Contents:

Chapter 1. Executive summary Scope of the analysis 3 Insight into the colorectal cancer market 4 High incidence of colorectal cancer and unmet needs in diagnosis and treatment present a significant opportunity for pharmaceutical and biotechnology companies 4 The emergence of third-generation cytotoxics has shifted the colorectal cancer treatment paradigms in recent years, significantly improving patient prognosis and resulting in high uptake of these drugs. However, Pfizers Camptosar/Campto (irinotecan) and Sanofi-Aventiss Eloxatin (oxaliplatin) will face generic competition, especially in the EU, in the coming years, and sales are expected to decline during the forecast period 4 Genentech/Roches Avastin (bevacizumab) will continue to show strong sales growth, particularly in Europe where it has yet to become widely used. However, the launch of Amgens Vectibix (panitumumab) will signficantly affect sales of BMS/Merck KGaA/ImClones Erbitux (cetuximab) due to clinical and cost advantages of the former 5 There are few drugs currently in Phase III development for colorectal cancer despite the high unmet needs in the disease. We believe that Amgens Vectibix (panitumumab), approved in September 2006 is likely to overtake Erbitux as the leading monoclonal antibody EGFR inhibitor for colorectal cancer and is predicted to achieve blockbuster status by 2015 6 Key metrics 8 Incidence 8 Sales forecasts to 2015 8 Pipeline assessment summary 10 Chapter 2. Patient potential Overview 21 Definition of colorectal cancer 21 Epidemiology 22 Incidence 22 Comparison of incidence with other major tumor types 24 Prevalence 26 Unmet need in colorectal cancer 27 Lack of identifiable risk factors 27 Lack of effective diagnostic tests as screening tools 28 Poor prognosis 29 Disease recurrence 31 Chapter 3. Country market assessments Current and future opportunities and threats in the cancer market 32 Global opportunities and threats 32 Opportunities 32 Threats 36 US: opportunities and threats 41 Opportunities 41 Threats 42 Japan: opportunities and threats 43 Opportunities 43 Threats 44 EU5: opportunities and threats 46 Opportunities 46 Threats 49 France: opportunities and threats 51 Opportunities 51 Threats 51 Germany: opportunities and threats 53 Opportunities 53 Threats 53 Italy: opportunities and threats 55 Opportunities 55 Threats 56 Spain: opportunities and threats 58 Opportunities 58 Threats 58 UK: opportunities and threats 59 Opportunities 59 Threats 60 Summary of environmental issues affecting the cancer market size 62 Chapter 4. R&d approach Classification of pipeline and marketed products for colorectal cancer 63 Cytotoxics 63 L1A Alkylating agents 63 L1B Antimetabolites 64 L1C Vinca alkaloids and other plant-derived products 64 L1D Antineoplastic antibiotics 64 L1X2 Platinum compounds 65 Targeted therapies 65 L1X3 Antineoplastic monoclonal antibodies 65 L1X9 All other antineoplastics 65 Chapter 5. Marketed drug analysis & forecasts Marketed drugs 67 Roche/Chugais Xeloda (capecitabine) 68 Leading agent in the third-line market 68 Growth from the adjuvant market 69 Avastin as a suitable partner? 70 Pfizer/Yakult/Daiichis Camptosar/Campto/Topotecin (irinotecan) 73 Irinotecans stigma of toxicity 73 Camptosar losing grounds to competitors 74 EU physicians use irinotecan due to Avastins labeling 77 Irinotecan limited to second-line use 77 Patent expiry 77 Sanofi-Aventiss Eloxatin (oxaliplatin) 78 Gold standard for colorectal cancer 79 Neuropathy remains the main barrier 80 Generic oxaliplatin entering the EU markets 81 US patent remains protected until 2013 82 Elplat surpassing Campto in Japan 82 Genentech/Roche/Chugais Avastin (bevacizumab) 82 Avastin is the gold standard in the US 83 Limitations in Europe 83 Market expansion potential 84 Is toxicity a major limiting factor? 