ABOUT DATAMONITOR HEALTHCARE

• About the Infectious Diseases Pharmaceutical Analysis team

EXECUTIVE SUMMARY

• Scope of the analysis
• Datamonitor insight into the influenza vaccine market
• Key metrics
• Datamonitor Pipeline Assessment Summary

EPIDEMIOLOGY

• Incidence
• Risk groups
• Transmission and symptoms
• Diagnosis
• Virus subtypes
• Prevention and treatment
- Vaccination prevents influenza infection
- Antivirals can provide symptom relief and accelerate recovery
• Antigenic shift and drift
• Seasonal influenza epidemics
• Influenza pandemics
- Recent pandemics - fearsome lessons
- Current pandemic status - waiting for the wave
- H5N1 - the next pandemic virus?
- Pandemic scenario - dramatic outlook for public health and economy
- Preparing for disaster - national and international pandemic planning

MARKET DEFINITION AND OVERVIEW

• Market size and growth estimates
• Current vaccine classes
- Trivalent inactivated vaccines
- Life-attenuated influenza vaccines
• Vaccine manufacturing
- Egg-based manufacturing is lengthy and inflexible
- Cell-based manufacturing would offer big advantages
• Influenza vaccine supply - a yearly gamble
- The number of vaccine manufacturers is fluctuating
- Manufacturing capacities are expanding, but still not sufficient to meet global needs
- Manufacturing problems can have a dramatic impact - the Chiron case
- Influenza vaccine demand fluctuates considerably and is hard to predict
- Complex distribution pathways can delay timely vaccine supply
• Country analysis
- US - actively encouraging increased vaccination and influenza research
- EU5 - slowly waking up to the influenza challenge
- Japan - low awareness and distrust hamper vaccine uptake
• Unmet needs in influenza vaccines
- Pandemic vaccines could moderate the impact of a flu pandemic
- Extending of manufacturing capacities would guarantee sufficient vaccine supply
- Adjuvants could lead to better efficacy of vaccines in the elderly and reduce the amount of antigen needed for immunization
- Faster manufacturing techniques would make vaccine production more flexible
- Universal vaccines could eliminate the need for yearly updates
- Needle-free administration methods would make vaccination more convenient

CURRENT PLAYERS AND THEIR STRATEGIES

• Overview
• Sanofi pasteur - expanding market leadership
- Current position
- Strategic development
• Novartis Vaccines - recovering from Chiron's failure
- Current position
- Strategic development
• GSK - the lucky third
- Current position
- Strategic development
• MedImmune - new hope in pediatric treatment
- Current position
- Strategic development
• CSL - preparing to enter the US market
- Current position
- Strategic development
• Solvay - failing to commercialize on Influvac TC
- Current position
- Strategic development

PATIENT-BASED FORECAST ANALYSIS

• Datamonitor's patient-based forecasting model
• Limitations of the patient-based forecasting model R&D APPROACH
• Classification of pipeline products
- Seasonal influenza vaccines
- Pandemic influenza vaccines
• Clinical trial design in influenza vaccine studies

PIPELINE ANALYSIS SEASONAL INFLUENZA

• Pipeline overview for seasonal influenza
- Late-stage pipeline summary
- Comparative assessment
- Definition of current comparator therapy
• Optaflu (Novartis Vaccines)
- Drug overview
- Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
- Datamonitor drug assessment summary
• FluBlØk (Protein Sciences/UMN Pharma)
- Drug overview
- Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
- Datamonitor drug assessment summary
• Flu Improved (GlaxoSmithKline)
- Drug overview
- Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
- Datamonitor drug assessment summary
• Seasonal flu vaccines (Sanofi pasteur)
- Flu Micro-Injection
- Flu Infants
- Flu vaccine - new formulation
• FluInsure (GlaxoSmithKline)
- Drug overview
- Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
- Datamonitor drug assessment summary
• Immunostimulant seasonal influenza vaccine (Iomai)
- Drug overview
- Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
- Datamonitor drug assessment summary
• Late-stage pipeline vaccines developed outside the seven major markets
- Influsome-Vac (NasVax)
- LAIV (BioDiem, Nobilon)
• Early-stage vaccines for prevention of seasonal influenza
- DNA vaccines
- Universal vaccines
• Late-stage development compounds recently discontinued
- InfluJect (Baxter) - an uncertain future

