Novavax, Inc. · NASDAQ:NVAX
Novavax — Atlantic Vaccine Conference (2015)
35 slides from Novavax's conference presentation, Oct 4, 2015
Slide 1: Rapid Responses to Novel Lethal Viruses: Recombinant Nanoparticle Vaccines
Rapid Responses to Novel Lethal Viruses: The Potential of Recombinant Nanoparticle Vaccines Produced in a Baculovirus Insect Cell System Gregory M. Glenn M.D. SVP R&D Novavax, Rockville, MD EBOV/Makona GP Nanoparticle
Slide 2: Presentation Overview
Presentation Overview Response to H7N9 and Ebola viruses: Case study on how the recombinant nanoparticle vaccine technology can be applied to challenges posed by novel lethal viruses • H7N9 (2013) Influenza Vaccine Response • Ebola Vaccine Response (2014-15) Background Novavax Ebola/Makona Glyop
Slide 3: Novavax Overview
Novavax Overview • Novavax (Nasdaq: NVAX) is a clinical-stage vaccine company committed to delivering novel products to prevent a broad range of infectious diseases. • Our recombinant nanoparticles and Matrix-M™ adjuvant technology are the foundation for ground-breaking innovation that improves glob
Slide 4: Pipeline
Pipeline Program Preclinical Phase 1 Phase 2 Phase 3 Funding Support RSV Elderly Infants (Maternal Immunization) Pediatrics (6 mos – 6 yrs) Influenza Quadrivalent Seasonal BARDA Pandemic (H7N9 + Matrix-M) BARDA New Vaccines Combination Respiratory Ebola + Matrix-M 4 4
Slide 5: Novavax Recombinant Vaccine Technology Overview
Novavax Recombinant Vaccine Technology Overview • Select and engineer genetic sequences encoding vaccine antigens into baculovirus, infect insect cells • Insect cell cellular machinery produces correctly modified and folded proteins • Full-length antigens expressed in native conformation assemble in
Slide 6: Recombinant Baculovirus-Sf9 Technology Enables a Rapid Vaccine Response
Recombinant Baculovirus-Sf9 Technology Enables a Rapid Vaccine Response to Novel Lethal Viruses Viral Threats Response Process Development & GMP Production • Vaccine candidate development • Process & assay development • Preclinical study expertise • 1000L GMP production Clinical study expertise • Re
Slide 7: 3-month Response Time from Gene Sequence to GMP Batch Release
3-month Response Time from Gene Sequence to GMP Batch Release for recombinant H7N9, Ebola Vaccines H7N9 A/Anhui VLP • Highly lethal virus • Novel • Pandemic potential • Became endemic Ebola GP Particle • Highly lethal virus • Novel • Pandemic potential • Became endemic 7 7
Slide 8: H7N9 VLP Vaccine Protects Mice from Lethal Avian H7 Challenge
Novavax H7N9 VLP Vaccine with and w/o Saponin Adjuvant Protect Mice from Lethal Avian H7 Virus Challenge A lethal A/Anhui wild type virus mouse challenge model was rapidly developed Mice were immunized with VLP vaccines w/wo saponin adjuvant Both H7N9 vaccines protected the mice from death, even wit
Slide 9: Clinical Immunogenicity: A/Anhui/1/2013 HAI Response to H7N9 Vaccine
Clinical Immunogenicity: A/Anhui/1/2013 HAI Response to H7N9/saponin adjuvanted vaccine at d 28 in 225 subjects vaccinated at d 0 and 21 Low Dose Adjuvant Vaccine 9 9
Slide 10: Novavax Avian Influenza H7N9 Results and Outcomes
Novavax Avian Influenza H7N9 Results and Outcomes H7N9 VLP alone or with Saponin Adjuvant (2013) • 225 subjects vaccinated 91 days post publication of gene sequence • Achieved dose-sparing goals with 5 μg dose • Seroconversion and seroprotection rates: 81% HAI, 97% NAI • Achieved within 45 days of i
Slide 11: Timeliness of Vaccine Production Provides the Greatest Impact in a Pandemic
Timeliness of Vaccine Production Provides the Greatest Impact in a Pandemic 11 11
Slide 12: Ebola: Epidemic Status and History
Ebola: Epidemic Status and History • New cases continue to appear in Guinea and Sierra Leone • 20+ known Filovirus outbreaks since 1976 • Three studies published in 1986 documented Ebola antibody prevalence rates of 10.6, 13.4 and 14 percent in northwestern Liberia Trop Geogr Med. 1986 Sep;38(3):209
