Novavax, Inc. · NASDAQ:NVAX
Novavax — Technical Presentation (October 2013)
24 slides from Novavax's technical presentation, Oct 15, 2013
Slide 1: RSV Nanoparticle Vaccine in the Elderly: Day 56 Results of NVX757.102
RSV Nanoparticle Vaccine in the Elderly Day 56 Results of NVX757.102 15 October 2013 1
Slide 2: Clinical Applications for an RSV Vaccine
Clinical Applications for an RSV Vaccine • RSV infects all children by age 2 years • RSV is the leading cause of infant hospitalization 75,000 to 125,000 hospitalizations annually (in US) • RSV is a leading cause of pneumonia in older adults In some seasons, disease burden can be similar to flu
Slide 3: Background
Background • The Novavax RSV F protein vaccine elicits: ‒ serum IgG responses to F protein, including antigenic site II linear peptides, ‒ antibodies that compete with palivizumab for binding to RSV F, ‒ increases of 3 to 4-fold in neutralizing titers of young adult sera, over 6- fold in in those yo
Slide 4: Study Objectives
Study Objectives • To describe the safety in subjects ≥ 60 y.o. of the RSV F protein vaccine, at 60 or 90µg doses, with or without AlPO4, and co- administered with standard dose, licensed trivalent inactivated influenza vaccine (TIV). • To describe the immunogenicity of the RSV F vaccine, at 60 or 9
Slide 5: Treatment Assignments
Treatment Assignments Study Day 0[1] Study Day 28 ± 2[2] Treatment Subjects RSV-F Group Per Group Aluminum Saline Influenza Saline Influenza Antigen Adjuvant [3] Placebo Vaccine Placebo Vaccine Content A 40 60µg Yes -- Yes -- Yes B 40 60µg -- -- Yes -- Yes C 40 90µg Yes -- Yes -- Yes D 40 90µg -- --
Slide 6: Safety Monitoring
Safety Monitoring • Standardized local and systemic AEs solicited according to defined grading scale x 7 days after the investigational dose ‒ Injection site pain, bruising, redness and swelling ‒ Fever, chills, arthralgia, myalgia, headache, fatigue, nausea, vomiting, diarrhea • Unsolicited AEs at
Slide 7: Immunologic Monitoring
Immunologic Monitoring • Serum IgG antibody levels specific for the RSV F protein ‒ Readout in ELISA units (EU) anchored to a standard reference pool • Serum titers of antibodies competitive with palivizumab for binding to RSV F protein ‒ Readout is serum titer yielding 50% inhibition of labeled pal
Slide 8: Study Population and Disposition
Study Population and Disposition Treatment Groups, Counts (%) Placebo 60µg + Al 60µg - Al 90µg + Al 90µg - Al Enrolled 60 40 40 40 40 Completed Day 56 59 (98)* 40 (100) 39 (98)* 40 (100) 40 (100) Discontinued 0 0 0 0 0 Due to AE 0 0 0 0 0 Voluntary, non-AE 0 0 0 0 0 Lost to f/u 0 0 0 0 0 Investigato
Slide 9: Demography
Demography Treatment Groups Placebo 60µg + Al 60µg - Al 90µg + Al 90µg - Al Gender Female (%) 38 (63) 22 (55) 24 (60) 19 (48) 23 (58) Male (%) 22 (37) 18 (45) 16 (40) 21 (52) 17 (42) Mean age (SD) yrs 69.1 (5.5) 69.1 (5.8) 67.7 (5.6) 68 (5.8) 68.7 (5.7) 60 - <75 yrs (%) 51 (85) 34 (85) 34 (85) 34 (8
Slide 10: Safety Summary
Safety Summary Treatment Groups, Counts of Subjects with Events (%) Placebo 60µg + Al 60µg - Al 90µg + Al 90µg – Al Safety N 60 40 40 40 40 Any AE 42 (70) 30 (75) 25 (63) 27 (68) 23 (58) Any solicited AE 28 (47) 22 (55) 12 (30) 21 (53) 19 (48) Local 14 (23) 17 (43) 9 (23) 17 (43) 15 (38) Systemic 22
Slide 11: Anti-F IgG – Geometric Mean EU
Anti-F IgG – Geometric Mean EU 1111
Slide 12: Formulation-finding and dosing using Anti-F fold-increase metric
