ABOUT DATAMONITOR HEALTHCARE

EXECUTIVE SUMMARY

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

PIPELINE OVERVIEW AND DYNAMICS

• Pipeline overview
- Traditional, well-stocked pipeline
- Growing PTH class hints at upcoming innovation
- Osteoporosis drug development not limited to big pharma
• Key companies involved in the osteoporosis pipeline
- Merck & Co.: coping with change
- Novartis: an old player with new strategies
- GlaxoSmithKline: A newcomer with a long-term approach
• Key R&D company strategies
- Optimizing administration
- The addition of mineral supplements: calcium and vitamin D
- Genericization: if you can not beat them, join them

OSTEOPOROSIS - MARKET POTENTIAL

• Definition of osteoporosis
- Etiology of osteoporosis
• Segmentation of osteoporosis
• Severity
- Gender: osteoporosis in men
- Niche populations
• Epidemiology of osteoporosis
- Methodological difficulties in assessing prevalence
- Prevalence of osteoporosis and osteopenia in postmenopausal women
- Prevalence of osteoporosis and osteopenia in men
- Osteoporotic fractures, their implications and minor risk groups
- Epidemiological trends
• Unmet needs in osteoporosis
- Unmet clinical needs
- Unmet environmental needs

R&D APPROACH

• Classification of pipeline products
- Bisphosphonates
- SERMs
- Calcitonins
- Parathyroid hormone (PTH) and analogues
- Dual action bone agents (strontium ranelate)
- Hormone replacement therapy (HRT)
- Vitamin D
- Other mechanisms of action
• Clinical trial design in osteoporosis
- Clinical trial guidelines
- Osteoporosis trial design and execution: can anything replace fracture data?
• Clinical trial endpoints in osteoporosis
- Fracture rate
- Changes in BMD
- Biochemical markers of bone turnover
- Surrogate endpoints: predicting fracture risk
- Changes in bone microarchitecture

BISPHOSPHONATE LATE-STAGE DRUG ANALYSIS AND FORECASTS

• Comparative forecasts
• Comparative Datamonitor drug assessment summaries
• Overview for bisphosphonates
- Definition of current comparator therapy - Fosamax
• Aclasta/Reclast (zoledronate/zoledronic acid)
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
• Bisponal/ONO-5920 (minodronic acid hydrate)
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
• MER-103 (alendronate sodium)
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
• Other drugs in the bisphosphonate class
- Nerixia (neridronic acid)

SERMS LATE-STAGE DRUG ANALYSIS AND FORECASTS

• Overview for SERMs
- Definition of current comparator therapy - Evista
• Bazedoxifene
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
• Other drugs in the SERM class
- Arzoxifene (LY353381)
- PSK-3471

CALCITONIN LATE-STAGE DRUG ANALYSIS AND FORECASTS

• Overview for calcitonins
- Definition of current comparator therapy - Miacalcin
• BN-002
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
PTH LATE-STAGE DRUG ANALYSIS AND FORECASTS
• Comparative forecasts
• Comparative Datamonitor drug assessment summaries
• Overview of PTH
- Definition of current comparator therapy - Forteo
• hPTH (1-34)
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
• Ostabolin-C
- Drug profile
- Satisfaction of unmet need
- Forecasts to 2016
- Datamonitor drug assessment summary
• Other drugs in the PTH class
• MBRI-93.02 (hPTH)

• Comparative forecasts
• Comparative Datamonitor drug assessment summaries
• Overview of 'other drugs'
- Definition of current comparator therapy
• Denosumab (AMG-162)
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
• ED-71
- Drug profile
- Satisfaction of unmet needs
- Forecasts to 2016
- Datamonitor drug assessment summary
• Other drugs in the class
- MK-0822
- NBS-101
- SHT-546

