Novavax, Inc. · NASDAQ:NVAX
Novavax — Investor Day (July 2017)
49 slides from Novavax's investor day presentation, Jul 24, 2017
Slide 1: Positive Topline Data from Phase 2 Older Adult Trial and Path Forward for RSV F Vaccine Programs
Positive Topline Data from Phase ` 2 Older Adult Trial and Path Forward for RSV F Vaccine Programs Investor Slide Deck July 24, 2017
Slide 2: Safe Harbor Statement
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 forward- looking statements within the meaning of the Priva
Slide 3: Agenda
Agenda Introduction Stanley C. Erck President and CEO RSV F Vaccine for Older Adults Gregory M. Glenn, M.D. • Review of findings and clinical results President, Research and Development • Path forward Louis Fries, III, M.D. SVP, Chief Medical Officer RSV F Vaccine for Infants via Gregory M. Glenn, M
Slide 4: Thorough Review of Data from Older Adult Program Supports Continued Clinical Development
Thorough Review of Data from Older Adult Program Supports Continued Clinical Development We have learned: • RSV F Vaccine demonstrated evidence of efficacy in several trials • OA Phase 2 • Including in follow-up trial with repeat dosing over 2 seasons • IVM Program (2 seasons) • Primate Challenge Tr
Slide 5: RSV Vaccine Development Remains a Core Strength of Novavax
RSV Vaccine Development Remains a Core Strength of Novavax We remain the leader in RSV Vaccination Older Adults • Expect to conduct Phase 2 efficacy trial in higher risk groups, including COPD • COPD represents a very large market opportunity • Expand into all older adults Infants via Maternal Immun
Slide 6: Significant Developments in Influenza Program Support Entry into First Clinical Trial This Quarter
Significant Developments in Influenza Program Support Entry into First Clinical Trial This Quarter • Important new data in a challenge study comparing our candidate with Sanofi’s High Dose flu vaccine • Leading to a first clinical trial with our Matrix-M ™ adjuvanted recombinant nanoparticle flu vac
Slide 7: RSV Vaccine Construct Update
RSV Vaccine Construct ` Update Gregory M. Glenn, M.D.
Slide 8: The Novavax RSV F Vaccine Development Path
The Novavax RSV F Vaccine Development Path Clinical Vaccinology Approach: Following compelling clinical evidence to move to Phase 3 Clinical Signals: Stable RSV F Vaccine in Animal Model RSV-101: 1st Clinical Trial Pali, Mota, PFP, Infectious Immunity • Cotton rats protected from RSV (POC) • PCA and
Slide 9: Review of RSV F Vaccine Clinical Development Program for Older Adults
Review of RSV F Vaccine Clinical Development Program for Older Adults 2014/2015 2015/2016 2016/2017 E-201 E-202 E-205 Safety & Efficacy Repeat Dosing Adjuvant/Formulation E-301 (Resolve) Pivotal Efficacy 9
Slide 10: Outline of Findings
Outline of Findings RSV F Vaccine Construct • New insights into the vaccine responses confirm its potency • Preclinical and clinical data confirm its potential for protection Dosing and Adjuvantation (E-205) • Adjuvants and/or 2 dose regimens significantly improve multiple important measures of immu
Slide 11: F Protein Structure Evolves During Infection
F Protein Structure Evolves During Infection RSV Entry into Host Cells and the Fusion (F) Protein Processing Leads to an Activated F Protein, Membrane Fusion and Delivery of RSV RNA into the Cytoplasm RSV Macropinocytes RSV F cleavage RSV F virus–cell membrane fusion RSV RNA Prefusogenic F Prefusion
Slide 12: F Protein States Found in Nature: The Novavax RSV Vaccine is Similar to the Prefusogenic F
