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 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 Genes
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,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
Janus Kinase 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
Rheumatoid Arthritis 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