March 26-28, 2008 Pennsylvania Convention Center

1. Disposable Manufacturing System for Rapid Mass Production of Influenza Vaccine James Robinson, PE Vice President, Technical & Quality Operations Novavax, Inc. Bob Bader Senior Manager Technology - Pharma Bio Jacobs Engineering March 26-28, 2008 Pennsylvania Convention Center

2. Influenza Vaccine Manufacturing Today Agenda • Today’s Flu Vaccines • The ‘Ideal’ Flu Vaccine • Virus-Like Particle Flu Vaccine in Insect Cells • Advantages of VLP Vaccine Manufacturing • Economic Impact of Disposable Manufacturing Systems in Influenza Manufacturing • Summary

3. Influenza Vaccine Manufacturing Today US Licensed • Inactivated influenza vaccines • Whole virion • Split virion • Live-attenuated vaccines Approaching Licensure • Adjuvanted inactivated vaccines* • Recombinant HA vaccine In Development • Virus-Like Particles • DNA Vaccines • Universal Flu Vaccines *some licensed in EU

4. Influenza Vaccine Manufacturing Today • Vast majority (>90%) of licensed capacity is in egg-based products • Reliable process for seasonal production • Potential loss of supply in an avian flu outbreak • First cell culture facilities are coming on line in Europe • Significant investment in new US facilities continues • Egg ($1.5 capital/dose capacity) and cell-culture ($3/dose) • Demand promises to grow with supply • Expanded recommendations • Pandemic preparedness • Market shortages globally

5. Pandemic Influenza Vaccine Manufacturing Challenges • Non-adjuvanted pandemic vaccines to date have required increased doses for a protective HAI response • Yield of pandemic vaccine production in eggs is lower than seasonal strains • The likelihood of a pandemic event is driving increased capacity and advances in flu technology • Risk of overcapacity for seasonal markets • The time required to obtain high-producing non-pathogenic strains challenges a fast delivery of pandemic vaccine once a pandemic is declared • Virus mutations could greatly reduce the value of the vaccine stockpiles created.

6. Influenza Vaccine Manufacturing Tomorrow • Vaccine supply that does not rely on egg-based production • High yielding process supporting a robust response with less investment • Fast response to an emerging influenza strain • Cross-protective product for antigenic drift • Flexible facility that supports other products when not producing for a pandemic threat • Rapid scale-up • Improved stability • Available regionally    +/-     +/-   

7. Influenza Vaccine Manufacturing in Insect Cells • Novavax, Inc. is developing an Influenza Virus-Like Particle (VLP) Vaccine as an alternative to traditional influenza vaccines • The process uses recombinant baculovirus to infect and express VLPs that contain Hemagglutinin (HA), Neuraminidase (NA), and Matrix (M1) Protein • The proteins self-assemble as particles that resemble influenza virus, but do not contain flu RNA • The approach has a number of quality and manufacturing advantages to the traditional influenza manufacturing processes

8. Cryo-electron Microscopy of Pleomorphic VLPs A/Indo H5N1 VLPs

9. Why Recombinant Influenza VLP Vaccine • Speed from strain selection to product release is weeks • Exact genetic match • Recombinant VLP’s are clinically proven (HPV, HBsAg) with a broad immune response • Improved immunogenicity of flu VLPs (vs. split virion vaccine) in preclinical studies • No eggs • Yields are higher than egg-based production; potential for additional increase in yield • No pathogenic virus in manufacturing • Controlled cell culture process (Serum-free, Protein-free, Suspension Culture) • The use of this approach has allowed Novavax, Inc to develop a process that uses disposable equipment and closed systems for product processing

10. Faster Delivery of First Dose 9+ week advantage Product Availability Cloning & Seed Prep Mfg & Fill 1st Lot Release & Ship NOVAVAX 24 wks 28 wks 8 wks 12 wks 16 wks 20 wks 4 wks Traditional Wait for Reagents RG pathogenicity Form/Fill, Release & Ship Mfg sequence available

11. Remove Cells, Purify Virus Inactivate Virus Cell Substrate Preparation Infect & Incubate Influenza Vaccine Production Traditional Flu Vaccine Production*: LS/HS Centrifugation, Diafiltration, Chromatography Grow, Collect, & Fertilize Eggs Treat with Formaldehyde (subvirion products treated with detergent) Infect with Influenza Virus Incubate Thaw vial from WCB Grow to Mfg Scale Insect Cell Culture-Based Flu Vaccine Production: Infect with Recombinant Baculovirus, Incubate Thaw vial from WCB Grow to Mfg Scale baculovirus inactivated MF/DF, Chromatography

