Transforming Drug DiscoveryInnovative Platforms
Transforming Drug DiscoveryTransforming Drug DiscoveryInnovativeInnovative PlatformsPlatforms
Martin Mackay, Ph.D.Martin Mackay, Ph.D.Senior Vice PresidentSenior Vice President
Worldwide Research and TechnologyWorldwide Research and Technology
Valid as of November 30, 2006
From a Linear ProcessFrom a Linear Process
To a Parallel ProcessTo a Parallel Process
Drug CDrug CDrug C
More, Better, FasterMore, Better, Faster
SingleTargetSingleTarget
Gene Families
of Targets
Gene Families
of Targets
Drug ADrug ADrug A
Drug BDrug BDrug B
N
N
N
O
O
S NO
O
N
N
N
N
O
O
S NO
O
N
N
N
N
O
O
S NO
O
N
N
N
N
O
O
S NO
O
N
N
N
N
O
O
S NO
O
N
Valid as of November 30, 2006
Drug Discovery at ScaleDrug Discovery at Scale
PDEPDE--1b 1b –– ADHDADHDPDEPDE--2 2 –– Bone Healing, Bone Healing, Cognition, Inflammatory PainCognition, Inflammatory PainPDEPDE--4 4 –– COPD, AsthmaCOPD, AsthmaPDEPDE--4B 4B –– CognitionCognitionPDEPDE--5 5 –– Erectile Dysfunction, Erectile Dysfunction, HypertensionHypertensionPDEPDE--7B 7B –– Neuropathic Pain, Neuropathic Pain, SchizophreniaSchizophreniaPDEPDE--8B 8B –– DiabetesDiabetesPDEPDE--9 9 –– Diabetes, CognitionDiabetes, CognitionPDEPDE--10A 10A –– Schizophrenia, Schizophrenia, Diabetes, ObesityDiabetes, Obesity
Valid as of November 30, 2006
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
The Kinome The Kinome A Substantial DrugA Substantial Drug--Discovery OpportunityDiscovery Opportunity
Manning et al., Science 298: 1912, 2002Manning et al., Science 298: 1912, 2002Manning et al., Science 298: 1912, 2002
Valid as of November 30, 2006
*Discovered at Pfizer, owned by OSI/Genentech*Discovered at Pfizer, owned by OSI/Genentech
Name Target Status
Tarceva® * EGFR Launched 2004
Sutent® Multi Tyr Launched 2006Kinase
Axitinib Multi Tyr Phase 3Kinase
Name Target Status
Tarceva® * EGFR Launched 2004
Sutent® Multi Tyr Launched 2006Kinase
Axitinib Multi Tyr Phase 3Kinase
Early Success at PfizerEarly Success at Pfizer
Valid as of November 30, 2006
A Dazzling Kinase PortfolioA Dazzling Kinase Portfolio
OncologyOncology
InflammationInflammation
Allergy &Allergy &RespiratoryRespiratory
CVMEDCVMED
NeuroscienceNeuroscienceDermatologyDermatology
GI/HepatitisGI/HepatitisOphthalmologyOphthalmology
PainPain
56 Kinase Programs56 Kinase ProgramsAcross 9 Therapeutic AreasAcross 9 Therapeutic Areas
Valid as of November 30, 2006
Kinase Targeted Library (KTL)Kinase Targeted Library (KTL)
Kinase Selectivity Kinase Selectivity Panel (KSS)Panel (KSS)
Kinase CoKinase Co--Crystal Structure DB Crystal Structure DB
Integrated Knowledge Integrated Knowledge Platform (K2B)Platform (K2B)
KinaseKinaseCenter ofCenter ofEmphasisEmphasis
Pfizer Leads in Number of Kinase Patents20% from Jubiliant Database Published to 2005
Pfizer Leads in Number of Kinase Patents20% from Jubiliant Database Published to 2005
WorldWorld--Class InfrastructureClass Infrastructure
