At any given time, a number of drug targets are attracting considerable interest from different pharmaceutical companies. The emergence of such targets as hot topics of research usually becomes apparent before the introduction of clinical candidates by a rapid increase in the level of patenting and research activity directed toward them. Metabolic and Inflammatory Disease R&D: An Assessment of 5 Highly Promising Therapeutic Classes, by Peter Norman, MBA, PhD, a new report from Insight Pharma Reports, details targets of high interest that are primarily of relevance to inflammatory or metabolic diseases and toward which few, if any, compounds have progressed into Phase II studies.Such extensive patenting and research focus is no guarantee of commercial success, as illustrated by the recent examples of lipoxygenase inhibitors and leukotriene antagonists—with the more intensive activity directed at the former providing negligible commercial returns while the latter led to 3 successful products. To help deal with such uncertainty, Metabolic and Inflammatory Disease R&D: An Assessment of 5 Highly Promising Therapeutic Classes identifies and assesses the potentially successful efforts in each of 5 different areas:Chemokine antagonists Toll-like receptors Melanin-concentrating hormone antagonists Melanocortin MC4 agonists 11b-hydroxysteroid dehydrogenase inhibitors Selection of these 5 compound classes was based on an assessment of the levels of patenting and R&D activity directed against various targets currently of considerable interest in creating new agents for the treatment of inflammatory, autoimmune, or metabolic disorders. For instance:In January 2007, 11 chemokine antagonists from 9 different companies were in clinical development for the treatment of inflammatory disorders, with 2 of these drugs being the focus of high-value commercial deals. Many more chemokine antagonists are either in preclinical development or lead optimization, and most of the major pharmaceutical companies have current R&D efforts directed at chemokine receptor targets. For the 10 identified toll-like receptors (TLRs), current activity centers around development of both TLR agonists and antagonists to treat conditions ranging from sepsis to cancer. Metabolic and Inflammatory Disease R&D: An Assessment of 5 Highly Promising Therapeutic Classes provides a thorough analysis of these TLR potentials, plus succinct charts of Strengths, Weaknesses, Opportunities, and Threats for these and other products in development.   

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Metabolic and Inflammatory Disease R&D: An Assessment of 5
Highly Promising Therapeutic Classes
Published on April 2007
Report Summary
At any given time, a number of drug targets are attracting considerable interest from different pharmaceutical companies. The
emergence of such targets as hot topics of research usually becomes apparent before the introduction of clinical candidates by a
rapid increase in the level of patenting and research activity directed toward them. Metabolic and Inflammatory Disease R&D: An
Assessment of 5 Highly Promising Therapeutic Classes, by Peter Norman, MBA, PhD, a new report from Insight Pharma Reports,
details targets of high interest that are primarily of relevance to inflammatory or metabolic diseases and toward which few, if any,
compounds have progressed into Phase II studies.
Such extensive patenting and research focus is no guarantee of commercial success, as illustrated by the recent examples of
lipoxygenase inhibitors and leukotriene antagonists—with the more intensive activity directed at the former providing negligible
commercial returns while the latter led to 3 successful products. To help deal with such uncertainty, Metabolic and Inflammatory
Disease R&D: An Assessment of 5 Highly Promising Therapeutic Classes identifies and assesses the potentially successful efforts in
each of 5 different areas:Chemokine antagonists Toll-like receptors Melanin-concentrating hormone antagonists Melanocortin MC4
agonists 11b-hydroxysteroid dehydrogenase inhibitors Selection of these 5 compound classes was based on an assessment of the
levels of patenting and R&D activity directed against various targets currently of considerable interest in creating new agents for the
treatment of inflammatory, autoimmune, or metabolic disorders. For instance:In January 2007, 11 chemokine antagonists from 9
different companies were in clinical development for the treatment of inflammatory disorders, with 2 of these drugs being the focus of
high-value commercial deals. Many more chemokine antagonists are either in preclinical development or lead optimization, and most
of the major pharmaceutical companies have current R&D efforts directed at chemokine receptor targets. For the 10 identified toll-like
receptors (TLRs), current activity centers around development of both TLR agonists and antagonists to treat conditions ranging from
sepsis to cancer. Metabolic and Inflammatory Disease R&D: An Assessment of 5 Highly Promising Therapeutic Classes provides a
thorough analysis of these TLR potentials, plus succinct charts of Strengths, Weaknesses, Opportunities, and Threats for these and
other products in development.
Table of Content
Chapter 1INTRODUCTION1.1 Target-Based Approaches to Drug Discovery1.2 Identification of Current High-Profile Targeted
ApproachesInflammatory and Immune DiseasesMetabolic Diseases1.3 Does Extensive Activity Predict Success'Success from High
ActivityLeukotriene CysLT1 Receptor AntagonistsPDE5 InhibitorsCOX-2 InhibitorsFailures Despite Intense Efforts5-Lipoxygenase
InhibitorsRenin InhibitorsThromboxane AntagonistsLong-lived Effortsp38 MAP KinasePDE4 Inhibitors1.4 Reasons for Failures
Chapter 2METHODOLOGY: IDENTIFYING HIGH-PROFILE AREAS OF EFFORT2.1. Medical Advances2.2. Literature Activity2.3.
