Triple Analysis: Apoptosis Agents, Protein Kinase Inhibitors and Anti-Angiogenic Agents in Oncology

Content

• 1 Executive Summary
• 2 Methodology
• 3 Table of Contents
  • 3.1 List of Boxes
  • 3.2 List of Figures
  • 3.3 List of Tables
• 4 Apoptosis in Oncology
  • 4.1 Introduction
  • 4.2 Apoptosis Competitive Landscape in Oncology
    • 4.2.1 Countries & Players: Who are In the Lead?
      • 4.2.1.1 Top 10 Players Dominate The Developmental Pipeline
      • 4.2.1.2 Deals & Alliances in Apoptosis Drug Development
      • 4.2.1.3 Review of Deals and Alliances Initiated in 2006
      • 4.2.1.4 Review of Deals and Alliances Initiated in 2005
      • 4.2.1.5 Review of Deals and Alliances Initiated in 2004
      • 4.2.1.6 Review of Deals and Alliances Initiated in 2003
      • 4.2.1.7 Review of Deals and Alliances Initiated in 2002
      • 4.2.1.8 Review of Deals and Alliances Initiated in 2001
  • 4.3 Approved Apoptopic Cancer Drugs: Performance
  • 4.4 Target Analysis in Apoptosis
    • 4.4.1 Targets of Late Stage Apoptopic Drugs in Development
      • 4.4.1.1 B-cell CLL/lymphoma 2
      • 4.4.1.2 Caspase 3
      • 4.4.1.3 CD4 molecule
      • 4.4.1.4 Cytosolic ovarian carcinoma antigen 1
      • 4.4.1.5 Eukaryotic translation elongation factor 2
      • 4.4.1.6 Farnesyltransferase, CAAX box, alpha
      • 4.4.1.7 Fc fragment of IgE
      • 4.4.1.8 Histone deacetylase 1
      • 4.4.1.9 Histone deacetylase 2
      • 4.4.1.10 Interleukin 13 receptor, alpha 1
      • 4.4.1.11 Phosphodiesterase 2A, cGMP-stimulated
      • 4.4.1.12 Phosphodiesterase 5A, cGMP-specific
      • 4.4.1.13 Protein kinase C, beta 1
      • 4.4.1.14 Steroid 5-alpha-reductase, alpha polypeptide 1
      • 4.4.1.15 Topoisomerase (DNA) I
      • 4.4.1.16 Topoisomerase (DNA) II alpha
      • 4.4.1.17 Tubulin, beta polypeptide
      • 4.4.1.18 p53 protein
    • 4.4.2 Apoptopic Drugs and Their Targets According to Top 5 Cancer Indications
      • 4.4.2.1 Targets in Breast Cancer
      • 4.4.2.2 Targets in Leukemia
      • 4.4.2.3 Targets in Lung Cancer
      • 4.4.2.4 Targets in Lymphoma
      • 4.4.2.5 Targets in Prostate Cancer
  • 4.5 Apoptopic Drugs in Development: By Major Indications
    • 4.5.1 General Drug Developmental Overview
      • 4.5.1.1 Apoptopic Drugs in Phase III Clinical Development
      • 4.5.1.2 Failed Apoptopic Drugs in Oncology
    • 4.5.2 Progress Analysis - Breast Cancer
      • 4.5.2.1 Phase I Clinical Development
      • 4.5.2.2 Phase II Clinical Development
      • 4.5.2.3 Phase III Clinical Development
    • 4.5.3 Progress Analysis - Leukemia
      • 4.5.3.1 Phase I Clinical Development
      • 4.5.3.2 Phase II Clinical Development
      • 4.5.3.3 Phase III Clinical Development
    • 4.5.4 Progress Analysis - Lung Cancer
      • 4.5.4.1 Phase I Clinical Development
      • 4.5.4.2 Phase II Clinical Development
      • 4.5.4.3 Phase III Clinical Development
    • 4.5.5 Progress Analysis - Lymphoma
      • 4.5.5.1 Phase I Clinical Development
      • 4.5.5.2 Phase II Clinical Development
      • 4.5.5.3 Phase III Clinical Development
    • 4.5.6 Progress Analysis - Prostate Cancer
      • 4.5.6.1 Phase I Clinical Development
      • 4.5.6.2 Phase II Clinical Development
      • 4.5.6.3 Phase III Clinical Development
• 5 Protein Kinase Inhibitors
  • 5.1 Rationale for Development of Kinase Inhibitors in Oncology
  • 5.2 Protein Kinase Targets - A Growing Family
  • 5.3 Challenges in Protein Kinase Drug Discovery
    • 5.3.1 Enabling Structure-Based Drug Design is the Key
    • 5.3.2 Specific Kinase Inhibitors without Kinase Profiling?