F Protein States Found in Nature: The Novavax RSV Vaccine is Similar to the Prefusogenic F S RSV F0 P F2 p27 FP F1 TM Pre-fusogenic F2 p27 FP F1 TM Prefusion & F2 FP F1 TM Postfusion Novavax’ F2 p27 FP FP F1 TM RSV Vaccine1 Deletions = Furin Cleavage sites 12 1Smith G et al. PLoS ONE. 2012;7(11):e50
Slide 13: All RSV F Vaccine Constructs are "Like" Constructs
All RSV F Vaccine Constructs are “Like” Constructs Novavax Stable Prefusogenic Vaccine F2 p27 FP F1 TM 574 Prefusion (NIH DS-Cav1) S155C S190F V207L S290C F2 FP F1 FF 513 Postfusion (NIH sF) F2 FP F1 513 13
Slide 14: Our Vaccine Construct is a Stable Prefusogenic RSV F Nanoparticle
Our Vaccine Construct is a Stable Prefusogenic RSV F Nanoparticle RSV F Vaccine Structure Prefusogenic F protein trimers 40nm protein/detergent nanoparticles Highly stable – resists denaturation and aggregation Phase 3 manufacturing process appropriate for commercialization RSV F Vaccine Act
Slide 15: Preclinical and Clinical Evidence of Vaccine Efficacy
Preclinical and Clinical Evidence of Vaccine Efficacy • Cotton rat protection against virus challenge including mutants that are resistant to mAb-induced resistant strains1,2 • Protection against challenge of infant baboons born to immunized mothers3 • Prevention of infection in young women in two s
Slide 16: Key References
Key References No. References Links 1 Smith G et al. PLoS ONE. 2012;7(11):e50852. PubMed 2 Raghunandan R et al. Vaccine. 2014;32(48):6485-92. PubMed Welliver R Sr. et al. Poster presented at: 54th 3 Interscience Conference on Antimicrobial Agents and Presentation Chemotherapy; Sept 2014; Washington,
Slide 17: E-205: Design and Results
` E-205: Design and Results Lou Fries III, M.D.
Slide 18: E-205 Evaluation of Adjuvants and Dose Regimens with RSV F Vaccine
E-205 Evaluation of Adjuvants and Dose Regimens with RSV F Vaccine Trial initiated in Jan 2017 in Australia When Topline serology data through Day 119 now available for most parameters (Day 56 for RSV MN) 300 healthy older adults Design Randomized, observer-blinded, placebo-controlled, evalu
Slide 19: Why Pursue a Quantitatively Better Immune Response?
Why Pursue a Quantitatively Better Immune Response? Day 28 Distribution of RSV MN Titers in E-301 Vaccinees with and Without RSV ARD* Broken line = Solid line = Subjects with RSV disease Matched controls without RSV disease Log2 RSV MN Titer Study participants without RSV disease had higher titers o
Slide 20: E-205 Treatment Groups
E-205 Treatment Groups Study Day Day 0 Day 21 Treatment Subjects RSV F Aluminum Matrix- RSV F Aluminum Matrix- Group Per Group Dose Dose M1 Dose Dose Dose M1 Dose A 25 135 µg 0 0 0 0 0 B 25 95 µg 0.3 mg 0 0 0 0 C 25 95 µg 0.3 mg 0 95 µg 0.3 mg 0 D 25 120 µg 0.4 mg 0 0 0 0 E 25 120 µg 0.4 mg 0 120 µg
Slide 21: Kinetics of Anti-F IgG in Representative Groups
Kinetics of Anti-F IgG in Representative Groups: Adjuvant Effect, 2nd Dose Effect and Durability of Responses Enhanced Fold Rises in Anti-F IgG 14 12 Geometric Mean Rise from Day 0 (95%CI) 10 135µg F x 1 8 135µg F + MxM x 1 135µg F + MxM x 2 6 p <0.0001 p = 0.0099 4 2 0 0 20 40 60 80 100 120 140 Stu
Slide 22: Kinetics of PCA in Representative Groups
Kinetics of PCA in Representative Groups: Adjuvant Effect, 2nd Dose Effect and Durability of Responses Enhanced Fold Rises in PCA 12 10 Geometric Mean Rise from Day 0 (95% CI) 135µg F x 1 8 135µg F + MxM x 1 135µg F + MxM x 2 p <0.0001 6 p = 0.004 4 2 0 0 20 40 60 80 100 120 140 Study Days from Dose
Slide 23: Enhancement of Neutralizing Antibody Responses
Enhancement of Neutralizing Antibody Responses Induction of Antibodies to Prefusion Epitopes E-205: Day 56 serum 800 800 R S V F c o m p e titiv e m A b s e r u m (µ g /m l) S ite φ D 2 5 S ite V III h R S V 9 0 600 600 S ite IIb M o ta v iz u m a b G M T R S V M N S ite IV N V X 1 .4 2 400 400 R S
