Novavax, Inc. · NASDAQ:NVAX
Novavax — World Vaccine Congress Webcast 2020
30 slides from Novavax's conference presentation, May 18, 2020
Slide 1: NVX-CoV2373 Vaccine for COVID-19
NVX - CoV2373 Vaccine for COVID - 19 Dr. Gregory Glenn, World Vaccine Congress Webcast 13 May 2020
Slide 2: Executive summary
2 novavax.com Executive summary • Novavax has a prefusion, stable recombinant SARS - CoV - 2 Spike protein nanoparticle vaccine candidate (NVX - CoV2373) that has been highly immunogenic in mice and nonhuman primates • Novavax is employing a mature vaccine platform to address the current COVID 19 pa
Slide 3: Novavax vaccine pipeline
3 novavax.com 1 Supported by grant from CEPI of up to $388 million 2 Supported by the $89.1 million grant from the Bill and Melinda Gates Foundation. Novavax vaccine pipeline PHASE 1 PHASE 2 PHASE 3 CLINICAL PRECLINICAL PROGRAM DESCRIPTION NanoFlu™ – Nanoparticle Seasonal Influenza Vaccine - Older A
Slide 4: Recombinant Protein Nanoparticles platform technology
4 novavax.com Recombinant Protein Nanoparticles Platform technology: previous experience allows directional confidence in early development Experience with RSV, Seasonal Influenza and Ebola instructive Susan Krueger, et al Structural Characterization and Atomistic Modeling of a Respiratory Syncytial
Slide 5: Highlights from seasonal influenza NanoFlu nanoparticle vaccine
5 novavax.com Highlights From Seasonal Influenza NanoFlu Nanoparticle Vaccine ( qNIV ) Novavax qNIV released primary results from their P3 pivotal trial in March 2020 in adults older than 65 years. The trial remains ongoing for long term safety Recombinant adjuvanted vaccine addresses drift, egg ada
Slide 6: Ebola GP nanoparticle vaccine induces T cell responses in mice
6 novavax.com The picture can't be displayed. The picture can't be displayed. In mice, Ebola glycoprotein (EBOV GP) nanoparticle vaccine, administered with Matrix - M, induced potent polyfunctional CD4+ and CD8+ T cell responses Matrix - M adjuvant enhances antibody, cellular and protective immune r
Slide 7: Ebola GP vaccine neutralizing antibody responses and protection in mice
7 novavax.com The picture can't be displayed. The picture can't be displayed. In mice, EBOV GP nanoparticle vaccine, administered with Matrix - M, induced potent neutralizing antibody responses, with dose sparing, and protection from lethal challenge Matrix - M adjuvant enhances antibody, cellular a
Slide 8: Ebola GP vaccine with Matrix-M in baboons
8 novavax.com In baboons, EBOV GP nanoparticle vaccine with Matrix - M adjuvant was predictive of immunogenicity in humans - Robust antibody and T cells - Key role of adjuvant - Dose sparing with Matrix - M - Persistence of immunity - Value of prime - boost Fries, et al. Ebolavirus glycoprotein subu
Slide 9: Ebola GP vaccine in humans: durable antibody responses
9 novavax.com In humans, EBOV GP nanoparticle vaccine, administered with Matrix - M, in a 2 dose schedule, induced potent and durable ELISA and neutralizing antibody responses over a year, with dose sparing 9 • Design 1 : phase 1 (off IND), placebo - controlled, dose - escalation trial conducted in
Slide 10: EBOV GP nanoparticle vaccine Phase 1 human immunogenicity
