Contents:

Executive Summary Chapter 1 Kinases as drug targets Summary Introduction Overview of human protein kinases Classification schemes Kinases in signal transduction pathways MAPK pathways MAPK (ERK) pathway JNK/SAPK pathway MAPK14 pathway PI3K/AKT signaling JAK/STAT signaling NFKB pathway Insulin receptor signaling Immune cell signaling T cell receptor signaling B-cell receptor complexes Signaling in vascular morphogenesis VEGF receptor signaling EGF receptor signaling Cyclic nucleotide metabolism Cell cycle checkpoint controls Categories of kinase-targeted drugs Small molecules Monoclonal antibodies Emerging biopharmaceuticals Kinase drug audit Chapter 2 Small molecule kinase inhibitor discovery Summary Introduction Mechanisms of kinase inhibition ATP competitive inhibitors Irreversible inhibitors Allosteric inhibitors Approaches to kinase inhibitor discovery Traditional kinase inhibitor discovery High-throughput screening of compound libraries Lead optimization Synthesis of inhibitor analogs Structure-informed drug design Structure-informed drug re-design Fragment-based drug discovery Kinase inhibitor selectivity assays Protein selectivity assays Kinase activity assays Kinase binding assays Cellular selectivity assays Identifying substrates of kinases Chapter 3 Targeting kinases in cancer Summary Overview of cancer Established and emerging therapies Therapeutic potential of kinase inhibition Types of kinase targets Mutationally-activated kinases Kinases which sustain tumor growth Kinases with roles in tumorigenesis Top 20 kinase targets Group: TK ABL1 (Abl family) Target characteristics Inhibitors on the market Inhibitors in development EGFR and ERBB2 (EGFR family) Target characteristics Approaches to EGFR inhibition Inhibitors on the market Inhibitors in development FLT3, KIT, PDGFRA, and PDGFRB (PDGFR family) Target characteristics Inhibitors on the market Inhibitors in development FLT1, FLT4, and KDR (VEGFR family) Target characteristics Inhibitors on the market Inhibitors in development JAK2 (JakA family) Target characteristics Drugs in development MET (Met family) Target characteristics Agents in development Group: AGC AKT1 (AKT family) Target characteristics Drugs in development Group: CMGC CDC2 and CDK2 (CDK family; CDC2 subfamily) Target characteristics Drugs in development Group: Other AURKA and AURKB (AUR family) Target characteristics Drugs in development PLK1 (PLK family) Target characteristics Drugs in development Group: Atypical Target characteristics Inhibitors on the market Inhibitors in development Dual specificity lipid/protein kinases PIK3CA (PI3K) Target characteristics Inhibitors in development Future trends Chapter 4 Non-cancer applications of kinase drugs Summary Introduction Chronic inflammation and kinases Leading indications Arthritis Diabetes Inflammation Immunosuppression Ophthalmology Psoriasis Pulmonary diseases Cardiovascular Myelodysplastic disorders GI disorders Pain Leading kinase targets MAPK14 Target characteristics Inhibitors in development FRAP1 Target characteristics Inhibitors on the market Inhibitors in development JAK3 Target characteristics Inhibitors in development NTRK1 Target characteristics Inhibitors in development ROCK1 Target characteristics Inhibitors on the market Inhibitors in development Chapter 5 Leading kinase drug originating companies Summary/Introduction 5.1 Abbott Laboratories Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Ambit Biosciences Corp Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Amgen Inc Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Array BioPharma Inc Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline AstraZeneca plc Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Avila