Angiogenesis Modulators: Strategies for Drug Discovery

TABLE OF CONTENTS

Chapter 1: Executive Summary

Chapter 2: Introduction To Angiogenesis

• Overview of Angiogenesis
• The Process of Angiogenesis
• Molecules Involved in Angiogenesis
  • Growth Factors and Other Angiogenic Proteins
  • Receptor Tyrosine Kinases
  • Proteases
  • Cell Adhesion Molecules
  • Endogenous Antiangiogenic Proteins
• Role of Angiogenesis in Disease
• Approaches to Angiogenesis Modulation
  • Types of Drugs under Development
  • Small-Molecule Drugs
  • Biopharmaceuticals
• Assays for Angiogenesis

Chapter 3: Angiogenesis In Cancer

• Overview of Cancer
• Cancer Therapy
  • Molecular Targeted Therapies
• Angiogenesis in Cancer
  • Angiostatic versus Angiolytic Therapies
• Targets for Angiostatic Therapies
  • Growth Factors and Their Receptors
    • VEGF-A
    • VEGFR Family
    • EGFR Family
    • Small-Molecule Drugs
    • Monoclonal Antibody Drugs
    • Other Growth Factors/Receptors
    • Tie2 Receptor
    • IGF1R
    • FGF-2
    • VEGF-C, VEGF-D/VEGFR-3
    • PDGF(R)
    • Multi-Target Strategies
    • Applications in Hematologic Malignancies
  • ECM-Degrading Enzymes
    • Matrix Metalloproteases
    • Heparanase
  • Proteases (other than MMPs)
    • ADAMs Family
    • uPA
    • Other Proteases
  • Cell Adhesion Receptors
    • Alpha(v) Integrins
    • Other Cell Adhesion Receptors
  • Agents Based on Human Antiangiogenic Factors
    • Endogenous Antiangiogenic Factors
    • Antiangiogenic Gene Therapy
  • Agents of Non-Human Origin
  • Miscellaneous Agents
    • Thalidomide-Related Drugs
    • Other Drugs
• Angiolytic Vascular Targeting Agents
  • Small-Molecule VTAs
    • Tubulin-Binding Agents
    • Other Small-Molecule Agents
  • Ligand-based and Other VTAs
• Exploiting Angiogenesis for Drug Delivery

Chapter 4: Angiogenesis In Cardiology

• Overview of Cardiovascular Disease
  • Coronary Artery Disease
    • Established Treatments
  • Myocardial Infarction
    • Current Treatments
  • Peripheral Vascular Disease
    • Current treatments
  • Congestive Heart Failure
    • Current Treatments
• Angiogenesis in Ischemia
  • Physiological Responses to Ischemia
  • Stimulation of Angiogenesis in Ischemia
    • Transmyocardial Revascularization
    • Therapeutic Angiogenesis
    • Cell Therapy
• Challenge of Pathologic Angiogenesis
  • Atherogenesis and Atheroscleropathy
  • Percutaneous Coronary Interventions
    • Approaches to Restenosis Prevention
• Angiogenic Products in Commercial Development
  • Protein and Small Molecule Therapies
  • Gene Therapies
  • Cell Therapies
    • Stem and Progenitor Cell Therapies

Chapter 5: Angiogenesis In Ophthalmology

• Eye Diseases Involving Neovascularization
  • Age-related Macular Degeneration
  • Diabetic Retinopathy
  • Other Disorders
• Angiolytic Photodynamic Therapy
• Angiogenesis-targeting Drugs
  • Angiostatic Drugs
    • Targeting VEGF/VEGFR
    • Miscellaneous Targets
  • Vascular Targeting Agents

Chapter 6: Other Applications Of Angiogenic Modulation

• Introduction
• Skin Diseases
  • Chronic Wounds
  • Vascular Lesions
  • Psoriasis
  • Rosacea
  • Other Vascular Lesions
• Chronic In.ammatory Diseases
  • Rheumatoid Arthritis
  • Periodontitis
  • In.ammatory Bowel Disease
  • In.ammatory Lung Diseases
  • Complex Regional Pain Syndrome
  • Fibrodysplasia Ossi.cans Progressiva
• Transplant Rejection
• Orthodontic Applications
• Spinal Cord Injuries
• Other Potential Applications
  • Endometriosis
  • Obesity
  • Erectile Dysfunction
  • Benign Tumors

