Novavax, Inc. · NASDAQ:NVAX
Novavax — ISBioTech (March 2015)
40 slides from Novavax's conference presentation, Mar 10, 2015
Slide 1: Rapid Manufacture and Release of a GMP Batch of Zaire Ebolavirus Glycoprotein Vaccine
Rapid Manufacture and Release of a GMP Batch of Zaire Ebolavirus Glycoprotein Vaccine Made Using Recombinant Baculovirus-Sf9 Insect Cell Culture Technology Tim Hahn SVP, Global Manufacturing Operations Novavax, Inc. 10 March 2015 1
Slide 2: Presentation Overview
Presentation Overview • Ebola Background • Novavax Ebola/Mak Glyoprotein Vaccine • Novavax saponin-based Matrix-M™ Adjuvant • Rapid Manufacturing Timeline • Pre-clinical Data 22
Slide 3: Ebola Background
Ebola Background • A new virus was discovered in 1976 ‒ Caused hemorrhagic fever ‒ Later named genus Ebolavirus ‒ Five Ebola virus species including Zaire Ebola virus (EBOV) • From 1976 to 2013 ‒ Several outbreaks of Ebola Virus Disease (EBV) ‒ Average EVD case fatality rate is about 50% ‒ Most outb
Slide 4: Span of Endemic
Span of Endemic • Most cases in Guinea, Liberia, and Sierra Leone • Infections also reported in: • Nigeria • Democratic Republic of Congo • Senegal • United States • Spain • Mali • United Kingdom 4
Slide 5: Presentation Overview
Presentation Overview • Ebola Background • Novavax Ebola/Mak Glyoprotein Vaccine • Novavax saponin-based Matrix-M™ Adjuvant • Rapid Manufacturing Timeline • Pre-clinical Data 55
Slide 6: Guinea Ebola (EBOV) Gene Sequence for Cluster 3 Virus
Guinea Ebola (EBOV) Gene Sequence for Cluster 3 Virus Science September 12, 2014 • In Sierra Leone May 2014 at funeral of a Guinea EVD case, attendees were infected with two distinct Ebola cluster 1,2 viruses leading to cluster 3 sustained human-to-human transmission. • “Because many of the mutation
Slide 7: Novavax EBOV/Mak GP recombinant nanoparticle vaccine
Novavax EBOV/Mak GP recombinant nanoparticle vaccine Recombinant EBOV/Makona Glycoprotein (GP) • GenBank #AIG96283 • EBOV [H.sapiens -wt/SLE/2014/Makona-G3798] • Full length, unmodified GP gene • Synthetic, codon optimized • Cloned into a baculovirus vector rBV-GP CLONING EXPRESSION PURIFICATION Bac
Slide 8: Novavax EBOV/Makona Glycoprotein (GP) Vaccine
Novavax EBOV/Makona Glycoprotein (GP) Vaccine 1Nonsynonymous AA: 2014 EBOV/Makona GP and 1976 EBOV/Mayinga GP 20 AA changes mAb 13F6 1Gire, et al, Science 12 Sept 2014 8
Slide 9: Anti-Ebola ELISA EC50 of mAb 13C6, 6D8 and KZ52
Anti-Ebola ELISA EC50 of mAb 13C6, 6D8 and KZ52 Ebola mAb ELISA 4 KZ52, 13C6, 6D8 3 2 1 13F6 0 1e-5 1e-4 0.001 0.01 0.1 1 10 100 1000 10000 conccentration (ug/ml) 4-P Fit: y = (A - D)/( 1 + (x/C)^B ) + D: A B C D R^2 mAb c13c6 (Group01: Dilution vs Values) 0.0539 1.14 EC 50 (g/mL) 0.0623 3.46 0.998
Slide 10: Structure of Ebolavirus Glycoprotein
Structure of Ebolavirus Glycoprotein • The crystal structure of Ebolavirus GP reveals a three- lobed chalice-like structure. • The three GP1 subunits (colored blue and green), mediate attachment to new host cells and are tethered together by the three GP2 subunits (white). • GP2 forms the protein ma
Slide 11: Comparison of crystal structure and vaccine nanoparticle
Comparison of crystal structure and vaccine nanoparticle GP1 GP2 2D TEM – Manual coloration Research conducted by J.E. Lee, M.L. Fusco, W.B. Oswald, A.J. Hessell, D.R. Burton, and E.O. Saphire (The Scripps Research Institute). Research Funding: U.S. National Institutes of Health, the Burroughs Wellc
Slide 12: Presentation Overview
Presentation Overview • Ebola Background • Novavax Ebola/Mak Glyoprotein Vaccine • Novavax saponin-based Matrix-M™ Adjuvant • Rapid Manufacturing Timeline • Pre-clinical Data 1212
Slide 13: Matrix-M Adjuvant Background - Saponins
Matrix-M Adjuvant Background - Saponins • Quillaja saponaria, the soap bark tree, is an evergreen tree native to Chile • Saponins (glycosides of terpenes and steroids) are extracted and purified from the bark of the tree General uses of saponins: Food – foaming agent in beverages (produce a stable
Slide 14: Matrix-M Adjuvant Background - Nanoparticle
Matrix-M Adjuvant Background - Nanoparticle 1414
Slide 15: Presentation Overview
Presentation Overview • Ebola Background • Novavax Ebola/Mak Glyoprotein Vaccine • Novavax saponin-based Matrix-M™ Adjuvant • Rapid Manufacturing Timeline • Pre-clinical Data 1515
Slide 16: Phase I: Manufacture 200L scale EBOV/Mak GP
