Report: Strategic Outlook on Protein Kinase Inhibitors in Oncology TOC

1 Executive Summary _______________________________________________2
2 Cancer Highlights ________________________________________________3
3 Methodology_____________________________________________________4
4 Table of Contents _________________________________________________6
- 4.1 List of Boxes______________________________________________________ 7
- 4.2 List of Figures ____________________________________________________ 7
- 4.3 List of Tables _____________________________________________________ 7
5 Rationale for Development of Kinase Inhibitors in Oncology______________9
6 Protein Kinase Targets -- A Growing Family __________________________11
- 6.1 Challenges in Protein Kinase Drug Discovery _________________________ 15
  - 6.1.1 Enabling Structure-Based Drug Design is the Key ____________________________15
  - 6.1.2 Specific Kinase Inhibitors without Kinase Profiling? __________________________16
- 6.2 Drugs according to Target _________________________________________ 19
  - 6.2.1 Cyclin-dependent Kinase Target Inhibitors __________________________________19
  - 6.2.2 Aurora Kinase Target Inhibitors __________________________________________21
  - 6.2.3 Cell Cycle Checkpoint Target Controls Inhibitors ____________________________22
  - 6.2.4 Tyrosine Kinase Receptor Inhibitors _______________________________________23
  - 6.2.5 Other Serine/Threonine Kinase Target Inhibitors _____________________________32
- 6.3 Dual or Multiple Kinase Inhibitor Analysis ___________________________ 35
  - 6.3.1 Presentation of Drugs Targeting A to F Kinases ______________________________35
  - 6.3.2 Presentation of Drugs Targeting G to T Kinases ______________________________38
- 6.4 Targets According to Indication ____________________________________ 41
  - 6.4.1 Breast Cancer_________________________________________________________41
  - 6.4.2 Prostate Cancer: What Cannot be Found in the 'Groins'?_______________________42
  - 6.4.3 Lung Cancer: A Need for Improved Survival Rates ___________________________43
  - 6.4.4 Colorectal Cancer: EGFR & VEGFR are Strong Targets but there are Others _______45
  - 6.4.5 Leukemia: Show Me the Power of PKI _____________________________________47
  - 6.4.6 Melanoma ___________________________________________________________48
  - 6.4.7 Lymphoma: We Are In _________________________________________________50
7 Growing Competition in the Field___________________________________51
- 7.1 Big Pharma Outlook: The Race is On________________________________ 52
  - 7.1.1 Novartis Deals - Digs Deeper into Cell Cycle Inhibitors________________________52
  - 7.1.2 AstraZeneca -- Wheeling and Dealing ______________________________________55
  - 7.1.3 Pfizer's Long Look at OSI Pharmaceuticals _________________________________57
  - 7.1.4 GlaxoSmithKline Gains Momentum _______________________________________59
- 7.2 Strategic Deals Creating Competitive Edge ___________________________ 61
  - 7.2.1 Mergers _____________________________________________________________61
  - 7.2.2 Astex -- the PKI Switchboard_____________________________________________62
  - 7.2.3 Big Pharma's Darling __________________________________________________63
8 Current Protein Kinase Inhibitors in Therapy _________________________65
- 8.1 Mechanism, Target and Developmental History _______________________ 65
- 8.2 Approvals: Indications & Markets __________________________________ 69
9 Protein Kinase Inhibitors in Drug Development -- A Progress Analysis_____72
- 9.1 Progress Analysis - Breast Cancer___________________________________ 74
- 9.2 Progress Analysis - Prostate Cancer _________________________________ 76
- 9.3 Progress Analysis - Lung Cancer____________________________________ 78
- 9.4 Progress Analysis - Colorectal Cancer _______________________________ 81
- 9.5 Progress Analysis - Leukemia ______________________________________ 84
- 9.6 Progress Analysis -- Melanoma _____________________________________ 87
- 9.7 Progress Analysis - Lymphoma _____________________________________ 88
10 Selected Company profiles_______________________________________91
11 Disclaimer____________________________________________________98
12 Drug Index ___________________________________________________99
13 Company Index ______________________________________________105