Therapeutics Inc Company overview Kinase drug pipeline Boehringer Ingelheim GmbH Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Bristol-Myers Squibb Co Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Cephalon Inc Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Deciphera Pharmaceuticals LLC Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Eli Lilly Co Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Exelixis Inc Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline GlaxoSmithKline plc Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Hoffmann-La Roche Ltd Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Johnson & Johnson Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Kyowa Hakko Kirin Co Ltd Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Novartis International AG Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Pfizer Inc Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Sanofi-Aventis Group Company overview Kinase drug pipeline Wyeth Company overview Kinase-related collaborations (2005 onwards) Kinase drug pipeline Chapter 6 Market Analysis: Trends and Forecasts Summary Prevalence of targeted diseases Analyses and Forecasts by Type of Agent Limus agents/mTOR inhibitors Overview Standalone mTOR inhibitors Drug-eluting stents Drug-eluting stent market Sirolimus-eluting stents Everolimus- and zotarolimus-eluting stents Sales trends in mTOR inhibitors Forthcoming mTOR inhibitors EGFR Family inhibitors Overview Trastuzumab Erlotinib Cetuximab Gefitinib Panitumumab Lapatinib Nimotuzumab Sales trends in EGFR Family inhibitors Forthcoming EGFR Family Inhibitors ABL/FLT3 Group Inhibitors Overview Imatinib Dasatinib Nilotinib Sales trends in ABL1/FLT3 Family Inhibitors Forthcoming ABL1/FLT3 Family Inhibitors VEGFR Family Overview Sunitinib Sorafenib Sales trends in VEGFR Family inhibitors Forthcoming VEGFR Family Inhibitors Other launched agents Overview Fasudil Pirfenidone Sales trends of other agents Other forthcoming agents Company sales and trends Patenting trends Appendix 1 Kinase-related targets and their abbreviations Appendix 2 Other abbreviations and acronyms Appendix 3 Research Methodology Index List of Figures Figure 1.1: Leading kinase-targeted drug applications Figure 1.2: Kinase target landscape Figure 6.3: Kinase originator market shares List of Tables Table 1.1: Human Kinase Gene Audit Table 1.2: Hanks Classification of Protein Kinases (1995) Table 1.3: Hanks Classification of Protein Kinases (1995) (continued) Table 1.4: Kinase Agents by Development Stage Table 1.5: Kinase Drugs by Product Type Table 1.6: Leading developers of therapeutic kinase-targeted drugs Table 1.7: Kinase Agonists and Stimulants Table 3.8: Kinases implicated in human cancer Table 3.9: Kinases implicated in human cancer (continued) Table 3.10: Top 20 Kinase Targets in Cancer Table 3.11: Overview of ABL1-targeted agents in cancer Table 3.12: Overview of ABL1-targeted agents in cancer (continued 1) Table 3.13: Overview of ABL1-targeted agents in cancer (continued 2) Table 3.14: Overview of EGFR-targeted agents in cancer Table 3.15: Overview of EGFR-targeted agents in cancer (Phase III and above) Table 3.16: Overview of EGFR-targeted agents in cancer (Phase II) Table 3.17: Overview of EGFR-targeted agents in cancer (Phase I) Table 3.18: Overview of EGFR-targeted agents in cancer (Preclinical) Table 3.19: Overview of ERBB2-targeted agents in cancer (Phase III and above) Table 3.20: Overview of ERBB2-targeted agents in cancer (Phase II) Table 3.21: Overview of ERBB2-targeted agents in cancer (Phase I and Preclinical) Table 3.22: Overview of FLT3-targeted agents in cancer (Launched) Table 3.23: Overview of FLT3-targeted agents in cancer (Phase II and III) Table 3.24: