Metabolic and Inflammatory Disease R&D: An Assessment of 5 Highly Promising Therapeutic Classes

Table of Contents

• INTRODUCTION
• 1.1 Target-Based Approaches to Drug Discovery
• 1.2 Identification of Current High-Profile Targeted Approaches
  • Inflammatory and Immune Diseases
  • Metabolic Diseases
• 1.3 Does Extensive Activity Predict Success?
  • Success from High Activity
  • Leukotriene CysLT1 Receptor Antagonists
  • PDE5 Inhibitors
  • COX-2 Inhibitors
  • Failures Despite Intense Efforts
  • 5-Lipoxygenase Inhibitors
  • Renin Inhibitors
  • Thromboxane Antagonists
  • Long-lived Efforts
  • p38 MAP Kinase
  • PDE4 Inhibitors
• 1.4 Reasons for Failures

• METHODOLOGY: IDENTIFYING HIGH-PROFILE AREAS OF EFFORT
• 2.1. Medical Advances
• 2.2. Literature Activity
• 2.3. Meetings
• 2.4. Patenting Activity
• 2.5. Commercial Deals

• HIGH-PROFILE TOPICS IN INFLAMMATORY AND METABOLIC DISEASES
• 3.1. Inflammatory Diseases
  • Respiratory Diseases
  • Arthritis
• 3.2. Metabolic Diseases
  • Diabetes
  • Obesity
  • Metabolic Syndrome
  • Lipid Disorders

• CHEMOKINE ANTAGONISTS
• 4.1. Chemokines
• 4.2. Targets
  • CCR Receptors
  • CXCR Receptors
• 4.3. Pathophysiological Role(s)
  • Inflammatory Processes
  • HIV Infection
• 4.4. Potential Therapeutic Indications
  • Atherosclerosis
  • Allergic Rhinitis
  • Asthma
  • Chronic Obstructive Pulmonary Disease
  • Multiple Sclerosis
  • Rheumatoid Arthritis
  • Cancer
• 4.5. Possible Pitfalls
  • CCR Receptors
  • CXCR Receptors
  • CCR1 Antagonists
  • SH-T-04268-H
  • CCR2 Antagonists
  • Chemokine Antagonists: Strong Evidence ... Well Validated. Q&A with Dr. Kris Vaddi, vice president, Preclinical Biology, Incyte, and Dr. Robert Newton, Drug Discovery Biology, Incyte
  • CCR3 Antagonists
  • CCX-282
  • CXCR2 Antagonists
  • SCH-527123
  • GSK-656933
  • DF-1681
  • CTCE-9908
  • Preclinical Efforts
• 4.6. Active Major Companies
  • Amgen
  • Astellas
  • AstraZeneca
  • Bayer Schering
  • Boehringer Ingelheim
  • Bristol-Meyers Squibb
  • Daiichi Sankyo
  • GlaxoSmithKline
  • Hoffmann-La Roche
  • Janssen
  • Merck
  • Novartis
  • Pfizer
  • sanofi-aventis
  • Schering-Plough
  • Takeda
  • Wyeth
• 4.7. Other Active Companies
  • AnorMED
  • ChemoCentryx
  • Chemokine Therapeutics
  • Dompe
  • Incyte
  • Millennium Pharmaceuticals
  • Ono Pharmaceutical
  • Pharmacopeia Drug Discovery
  • UCB SA
• 4.8. Significant Commercial Deals
• 4.9. Current Outlook