Chapter 7: Company Profiles

• Introduction
• Abbott Laboratories
• AEterna Zentaris Inc
• Alcon Laboratories Inc
• Amgen Inc
• Angiotech Pharmaceuticals Inc
• Antisoma Plc
• AstraZeneca Plc
• Bayer AG
• Boston Scienti.c Corporation
• Celgene Corporation
• Collagenex Pharmaceuticals Inc
• Collateral Therapeutics Inc
• Corautus Genetics Inc
• EntreMed Inc
• EyeTech Pharmaceuticals Inc
• Genaera Corporation
• Genentech Inc
• Genzyme Corporation
• GlaxoSmithKline Plc
• Human Genome Sciences
• ImClone Systems Inc
• Merck KGaA
• Merck & Co Inc
• Novartis Pharma AG
• OSI Pharmaceuticals Inc
• OXiGENE Inc.
• P.zer Inc
• Regeneron Pharmaceuticals Inc.
• Sirna Therapeutics Inc

Chapter 8: The Angiogenesis Modulation Market To 2009

• Introduction
• Cancer
  • Overview
  • Established Cancer Therapies
  • The Anti-Cancer Drug Market
• Cardiology
  • Overview
  • Coronary Artery Disease
  • Myocardial Infarction
  • Congestive Heart Failure
  • Established Treatments
  • Cardiology drug market
• Ophthalmology
  • Overview
  • Age-related Macular Degeneration
  • Diabetic Retinopathy
  • Other Eye Disorders
  • Ophthalmology Drug Market
• Dermatology
  • Overview
  • Psoriasis
  • Benign Vascular Lesions
  • Impaired Wound Healing
  • Dermatology Drug Market
• Other Indications
• Market Forecasts

Chapter 9: Conclusions, Trends, and Opportunities

• Gap Narrows between Experimental and Clinical Data
• VEGF Inhibitors Lead the Way
• Cancer: Opportunities Expand
  • Accelerating Approvals
  • Learning from Clinical Trials
  • Optimizing Therapies
  • Towards Pharmacogenomic Testing
  • Towards Angiogenic Pro.ling
  • Taking Advantage of Vascular Targeting
  • Future Horizons—Cancer Prevention?
• AMD: Breakthrough Treatments Emerge
• Cardiology: Interest Peaks Despite Slow Progress
• Other Diseases: Largely Unexplored Opportunities
• Exploiting Unexpected Angiomodulatory Effects

TABLE OF EXHIBITS

• Exhibit 2.1 Partial List of Endogenous Angiogenic Factors
• Exhibit 2.2 Partial List of Endogenous Antiangiogenic Factors
• Exhibit 3.1 Cancer: Inhibitors of Growth Factors/receptors Listed by Drug Target
• Exhibit 3.2 Cancer: Inhibitors of ECM-degrading Enzymes, List by Drug Target
• Exhibit 3.3 Cancer: Inhibitors of Proteases (other than MMPs), Listed by Drug Target
• Exhibit 3.4 Cancer: Inhibitors of Cell Adhesion Receptors
• Exhibit 3.5 Cancer: Agents Based on Human Antiangiogenic Factors
• Exhibit 3.6 Cancer: Antiangiogenic Substances of Non-human Origin
• Exhibit 3.7 Cancer: Miscellaneous Agents with Antiangiogenic Properties
• Exhibit 3.8 Cancer: Vascular Targeting Agents
• Exhibit 4.1 Cardiovascular Diseases: Angiogenic Therapies
• Exhibit 5.1 Vascular Eye Diseases: Antiangiogenic Therapies
• Exhibit 6.1 Dermatology: Angiogenic and Antiangiogenic Therapies
• Exhibit 6.2 Miscellaneous Indications: Antiangiogenic Therapies
• Exhibit 7.1 The 25 Most Active Organizations in Angiogenesis-related US Patenting,  1995 - 2004 (Granted Patents)
• Exhibit 7.2 The 25 Most Active Organizations in Angiogenesis-related US Patenting, 2002 - 2004 (Published Applications)
• Exhibit 7.3 The 25 Most Frequently Cited Angiogenesis-related US Patents, 1995 - 2004
• Exhibit 8.1 World Prevalence Of Angiogenesis-Related Diseases
• Exhibit 8.2 World Market For Angiogenesis-Related Diseases
• Exhibit 8.3 World Pharma Market In 2004 and 2009
• Exhibit 8.4 Angiogenesis-Related Markets By Indication
• Exhibit 8.5 World Angiogenesis-Related Market In 2004 And 2009