87 Cost implications of Avastin plus Erbitux 88 Bristol-Myers Squibb/Merck KGaA/ImClones Erbitux (cetuximab) 89 Standard therapy in third line 89 Futility of EGFR tests 90 Line extensions in colorectal cancer 91 Cost hampering the uptake 93 Competition from Vectibix 93 Forecasting assumptions and events 95 Sales forecasts to 2015 97 Chapter 6. Pipeline analysis Pipeline overview 99 Pre-registration/Phase III pipeline drugs 101 Phase II pipeline drugs 101 Phase I/II pipeline drugs 103 Pipeline drugs by class 104 Key companies 106 Key companies involved in current products for colorectal cancer 106 Sanofi-Aventiss over-reliance on colorectal cancer 107 Low reliance on colorectal cancer for Roche 107 Genentechs sales are almost exclusively from the cancer franchise 107 Chapter 7. Late-stage pipeline drug analysis & forecasts Pipeline 110 Amgens Vectibix (panitumumab) 110 Clinical trial data 111 Factors driving sales of Vectibix 116 ADVENTRX Pharmaceuticals CoFactor (ANX-510) 116 Phase II trials 117 Ongoing trials 117 Merck Eprova and ADVENTRX 118 The rise of Xeloda will make CoFactor redundant 118 Need to corner the adjuvant market 119 Pro-Pharmaceuticals Davanat 119 Ongoing trials 120 Dearth of data 121 Novartis/Schering AGs vatalanib (PTK-787) 121 Anticipated regulatory filing for vatalanib in colorectal cancer is becoming increasingly unlikely following disappointing CONFIRM-1 and CONFIRM-2 interim results 121 Vatalanib unlikely to compete with Avastin 122 Two possible strategies to salvage vatalanib 122 Go or no-go? 123 Forecasting assumptions 124 Sales forecasts to 2015 124 Drug assessment summary 126 Chapter 8. Commercial impact & lifecycle management: case studies Case study 1 128 Lifecycle management of Eloxatin 128 Eloxatin events 128 FOLFOX as standard therapy 129 Consolidation of Eloxatin with aqueous formulation 132 Minimizing neuropathy 133 Genericization of oxaliplatin in the EU 134 Case study 2 134 Cost-scenario-based forecasts for Vectibix 134 Higher cost will lead to lower uptake 134 Sales forecasts for Vectibix in different cost scenarios 135 Chapter 9. Appendix a Market forecasts 139 US forecasts 139 Japan forecasts 139 France forecasts 140 Germany forecasts 140 Italy forecasts 141 Spain forecasts 141 UK forecasts 142 Five EU market forecasts 142 Seven major market forecasts 143 Market data 143 Chapter 10. Appendix b Contributing experts 146 Reference 146 Report methodology 150 Epidemiology forecasts 150 Product forecast methodology 150 Estimating peak sales 150 Treatable population size 150 Market penetration rate 151 Drug costs 152 Treatment duration 152 Eventing 152 Plotting the sales curve 153 Drug assessment summary List of Tables List of Figures Table 1: Incidence forecasts of colorectal cancer in the seven major pharmaceutical markets, 2002-2016 8 Table 2: Sales forecasts for marketed and pipeline drugs in the seven major markets between 2006 and 2015 9 Table 3: Summary of commercial and research/clinical attractiveness of late-phase drugs for colorectal cancer, 2006 10 Table 4: Crude incidence rates of colorectal cancer by gender (per 100,000 population) in the seven major pharmaceutical markets, 2002 22 Table 5: Incidence of colorectal cancer in the seven major pharmaceutical markets, 2002-2016 23 Table 6: Comparative incidence of major tumor types, 2002 24 Table 7: One-, three- and five-year prevalence of colorectal cancer in the seven major markets 26 Table 8: Incidence of colorectal cancer by risk category 28 Table 9: Summary of characteristics of screening tests 29 Table 10: Definition of the cancer market, based on the Anatomical Therapeutic Chemical Classification System, 2006 63 Table 11: Marketed drugs for colorectal cancer 68 Table 12: Global sales growth of Xeloda between 2002 and 2005 69 Table 13: Quarter-by-quarter sales and sales growth of Avastin in the US 84 Table 14: Ongoing Phase III trials for Erbitux 92 Table 15: Cost of major drug regimens for colorectal cancer 93 Table 16: Unevented forecasting assumptions for marketed drugs for colorectal cancer in the seven major markets 95 Table 17: Events used in sales forecast estimation of marketed drugs for colorectal cancer in the seven major markets 96 Table 18: Evented sales forecasts for marketed drugs in the seven major markets between 2006 and 2015 97 Table 19: Number of marketed and pipeline colorectal cancer drugs 99 Table 20: Phase III pipeline drugs for colorectal cancer 101 Table 21: Phase II pipeline drugs for colorectal cancer 102 Table 22: Phase I and Phase I/II pipeline drugs for colorectal cancer 103 Table 23: Number of pipeline drugs for colorectal cancer by class and phase 104 Table 24: Reliance of key companies on the oncology franchise and colorectal cancer, 2005 106 Table 25: Phase III pipeline drugs for colorectal cancer 110 Table 26: Ongoing clinical trials of Vectibix for colorectal cancer 111 Table 27: Ongoing clinical trials involving CoFactor in metastatic colorectal cancer, 2006 