Formulation-finding and dosing using Anti-F fold-increase metric • Q: Is there a positive effect of AlPO4? A: Yes ‒ Effect of aluminum is only 1.1-fold at day 28 (p = 0.432), but ‒ Effect of aluminum is 1.4-fold at day 56 (p = 0.004) ‒ Similar to effect of aluminum in young adults. • Q: Is 90µg bett
Slide 13: Immune Responses to Antigenic Site II Linear Peptide
Immune Responses to Antigenic Site II Linear Peptide 1313
Slide 14: Palivizumab-Competitive ELISA: Assay Methodology
Palivizumab-Competitive ELISA: Assay Methodology Biotin-palivizumab 14
Slide 15: Induction of Palivizumab-competitive Antibodies
Induction of Palivizumab-competitive Antibodies 1515
Slide 16: RSV A Microneutralization Titers – Geometric Mean Titers
RSV A Microneutralization Titers – Geometric Mean Titers Treatment Groups Placebo 60µg + Al 60µg – Al 90µg + Al 90µg – Al Day 0 (Baseline) 326 258 247 269 347 (251, 422) (193, 345) (190, 321) (199, 366) (245, 491) Day 7 334 305 258 305 416 (259, 430) (225, 413) (202, 331) (230, 403) (306, 566) Day 2
Slide 17: HAI – Geometric Mean Titers
HAI – Geometric Mean Titers Treatment Groups HA Strain Placebo 60µg + Al 60µg – Al 90µg + Al 90µg – Al Day 0 35.6 42.2 40.0 27.3 41.9 (24.4, 51.9) (28.1, 63.5) (24.3, 65.9) (15.9, 46.6) (27.0, 65.1) A/California/07/200 Day 28 154.1 183.5 195.8 154.2 157 9 (103.7, 229.0) (121, 278.3) (120.7, 317.8) (
Slide 18: Conclusions: It's Feasible
Conclusions: It’s Feasible • Safety ‒ Primary finding is increase local reactogenicity concentrated in subjects receiving aluminum compared to placebo. ‒ No severe-related events • Immunogenicity ‒ No negative effects on trivalent influenza HAI responses ‒ By Anti-F IgG, aluminum and higher dose imp
Slide 19: An Intriguing Option for the Elderly: RSV F and Influenza VLP Combination
An Intriguing Option for the Elderly (or Anyone): RSV F and Influenza VLP Combination Vaccine Some immediate questions: • Can a formulation be developed that will accommodate both antigens? • Will they impair each other’s immune responses if co-injected? 1919
Slide 20: An Initial Combination Vaccine Study in Balb/C Mice
An Initial Combination Vaccine Study in Balb/C Mice RSV F Tri- Flu Immunization Group Antigen Mice (N) Antigen *Dose in µg Days Dose in µg 1 Trivalent Flu + RSV 8 3 3 0, 21 2 Trivalent Flu + RSV 8 9 9 0, 21 3 Flu + Buffer (Flu) 8 3 ----- 0, 21 4 Flu + Buffer (Flu) 8 9 ----- 0, 21 5 RSV + Buffer (RSV
Slide 21: Anti-F IgG Responses in the Presence of VLP Influenza Vaccine
Anti-F IgG Responses in the Presence of VLP Influenza Vaccine • Background day 0 anti-F IgG levels < 100 • Superscript 1 = Influenza vaccine buffer, 2 = RSV vaccine buffer • RSV microneutralization titers and palivizumab-competitive titers show the same pattern 2121
Slide 22: B/Wisconsin Immunogenicity in the Presence of RSV F
B/Wisconsin Immunogenicity in the Presence of RSV F • Background day 0 B/Wisconsin HAI < 20 • Superscript 1 = Influenza vaccine buffer, 2 = RSV vaccine buffer • A/California and A/Victoria HAI titers show the same pattern 2222
Slide 23: Impact of Adding Palivizumab to Serum MN Titers
The Impact of Adding Palivizumab (or Palivizumab-equivalent) to Serum MN Titers Depends on Where You Start 2323
Slide 24: Why Doesn't Palivizumab-like Activity Lead to Big Fold-Rises in MN Titer
Why Doesn’t a Large Amount of Palivizumab-like Activity Lead to Big Fold-Rises in MN Titer Let 40µg/mL of palivizumab give a MN titer of 64 (about right) Now add it to sera of increasing base MN tier: Starting Starting Added Final MN Final MN Fold-rise MN titer MN titer antibody titer titer in Titer