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.


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


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


To PreventionTo PreventionObesityObesityDiabetesDiabetesInsulin ResistanceInsulin ResistanceHyperlipidemiaHyperlipidemiaMuscle LossMuscle LossBone MetabolismBone Metabolism

InterventionInterventionThrombosisCoronary Heart DiseaseDiabetes (e.g. Insulin)Growth Hormone DeficiencyBone Healing

An Evolving StrategyAn Evolving Strategy


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


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


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


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


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


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

ody

Wei

ght %

Cha

nge PlaceboPlacebo

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


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

y W

eigh

t % C

hang

eB

ody

Wei

ght %

Cha

nge

* * Extrapolation Full ITT RIO EU; PBOExtrapolation Full ITT RIO EU; PBO--AdjustedAdjusted


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


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


DayDay--1010 00 1010 2020 3030 4040 5050 6060 7070 8080 9090 100100 110110 120120 130130

Mea

n Se

rum

Cho

lest

erol

(ng/

mL)

Mea

n Se

rum

Cho

lest

erol

(ng/

mL)

00

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


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

nge

-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


CVMED R&D CVMED R&D

AtherosclerosisAtherosclerosis

ObesityObesity

DiabetesDiabetes

Bone and Muscle HealthBone and Muscle Health

ThrombosisThrombosis


Capitalizing On Expanded Opportunities Cardiovascular ... · CVMED Disease Burden. STRATEGY To...

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