TransformingTransforming DrugDrug DiscoveryDiscovery InnovativeInnovativePlatforms Platforms

Martin Mackay, Ph.D. Senior Vice President Worldwide Research and Technology

Valid as of November 30, 2006 N SN O O N N N O O Drug B Drug A Drug C Drug B Drug A Drug C Drug B Drug A Drug C Valid as of November 30, 2006 Gene Single Target Single Target Families Families of Targets of Targets N SN O O N N N N SN O O O O N N N O O More, Better, Faster More, Better, Faster N N SN O O SN O O N N N N N N

From a Linear Process From a Linear Process To a ParallelTo a Parallel Process Process O O O O DrugDrug DiscoveryDiscovery atat ScaleScale

‹ PDE-1b – ADHD

‹ PDE-2 – Bone Healing, Cognition, Inflammatory Pain

‹ PDE-4 – COPD, Asthma

‹ PDE-4B – Cognition

‹ PDE-5 – Erectile Dysfunction, Hypertension

‹ PDE-7B – Neuropathic Pain, Schizophrenia

‹ PDE-8B – Diabetes

‹ PDE-9 – Diabetes, Cognition

‹ PDE-10A – Schizophrenia, Diabetes, Obesity

Valid as of November 30, 2006 TheThe KinomeKinome A Substantial Drug-Discovery Opportunity

‹ 30,000-40,000 Human

‹ 3,000-4,000 Druggable Targets

‹ 518 Kinases In Genome

‹ 17 Major Kinase Groups, 134 Kinase Families

‹ 214 Kinases Implicated in Disease

ManningManning etet al.,al., ScienceScience 298:298: 1912,1912, 20022002

Valid as of November 30, 2006 EarlyEarly SuccessSuccess atat PfizerPfizer

NameName Target Target Status Status

TarcevaTarceva®® ** EGFR EGFR Launched Launched 20042004

SutentSutent®® MultiMulti TyrTyr Launched Launched 20062006 KinaseKinase

AxitinibAxitinib Multi Multi TyrTyr Phase Phase 33 KinaseKinase

*Discovered*Discovered atat ,Pfizer, ownedowned byby OSI/GenentechOSI/Genentech

Valid as of November 30, 2006 AA DazzlingDazzling KinaseKinase PortfolioPortfolio

56 Kinase Programs Across 9 Therapeutic Areas

Ophthalmology GI/Hepatitis Pain Oncology Dermatology Neuroscience Allergy & Respiratory

CVMED

Inflammation

Valid as of November 30, 2006 WorldWorld--ClassClass InfrastructureInfrastructure

PfizerPfizer LeadsLeads inin NumberNumber ofof KinaseKinase PatentsPatents 20%20% fromfrom JubiliantJubiliant DatabaseDatabase PublishedPublished toto 20052005

Kinase Targeted Library (KTL) Kinase Co-Crystal Structure DB

Kinase Center of Emphasis

Kinase Selectivity Integrated Knowledge Panel (KSS) Platform (K2B)

Valid as of November 30, 2006 AA NewNew EraEra ofof KinaseKinase InhibitorsInhibitors

‹ 3 (JAK 3)

‹ c-Met

Valid as of November 30, 2006 CPCP--690,550690,550 Shows Potential Across Many Diseases

‹ Human Genetics Implicated JAK 3 as Target for Immune- System Disorders

‹ CP-690,550 Shown to be Effective in Organ Transplant

‹ is an Autoimmune Disorder Hence our Desire to Test in this Indication

Valid as of November 30, 2006 CPCP--690,550690,550 Promising Results in RA

CPCP-690,550-690,550 HumiraHumira®® 100 100 100100

8080 8080

6060 6060

4040 4040

2020 2020

00 00 02460246024681012024681012

WeeksWeeks WeeksWeeks 55 mgmg 1515 mgmg 3030 mgmg PlaceboPlacebo 2020 mgmg 4040 mgmg 8080 mgmg PlaceboPlacebo

PatientsPatients WithWith ACR20ACR20 ResponseResponse (%)(%)

Valid as of November 30, 2006 cc--MetMet InhibitorsInhibitors Offer a New Treatment for Cancer c-Metc-Met DysregulationDysregulation AlteredAltered Tumor-CellTumor-Cell GrowthGrowth

TumorTumor AngiogenesisAngiogenesis

Gene Amplification

Extracellular TM R988C Intracellular T1010I TumorTumor InvasionInvasion andand MetastasisMetastasis H1094R P Y P Kinase Y Y1230C M1250T P YY P YY Activating Mutations

Valid as of November 30, 2006 PFPF--2,341,0662,341,066 Significantly Reduces Tumor Burden in Mice

1600 Control

1200

800

PF-2341066 400 Tumor Volume (mm3) Tumor Volume (mm3)

0 10 20 30 40 50 60

Time (days)

Valid as of November 30, 2006 AA WinningWinning StrategyStrategy

LeadingLeading KinaseKinase CollaborationsCollaborations

‹‹ AcademicAcademic InstitutionsInstitutions -- e.g. e.g. LauffenbergLauffenbergerer andand Sorger,Sorger, MIT,MIT, KinaseKinase PathwayPathway Analysis;Analysis; I.I. Hunter,Hunter, MIT,MIT, NovelNovel TechnologyTechnology forfor Kinase-cmpdKinase-cmpd Analysis Analysis

‹‹ BiotechBiotech CompaniesCompanies -- e.g. e.g. Caliper,Caliper, BiosourceBiosource,, NovelNovel KinaseKinase ScreeningScreening TechnologiesTechnologies

‹‹ KinaseKinase DrugDrug PfinderPfinder programprogram e.g.e.g. J.J. Blenis-Harvard,Blenis-Harvard, S6S6K;K; J.J. Liao-B&WLiao-B&W Hospital,Hospital, RhoRho Kinase;Kinase; Dr.Dr. Tsichlis-TuTsichlis-Tufts,fts, Cot;Cot; L.L. Rameh-BBRI,Rameh-BBRI, PI5P4KPI5P4K

Valid as of November 30, 2006