PIPELINE ANALYSIS PANDEMIC INFLUENZA

• Pipeline overview for pandemic influenza
- Late-stage pipeline summary
- Comparative assessment
- Definition of current comparator therapy
• H5N1 vaccines
- Sanofi pasteur
- GSK
- Novartis Vaccines
- Baxter
- CSL
• H9N2 vaccines
- Novartis Vaccines
- GSK
- Crucell
• H2N2 vaccines
- GSK
• Early-stage vaccines for prevention of pandemic influenza

APPENDIX A - BIBLIOGRAPHY

APPENDIX B

• Limitations of IMS data
• About Datamonitor
- About Datamonitor Healthcare
• Datamonitor Healthcare's therapy area capabilities
- About the Infectious Diseases analysis team
- Key therapy team members
- Disclaimer

LIST OF TABLES

Table 1: Key influenza parameters for the seven major markets
Table 2: Companies developing cell-based manufacturing and US funding for cell culture development
Table 3: Current and future production capacity of key influenza vaccine manufacturers
Table 4: Influenza vaccination rates in the US, 2004
Table 5: Influenza vaccine catalog prices by manufacturer, US. 2005-06
Table 6: Influenza pandemic contracts announced to date
Table 7: Key needle-free influenza vaccine administration methods in development, 2007
Table 8: Acquisitions in the influenza vaccine space, 2005-06
Table 9: Fluzone dosages
Table 10: Fluvax dosages by age group
Table 11: Late-stage pipeline seasonal influenza, February 2007
Table 12: Datamonitor drug assessment parameters
Table 13: Fluzone (Sanofi pasteur) - product profile
Table 14: Fluzone formulations, 2006-07
Table 15: Fluzone - efficacy in children aged 6-24 months
Table 16: Optaflu (Novartis) - product profile
Table 17: Optaflu - clinical trial summary
Table 18: FluBlØk (Protein Sciences) - product profile
Table 19: FluBlØk - clinical trial summary
Table 20: Flu Improved (GSK) - product profile
Table 21: Flu Improved - clinical trial summary
Table 22: FluInsure (GSK) - product profile
Table 23: FluInsure - clinical trial summary
Table 24: Immunostimulant seasonal influenza vaccine (Iomai) - product profile
Table 25: Early-stage seasonal and universal influenza vaccines, February 2007
Table 26: Key DNA flu vaccines in development
Table 27: Recently discontinued late-stage influenza vaccines
Table 28: Pandemic influenza - late-stage pipeline overview
Table 29: H5N1 influenza virus vaccine (Sanofi pasteur) - product profile
Table 30: Daronrix (GSK) - product profile
Table 31: H5N1-007 (GSK) - product profile
Table 32: Focetria (Novartis) - product profile
Table 33: H5N1 pandemic vaccine (Baxter) – product profile
Table 34: H5N1 pandemic vaccine (CSL) - product profile
Table 35: H9N2 pandemic vaccine (Novartis) – product profile
Table 36: H9N2 pandemic vaccine (GSK) - product profile
Table 37: H9N2 pandemic vaccine (Crucell) – product profile
Table 38: H2N2 pandemic vaccine (GSK) - product profile
Table 39: Early stage pipeline pandemic influenza vaccines, February 2007