Slide 24: Enhancement of Antibody Avidity by Adjuvanted Regimens
Enhancement of Antibody Avidity by Adjuvanted Regimens Avidity Maturation of Site II Antibodies 100% 90% 80% 70% Site II antibodies Koff Percentage of Subjects 60% <10^0 to -1 <10^-1 to -2 50% <10^-2 to -3 <10^-3 to -4 40% < 10^-4 to -5 30% < 10^-5 20% 10% 0% day 0 day 21 day 56 day 0 day 21 day 56
Slide 25: F Protein-specific Memory B Cell ELISpot Responses are Strong with All Formulations
F Protein-specific Memory B Cell ELISpot Responses are Strong with All Formulations Counts of Memory B Cells Specific for RSV F per 106 PBMC at Day 28 1600 Mean (SEM) Counts of Memory B cells Specific for RSV F Day Day Treatment Doses 1400 0 28 1200 Placebo 2 68 48 1000 135µg F 1 52 630 800 120µg F
Slide 26: Matrix-M Adjuvantation Enhances Triple Cytokine Positive RSV F-specific CD4+ Responses
Matrix-M Adjuvantation Enhances Triple Cytokine Positive RSV F-specific CD4+ Responses CD4+ T Cell Responses by Intracellular Staining CD4+ T cells Producing IFNγ, TNFα, and IL-2 After Stimulation with RSV F Peptide Pools 0.7 Day Day Mean % (SEM) of Peripheral CD4+ T cells Producing Three Treatment
Slide 27: E-205 Conclusions
E-205 Conclusions Adjuvant effects • The adjuvants meaningfully increased immunity in measures shown to decrease infection and 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
Slide 28: Evidence Base for RSV F Vaccine in Older Adults
Evidence Base for RSV F` Vaccine in Older Adults Lou Fries III, M.D.
Slide 29: Hypothesis for Outcomes: Susceptibility
Hypothesis for Outcomes 2014-2015 2015-2016 Attack Rates E-201 Lower in 2015/16 on basis E-301 RSV OA RSV ARD 4.9% of trial data; confirmed by 2.0% RSV msLRTD 1.8% external data 0.4% Circulation Similar on basis of RSV RSVAlert® data Susceptibility E-201 Lower in 2015/16 on basis E-301 RSV MN-B (GMT
Slide 30: Baseline RSV Immunity in E-201 and E-301
Baseline RSV Immunity in E-201 and E-301 RSV MN Titer Distributions at Baseline 0.3 0.25 0.2 Proportion of Population E-201 E-301 0.15 0.1 0.05 0 </=3 >3 to 4 >4 to 5 >5 to 6 >6 to 7 >7 to 8 >8 to 9 >9 to 10 >10 to 11 >11 to 12 >12 to 13 >13 to 14 >14 Log2 RSV MN Titers 30
Slide 31: Hypothesis for Outcomes: Susceptibility and Vaccine Efficacy
Hypothesis for Outcomes 2014-2015 2015-2016 Attack Rates E-201 Lower in 2015/16 on basis E-301 RSV OA RSV ARD 4.9% of trial data; confirmed by 2.0% RSV msLRTD 1.8% external data 0.4% Circulation Similar on basis of RSV RSVAlert® data Susceptibility E-201 Lower in 2015/16 on basis E-301 RSV MN-B (GMT
Slide 32: Flu Examples of Attack Rate Effects
Flu Examples of Attack Rate Effects Series Author Year Placebo Circulating Strain(s) Case Efficacy Attack Rate Match to Vaccine Defined by: 1 Ohmit et al1 2004-5 7.8% Drifted Culture or 75% PCR (42, 90) Ohmit et al2 2005-6 1.8% Good match 16% (-171,70) Monto et al3 2007-8 10.8% Low level drift 68% (
Slide 33: More Susceptible Populations May Provide a Window to Show Efficacy
More Susceptible Populations May Provide a Window to Show Efficacy • Even in a season characterized by low population susceptibility/high population immunity, there are individuals or subsets of individuals who succumb to infection and/or complications of infection because of heightened susceptibili
Slide 34: Impact of Vaccine on COPD Exacerbations
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 0-182 Placebo Vaccine VE% 95% CI p value COPD hospitalization rate in all 23/5935 (0.39%) 9/5921 (0.15%) 60.8% 15.2—81.9 0.017 subj