Overview of FLT3-targeted agents in cancer (Phase I and II) Table 3.25: Overview of FLT3-targeted agents in cancer (Preclinical and Phase I) Table 3.26: Overview of KIT-targeted agents in cancer Table 3.27: Overview of KIT-targeted agents in cancer (Continued 1) Table 3.28: Overview of KIT-targeted agents in cancer (Continued 2) Table 3.29: Overview of KIT-targeted agents in cancer (Continued 3) Table 3.30: Overview of KIT-targeted agents in cancer (Continued 4) Table 3.31: Overview of KIT-targeted agents in cancer (Continued 4) Table 3.32: Overview of PDGFRA-targeted agents in cancer Table 3.33: Overview of PDGFRA-targeted agents in cancer (Continued 1) Table 3.34: Overview of PDGFRA-targeted agents in cancer (Continued 2) Table 3.35: Overview of PDGFRA-targeted agents in cancer (Continued 3) Table 3.36: Overview of PDGFRB-targeted agents in cancer (Phase II and Phase III) Table 3.37: Overview of PDGFRB-targeted agents in cancer (Preclinical and Phase I) Table 3.38: Overview of FLT1-targeted agents in cancer Table 3.39: Overview of FLT1-targeted agents in cancer (Continued 1) Table 3.40: Overview of FLT1-targeted agents in cancer (Continued 2) Table 3.41: Overview of FLT1-targeted agents in cancer (Continued 3) Table 3.42: Overview of FLT4-targeted agents in cancer Table 3.43: Overview of FLT4-targeted agents in cancer (Continued 1) Table 3.44: Overview of FLT4-targeted agents in cancer (Continued 2) Table 3.45: Overview of KDR-targeted agents in cancer Table 3.46: Overview of KDR-targeted agents in cancer (Continued 1) Table 3.47: Overview of KDR-targeted agents in cancer (Continued 2) Table 3.48: Overview of KDR-targeted agents in cancer (Continued 3) Table 3.49: Overview of KDR-targeted agents in cancer (Continued 4) Table 3.50: Overview of KDR-targeted agents in cancer (Continued 5) Table 3.51: Overview of JAK2-Targeted Agents in Cancer Table 3.52: Overview of JAK2-Targeted Agents in Cancer (continued) Table 3.53: Overview of MET-Targeted Agents in Cancer (continued) Table 3.54: Overview of MET-Targeted Agents in Cancer (continued) Table 3.55: Overview of AKT1-Targeted Agents in Cancer (continued) Table 3.56: Overview of AKT1-Targeted Agents in Cancer (continued) Table 3.57: Overview of CDC2-Targeted Agents in Cancer Table 3.58: Overview of CDK2-Targeted Agents in Cancer Table 3.59: Overview of CDK2-Targeted Agents in Cancer (continued) Table 3.60: Overview of AURKA-Targeted Agents in Cancer Table 3.61: Overview of AURKA -Targeted Agents in Cancer (continued) Table 3.62: Overview of AURKB -Targeted Agents in Cancer Table 3.63: Overview of PLK1 -Targeted Agents in Cancer Table 3.64: Overview of FRAP1 -Targeted Agents in Cancer Table 3.65: Overview of FRAP1 -Targeted Agents in Cancer (Continued 1) Table 3.66: Overview of FRAP1 -Targeted Agents in Cancer (Continued 2) Table 3.67: Overview of PIK3CA -Targeted Agents in Cancer Table 3.68: Overview of PIK3CA -Targeted Agents in Cancer (Continued) Table 4.69: Kinase-Targeted Agents With Anti-Arthritic Applications Table 4.70: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 1) Table 4.71: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 2) Table 4.72: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 3) Table 4.73: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 4) Table 4.74: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 5) Table 4.75: Kinase-Targeted Agents With Diabetes Applications Table 4.76: Kinase-Targeted Agents With Diabetes Applications (continued 1) Table 4.77: Kinase-Targeted Agents With Diabetes Applications (continued 2) Table 4.78: Kinase-Targeted Agents With Inflammatory Applications Table 4.79: Kinase-Targeted Agents With Inflammatory Applications (Continued 1) Table 4.80: Kinase-Targeted Agents