  • 5.4 Drugs according to Target
    • 5.4.1 Cyclin-dependent Kinase Target Inhibitors
    • 5.4.2 Aurora Kinase Target Inhibitors
    • 5.4.3 Cell Cycle Checkpoint Target Controls Inhibitors
    • 5.4.4 Tyrosine Kinase Receptor Inhibitors
      • 5.4.4.1 Epidermal Growth Factor Receptor Target Inhibitors
      • 5.4.4.2 Fms-related Tyrosine Kinase Target Inhibitors
      • 5.4.4.3 Platelet-derived Growth Factor Receptor Target Inhibitors
      • 5.4.4.4 Kinase Insert Domain Target Inhibitors
      • 5.4.4.5 The PI3K/Akt/mTOR pathway
      • 5.4.4.6 The Ras-Raf-MEK-ERK (ERK) pathway
    • 5.4.5 Other Serine/Threonine Kinase Target Inhibitors
  • 5.5 Dual or Multiple Kinase Inhibitor Analysis
    • 5.5.1 Presentation of Drugs Targeting A to F Kinases
    • 5.5.2 Presentation of Drugs Targeting G to T Kinases
  • 5.6 Targets According to Indication
    • 5.6.1 Breast Cancer
    • 5.6.2 Prostate Cancer: What Cannot be Found in the 'Groins'?
    • 5.6.3 Lung Cancer: A Need for Improved Survival Rates
    • 5.6.4 Colorectal Cancer: EGFR & VEGFR are Strong Targets but There are Others
    • 5.6.5 Leukemia: Show Me the Power of PKI
    • 5.6.6 Melanoma
    • 5.6.7 Lymphoma: We Are In
  • 5.7 Growing Competition in the Field
  • 5.8 Big Pharma Outlook: The Race is On
    • 5.8.1 Novartis Deals - Digs Deeper into Cell Cycle Inhibitors
    • 5.8.2 AstraZeneca - Wheeling and Dealing
    • 5.8.3 Pfizer's Long Look at OSI Pharmaceuticals
    • 5.8.4 GlaxoSmithKline Gains Momentum
  • 5.9 Strategic Deals Creating Competitive Edge
    • 5.9.1 Mergers
    • 5.9.2 Astex - the PKI Switchboard
    • 5.9.3 Big Pharma's Darling
  • 5.10 Current Protein Kinase Inhibitors in Therapy
    • 5.10.1 Mechanism, Target and Developmental History
    • 5.10.2 Approvals: Indications & Markets
  • 5.11 Protein Kinase Inhibitors in Drug Development - A Progress Analysis
    • 5.11.1 Progress Analysis - Breast Cancer
    • 5.11.2 Progress Analysis - Prostate Cancer
    • 5.11.3 Progress Analysis - Lung Cancer
    • 5.11.4 Progress Analysis - Colorectal Cancer
    • 5.11.5 Progress Analysis - Leukemia
    • 5.11.6 Progress Analysis - Melanoma
    • 5.11.7 Progress Analysis - Lymphoma
• 6 Antiangiogenesis and Vascular Targeting
  • 6.1 Introduction
    • 6.1.1 Neoplastic Angiogenesis & Tumor Vasculature
      • 6.1.1.1 Tumor Vasculature
      • 6.1.1.2 The Current Model of Sprouting Angiogenesis
    • 6.1.2 Main Angiogenic Factors
      • 6.1.2.1 Vascular Endothelial Growth Factor
      • 6.1.2.2 The Angiopoietins and Platelet Derived Growth Factor
      • 6.1.2.3 Integrins in Angiogenesis
      • 6.1.2.4 Inhibitors of Angiogenesis
    • 6.1.3 Vascular Targeting Agents
    • 6.1.4 Vascular Disruptive Agents
  • 6.2 Competitive Landscape in Anti-Angiogenesis and Vascular Targeting in Oncology
    • 6.2.1 Countries & Players: Who are In the Lead?
