Capitalizing On Expanded Opportunities Cardiovascular ... · CVMED Disease Burden. STRATEGY To...
Transcript of Capitalizing On Expanded Opportunities Cardiovascular ... · CVMED Disease Burden. STRATEGY To...
Capitalizing On Expanded OpportunitiesCapitalizing On Expanded OpportunitiesCardiovascular, Metabolic, and Cardiovascular, Metabolic, and
Endocrine Disease (CVMED)Endocrine Disease (CVMED)
Steven Ryder, M.D.Steven Ryder, M.D.Senior Vice PresidentSenior Vice President
Therapeutic Area Development HeadTherapeutic Area Development Head
Valid as of November 30, 2006
Vision And Strategy Vision And Strategy
VISIONVISIONTo Deliver Innovative Products and Solutions To Deliver Innovative Products and Solutions
that Maintain Health and Reduce that Maintain Health and Reduce CVMED Disease Burden.CVMED Disease Burden.
STRATEGYSTRATEGYTo Achieve a CVMED Portfolio Mix and Create To Achieve a CVMED Portfolio Mix and Create
an Environment that Maximizes Value by Pursuing an Environment that Maximizes Value by Pursuing LongLong--term Growth Investments in Prevention term Growth Investments in Prevention
and Disease Treatment. and Disease Treatment.
Valid as of November 30, 2006
InIn--Line Portfolio Focused on RiskLine Portfolio Focused on Risk--Factor Factor Modification and Disease InterventionModification and Disease Intervention
RiskRisk--Factor Factor ModificationModification
DiseaseDiseaseInterventionIntervention
NorvascNorvasc
Healthy AgingPopulation
Healthy AgingPopulation
Valid as of November 30, 2006
Development Portfolio Focused on RiskDevelopment Portfolio Focused on Risk--Factor Factor Modification and Disease InterventionModification and Disease Intervention
Phase 3/Registration
Phase 2
Phase 1
HealthyHealthyAging Aging
PopulationPopulation
HealthHealthMaintenanceMaintenance
RiskRisk--FactorFactorModificationModification
DiseaseDiseaseInterventionIntervention
* = new disclosure
CombosObes & DM
CombosObes & DM
DPPIVDiabetes
DPPIVDiabetes
PPARαLipid/IRPPARαLipid/IR
MTPi* ObesityMTPi*
Obesity
µ opioidObesityµ opioidObesity
11β HSDDiabetes11β HSDDiabetes
CCKaObes & DM
CCKaObes & DM
TorcetrapibHDL
TorcetrapibHDL
PPARαLipid/IRPPARαLipid/IR
CETPi HDL
CETPi HDL
PDE5i CV
PDE5i CV
EsperionCV
EsperionCV
PD-348,592*ThrombosisPD-348,592*Thrombosis
CP-533,536*Bone HealingCP-533,536*
Bone Healing
Peg GHGH Deficiency
Peg GHGH Deficiency
CP-945,593Obesity
CP-945,593Obesity
Valid as of November 30, 2006
To PreventionTo PreventionObesityObesityDiabetesDiabetesInsulin ResistanceInsulin ResistanceHyperlipidemiaHyperlipidemiaMuscle LossMuscle LossBone MetabolismBone Metabolism
InterventionInterventionThrombosisCoronary Heart DiseaseDiabetes (e.g. Insulin)Growth Hormone DeficiencyBone Healing
An Evolving StrategyAn Evolving Strategy
Valid as of November 30, 2006
Expanding Scope Of CVMED R&DExpanding Scope Of CVMED R&D
Phase 1Phase 1
PreclinicalPreclinical
Phase 3Phase 3
InIn--Line Line PortfolioPortfolio
Phase 2Phase 2
Torcetrapib/AtorvastatinTorcetrapib/AtorvastatinCB-1CB-1
PEGylated GHPEGylated GH
PGE2PGE2
MTPiMTPi Factor XaFactor Xa
PPARαPPARα
EsperionEsperion DPPIVDPPIV