Slide 13: Ebola transmission in Sierra Leone and Guinea, May 2014
• In Sierra Leone May 2014 at funeral in Guinea attendees were infected with cluster 1, 2 viruses leading to cluster 3 Ebola and sustained human-to- human transmission in West Africa. 13 13
Slide 14: Strategy for Development of a Recombinant Viral Vaccine: EBOV
Strategy for Development of a Recombinant Viral Vaccine: EBOV Recombinant GP EBOV mAb(s) • Full length • Protective in NHPs EBOV/Makona Gene • Similar activity produced by RSV • Recombinant GP the vaccine? from insect cells • Multiple mAbs=multiple • Purified GP trimers targets on the GP protein for
Slide 15: Ebola transmission in Sierra Leone and Guinea, May 2014
• In Sierra Leone May 2014 at funeral in Guinea attendees were infected with cluster 1, 2 viruses leading to cluster 3 Ebola and sustained human- to-human transmission in West Africa. 15 15
Slide 16: Novavax begins development of recombinant EBOV/Makona GP subunit vaccine
Sept 12, 2014 Novavax begin development of recombinant EBOV/Makona GP subunit vaccine Recombinant EBOV/Makona Glycoprotein (GP) • GenBank #AIG96283 • EBOV [H.sapiens -wt/SLE/2014/Makona-G3798]; cluster 3 • Full length, unmodified GP gene • Synthetic, codon optimized • Cloned into a baculovirus vecto
Slide 17: EBOV/Makona GP nanoparticle TEM negative stain image
EBOV/Makona GP nanoparticle TEM negative stain image and 2D class averaging • Central core region with GP2/hydrophobic domains (blue) • Six visible chalice-like GP1/mucin domain trimers extending concentrically from a central core (pink) 17 CONFIDENTIAL 17
Slide 18: Matrix M Adjuvant: Enhances Magnitude and Quality of Immune Responses
Matrix M Adjuvant: Enhances Magnitude and Quality of Immune Responses Saponin-based adjuvant • Adjuvant nano-particulate formulation (approx 40 nm particles, cage-like) • EBOV GP is stable in co-formulation with Matrix-M1 at 2-80C + Clinical Experience • 7 GLP-compliant toxicity studies, benign resu
Slide 19: Strategy for Development of a Recombinant Viral Vaccine: EBOV
Strategy for Development of a Recombinant Viral Vaccine: EBOV Recombinant GP EBOV mAb(s) • Full length • Protective in NHPs EBOV/Makona Gene • Similar activity produced by RSV • Recombinant GP the vaccine? from insect cells • Multiple mAbs=multiple • Purified GP trimers targets on the GP protein for
Slide 20: Binding kinetics of recombinant EBOV/Mak GP to functional EBOV mAb
Binding kinetics purified recombinant EBOV/Mak GP to functional EBOV mAb: High Affinity Binding SPR mAb EBOV GP Epitope KD (nM) aa 42-43, 513, 550-553, 556 Conformational KZ52 GP1/GP2 Pre-fusion GP2 2.36 Conformational 13C6 aa 1-295 GP1 In ZMapp 8.35 aa 389-405 GP1 6D8 HNTPVYKLDISEATQVE Linear 3.67
Slide 21: Strategy for Development of a Recombinant Viral Vaccine: EBOV
Strategy for Development of a Recombinant Viral Vaccine: EBOV Recombinant GP EBOV mAb(s) • Full length • Protective in NHPs EBOV/Makona Gene • Similar activity produced by RSV • Recombinant GP the vaccine? from insect cells • Multiple mAbs=multiple • Purified GP trimers targets on the GP protein for
Slide 22: Baboon Immunogenicity Study: anti-EBOV/Makona GP ELISA
Baboon Immunogenicity Study: anti-EBOV/Makona GP ELISA and Competition ELISA with 13C6 mAb Day 21 Day 31 Day 0 1 dose 2 dose regimen Group Vaccine regimen 13C6 EC90 EC90 EC90 µg/ml 1 60µg EBOV GP <100 631 1,517 <4 60µg EBOV GP 2 <100 19,227 285,206 20 800µg AlPO4 60µg EBOV GP 3 <100 13,115 6,870,339
Slide 23: Baboons – Durability anti-EBOV GP IgG response
Baboons – Durability anti-EBOV GP IgG response Anti-Makona GP IgG ELISA - EC90 10 8 10 7 E L IS A E C 9 0 G M T 10 6 Day150 GMT 10 5 5 µ g G P + M a t r ix Group ELISA EC90 6 0 µ g G P + M a t r ix 10 4 5ug GP + Matrix 46,651 6 0 µ g G P + A lP O 4 6 0 µ g G P 60ug GP + Matrix 38,694 10 3 60ug GP +