With Inflammatory Applications (Continued 2) Table 4.81: Kinase-Targeted Agents With Immunosuppresive Applications Table 4.82: Kinase-Targeted Agents With Immunosuppresive Applications (continued) Table 4.83: Kinase-Targeted Agents With Ophthalmological Applications Table 4.84: Kinase-Targeted Agents With Ophthalmological Applications (continued) Table 4.85: Kinase-Targeted Agents With Psoriasis Applications (continued) Table 4.86: Kinase-Targeted Agents With Psoriasis Applications (continued) Table 4.87: Kinase-Targeted Agents With PulmonaryApplications (Launched) Table 4.88: Kinase-Targeted Agents With PulmonaryApplications (Phase I-III) Table 4.89: Kinase-Targeted Agents With PulmonaryApplications (Preclinical) Table 4.90: Kinase-targeted agents with cardiovascular applications Table 4.91: Kinase-targeted agents with cardiovascular applications (continued) Table 4.92: Kinase-targeted agents with myelodysplastic disorder applications Table 4.93: Kinase-targeted agents with myelodysplastic disorder applications (continued) Table 4.94: Kinase-targeted agents with myelodysplastic disorder applications (continued 2) Table 4.95: Kinase-targeted agents with myelodysplastic disorder applications (continued 3) Table 4.96: Kinase-targeted agents with GI disorder applications Table 4.97: Kinase-targeted agents with GI disorder applications Table 5.98: Overview of Abbott's kinase pipeline by status Table 5.99: Overview of Ambit Biosciences' Kinase Pipeline by Status Table 5.100: Overview of Amgen's kinase pipeline by status Table 5.101: Overview of Array BioPharma's kinase pipeline by status Table 5.102: Overview of AstraZeneca’s kinase pipeline by status Table 5.103: Overview of Avila Therapeutics' kinase pipeline by status Table 5.104: Overview of Boehringer Ingelheim's kinase pipeline by status Table 5.105: Overview of Bristol-Myers Squibb's (BMS) kinase pipeline by status Table 5.106: Overview of Cephalon's kinase pipeline by status Table 5.107: Overview of Deciphera Pharmaceuticals' kinase pipeline by status Table 5.108: Overview of Eli Lilly’s kinase pipeline by status Table 5.109: Overview of Eli Lilly’s kinase pipeline by status (continued) Table 5.110: Overview of Exelixis’ kinase pipeline by status Table 5.111: Overview of Exelixis’ kinase pipeline by status Table 5.112: Overview of Hoffmann-La Roche's kinase pipeline by status Table 5.113: Overview of Johnson & Johnson's kinase pipeline by status Table 5.114: Overview of Kyowa Hakko Kirin's kinase pipeline by status Table 5.115: Overview of Novartis’ kinase pipeline by status Table 5.116: Overview of Novartis’ kinase pipeline by status (continued) Table 5.117: Overview of Pfizer’s kinase pipeline by status Table 5.118: Overview of Sanofi-Aventis' kinase pipeline by status Table 5.119: Overview of Wyeth’s kinase pipeline by status Table 6.120: World Prevalence Of Diseases Table 6.121: World Pharma Market by Indication (US$m), 2008-2013 Table 6.122: World Pharma Market by Region (US$m), 2008-2013 Table 6.123: Kinase Drug Analysis (in 2007-2008) and Forecasts, 2009-2013 ($USm) Table 6.124: Kinase Inhibitors by Geography ($USm), 2008 and 2013 Table 6.125: Manufacturer Analysis (2008) and Forecasts (US$m), 2009-2013 Table 6.126: Major Kinase Patent Indications Table 6.127: Leading Kinase Patent Assignees

Companies Mentioned

- Abbott Laboratories - Ambit Biosciences Corp - Amgen Inc - Array BioPharma Inc - AstraZeneca plc - Avila Therapeutics Inc - Boehringer Ingelheim GmbH - Bristol-Myers Squibb Co - Cephalon Inc - Deciphera Pharmaceuticals LLC - Eli Lilly Co - Exelixis Inc - GlaxoSmithKline plc - Hoffmann-La Roche Ltd - Johnson & Johnson - Kyowa Hakko Kirin Co Ltd - Novartis International AG - Pfizer Inc - Sanofi-Aventis Group - Wyeth