      • 6.2.1.1 Top 10 Players Dominate The Developmental Pipeline
    • 6.2.2 Deals & Alliances in Anti-Angiogenesis and Vascular Targeting
      • 6.2.2.1 Review of Deals and Alliances Initiated in 2005
      • 6.2.2.2 Review of Deals and Alliances Initiated in 2004
      • 6.2.2.3 Review of Deals and Alliances Initiated in 2003
  • 6.3 Approved Anti-Angiogenic Cancer Drugs: Performance
  • 6.4 Target Analysis in Anti-Angiogenesis and Vascular Targeting
    • 6.4.1 Targets of Late Stage Anti-Angiogenic Drugs in Development
      • 6.4.1.1 Drugs with Epidermal Growth Factor Receptor as a Target
      • 6.4.1.2 Drugs with FMS-related Tyrosine Kinase 1 as a Target
      • 6.4.1.3 Drugs with FMS-related Tyrosine Kinase 4 as a Target
      • 6.4.1.4 Drugs with Kinase Insert Domain Receptor as a Target
      • 6.4.1.5 Drugs with Phosphodiesterase 2A, cGMP-stimulated as a Target
      • 6.4.1.6 Drugs with Phosphodiesterase 5A, cGMP-specific as a Target
      • 6.4.1.7 Drugs with Patelet-Derived Growth Factor Receptor, alpha Polypeptide as a Target
      • 6.4.1.8 Drugs with Platelet-Derived Growth Factor, beta Polypeptide as a Target
      • 6.4.1.9 Drugs with Protein Kinase C, beta 1 as a Target
      • 6.4.1.10 Drugs with Ret Proto-Oncogene as a Target
      • 6.4.1.11 Drugs with v-kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog as a Target
      • 6.4.1.12 Drugs with v-raf-1 Murine Leukemia Viral Oncogene Homolog 1 as a Target
      • 6.4.1.13 Drugs with Vascular Endothelial Growth Factor as a Target
    • 6.4.2 Anti-Angiogenic Drugs and Their Targets According to Top 5 Cancer Indications
      • 6.4.2.1 Targets in Breast Cancer
      • 6.4.2.2 Targets in Colorectal Cancer
      • 6.4.2.3 Targets in Lung Cancer
      • 6.4.2.4 Targets in Prostate Cancer
      • 6.4.2.5 Targets in Renal Cancer
  • 6.5 Anti-angiongenesis and Vascular Targeting Drugs in Development: By Major Indications
    • 6.5.1 General Drug Developmental Overview
    • 6.5.2 Progress Analysis - Breast Cancer
      • 6.5.2.1 Phase I Clinical Development
      • 6.5.2.2 Phase II Clinical Development
      • 6.5.2.3 Phase III Clinical Development
    • 6.5.3 Progress Analysis - Colorectal Cancer
      • 6.5.3.1 Phase I Clinical Development
      • 6.5.3.2 Phase II Clinical Development
      • 6.5.3.3 Phase III Clinical Development
    • 6.5.4 Progress Analysis - Lung Cancer
      • 6.5.4.1 Phase I Clinical Development
      • 6.5.4.2 Phase II Clinical Development
      • 6.5.4.3 Phase III Clinical Development
    • 6.5.5 Progress Analysis - Prostate Cancer
      • 6.5.5.1 Phase I Clinical Development
      • 6.5.5.2 Phase II Clinical Development
      • 6.5.5.3 Phase III Clinical Development
    • 6.5.6 Progress Analysis - Renal Cancer
      • 6.5.6.1 Phase I Clinical Development
      • 6.5.6.2 Phase II Clinical Development
      • 6.5.6.3 Phase III Clinical Development
  • 6.6 Disclaimer
  • 6.6 Liability
  • 6.7 Completeness
• 7 Appendix
  • 7.1 Appendix 1: Complete List of Apoptopic Drugs in Development in Oncology
  • 7.2 Appendix 2: Complete List of Angiogenic and Vascular Target Agents in Development in Oncology
• 8 Drug Index
• 9 Company Index
• 3.1 List of Boxes
  • Box 1: Business & Market - PXD-101
  • Box 2: Business & Market - MG-98
  • Box 3: Business & Market - VX-680
  • Box 4: Business & Market - Ceflatonin