Slide 24: EBOV/Mak GP vaccine IFNγ-Elispot response in baboons
EBOV/Mak GP vaccine IFNγ-Elispot response in baboons day 31 Robust IFNγ-Elispot responses to 5ug EBOV GP + Matrix-M vaccine 24 CONFIDENTIAL 24
Slide 25: Ebola-GP/Matrix-M induced multifunctional T cell response in baboons
Ebola-GP/Matrix-M induced multifunctional T cell response in baboons Single cytokine Double cytokine Triple cytokine s in g le c y to k in e s d o u b le c y to k in e s trip le c y to k in e s % o f c y to k in e p r o d u c in g c e lls 0 .2 0 0 .0 4 0 .0 1 0 0 .1 5 0 .0 3 CD4+ 0 .1 0 0 .0 2 0 .0
Slide 26: Strategy for Development of a Recombinant Viral Vaccine: EBOV
Strategy for Development of a Recombinant Viral Vaccine: EBOV Recombinant GP EBOV mAb(s) • Full length • Protective in NHPs EBOV/Makona Gene • Similar activity produced by RSV • Recombinant GP the vaccine? from insect cells • Multiple mAbs=multiple • Purified GP trimers targets on the GP protein for
Slide 27: EBOV/Makona Vaccine Antibody Responses and Challenge Results
EBOV/Makona vaccine anti-EBOV/Makona GP Antibody Responses and Challenge Results Immunogenicity Challenge: 100% Protection Challenge Study: Ricardo Carrion, Jr, Rob Davey, Manu Anantpadama, Gabriela Worwa, Texas Biomedical Research Institute San Antonio, TX 27 27
Slide 28: DMID/NIAID: IgG ELISA and 100% Protection
DMID/NIAID: EBOV/Makona vaccine anti-EBOV/Makona GP IgG ELISA (EC50) and 100% Protection Group G (n=2) Group F (n=2) 5µg GP + Matrix-M Ebola/Kikwit 5µg GP + Matrix-M Ebola/Kikwit 0wk 3wk wk9; 100 pfu 0wk 6wk wk12; 100 pfu 10 6 10 6 E L IS A E C 5 0 T i t e r Challenge Results: E L IS A E C 5 0 T i t
Slide 29: Guinea EBOV GP vaccine IgG and neutralizing antibody responses in mice
Guinea EBOV GP vaccine EC90 IgG and neutralizing antibody responses in mice (day 28) 2014 Guinea EBOV GP IgG ELISA (EC90) 1976 Mayinga EBOLA (PsVNA50) 1 × 1 066 1 × 1 055 10 10 Group (n=10) Control 1 × 1 055 ELISA EC90 Titer 10 PsVNA50 Titer 1 × 1 044 10 5µg EBOV GP 5µg EBOV GP + AlPO4 1 × 1 044 10
Slide 30: 2014 Guinea EBOV GP vaccine protects mice against 1976 Mayinga ebolavirus
2014 Guinea EBOV GP vaccine protects mice against challenged with 1976 Mayinga ebolavirus: Active Group Control ----- 5µg EBOV GP ----- 5µg EBOV GP + AlPO4 ----- 5µg EBOV GP + Matrix M----- Methods. Mice were immunized on day 0, 14 and 28 and on Day 42 mice were challenged by intraperitoneal inocula
Slide 31: Strategy for Development of a Recombinant Viral Vaccine: EBOV
Strategy for Development of a Recombinant Viral Vaccine: EBOV Recombinant GP EBOV mAb(s) • Full length • Protective in NHPs EBOV/Makona Gene • Similar activity produced by RSV • Recombinant GP the vaccine? from insect cells • Multiple mAbs=multiple • Purified GP trimers targets on the GP protein for
Slide 32: Purified fully human anti-rGP polyclonal antibody: passive protection
Purified fully human anti-rGP (Guinea, 2014) polyclonal antibody: passive protection Tc bovine (Human IgG) were immunized with recombinant Guinea Ebola GP vaccine Fully human anti-GP polyclonal antibodies were purified from plasma Polycloncal Anti-GP IgG given i.p.. at 24 or 48 hrs post challe
Slide 33: Clinical Study: Novavax EBOV-H-101
Clinical Study: Novavax EBOV-H-101 • Phase 1, blinded, controlled in 230 adults 18 to <50 y.o. • Dose ranging, 1 and 2 dose regimens w/wo Matrix-M adjuvant • Immune responses thru 1 year o GP EC50 ELISA, PRNT, PsVNA, anti-13C6, and T-cell responses 33 33
Slide 34: Summary
Summary • Novavax: is a mid-size recombinant vaccine company that is uniquely capable of responding to novel lethal viral threats • Recombinant tools/adjuvants allow NVAX scientists to solve difficult vaccine puzzles • Demonstrated in the context of H7N9 Vaccine and Ebola Vaccines • Path forward, re
Slide 35: Acknowledgement – Novavax Ebola vaccine SWOT Team
Acknowledgement – Novavax Ebola vaccine SWOT Team 35 35