Meetings2.4. Patenting Activity2.5. Commercial DealsChapter 3HIGH-PROFILE TOPICS IN INFLAMMATORY AND METABOLIC
DISEASES3.1. Inflammatory DiseasesRespiratory DiseasesArthritis3.2. Metabolic DiseasesDiabetesObesityMetabolic SyndromeLipid
DisordersChapter 4CHEMOKINE ANTAGONISTS4.1. Chemokines4.2. TargetsCCR ReceptorsCXCR Receptors4.3.
Pathophysiological Role(s)Inflammatory ProcessesHIV Infection4.4. Potential Therapeutic IndicationsAtherosclerosisAllergic
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RhinitisAsthmaChronic Obstructive Pulmonary DiseaseMultiple SclerosisRheumatoid ArthritisCancer4.5. Possible PitfallsCCR
ReceptorsCXCR ReceptorsCCR1 AntagonistsSH-T-04268-HCCR2 AntagonistsChemokine Antagonists: Strong Evidence ¡- Well
Validated. Q&A with Dr. Kris Vaddi, vice president, Preclinical Biology, Incyte, and Dr. Robert Newton, Drug Discovery Biology,
IncyteCCR3 AntagonistsCCX-282CXCR2 AntagonistsSCH-527123GSK-656933DF-1681CTCE-9908Preclinical Efforts4.6. Active
Major CompaniesAmgenAstellasAstraZenecaBayer ScheringBoehringer IngelheimBristol-Meyers SquibbDaiichi
SankyoGlaxoSmithKlineHoffmann-La RocheJanssenMerckNovartisPfizersanofi-aventisSchering-PloughTakedaWyeth4.7. Other
Active CompaniesAnorMEDChemoCentryxChemokine TherapeuticsDomp¨¦IncyteMillennium PharmaceuticalsOno
PharmaceuticalPharmacopeia Drug DiscoveryUCB SA4.8. Significant Commercial Deals4.9. Current OutlookChapter 5TOLL-LIKE
RECEPTOR MODULATORS5.1. Pathophysiological Role(s)5.2. Potential Therapeutic Indications5.3. Possible Pitfalls5.4. Level of
Activity, 2000 to 20065.5. Development CompoundsTLR-3 AgonistsAmpligenTLR-4 ModulatorsEritoranTAK-242CRX-675TLR-7
Agonists852AIsatoribine and ANA-975ANA-773Toll-like Receptors: Opportunities in Numerous Disease States. Q&A with Professor
Luke O¡¯Neill, Opsana TherapeuticsTLR-9 AgonistsPF-3512676Tolamba, Heplisav, and ISS-1018CpG-10101IMO-2055Preclinical
Agents5.6. Active Major CompaniesAstraZenecaEisaiGlaxoSmithKlineNovartisPfizersanofi-aventisTakeda5.7. Other Active
Companies3M PharmaceuticalsAnadysColey PharmaceuticalsDynavax TechnologiesHemispherx BiopharmaIdera
PharmaceuticalsInnate PharmaOpsona Therapeutics5.8. Significant Commercial Deals5.9. Current OutlookChapter
611¦Â-HYDROXYSTEROID DEHYDROGENASE INHIBITORS6.1. 11¦Â-Hydroxysteroid Dehydrogenase11¦Â-HSD111¦Â-HSD26.2.
Pathophysiological Role(s)6.3. Potential Therapeutic IndicationsType 2 Diabetes11¦Â-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, IpsenMetabolic SyndromeObesityMemory DisordersInflammation6.4. Possible Pitfalls
INCB-13739AMG-221Preclinical Efforts6.5. Active Major CompaniesAbbottAmgenAstraZenecaHoffman-La
RocheJanssenMerckPfizerTakedaWyeth6.6. Other Active CompaniesBionetworks GmbHBiovitrum ABEvotec AGIncyteSterix6.7.
Significant Commercial Deals6.8. Current OutlookChapter 7MELANOCORTIN RECEPTOR MODULATORS7.1. Melanocortin
Receptors7.2. Drug Targets7.3. Pathophysiological Role(s)7.4. Potential Therapeutic IndicationsObesitySexual
DysfunctionDepression and Anxiety7.5. Possible PitfallsBremelanotideAP-214Preclinical EffortsMC4 AgonistsMC4 Antagonists7.6.
Active Major CompaniesEli LillyMerckNovartisNovo NordiskRoche7.7. Other Active CompaniesAction PharmaIpsenMillennium
PharmaceuticalsNeurocrine BiosciencesPalatin TechnologiesProcter & GambleSantheraTaisho7.8. Significant Commercial Deals7.9.
Commercial OutlookChapter 8MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS8.1. Melanin-Concentrating
Hormone8.2. MCH-1 Receptor8.3. Pathophysiological Role(s)8.4. Potential Therapeutic IndicationsObesityDepression and Anxiety
8.5. Possible Pitfalls8.6. Development Compounds8.7. Clinical CompoundsAMG-076856464NGD-4715Preclinical Efforts8.8. Active
Major CompaniesAbbott LaboratoriesAmgenAstraZenecaBoehringer IngelheimEli
LillyGlaxoSmithKlineMercksanofi-aventisSchering-PloughTakeda8.9. Other Active Companies7TM Pharma A/SArena
PharmaceuticalsBiovitrumLundbeckNeurocrine BiosciencesNeurogenProcter & GambleTaisho Pharmaceuticals8.10. Significant
Commercial Deals8.11. Current OutlookReferencesGlossary of Selected Terms Company Index with Web Addresses
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