  • Box 5: Business & Market - Oblimersen sodium
  • Box 6: Business & Market - motexafin gadolinium
  • Box 7: Business & Market - 1D09C3
  • Box 8: Business & Market - PCK-3145
  • Box 9: Business & Market - ME-2
  • Box 10: The Power of Ambit's Kinase Profiling
  • Box 11: Summary Terms of the Exelixis Transaction
  • Box 12: Nexavar's Clinical Data That Lead To Its EMEA Approval Myeloma
  • Box 13: Thalomid Delays Time to Disease Progression in Newly Diagnosed Multiple Myeloma
  • Box 14: Strong Clinical Data Suggests Approval to Market Avastin For The Treatment of Both Breast Cancer and NSCLC
  • Box 15: Avastin Fails to Meet Primary Endpoint in Advanced Pancreatic Cancer
  • Box 16: Business & Market - Cilengitide
  • Box 17: Business & Market - Exherin
  • Box 18: Business & Market - WX-UK1
  • Box 19: Business & Market - Combretastatin A-4 phosphate
  • Box 20: Business & Market - GCS-100LE
  • Box 21: Business & Market - PTK/ZK
  • Box 22: Business & Market - AS-1404
  • Box 23: Business & Market - Phosphomannopentaose sulfate
  • Box 24: Business & Market - Squalamine
  • Box 25: Business & Market - talactoferrin alfa
  • Box 26: Business & Market - ZD-6474
  • Box 27: Business & Market - AP-23573
  • Box 28: Business & Market - Volociximab
  • Box 29: Business & Market - XL-999
• 3.2 List of Figures
  • Figure 1: 5 Countries in Apoptopic Cancer Research
  • Figure 2: Top 10 Companies' Clinical Trial Progress in Apoptopic Drug Development
  • Figure 3: Trial Distribution of the Entire Apoptopic Pipeline in Oncology
  • Figure 4: Distribution of ApoptopicTrials in Breast Cancer
  • Figure 5: Distribution of Apoptopic Drug Trials in Leukemia
  • Figure 6: Distribution of Apoptopic Drug Trials in Lung Cancer
  • Figure 7: Distribution of Apoptopic Drug Trials in Lymphoma
  • Figure 8: Distribution of Apoptopic Drug Trials in Prostate Cancer
  • Figure 9 Top 10 PKI Drug Developing Companies
  • Figure 10 Clinical Trial Distribution in Breast Cancer for PKI Drugs
  • Figure 11 Clinical Trial Distribution in Prostate Cancer for PKI Drugs
  • Figure 12 Clinical Trial Distribution in Lung Cancer for PKI Drugs
  • Figure 13 Clinical Trial Distribution in Colorectal Cancer for PKI Drugs
  • Figure 14 Clinical Trial Distribution in Leukemia for PKI Drugs
  • Figure 15 Clinical Trial Distribution in Melanoma for PKI Drugs
  • Figure 16: Clinical Trial Distribution in Lymphoma for PKI Drugs
  • Figure 17: Establishment of Blood Supply to Tumors
  • Figure 18: Sprouting Angiogenesis
  • Figure 19: Top 5 Countries in Cancer Angiogenesis and Vascular Targeting Research
  • Figure 20: Top 10 Companies' Clinical Trial Progress in Anti-Angiogenesis and Vascular Targeting
  • Figure 21: Deals & Alliances in Anti-Angiogenesis and Vascular Targeting 2001-2005
  • Figure 22: Annual Sales of Avastin on US and Non US Markets
  • Figure 23: Trial Distribution of the Entire Anti-Angiogenic and Vascular Target Agent Field in Oncology
  • Figure 24: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Breast Cancer
  • Figure 25: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Colorectal
  • Figure 26: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Lung Cancer
  • Figure 27: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Prostate Cancer
  • Figure 28: Distribution of Anti-Angiogensis & Vascular Targeting Trials in Renal Cancer