Oporia (Registration)Oporia (Registration)
NorvascNorvasc
11β HSD11β HSDPDE5iPDE5i
CETPiCETPiTorcetrapibTorcetrapib
CCKaCCKaMTPiMTPi
µ opioidµ opioid CB-1CB-1
PPARαPPARαStatin PlusStatin Plus
5 HT2c5 HT2cMyostatin mAbMyostatin mAbDGATDGAT
RINATRINAT PYYPYY
SPTSPTOpRAOpRAMR-HTNMR-HTN
Exubera 2nd GenerationExubera 2nd Generation11β HSD11β HSD
DPPIVDPPIV
Valid as of November 30, 2006
Current WW Market Size/ Current WW Market Size/ Opportunity ($U.S. Billion)Opportunity ($U.S. Billion)
AtherosclerosisAtherosclerosis $34.0$34.0
ObesityObesity $35.0 $35.0
DiabetesDiabetes $19.5$19.5
Bone and Muscle HealthBone and Muscle Health $10.6$10.6
ThrombosisThrombosis $5.6$5.6
CVMED R&D CVMED R&D
Valid as of November 30, 2006
Metabolic Disease Metabolic Disease
ObesityObesity
Major Health ProblemMajor Health Problem
Risk Multiplier for Many DiseasesRisk Multiplier for Many Diseases
Unmet Medical NeedUnmet Medical Need
Managing the Entire PatientManaging the Entire Patient
Valid as of November 30, 2006
Multiple Approaches In ObesityMultiple Approaches In Obesity
PYYPYY
LeptinLeptinInsulinInsulin
CCKCCK
GhrelinGhrelin
Spinal NervesSpinal Nerves
VagueNerve
VagueNerve
Central & PeripheralCentral & PeripheralAnorecticsAnorectics
(Inhibit Desire to Eat)(Inhibit Desire to Eat)
Thermogenic & Thermogenic & Metabolic StimulatorsMetabolic Stimulators
(Increase Calorie Expenditure)(Increase Calorie Expenditure)
Absorption Inhibitors
(Limit FatAbsorption)
Absorption Absorption InhibitorsInhibitors
(Limit Fat(Limit FatAbsorption)Absorption)
5HT2c, CB5HT2c, CB--1, NPY5, MCR4, 1, NPY5, MCR4, Ghrelin, AGRP, NTGhrelin, AGRP, NT--1, 1,
MCH, 5MCH, 5--HTHT66, PYY, MTPi, , PYY, MTPi, CCKCCK--A, NTA, NT--1, PP,1, PP,
DGAT, SCDDGAT, SCD--11
MCR4, AGRP, CBMCR4, AGRP, CB--1,1,1111ββHSD, PPAR, DGAT, HSD, PPAR, DGAT,
GPRs, SCDGPRs, SCD--1, ACC, 1, ACC, Ghrelin, SGLT1Ghrelin, SGLT1
MTPiMTPi
Maximal Efficacy will Likely Require CoMaximal Efficacy will Likely Require Co--Administration Administration of Agents with Multiple Mechanistic Targetsof Agents with Multiple Mechanistic Targets
Valid as of November 30, 2006
Cannabinoid ReceptorCannabinoid Receptor––1 Antagonism1 Antagonism
GG--Coupled Protein CNSCoupled Protein CNS--Mediated EffectMediated Effect
CP-945,598 – Phase 3CPCP--945,598 945,598 –– Phase 3Phase 3
Valid as of November 30, 2006
CPCP--945,598 (CB945,598 (CB--1 Antagonist) 1 Antagonist) Phase 2 Study: % Change in Body WeightPhase 2 Study: % Change in Body Weight
-12-12-11-11-10-10-9-9-8-8-7-7-6-6-5-5-4-4-3-3-2-2-1-100
00 2828 5656 8484 112112 140140 168168 196196DaysDays
Bod
y W
eigh
t % C
hang
eB
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Wei
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Cha
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CP-945,598 5 mgCP-945,598 5 mg
CP-945,598 25 mgCP-945,598 25 mgCP-945,598 15 mgCP-945,598 15 mg
Valid as of November 30, 2006
CPCP--945,598945,598PlaceboPlacebo--Adjusted Percent Change In Weight At 6 MonthsAdjusted Percent Change In Weight At 6 Months
-10-10
-9-9
-8-8
-7-7
-6-6
-5-5
-4-4
-3-3
-2-2
-1-1
00
5 mg 5 mg ((--2.4%)2.4%)