4.1 List of Boxes

Box 1: The Power of Ambit's Kinase Profiling ......................................................................................17
Box 2: Summary Terms of the Exelixis Transaction...............................................................................60

4.2 List of Figures

Figure 1: Top 10 PKI Drug Developing Companies_______________________________________51
Figure 2: Clinical Trial Distribution in Breast Cancer for PKI Drugs_________________________74
Figure 3: Clinical Trial Distribution in Prostate Cancer for PKI Drugs _______________________77
Figure 4: Clinical Trial Distribution in Lung Cancer for PKI Drugs__________________________79
Figure 5: Clinical Trial Distribution in Colorectal Cancer for PKI Drugs _____________________82
Figure 6: Clinical Trial Distribution in Leukemia for PKI Drugs ____________________________85
Figure 7: Clinical Trial Distribution in Melanoma for PKI Drugs____________________________87
Figure 8: Clinical Trial Distribution in Lymphoma for PKI Drugs ___________________________89

4.3 List of Tables

Table 1: Overview of Targets in Commercial Development _________________________________14
Table 2: Cyclin-dependent Kinase Targets in Development _________________________________20
Table 3: Aurora Kinase Targets in Development _________________________________________22
Table 4: Cell Cycle Checkpoint Targets in Development ___________________________________23
Table 5: Epidermal Growth Factor Receptor Targets in Development ________________________25
Table 6: FMS-like tyrosine kinases and their Synonyms____________________________________26
Table 7: Fms-related Tyrosine Kinase Targets in Development ______________________________28
Table 8: Platelet-derived Growth Factor Receptor Targets in Development ____________________29
Table 9: Kinase Insert Domain Targets in Development ___________________________________30
Table 10: Drugs in Development Targeting the PI3K/Akt/mTOR pathway _____________________31
Table 11: Drugs in Development Targeting the Ras-Raf-MEK-ERK (ERK) pathway _____________32
Table 12: Serine/Threonine Kinase Inhibitors in Development ______________________________33
Table 13: Protein Kinase Targets in Clinical Trials for Breast Cancer ________________________41
Table 14: Protein Kinase Targets in Clinical Trials for Prostate Cancer ______________________42
Table 15: Protein Kinase Targets in Clinical Trials for Lung Cancer _________________________44
Table 16: Protein Kinase Targets in Clinical Trials for Colorectal Cancer_____________________46
Table 17: Protein Kinase Targets in Clinical Trials for Leukemia ____________________________48
Table 18: Protein Kinase Targets in Clinical Trials for Melanoma ___________________________49
Table 19: Protein Kinase Targets in Clinical Trials for Lymphoma___________________________50
Table 20: Drugs in Therapy -- Mechanism & Targets______________________________________65
Table 21: Current and Developmental History of PKI Drugs in Therapy ______________________68
Table 22: Approvals: Indications & Markets ____________________________________________71
Table 23: Top 10 Drugs in Terms of Number of Clinical Trials ______________________________72
Table 24: List of Cancer Indications Targeted by Protein Kinase Inhibitors ____________________73
Table 25: PKI Drugs in Development for Breast Cancer ___________________________________76
Table 26: PKI Drugs in Development for Prostate Cancer__________________________________78
Table 27: PKI Drugs in Development for Lung Cancer ____________________________________80
Table 28: PKI Drugs in Development for Colorectal Cancer________________________________83
Table 29: PKI Drugs in Development for Leukemia _______________________________________86
Table 30: PKI Drugs in Development for Melanoma ______________________________________88
Table 31: PKI Drugs in Development for Lymphoma______________________________________89

Strategic Outlook on Protein Kinase Inhibitors in Oncology

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