• 3.3 List of Tables
  • Table 1: Top 10's Apoptopic Pipeline Drugs
  • Table 2: Deals & Alliances in Apoptosis Drug Development in Oncology
  • Table 3: Companies with Apoptopic Cancer Drugs on the Market
  • Table 4: List of 120 Known Targets in Apoptosis Drug Development
  • Table 5: Known Targets of Late Stage Apoptopic Drugs Development
  • Table 6: Drugs with Bcl-2 as a Target
  • Table 7: Drugs with Casp-3 as a Target
  • Table 8: Drugs with CD4 molecule as a Target
  • Table 9: Drugs with Cova-1 as a Target
  • Table 10: Drugs with Eef-2 as a Target
  • Table 11: Drugs with Fnta as a Target
  • Table 12: Drugs with Fcer-2 as a Target
  • Table 13: Drugs with Hdac-1 as a Target
  • Table 14: Drugs with Hdac-2 as a Target
  • Table 15: Drugs with IL13-RA1 as a Target
  • Table 16: Drugs with Pde-2A as a Target
  • Table 17: Drugs with Pde-5A as a Target
  • Table 18: Drugs with Prkcb-1 as a Target
  • Table 19: Drugs with Srd-5A1 as a Target
  • Table 20: Drugs with Top-1 as a Target
  • Table 21: Drugs with Top-2A as a Target
  • Table 22: Drugs with Top-2A as a Target
  • Table 23: Drugs with p53 protein as a Target
  • Table 24: Breast Cancer Targets in Apoptopic Drug Development
  • Table 25: Leukemia Targets in Apoptopic Drug Development
  • Table 26: Lung Cancer Targets in Apoptopic Drug Development
  • Table 27: Lymhoma Targets in Apoptopic Drug Development
  • Table 28: Prostate Cancer Targets in Apoptopic Drug Development
  • Table 29: Top 10 Cancer Indications in Apoptopic Cancer Drugs
  • Table 30: Overview of Apoptopic Drugs in Phase III Clinical Development
  • Table 31: Recently Ceased or Discountinued Phase I to Phase III Apoptopic Drugs
  • Table 32: List of Phase I to Phase III Apoptopic Drugs in Development for Breast Cancer
  • Table 33: List of Phase I to Phase III Apoptopic Drugs in Development for Leukemia
  • Table 34: List of Phase I to Phase III Apoptopic Drugs in Development for Lung Cancer
  • Table 35: List of Phase I to Phase III Apoptopic Drugs in Development for Lymphoma
  • Table 36: List of Phase I to Phase III Apoptopic Drugs in Development for Prostate Cancer
  • Table 37: Overview of Targets in Commercial Development
  • Table 38: Cyclin-dependent Kinase Targets in Development
  • Table 39: Aurora Kinase Targets in Development
  • Table 40: Cell Cycle Checkpoint Targets in Development
  • Table 41: Epidermal Growth Factor Receptor Targets in Development
  • Table 42: FMS-like tyrosine kinases and their Synonyms
  • Table 43: Fms-related Tyrosine Kinase Targets in Development
  • Table 44: Platelet-derived Growth Factor Receptor Targets in Development
  • Table 45: Kinase Insert Domain Targets in Development
  • Table 46: Drugs in Development Targeting the PI3K/Akt/mTOR pathway
  • Table 47: Drugs in Development Targeting the Ras-Raf-MEK-ERK (ERK) pathway
  • Table 48: Serine/Threonine Kinase Inhibitors in Development
  • Table 49: Protein Kinase Targets in Clinical Trials for Breast Cancer
  • Table 50: Protein Kinase Targets in Clinical Trials for Prostate Cancer
  • Table 51: Protein Kinase Targets in Clinical Trials for Lung Cancer
  • Table 52: Protein Kinase Targets in Clinical Trials for Colorectal Cancer
  • Table 53: Protein Kinase Targets in Clinical Trials for Leukemia
  • Table 54: Protein Kinase Targets in Clinical Trials for Melanoma