• TOLL-LIKE RECEPTOR MODULATORS
• 5.1. Pathophysiological Role(s)
• 5.2. Potential Therapeutic Indications
• 5.3. Possible Pitfalls
• 5.4. Level of Activity, 2000 to 2006
• 5.5. Development Compounds
  • TLR-3 Agonists
  • Ampligen
  • TLR-4 Modulators
  • Eritoran
  • TAK-242
  • CRX-675
  • TLR-7 Agonists
  • 852A
  • Isatoribine and ANA-975
  • ANA-773
  • Toll-like Receptors: Opportunities in Numerous Disease States. Q&A with Professor Luke O' Neill, Opsana Therapeutics
  • TLR-9 Agonists
  • PF-3512676
  • Tolamba, Heplisav, and ISS-1018
  • CpG-10101
  • IMO-2055
  • Preclinical Agents
• 5.6. Active Major Companies
  • AstraZeneca
  • Eisai
  • GlaxoSmithKline
  • Novartis
  • Pfizer
  • sanofi-aventis
  • Takeda
• 5.7. Other Active Companies
  • 3M Pharmaceuticals
  • Anadys
  • Coley Pharmaceuticals
  • Dynavax Technologies
  • Hemispherx Biopharma
  • Idera Pharmaceuticals
  • Innate Pharma
  • Opsona Therapeutics
• 5.8. Significant Commercial Deals
• 5.9. Current Outlook

• 11β-HYDROXYSTEROID DEHYDROGENASE INHIBITORS
• 6.1. 11β-Hydroxysteroid Dehydrogenase
  • 11β-HSD1
  • 11β-HSD2
• 6.2. Pathophysiological Role(s)
• 6.3. Potential Therapeutic Indications
  • Type 2 Diabetes
  • 11β-HSD Inhibitors: Broad Applications in Metabolic Disease. Q&A with Dr. Greg Hollis, vice president, Advanced Technology, Incyte; Dr. Deborah Hunter, leader, Incyte; and Dr. Nigel Vicker, group leader, Discovery Chemistry, Ipsen
  • Metabolic Syndrome
  • Obesity
  • Memory Disorders
  • Inflammation
• 6.4. Possible Pitfalls
  • INCB-13739
  • AMG-221
  • Preclinical Efforts
• 6.5. Active Major Companies
  • Abbott
  • Amgen
  • AstraZeneca
  • Hoffman-La Roche
  • Janssen
  • Merck
  • Pfizer
  • Takeda
  • Wyeth
• 6.6. Other Active Companies
  • Bionetworks GmbH
  • Biovitrum AB
  • Evotec AG
  • Incyte
  • Sterix
• 6.7. Significant Commercial Deals
• 6.8. Current Outlook

• MELANOCORTIN RECEPTOR MODULATORS
• 7.1. Melanocortin Receptors
• 7.2. Drug Targets
• 7.3. Pathophysiological Role(s)
• 7.4. Potential Therapeutic Indications
  • Obesity
  • Sexual Dysfunction
  • Depression and Anxiety
• 7.5. Possible Pitfalls
  • Bremelanotide
  • AP-214
  • Preclinical Efforts
  • MC4 Agonists
  • MC4 Antagonists
• 7.6. Active Major Companies
  • Eli Lilly
  • Merck
  • Novartis
  • Novo Nordisk
  • Roche
• 7.7. Other Active Companies
  • Action Pharma
  • Ipsen
  • Millennium Pharmaceuticals
  • Neurocrine Biosciences
  • Palatin Technologies
  • Procter & Gamble
  • Santhera
  • Taisho
• 7.8. Significant Commercial Deals
• 7.9. Commercial Outlook

• MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS
• 8.1. Melanin-Concentrating Hormone
• 8.2. MCH-1 Receptor
• 8.3. Pathophysiological Role(s)
• 8.4. Potential Therapeutic Indications
  • Obesity
  • Depression and Anxiety
• 8.5. Possible Pitfalls
• 8.6. Development Compounds
• 8.7. Clinical Compounds
  • AMG-076
  • 856464
  • NGD-4715
  • Preclinical Efforts
• 8.8. Active Major Companies
  • Abbott Laboratories
  • Amgen
  • AstraZeneca
  • Boehringer Ingelheim
  • Eli Lilly
  • GlaxoSmithKline
  • Merck
  • sanofi-aventis
  • Schering-Plough
  • Takeda
• 8.9. Other Active Companies
  • 7TM Pharma A/S
  • Arena Pharmaceuticals
  • Biovitrum
  • Lundbeck
  • Neurocrine Biosciences
  • Neurogen
  • Procter & Gamble
  • Taisho Pharmaceuticals
• 8.10. Significant Commercial Deals
• 8.11. Current Outlook

References

Glossary of Selected Terms

Company Index with Web Addresses