INNOVATIVE EARLY-STAGE PROJECTS

• Key Phase I compounds in osteoporosis
• ACE-011
- Potential to pioneer the provision of anti-resorptive and anabolic activity
• 2MD
- A high risk strategy for Pfizer
• Raloxifene (extended release)
- A reformulation to rival Evista

BIBLIOGRAPHY

• Journal papers and conference abstracts
• Websites

APPENDIX A

• Methodology
- Datamonitor forecast methodology
- Datamonitor drug assessment summary
• Contributing experts
• Report methodology

APPENDIX B

• About Datamonitor
- About Datamonitor Healthcare
• Datamonitor Healthcare's therapy area capabilities
- About the Women's Health analysis team
- Disclaimer

LIST OF TABLES

Table 1: Forecast key pipeline products for osteoporosis in the seven major markets ($), 2006 2016
Table 2: R&D pipeline in osteoporosis, 2007
Table 3: Causes of secondary (Type III) osteoporosis
Table 4: World Health Organization classification of osteoporotic bone loss
Table 5: Epidemiology overview of osteoporosis
Table 6: Prevalence of osteopenia and osteoporosis in postmenopausal women across the seven
major markets, 2007
Table 7: Prevalence of osteopenia and osteoporosis in men over 50 in the seven major markets, 2007
Table 8: Prevalence of vertebral fractures in men and women over 50 in the seven major markets, 2007
Table 9: UN projected population aged 50 years and over in 2017
Table 10: Summary of therapeutic classes in osteoporosis, by ATC code in alphabetical order
Table 11: Overview of currently marketed bisphosphonates indicated for use in osteoporosis treatment and prevention, 2007
Table 12: Overview of currently marketed SERM indicated for use in osteoporosis treatment and
prevention, 2007
Table 13: Overview of currently marketed calcitonins indicated for use in osteoporosis treatment and prevention, 2007
Table 14: Overview of currently marketed PTH drugs indicated for use in osteoporosis treatment and prevention, 2007
Table 15: Overview of currently marketed DABA products indicated for use in osteoporosis treatment and prevention, 2007
Table 16: Quantitative measures used for clinical efficacy endpoints in osteoporosis
Table 17: Summary of the biochemical markers of bone resorption and formation used to measure rate of bone turnover
Table 18: Late-stage bisphosphonates in development for osteoporosis
Table 19: Fosamax: key facts
Table 20: Defining the gold standard: key clinical trial results for Fosamax
Table 21: Novartis's HORIZON trial design, 2003
Table 22: Key events, approval and launch dates impacting Aclasta revenue forecasts for osteoporosis in the seven major markets, 2007- 2016
Table 23: Key events, approval and launch dates impacting Bisponal revenue forecasts for osteoporosis in the seven major markets, 2007- 2016
Table 24: Key events, approval and launch dates impacting MER-103 revenue forecasts for
osteoporosis in the seven major markets, 2007- 2016
Table 25: Late-stage SERMs in development for osteoporosis
Table 26: Evista key facts
Table 27: Key events, approval and launch dates impacting bazedoxifene revenue forecasts for
osteoporosis in the seven major markets, 2007- 2016
Table 28: Late-stage calcitonins in development for osteoporosis
Table 29: Miacalcin: key facts
Table 30: Forthcoming trials for BN-002
Table 31: Key events, approval and launch dates impacting BN-002 revenue forecasts for
osteoporosis in the seven major markets, 2007- 2016
Table 32: Late-stage PTH in development for osteoporosis
Table 33: Forteo: key facts
Table 34: Key events, approval and launch dates impacting hPTH revenue forecasts for osteoporosis in the seven major markets, 2007- 2016
Table 35: Key events, approval and launch dates impacting Ostabolin-C revenue forecasts for
osteoporosis in the seven major markets, 2007- 2016
Table 36: Other late-stage drugs in development for osteoporosis
Table 37: Key events, approval and launch dates impacting Denosumab revenue forecasts for
osteoporosis in the seven major markets, 2007- 16
Table 38: Key events, approval and launch dates impacting ED-71 revenue forecasts for
osteoporosis in the seven major markets, 2007- 2016
Table 39: Drugs in Phase I and preclinical development for osteoporosis, 2007
Table 40: Summary of therapeutic classes in osteoporosis, by ATC code in alphabetical order
Table 41: Estimation of launch dates by phase of development
Table 42: Estimated generic discounts by country, 2006*
Table 43: Estimates of brand erosion by following patent expiry by country
Table 44: Weightings of research and clinical factors used for pipeline drug assessment
Table 45: Weightings of commercial factors used for pipeline drug assessment