10 novavax.com EBOV GP nanoparticle vaccine Phase 1 human immunogenicity Human EBOV GP Phase 1 i mmune r esponses in the FANG ELISA compared to vectored vaccines 1 2 4 8 16 32 64 128 256 512 1024 2048 4096 8192 16384 0 50 100 150 200 250 300 350 400 F A N G E L I S A G M E U ( 9 5 % C I ) Study Day
Slide 11: Recombinant Protein Nanoparticles: engineered for immunogenicity and stability
11 novavax.com Recombinant Protein Nanoparticles Platform technology: previous experience allows directional confidence in early development Engineered for immunogenicity, stability and productivity SARS - CoV - 2 Spike protein structure critical for protection, characterization tools well developed
Slide 12: NVX-CoV2373 full-length prefusion stabilized spike glycoprotein
12 novavax.com NVX - COV2373 full - length, prefusion stabilized SARS - CoV - 2 spike (S ) glycoprotein Novavax NVX - CoV2373 Vaccine Approach • Developed from a gene sequence to phase 1 in ~90 days nanoparticle vaccines against Ebola GP and influenza A/H7N9 HA with Matrix=M adjuvant • SARS CoV - 2
Slide 13: NVX-CoV2373 and Matrix-M: critical partners for immunogenicity
13 novavax.com NVX - CoV2373 and Matrix - M™ Critical partners for immunogenicity Matrix M Saponin Adjuvant SARS - CoV - 2 trimer hACE2 receptor Matrix - M Novavax, Inc. (U.S.) Novavax AB (Sweden) CoV2373 Antigen
Slide 14: Prefusion spike CryoEM
14 novavax.com NVX - CoV2373 prefusion spike CryoEM • 2D class average overlay with recently solved cryoEM of SARS - CoV - 2 trimeric spike protein (EMD ID 21374) • Wrapp , et al, 2020, Science , Cryo - EM structure of the 2019 - nCoV spike in the prefusion conormation The 2373 rSpike protein in the
Slide 15: Binds with high affinity to hACE2 receptor
15 novavax.com NVX - CoV2373 binds with high affinity to hACE2 receptor Binding is an indication of the correct prefusion structure, predicts induction of functional antibodies that will block infection
Slide 16: NVX-CoV2373 construct stability
16 novavax.com NVX - CoV - 2 construct stability NVX - COV2373 SARS - CoV - 2 prefusion S ACE2 binding 48 hr stress conditions Two proline (2P) mutation S2/HR1 as described: Wrapp , et al, 2020, Science , Cryo - EM structure of the 2019 - nCoV spike in the prefusion conformation.
Slide 17: Balb/C mice: anti-S IgG, hACE2 inhibition, neutralization
17 novavax.com Day 0 One dose Two dose 10 0 10 1 10 2 10 3 10 4 10 5 S A R S - C o V - 2 a n t i - S I g G ( E C 5 0 ) LOD Day 0 One dose Two dose 10 0 10 1 10 2 10 3 10 4 h A C E 2 I n h i b i t i o n ( 5 0 % ) LOD Day 0 One dose Two dose 10 0 10 1 10 2 10 3 10 4 10 5 S A R S - C O V - 2 N e u t r
Slide 18: Balb/C mice dose-ranging hACE2 receptor inhibition
18 novavax.com 10 g 0.01 g + Matrix 0.1 g + Matrix 1 g + Matrix 10 g + Matrix Placebo 4 8 16 32 64 128 256 512 1024 2048 h A C E 2 I n h i b i t i o n ( 5 0 % ) One dose Two dose LOD Balb/C Mice: NVX - CoV2373 vaccine 10ng - 10µg dose - ranging hACE2 receptor inhibition (50%) • Functional
Slide 19: Baboons: anti-S IgG, hACE2 inhibition, neutralization
19 novavax.com 25 g 1 g + Matrix M 5 g + Matrix M 25 g + Matrix M 10 1 10 2 10 3 10 4 10 5 10 6 S A R S - C o V - 2 a n t i - S I g G ( E C 5 0 ) LOD Day 0 One dose Two dose 25 g 1 g + Matrix M 5 g + Matrix M 25 g + Matrix M 10 0 10 1 10 2 10 3 10 4 S A R S - C o V - 2 N e u t r a l
Slide 20: Baboons: ELISPOT IFN-γ and IL-4 responses