LIST OF FIGURES

Figure 1: Drivers and restrictors in the influenza vaccine market
Figure 2: Influenza vaccine market size forecast (7MM), 2006-16
Figure 3: Datamonitor pipeline assessment summary - seasonal influenza vaccines
Figure 4: Datamonitor pipeline assessment summary - pandemic influenza vaccines
Figure 5: Global annual influenza disease burden
Figure 6: Population at high risk of influenza infection or influenza-associated complications
Figure 7: Influenza A virus: structure and electron micrograph
Figure 8: Antigenic drift versus antigenic shift
Figure 9: Recommended vaccination schedule and months of peak influenza activity, US 1976-2006
Figure 10: Development of a pandemic influenza virus
Figure 11: Overview over influenza pandemics in the 20^th century
Figure 12: WHO and CDC classification systems for pandemic threat
Figure 13: Emergence of new Influenza A subtypes, 1977- 2006
Figure 14: Cumulative number of confirmed human cases of avian Influenza A/(H5N1)
Figure 15: Spread of H5N1 in poultry, wild birds and humans, 1996-2006
Figure 16: Current spread of H5N1 in poultry and wild birds, January 2007
Figure 17: Geographical spread of influenza vaccine sales, 2006
Figure 18: Growth drivers of the flu vaccine market
Figure 19: TIV and LAIV - key common and differentiating factors
Figure 20: Steps of the influenza vaccine manufacturing process and involved stakeholders
Figure 21: Egg-based vaccine manufacturing
Figure 22: Comparative analysis of MDCK, Vero and
Per.C6 cells
Figure 23: Vaccine providers for the US market, 2000-06
Figure 24: Vaccine manufacturers in the seven major markets, 2006
Figure 25: Global influenza vaccine manufacturing capacity, 1994-2006
Figure 26: Influenza vaccine manufacturing facilities, 2006
Figure 27: High-risk individuals recommended for flu vaccination, US. 2004-05
Figure 28: Chiron - share price in response to events, Aug 2004- May 2005
Figure 29: Expected, delivered and demanded influenza vaccine supply for the US, 2004-05 season
Figure 30: Influenza vaccine supply versus demand in the US, 1980-2006
Figure 31: Flu vaccine supply and demand in relation to population recommended for vaccination, US 2003-06
Figure 32: Supply versus demand in a typical flu season
Figure 33: Global influenza vaccination coverage, 2002-03 season
Figure 34: Drivers and restrictors for influenza vaccination
Figure 35: US influenza vaccine distribution network
Figure 36: Use of different providers for influenza vaccination, US, 2005-06
Figure 37: US government strategies to foster growth of the national flu vaccine market
Figure 38: US average prices per dose in multi-dose vials, TIVs, 2002-06
Figure 39: Unmet needs in influenza vaccines
Figure 40: Leading players in the influenza vaccine market, US and EU5, 2005
Figure 41: Sanofi pasteur - influenza vaccine strategy
Figure 42: Novartis Vaccines - influenza vaccine strategy
Figure 43: GSK - influenza vaccine strategy
Figure 44: MedImmune - influenza vaccine strategy
Figure 45: CSL - influenza vaccine strategy
Figure 46: Solvay - influenza vaccine strategy
Figure 47: Influenza vaccine clinical trial process
Figure 48: Datamonitor's assessment of seasonal influenza pipeline vaccines
Figure 49: Fluzone - strengths and weaknesses
Figure 50: Comparison of seroprotection rates between Optaflu and Agrippal in EU Phase III trial, 2006
Figure 51: Optaflu - Datamonitor's competitive positioning analysis for seasonal influenza, 2007
Figure 52: FluBlØk: - efficacy results of Phase IIb trial
Figure 53: FluBlØk - Datamonitor's competitive positioning analysis for seasonal influenza, 2007
Figure 54: Flu Improved - Datamonitor's competitive positioning analysis for seasonal influenza, 2007
Figure 55: FluInsure - Datamonitor's competitive positioning analysis for seasonal influenza, 007
Figure 56: Iomai's immunostimulant seasonal influenza accine - Datamonitor's competitive positioning analysis for seasonal influenza, 2007
Figure 57: Pandemic versus pre-pandemic vaccination trategy
Figure 58: Datamonitor drug assessment summary - andemic influenza pipeline vaccines
Figure 59: Datamonitor's competitive positioning analysis of H5N1 influenza virus vaccine (Sanofi asteur) for pandemic influenza, 2007
Figure 60: Datamonitor's competitive positioning analysis of Daronrix (GSK) for pandemic influenza, 2007
Figure 61: Datamonitor's competitive positioning analysis of H5N1-007 (GSK) for pandemic influenza, 2007
Figure 62: Datamonitor's competitive positioning analysis of Focetria (Novartis) for pandemic influenza, 2007