slide 11: RSV Vaccine: Target Populations
RSV Vaccine: Target Populations Plan Needed for each population Young infants via Infants and Elderly Maternal Immunization Children 11
Slide 12: RSV Vaccine: Target Populations
RSV Vaccine: Target Populations Data in the target population Young infants via Infants and Elderly Maternal Immunization Children 12
Slide 13: RSV Vaccine - Summary of Completed Clinical Studies
RSV Vaccine - Summary of Completed Clinical Studies • Study 101: Safety and Immunogenicity in healthy adults complete ‒ Observed robust immune response, palivizumab/neutralizing antibodies (n=120) • Study M201: Safety and Immunogenicity, women of childbearing age ‒ Confirmation of safety and immunog
Slide 14: Principal Immunologic Findings
Principal Immunologic Findings • Populations with decades of repeat RSV infections develop neutralizing antibodies, but low to no palivizumab binding antibodies ‒ Explains limited effectiveness of immunity from natural infection? • The Novavax recombinant F nanoparticle vaccine induces robust immuni
Slide 15: M201-Women of Childbearing Age Towards Maternal Immunization
M201-Women of Childbearing Age Towards Maternal Immunization Young infants via Maternal Immunization 15
Slide 16: Phase II Randomized, Observer-Blinded, Placebo-Controlled, Dose-Ranging Study (M201)
A Phase II Randomized, Observer-Blinded, Placebo-Controlled, Dose-Ranging Study to Evaluate the Immunogenicity and Safety of an RSV F Protein Nanoparticle Vaccine, with or without Aluminum, in Healthy Women of Child-Bearing Age: M201 • Randomized, observer-blind, placebo controlled, multi-centered •
Slide 17: Demography, Safety Summary
Demography, Safety Summary • All female, mean age ~26 y/o, ~50% >26 years old, 38-54% with school-age children • Safety results of Phase II are generally confirmatory of phase I. ‒ Principal finding is mild-moderate injection site pain in 60-80% of aluminum-adjuvanted vaccinees, 35-65% of unadjuvant
Slide 18: Primary Immunogenicity Endpoint: Anti F IgG to Day 56
Primary Immunogenicity Endpoint: Anti F IgG to Day 56 • Fold Rise to day 56 18
Slide 19: Primary Immunogenicity Endpoint used Anti-F Data to Day 56
Primary Immunogenicity Endpoint used Anti-F Data to Day 56 • Q: Is there a positive effect of AlPO4? A: Yes Al vs. no Al within pooled Al vs. no Al within pooled 1-dose regimens 2-dose regimens Day 28 GMR (95% CI) 1.4 (1.1-1.7) 1.4 (1.1-1.7) p value 0.01 0.011 Day 56 GMR (95% CI) 1.4 (1.1-1.7) 1.7 (
Slide 20: Palivizumab-Competitive ELISA
Palivizumab-Competitive ELISA Labeled Palivizumab Human Immune Sera Vaccine-induced antibodies compete with palivizumab for binding to Site II on the F Protein Measure validated by the cotton rat model 20
Slide 21: Concordance of Anti-F IgG vs. Palivizumab-Competitive Antibodies - Study M201
Concordance of Anti-F IgG vs. Palivizumab-Competitive Antibodies -Study M201 Anti-F IgG responses closely tied to palivizumab- like antibodies 21
Slide 22: Adjuvant Groups only: Day 28
Adjuvant Groups only: Day 28 22
Slide 23: Palivizumab Competing Antibodies by Groups
Palivizumab Competing Antibodies by Groups • 25-30µg/ml decreases the lung viral load in a cotton rat by 2 log2 • LLoQ 33µg/ml in this assay 23
Slide 24: Modeling the Effect of Palivizumab-like Antibodies via Maternal Immunization
Modeling the Effect of Palivizumab-like Antibodies via Maternal Immunization: Protection of infants to 5-6 months 24
Slide 25: GMT: RSV/A Responses
GMT: RSV/A Responses • Baylor College of Medicine Assay • Risk reduction for Hospitalization of ~25% at log2 6 Protective Level 25
Slide 26: GMR: RSV/A Responses
GMR: RSV/A Responses • Fold Rise 26
Slide 27: GMT: RSV/B Responses
GMT: RSV/B Responses • BCM assay 27
Slide 28: GMR: RSV/B Responses
GMR: RSV/B Responses • Fold rise 28
Slide 29: MNA: Day 28 Comparison of Un-adjuvented and Adjuvented
MNA: Day 28 Comparison of Un-adjuvented and Adjuvented by Reverse Cumulative Distributions • 1- and 2-dose groups are pooled (identical at Day 28). • 60 and 90µg groups are pooled to show overall impact of alum adjuvant at Day 28. • Peak GMT log2 10.0-10.5 • Rise in MN proportional to rise in pali-
Slide 30: Women with Lowest Baseline MN Titers Benefit the Most, and Show a Strong Adjuvant Effect
Women with Lowest Baseline MN Titers Benefit the Most, and Show a Strong Adjuvant Effect 30
Slide 31: Expected and Observed Effects of Palivizumab in Human Serum
Expected and Observed Effects of Palivizumab in Human Serum-from Glenn et al, Vaccine, 2012 Impact of Exogenous Palivizumab on Human Adult Serum MN Titers Adult sera with high baseline titers consistent with baselines in this study show only modest fold- increases in MN activity despite adding high
Slide 32: Highlights of the Clinical Data to Date
Highlights of the Clinical Data to Date • The RSV F nanoparticle is immunogenic ‒ RSV F IgG that is in concordance with high affinity antibodies ‒ Palivizumab-like antibodies in excess of levels historically associated with protection in randomized clinical trials ‒ Neutralizing antibodies, rising c
Slide 33: RSV Vaccine - Planned Activities
RSV Vaccine - Planned Activities • M202 dose confirmation in women of childbearing age ‒ FSI Q4 2013-study underway ‒ Expanded safety data to support first pregnancy study ‒ Formulation-alum dose finding and confirmation ‒ Detailed antibody kinetics • M203 dose confirmation in 3rd trimester women (2