Valid as of November 30, 2006
A New Era of Kinase InhibitorsA New Era of Kinase Inhibitors
Janus Kinase 3 (JAK 3)Janus Kinase 3 (JAK 3)
cc--MetMet
Valid as of November 30, 2006
CPCP--690,550 690,550 Shows Potential Across Many DiseasesShows Potential Across Many Diseases
Human Genetics Human Genetics Implicated JAK 3 as Implicated JAK 3 as Target for ImmuneTarget for Immune--System DisordersSystem Disorders
CPCP--690,550 Shown to be 690,550 Shown to be Effective in Organ Effective in Organ TransplantTransplant
Rheumatoid Arthritis is Rheumatoid Arthritis is an Autoimmune Disorder an Autoimmune Disorder Hence our Desire to Test Hence our Desire to Test in this Indicationin this Indication
Valid as of November 30, 2006
CPCP--690,550 690,550 Promising Results in RAPromising Results in RA
Patients With ACR20 Response (%)Patients With ACR20 Response (%)Patients With ACR20 Response (%)
0
20
40
60
80
100
0 2 4 6
Weeks
5 mg 15 mg 30 mg Placebo
0
20
40
60
80
100
0 2 4 6
Weeks
5 mg 15 mg 30 mg Placebo
CP-690,550CPCP--690,550690,550
0
20
40
60
80
100
0 2 4 6 8 10 12
Weeks
20 mg 40 mg 80 mg Placebo
0
20
40
60
80
100
0 2 4 6 8 10 12
Weeks
20 mg 40 mg 80 mg Placebo
Humira®HumiraHumira®®
Valid as of November 30, 2006
cc--Met Inhibitors Met Inhibitors Offer a New Treatment for CancerOffer a New Treatment for Cancer
Gene Amplification
c-Met Dysregulationc-Met Dysregulation Altered Tumor-Cell GrowthAltered Tumor-Cell Growth
YYPP
YYPP
TMTM
YYPP
YYPP
YYPP
YYPP
TMTMExtracellular
Intracellular
YYPP
YYPP
H1094R
Y1230C
M1250T
Kinase
R988CT1010I
Activating Mutations
Tumor Invasion and MetastasisTumor Invasion and Metastasis
Tumor AngiogenesisTumor Angiogenesis
Valid as of November 30, 2006
PFPF--2,341,066 2,341,066 Significantly Reduces Tumor Burden in MiceSignificantly Reduces Tumor Burden in Mice
PFPF--23410662341066
Tum
or V
olum
e (m
m3)
Tum
or V
olum
e (m
m3)
ControlControl
Time (days)Time (days)
16001600
12001200
800800
400400
001010 2020 3030 4040 60605050
Valid as of November 30, 2006
A Winning StrategyA Winning Strategy
Leading Kinase CollaborationsLeading Kinase CollaborationsLeading Kinase CollaborationsAcademic Institutions - e.g. Lauffenberger and Sorger, MIT, Kinase Pathway Analysis; I. Hunter, MIT, Novel Technology for Kinase-cmpd Analysis
Biotech Companies - e.g. Caliper, Biosource, Novel Kinase Screening Technologies
Kinase Drug Pfinder program e.g. J. Blenis-Harvard, S6K; J. Liao-B&W Hospital, Rho Kinase; Dr. Tsichlis-Tufts, Cot; L. Rameh-BBRI, PI5P4K
Academic Institutions - e.g. Lauffenberger and Sorger, MIT, Kinase Pathway Analysis; I. Hunter, MIT, Novel Technology for Kinase-cmpd Analysis
Biotech Companies - e.g. Caliper, Biosource, Novel Kinase Screening Technologies
Kinase Drug Pfinder program e.g. J. Blenis-Harvard, S6K; J. Liao-B&W Hospital, Rho Kinase; Dr. Tsichlis-Tufts, Cot; L. Rameh-BBRI, PI5P4K
Valid as of November 30, 2006
