Innovations in Protein Kinase Therapies: Company pipelines, therapeutic applications and market forecasts

Table of Contents

Executive Summary

• Chapter 1 Kinases as drug targets
• Chapter 2 Small molecule kinase inhibitor discovery
• Chapter 3 Targeting kinases in cancer
• Chapter 4 Non-cancer applications of kinase drugs
• Chapter 5 Leading kinase drug originating companies
• Chapter 6 Market Analysis: Trends and Forecasts

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