  • Table 55: Protein Kinase Targets in Clinical Trials for Lymphoma
  • Table 56: Drugs in Therapy - Mechanism & Targets
  • Table 57: Current and Developmental History of PKI Drugs in Therapy
  • Table 58: Approvals: Indications & Markets
  • Table 59: Top 10 Drugs in Terms of Number of Clinical Trials
  • Table 60: List of Cancer Indications Targeted by Protein Kinase Inhibitors
  • Table 61: PKI Drugs in Development for Breast Cancer
  • Table 62: PKI Drugs in Development for Prostate Cancer
  • Table 63: PKI Drugs in Development for Lung Cancer
  • Table 64: PKI Drugs in Development for Colorectal Cancer
  • Table 65: PKI Drugs in Development for Leukemia
  • Table 66: PKI Drugs in Development for Melanoma
  • Table 67: PKI Drugs in Development for Lymphoma
  • Table 68: Top 10's Anti-angiogenic and Vascular Targeting Pipeline Drugs
  • Table 69: Deals & Alliances in 2005
  • Table 70: Deals & Alliances in 2004
  • Table 71: Deals & Alliances in 2003
  • Table 72: Companies with Cancer Anti-angiogenic Drugs on the Market
  • Table 73: 2006 Q2 Sales Revlimid and Thalomid
  • Table 74: 2006 Q2 Sales of Avastin
  • Table 75: List of 75 Known Targets in Ant-angiogenis and Vascular Targeting in Drug Development
  • Table 76: Known Targets of Late Stage Anti-Angiogenic Drugs in Development
  • Table 77: Drugs with Epidermal Growth Factor Receptor as a Target
  • Table 78: Drugs with FMS-related Tyrosine Kinase 1 as a Target
  • Table 79: Drugs with FMS-related Tyrosine Kinase 4 as a Target
  • Table 80: Drugs with Kinase Insert Domain Receptor as a Target
  • Table 81: Drugs with Phosphodiesterase 2A, cGMP-stimulated as a Target
  • Table 82: Drugs with Phosphodiesterase 5A, cGMP-specific as a Target
  • Table 83: Drugs with Patelet-Derived Growth Factor Receptor, alpha Polypeptide as a Target
  • Table 84: Drugs with Platelet-Derived Growth Factor, beta Polypeptide as a Target
  • Table 85: Drugs with Protein Kinase C, beta 1 as a Target
  • Table 86: Drugs with Ret Proto-Oncogene as a Target
  • Table 87: Drugs with v-kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog as a Target
  • Table 88: Drugs with v-raf-1 Murine Leukemia Viral Oncogene Homolog 1 as a Target
  • Table 89: Drugs with Vascular Endothelial Growth Factor as a Target
  • Table 90: Breast Cancer Targets in Anti-Angiogenic Drug Development
  • Table 91: Colorectal Cancer Targets in Anti-Angiogenic Drug Development
  • Table 92: Lung Cancer Targets in Anti-Angiogenic Drug Development
  • Table 93: Prostate Cancer Targets in Anti-Angiogenic Drug Development
  • Table 94: Renal Cancer Targets in Anti-Angiogenic Drug Development
  • Table 95: Top 10 Cancer Indications in Anti-Angiogenesis and Vascular Targeting Cancer Drugs
  • Table 96: Recent Ceased or Discountinued Phase I to Phase III Anti-angiogenic and Vascular Targeting Drugs
  • Table 97: Overview of Drugs in Phase III Clinical Development
  • Table 98: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Breast Cancer
  • Table 99: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Colorectal Cancer
  • Table 100: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Lung Cancer
  • Table 101: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Prostate Cancer
  • Table 102: List of Phase I to Phase III Anti-Angiogenesis and Vascular Targeting Agents in Development for Renal Cancer