LIST OF FIGURES

Figure 1: Datamonitor's osteoporosis drug assessment summary for the seven major markets, 2007- 2016
Figure 2: Osteoporosis pipeline breakdown by development phase, 2007
Figure 3: The osteoporosis pipeline by phase and class of drug, 2007
Figure 4: Osteoporosis drugs and their overlap into other indications
Figure 5: Unmet clinical needs in osteoporosis, 2007
Figure 6: Unmet environmental needs in osteoporosis, 2007
Figure 7: Schematic showing steps of vitamin D activation
Figure 8: Datamonitor's comparative forecast of sales for the bisphosphonates across the seven major markets ($m), 2007-2016e
Figure 9: Datamonitor's competitive positioning analysis for Aclasta, MER-103 and Bisponal in the seven major markets, 2007-2016
Figure 10: Datamonitor's forecast of sales for Aclasta across the seven major markets ($m), 2007- 2016
Figure 11: Datamonitor's competitive positioning analysis for Aclasta in the seven major markets, 2007- 2016
Figure 12: Datamonitor's forecast of sales for Bisponal across the seven major markets ($m), 2007- 2016
Figure 13: Datamonitor's competitive positioning analysis for Bisponal in the seven major markets, 2007- 2016
Figure 14: Datamonitor's forecast of sales for MER-103 across the seven major markets ($m), 2007- 2016
Figure 15: Datamonitor's competitive positioning analysis for MER-103 in the seven major markets, 2007- 2016
Figure 16: Datamonitor's forecast of sales for bazedoxifene across the seven major markets
($m), 2007-2016
Figure 17: Datamonitor's competitive positioning analysis for bazedoxifene in the seven major markets, 2007-2016
Figure 18: Datamonitor's forecast of sales for BN-002 across the seven major markets ($m), 2007- 2016
Figure 19: Datamonitor's competitive positioning analysis for BN-002 in the seven major markets, 2007- 2016
Figure 20: Datamonitor's comparative forecast of sales for PTH across the seven major markets ($m), 2007-2016
Figure 21: Datamonitor's competitive positioning analysis for Ostabolin-C and hPTH in the seven major markets, 2007-2016
Figure 22: Datamonitor's forecast of sales for hPTH across the seven major markets ($m), 2007-
2016 Figure 23: Datamonitor's competitive positioning analysis for hPTh in the seven major markets, 2007- 2016
Figure 24: Datamonitor's forecast of sales for Ostabolin-C across the seven major markets ($m), 2007- 2016
Figure 25: Datamonitor's competitive positioning analysis for Ostabolin-C in the seven major markets, 2007-2016
Figure 26: Datamonitor's comparative forecast of sales for 'other drugs' across the seven major markets ($m), 2007-2016
Figure 27: Datamonitor's competitive positioning analysis for Denosumab and ED-71 in the seven major markets, 2007-2016
Figure 28: Datamonitor's forecast of sales for Denosumab across the seven major markets ($m), 2007- 2016
Figure 29: Datamonitor's competitive positioning analysis for Denosumab in the seven major markets, 2007-2016
Figure 30: Datamonitor's forecast of sales for ED-71 across the seven major markets ($m), 2007- 2016
Figure 31: Datamonitor's competitive positioning analysis for ED-71 in the seven major markets, 2007- 2016