Slide 35: COPD Hospitalizations in E-301
COPD Hospitalizations in E-301 All-Cause COPD Exacerbation Hospitalization-Free Survival in E-301 1 Proportion of Population Free of COPD 0.9995 0.999 0.9985 Exacerbation 0.998 0.9975 Active 0.997 Placebo 0.9965 0.996 0.9955 0.995 0 50 100 150 200 250 300 350 Days From Treatment 35
Slide 36: Summary
Summary Vaccine Construct • Characterization has confirmed that our stable prefusogenic RSV-F protein is a highly potent immunogen that elicits broadly neutralizing antibodies to multiple epitopes Adjuvant Formulation and Regimen • The adjuvants and dose regimens significantly increased the magnitud
Slide 37: Phase 3 Study: Infants via Maternal Immunization
Phase` 3 Study: Infants via Maternal Immunization Gregory M. Glenn, M.D.
Slide 38: Novavax Phase 3 RSV F Vaccine For Infants Via Maternal Immunization Addresses Significant Unmet Medical Need
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 • RSV is largely a disease of healthy, full-term children in the United States and worldwide1 infants • RSV is
Slide 39: Policy Advances in Support of Maternal Immunization
Policy Advances in Support of Maternal Immunization 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
Slide 40: Novavax Has Conducted a Number of Phase 2 Trials with RSV F Vaccine
Novavax Has Conducted a Number of Phase 2 Trials with RSV F Vaccine Non-pregnant women • 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-tolerate
Slide 41: Phase 3 RSV F Vaccine for Infants via Maternal Trial: Goals and Design
Phase 3 RSV F Vaccine for Infants via Maternal Trial: Goals and Design Primary Determine the efficacy of maternal immunization with the RSV F Objective vaccine against symptomatic RSV lower respiratory tract infection (LRTI) with objective measures of medical significance of LRTI from 90-180 days of
Slide 42: The Phase 3 "Prepare Trial" has Entered its Third Year
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 S
Slide 43: Closing Remarks Question/Answer
Closing Remarks ` Question/Answer Stanley C. Erck
Slide 44: Summary
Summary Vaccine Construct • Characterization has confirmed that our stable prefusogenic RSV-F protein is a highly potent immunogen that elicits broadly neutralizing antibodies to multiple epitopes Adjuvant Formulation and Regimen • The adjuvants and dose regimens significantly increased the magnitud
Slide 45: Summary of COPD Opportunity
Summary of COPD Opportunity • Efficacy of Novavax’ RSV F vaccine on COPD exacerbations observed in E-301, and retrospectively confirmed in E-201 • COPD represents an at-risk population for RSV disease • A significant market opportunity exists with COPD, ~ $1.5 billion globally Prevention of acute ex
Slide 46: RSV Burden of Disease in Infants ≤6 Months of Age
RSV Burden of Disease in Infants ≤6 Months of Age ~3.9M Pregnant Women Eligible For Vaccination1 ~3.6M Babies in Applicable Birth Cohort2* RSV Infections 68.8/100 infant-years ≈ 1,915,682 1,915,682 (in 2015)3,* Pediatric Outpatient pediatric practice, annual visits4,* Outpatient Visits 262,531 Incid
Slide 47: NVAX RSV F Vaccine Franchise is On Track for Success
Summary NVAX RSV F Vaccine Franchise for Both Older Adults (OA) and Infants via Maternal (IVM) is On Track for Success • NVAX to initiate Phase 2 efficacy trial in OA in 2018 • Pivotal efficacy trial for IVM on target • Informational analysis expected by year-end • Interim analysis expected to be tr
Slide 48: Questions?
Questions? NOVAVAX 48 Creating Tomorrow's Vaccines Today
Slide 49: Creating Tomorrow's Vaccines Today
Creating Tomorre uber ANC = arn Www.novavax.com P|