Phase I: Manufacture 200L scale EBOV/Mak GP Master rBV 50L Wave Working rBV EBOV-GP EBOV-GP Sf9 WCB Culture flasks 50L Wave 200L Bioreactor Control Sf9 cells Harvest Cell Count 16
Slide 17: Purification EBOV/Mak GP
Purification EBOV/Mak GP 200L Cell Bioreactor harvest Cell harvest Centrifugation Cell lysis: GP trimers Filtration Anion exchange EBOV GP Affinity Cation exchange 0.2 µm filtration 30 – 40nm 17
Slide 18: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline 18
Slide 19: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Trigger Event 19
Slide 20: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Project Start Date 20
Slide 21: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Passage 1 recombinant baculovirus obtained 21
Slide 22: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Master Virus Seed (passage 2) available 22
Slide 23: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Drug substance manufacturing initiated to coordinate with MVS availability 23
Slide 24: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline The purification process needed to be defined prior to bioreactor harvest (and use available buffers) 24
Slide 25: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Purification process defined in time to update SOPs and batch records 25
Slide 26: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Drug product formulated and filled days after DS was manufactured. Formulation was based on protein assay 26
Slide 27: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline A critical item was the development of a “potency” assay for release and stability studies. This was never on the primary critical path 27
Slide 28: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline MVS, DS, and DP release testing occurred in parallel 28
Slide 29: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline Batch and QC record review occurred in parallel with processing and testing 29
Slide 30: EBOV/Mak GP Vaccine Manufacturing Timeline
EBOV/Mak GP Vaccine Manufacturing Timeline A GMP batch for a Phase I clinical study was released 3 months from project start 30
Slide 31: Matrix-M Manufacturing Timeline
Matrix-M Manufacturing was Matrix-M Manufacturing Timeline completed in 6 weeks and was never on the critical path 31
Slide 32: Presentation Overview
Presentation Overview • Ebola Background • Novavax Ebola/Mak Glyoprotein Vaccine • Novavax saponin-based Matrix-M™ Adjuvant • Rapid Manufacturing Timeline • Pre-clinical Data 3232
Slide 33: EBOV/Makona GP vaccine protected mice against lethal challenge with Ebola virus
EBOV/Makona GP vaccine protected mice against lethal challenge with Ebola virus Mice were challenged on day 42 with an intraperitoneal injection of 1,000 pfu mouse adapted EBOV/Mayinga 1976 strain 1One animal with an unrelated abdominal abscess and was dropped from the study. 33
Slide 34: Vaccine Response Story to be continued…
Vaccine Response Story to be continued… Wednesday, March 11, 2:15-3:00 34
Slide 35: Perspectives on Recombinant Baculovirus-Sf9 Platform Development and Manufacturing Process
Perspectives on Recombinant Baculovirus-Sf9 Platform Development and Manufacturing Process H7N9 Influenza VLP Vaccine 3535
Slide 36: Comparable Upstream Processes for VLP and Nanoparticle Vaccines
Comparable Upstream Processes for VLP and Nanoparticle Vaccines Advantages: • One master cell bank • Rapid generation of recombinant baculovirus • Platform cell expansion process • Known purification options 3636
Slide 37: 3-month Response Time from Gene Sequence to GMP Batch Release
3-month Response Time from Gene Sequence to GMP Batch Release Keys to success: • One master cell bank • Rapid generation of recombinant baculovirus • Platform cell expansion process • Known purification options • Rapid process confirmation at small scale • Rapid assay development • Forward processin
Slide 38: Recombinant Baculovirus-Sf9 Technology Enables a Rapid Response as a Countermeasure to Infectious Agent Threats
Recombinant Baculovirus-Sf9 Technology Enables a Rapid Response as a Countermeasure to Infectious Agent Threats Viral Threats Response Process Development & GMP Production • Vaccine candidate development • Process & assay development • Preclinical study expertise • 1000L GMP production Clinical stud
Slide 39: Ebola GP Vaccine - Author Recognition
Ebola GP Vaccine - Author Recognition 39
Slide 40: Ebola GP Vaccine – Employee Acknowledgements
Ebola GP Vaccine – Employee Acknowledgements 40