20 novavax.com Baboons: ELISPOT IFN - γ and IL - 4 responses PBMCs Day 28 25 g 1 g + Matrix M 5 g* + Matrix M 25 g + Matrix M 0 20 40 60 80 I F N - p r o d u c i n g c e l l s p e r 1 0 6 P B M C s IFN- producing PMBC Ag PMA Ag PMA Ag PMA Ag PMA 0 500 1000 1500 2000 I L - 4 p r o d u c i
Slide 21: Baboons: intracellular cytokine staining
21 novavax.com Baboons: Intracellular Cytokine Staining (IFN - γ , IL - 2, TNF - α) Multifunctional Ag - Specific CD4 T - cells day 28 25 g 1 g +Matrix M 5 g +Matrix M 25 g +Matrix M 0 50 100 150 T r i p l e c y t o k i n e + c e l l s ( p e r 1 0 6 C D 4 T c e l l s ) Triple cytokine+ CD4 T
Slide 22: Baboon/human: anti-CoV2373 S IgG responses
22 novavax.com Baboon/human: Anti - CoV2373 S IgG Responses 0 2 0 3 0 9 1 0 1 1 1 3 1 5 1 6 2 3 2 6 2 5 2 9 1 7 1 8 1 9 n H u 10 1 10 2 10 3 10 4 10 5 10 6 Human Convalescent Serum LOD S A R S - C o V - 2 a n t i - S I g G ( E C 5 0 ) COVID - 19 Convalescent Serum (Individual Subjects) NVX - CoV2373
Slide 23: Baboon/human: hACE2 receptor inhibition responses
23 novavax.com Baboon/human: hACE2 Receptor Inhibition Responses 25 g 1 g + Matrix M 5 g + Matrix M 25 g + Matrix M 10 1 10 2 10 3 h A C E 2 I n h i b i t i o n ( 5 0 % ) LOD Day 0 One dose Two dose 0 2 0 3 0 9 1 0 1 1 1 3 1 5 1 6 2 3 2 6 2 5 2 9 1 7 1 8 1 9 n H u 10 1 10 2 10 3 h A C E 2 I
Slide 24: Preclinical testing for enhanced disease
24 novavax.com Preclinical Testing NVX - CoV2373 Vaccine for Enhanced Disease • Mechanism of enhancement reported for SARS and MERS - CoV • Mice: Th2 dominance associated with eosinophils in lung lesions. • NHP: Virus - antibody immune complexes and cytokine storm associated with enhanced lung infla
Slide 25: NVX-CoV2373: Clinical Plan
NVX - CoV2373: Clinical Plan
Slide 26: Phase 1 clinical trial
26 novavax.com NVX - CoV2373 phase 1 clinical trial • Single protocol Phase 1/Phase 2 • Phase 1 – 130 subjects, 18 - 59 years of age • Data to be filed to US IND for Phase 2 initiation • Key Immune measurements: • ELISA • Receptor Binding Inhibition • Neutralization • CMI – Th1/Th2 • Key Safety • Re
Slide 27: Phase 2B clinical trial
27 novavax.com NVX - CoV2373 phase 2B clinical trial • Single protocol Phase 1/Phase 2 • Phase 2 proposed to follow closely on day 35 Phase 1 results • ~2200 Subjects, 1000 > Older Adults • US and Australia • Placebo controlled • Considerations 1 vs 2 doses, Fractional dosing • COVID - 19 disease en
Slide 28: CEPI $388M funding for COVID-19 vaccine development and manufacturing
28 novavax.com CEPI $388M Funding for NVX - CoV2373 COVID - 19 Vaccine Development and Manufacturing; May 11, 2020 • Richard Hatchett, CEO of CEPI: “The expansion of our partnership with Novavax represents CEPI’s single biggest investment to date.” • Support clinical development NVX - CoV2373 vaccin
Slide 29: Summary
29 novavax.com Summary • Novavax has selected a prefusion, hACE2 - binding, stable , immunogenic, SARS - CoV - 2 spike nanoparticle vaccine with Matrix - M adjuvant • GMP manufacturing of the NVX - CoV2373 and Matrix - M are being scaled up to 100M doses by the end of 2020 and > 1B doses in 2021 • C
Slide 30: Thank you to the Novavax Team, CEPI, and our many collaborators
Thank you to the Novavax Team, CEPI, and our many collaborators