117 Table 28: Ongoing clinical trials involving Davanat in metastatic colorectal cancer, 2006 120 Table 29: Unevented forecasting assumptions for pipeline drugs for colorectal cancer in the seven major markets 124 Table 30: Sales forecasts for pipeline drugs in the seven major markets between 2006 and 2015 124 Table 31: Summary of commercial and research/clinical attractiveness of late-phase drugs for colorectal cancer, 2006 126 Table 32: Sales of Eloxatin and Camptosar/Campto by quarter 131 Table 33: Forecasting assumptions for Vectibix for colorectal cancer in the seven major markets 135 Table 34: Scenario-based sales forecasts for Vectibix in the seven major markets between 2006 and 2015 137 Table 35: US forecasts for marketed and pipeline drugs in colorectal cancer to 2015 139 Table 36: Japan forecasts for marketed and pipeline drugs in colorectal cancer to 2015 139 Table 37: France forecasts for marketed and pipeline drugs in colorectal cancer to 2015 140 Table 38: Germany forecasts for marketed and pipeline drugs in colorectal cancer to 2015 140 Table 39: Italy forecasts for marketed and pipeline drugs in colorectal cancer to 2015 141 Table 40: Spain forecasts for marketed and pipeline drugs in colorectal cancer to 2015 141 Table 41: UK forecasts for marketed and pipeline drugs in colorectal cancer to 2015 142 Table 42: Five EU market forecasts for marketed and pipeline drugs in colorectal cancer to 2015 142 Table 43: Seven major market forecasts for marketed and pipeline drugs in colorectal cancer to 2015 143 Table 44: Xeloda: key facts 143 Table 45: Camptosar: key facts 144 Table 46: Eloxatin: key facts 144 Table 47: Avastin: key facts 145 Table 48: Erbitux: key facts 145 Table 49: Specific events used in Commercial/Pipeline Insight: Colorectal Cancer for sales forecast estimation of marketed drugs 153 Table 50: Sales of marketed drugs for colorectal cancer in 2005 155 Table 51: Drug assessment parameters List of Figures Figure 1: Sales forecasts for marketed and pipeline drugs in the seven major markets between 2006 and 2015 9 Figure 2: Drug assessment summary for pipeline colorectal cancer drugs, 2006 11 Figure 3: Incidence of colorectal cancer in the seven major pharmaceutical markets in 2006 and 2016 23 Figure 4: Comparative incidence of major tumor types, 2002 25 Figure 5: One-, three- and five-year cumulative prevalence of colorectal cancer in the seven major markets 27 Figure 6: Five-year survival rates for the four major tumors between 1975 and 1988 in the US 30 Figure 7: Seven market population aged 60 and over, 2000-50 32 Figure 8: Increasing incidence of colorectal cancer with age 33 Figure 9: Summary of global opportunities and threats affecting the cancer market, 2006 62 Figure 10: Improving survival with newer drug regimens in colorectal cancer 67 Figure 11: Global sales growth of Xeloda between 2002 and 2005 70 Figure 12: Percentage of first-line patients treated with oxaliplatin- and irinotecan-based regimens in the seven major markets 75 Figure 13: Global sales of Eloxatin and Campto/Camptosar by quarter 76 Figure 14: Proportion of Eloxatin sales in 2005 by market 79 Figure 15: Quarter-by-quarter sales and sales growth of Avastin in the US 85 Figure 16: Sales of Avastin by quarter in the US and Europe/RoW 86 Figure 17: Sales forecasts for marketed drugs in the seven major markets between 2006 and 2015 97 Figure 18: Number of marketed and pipeline colorectal cancer drugs 100 Figure 19: Number of pipeline drugs for colorectal cancer by class and phase 105 Figure 20: Reliance of key companies on the oncology franchise in 2005 108 Figure 21: Reliance of key companies on the oncology franchise in 2005 109 Figure 22: Sales forecasts for pipeline drugs in the seven major markets between 2006 and 2015 125 Figure 23: Drug assessment summary for pipeline colorectal cancer drugs, 2006 127 Figure 24: Event timeline for Eloxatin 128 Figure 25: Percentage of first-line patients treated with Eloxatin- and Camptosar-based regimens in the seven major markets 130 Figure 26: Sales of Eloxatin and Camptosar/Campto by quarter 132 Figure 27: Sales of aqueous and lyophilized formulations of Eloxatin in the US in 2005 133 Figure 28: Scenario-based sales forecasts for Vectibix in the seven major markets between 2006 and 2015 137 Figure 29: Example of Drug assessment scorecard 157 Figure 30: Example of Drug assessment graph 158