12. Remove Cells, Purify Virus Inactivate Virus Cell Substrate Preparation Infect & Incubate Influenza Vaccine Production Traditional Flu Vaccine Production*: Infect Incubate Candle Chill Harvest Insect Cell Culture-Based Flu Vaccine Production:

13. Remove Cells, Purify Virus Inactivate Virus Cell Substrate Preparation Infect & Incubate Influenza Vaccine Production Traditional Flu Vaccine Production*: Insect Cell Culture-Based Flu Vaccine Production:

14. Influenza Vaccine Production Relative Influenza Process Yield egg based current insect cell process Relative Yield (Doses/L) cell-based 15 30 45 90 mcg/dose

15. Influenza Vaccine Production Process Equipment Comparison

16. Influenza Vaccine Production Support Equipment Comparison

17. Influenza Vaccine Production Traditional Flu Vaccine Production Capital Costs: egg-based facility USA 100M doses/year (600K eggs/day) 140K square feet $150M mammalian cell culture facility USA 100M doses/year 140K square feet $300M Insect Cell Culture-Based Flu Vaccine Production: Novavax, Inc Insect Cell Culture Rockville, MD Disposable Approach 75M doses/year 55K square feet $40M Benchmark cell culture facility 2 – 5,000L reactors Traditional Approach Fully automated downstream $225M

18. Comparison of Project Duration Design Egg Based Process Construction Commissioning Qualification Validation Design Construction Commissioning Insect Cell Culture Qualification Validation Time Saved Time, yrs 0 1 2 3 4 Influenza Vaccine Production

19. Comparison of Project Duration Design Egg- Based Process Construction Commissioning Qualification Validation Design Earlier Revenue Generation Construction Commissioning Insect Cell Culture Qualification Validation Time Saved Time, yrs 0 1 2 3 4 Influenza Vaccine Production Faster Payback on Smaller Investment

20. 49% Utility Comparison 1.0 Egg Based Egg Based VLP 8% VLP 0.0 Process Utilities Building Utilities

21. Influenza Vaccine Production Traditional Flu Vaccine Production Unit Costs: Relative Variable costs Relative Fixed costs Egg-based materials labor depreciation utilities Mammalian cell culture materials labor depreciation utilities Insect Cell Culture-Based Flu Vaccine Production Unit Costs: Relative Variable costs Relative Fixed costs materials depreciation utilities labor COGS = unit variable costs + fixed costs units made Lower fixed cost reduces dependence on production volume for low unit cost. Higher yields drive lower variable costs.

22. Influenza Vaccine ProductionThe Disposable Approach • Advantages of Disposable/Closed Manufacturing Approach • Reduced process equipment complexity • Reduced facility complexity and cost • Faster Construction, Commissioning, and Launch • Rapid expansion of capacity • No change-over cleaning/validation between strains/products • LEAN manufacturing approach • Significant reduction in facility/equipment validation (>50%) • Manufacturing cost structure shifted to variable costs • Significant reduction in capital equipment costs (>70%) • Supports a regional manufacturing approach

23. Influenza Vaccine ProductionThe Disposable Approach Traditional Flu Vaccine Production: Large, central manufacturing facilities Located in developed countries Supported by complex site infrastructure ~100M doses $150 – $300M Egg Based Facility $150,000,000 Sq ft 145,000 Insect Cell Culture-Based Flu Vaccine Production: Facilities Distributed Globally Located where vaccine is needed Requiring little local infrastructure 10 – 20 M doses (75M dose plant for ~$40M) NVAX VLPs Facility $40,000,000 Sq ft 55,000

24. Influenza Vaccine ProductionThe Disposable Approach Summary • Production of Recombinant Influenza VLP Vaccine offers a favorable alternative to traditional manufacturing approaches • The elimination of the pathogenic virus in the manufacturing process eliminates containment concerns and allows use of disposable systems • Disposable systems provide significant economic benefits to influenza manufacturing • Lower Capital Cost • Faster Facility Start-up • Rapid Expansion of Capacity • Faster Investment Payback • These benefits are well aligned with the needs of a global influenza solution for pandemic and seasonal disease