15 mg15 mg(( --4.8%)4.8%)
25 mg25 mg((--4.4%)4.4%)(( --4.5%)4.5%)
5 mg 5 mg ((--2.4%)2.4%)
15 mg15 mg(( --4.8%)4.8%)
25 mg25 mg((--4.4%)4.4%)
Rimonabant*Rimonabant*(( --4.5%)4.5%)
CP-945,598 5 mgCP-945,598 5 mg
CP-945,598 25 mgCP-945,598 25 mg
CP-945,598 15 mgCP-945,598 15 mg
Bod
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eigh
t % C
hang
eB
ody
Wei
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Cha
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* * Extrapolation Full ITT RIO EU; PBOExtrapolation Full ITT RIO EU; PBO--AdjustedAdjusted
Valid as of November 30, 2006
CPCP--945,598 945,598 CBCB--1 Antagonist1 Antagonist
Well Tolerated in Phase 1 and 2Well Tolerated in Phase 1 and 2
Phase 3 StartedPhase 3 Started
Additional CbAdditional Cb--11--Antagonist Candidates in Antagonist Candidates in Phase 1 DevelopmentPhase 1 Development
Valid as of November 30, 2006
ObesityObesityThe Opportunity With MTP InhibitorsThe Opportunity With MTP Inhibitors
MTP (Microsomal Triglyceride Transfer Protein) MTP (Microsomal Triglyceride Transfer Protein) Continues to Emerge as One of the Most Continues to Emerge as One of the Most Compelling Targets in the CVMED PortfolioCompelling Targets in the CVMED Portfolio
LDL/VLDL Cholesterol ReductionsLDL/VLDL Cholesterol ReductionsClinical Weight Loss Better Than Current TherapyClinical Weight Loss Better Than Current TherapyPotential BestPotential Best--InIn--Class Therapy for ObesityClass Therapy for Obesity
Valid as of November 30, 2006
DayDay--1010 00 1010 2020 3030 4040 5050 6060 7070 8080 9090 100100 110110 120120 130130
Mea
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Cho
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erol
(ng/
mL)
Mea
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Cho
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mL)
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5050
100100
150150
200200
250250
300300
350350
Begin Study Drug AdministrationBegin Study Drug Administration
End Study Drug AdministrationEnd Study Drug AdministrationMTP InhibitorPlacebo MTP InhibitorPlacebo
MTP Inhibitor in DogsMTP Inhibitor in DogsSignificant Cholesterol ReductionSignificant Cholesterol Reduction
Valid as of November 30, 2006
MTP InhibitorMTP Inhibitor
66--month Weight Loss month Weight Loss With Rimonabant With Rimonabant (Extrapolation Full ITT RIO EU; not PBO(Extrapolation Full ITT RIO EU; not PBO--Adjusted)Adjusted)
Day of StudyDay of Study00 77 1414 2121 2828 3535 4242 4949 5656 6363 7070 7777 8484
Bod
y W
eigh
t %
Cha
nge
Bod
y W
eigh
t %
Cha
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-8-8
-6-6
-4-4
-2-2
00
22
PlaceboPlacebo
ActiveActive
Significant Weight Loss at 3 Months Comparable to Rimonabant at 6 Months
Significant Weight Loss at 3 Months Significant Weight Loss at 3 Months Comparable to Rimonabant at 6 MonthsComparable to Rimonabant at 6 Months
Valid as of November 30, 2006
CVMED R&D CVMED R&D
AtherosclerosisAtherosclerosis
ObesityObesity
DiabetesDiabetes
Bone and Muscle HealthBone and Muscle Health
ThrombosisThrombosis
Valid as of November 30, 2006