Pfizer Global Research

1
Pfizer Global Research Development
Where do drugs come from? Diane K. Jorkasky, MD
, FACP
2
Pfizer Products
2006 Key Products by Therapeutic Area
Ophthalmology
Xalatan Macugen
Central Nervous System
Cardiovascular/Metabolic
Aricept Cabaser Dilantin Geodon/Zeldox Lyrica
Mirapex Neurontin Rebif Relpax Xanax
XR
Zoloft/Zustrel
Accupril/Accuretic Glucotrol/Glucotrol XL Inspra
Lipitor Norvasc/Istin Procardia/Procardia XL
Tikosyn
Endocrine
Genotropin Somavert
Womens Health
Depo-Provera
Infectious Disease
Oncology
Diflucan Sulperazon Unasyn Vfend Viracept Zit
hromax
Zyvox
Aromasin Camptosar Ellence/ Pharmorubicin Sute
nt
Urology
Cardura/Cardura XL Detrol Viagra
Allergy/Respiratory
Pain/Inflammation
Spiriva/Daxas Zyrtec/Zyrtec D
Celebrex/Celebra Dynastat
Source Pfizer 2002 Year-End Corporate Earnings
Release
3
FDA Approved NCEs By Approval Decade
307
242
220
190
134
127
Esther Schmid and Dennis Smith, Drug Discovery
Today, August 2005
4
Pfizers RD Investment
(Billions)
Source Investments as reported in each years
Pfizer Annual Report
5
RD Pipeline Growth
152 New Molecular Entities
Early Development
Advanced Development
Mid Stage
111
30
5
In Registration
6
Champix Eraxis Exubera Indiplon Sutent Zeven

83 Product Line Extensions
235 Total Programs
8 Larger Than in December 2004
6
Productivity ImprovementFocus on Quality and
Quantity
Our Vision of Sustained Annual Productivity

• 45 New Candidates
• 31 First in Humans
• 24 First in Patients
• 6 Phase 3 Starts
• 5 NDAs
• 4 Products

4 Products for Every 45 Candidates
7
Candidates in Advanced Development
Torcetrapib/Atorvastatin Atherosclerosis
Varenicline Smoking Cessation Asenapine S
chizophrenia Ticilimumab Metastatic Melanoma
ProMune Lung, Breast Cancer Zithromax/
Chloroquine Malaria Maraviroc HIV / AIDS Z
even Bacterial Infections
Cardiovascular
Neurosciences
Oncology
Infectious Diseases
8
Pipeline Progress The Next Wave
Expected Near Term NDA Filings
2006 Maraviroc New Licensing Opportunity TBA
2007 Torcetrapib/Atorvastatin Asenapine Ticilim
umab
9
Champix (Varenicline) Alpha 4-Beta 2 Partial
Agonist Smoking Cessation

• Orally Effective Nicotinic Partial Agonist
• Reduces Nicotine Cravings
• 1.3 Billion Smokers Worldwide
• Average 50 Continuous Quit Rate After 12 Week
  Treatment Compared to 12 With Placebo
  

10
Maraviroc HIV Entry Inhibitor
HIV Cell Entry Inhibition

• First-in-Class
• Selective, Reversible Binding to the CCR-5
  Receptor
  
• Excellent Pharmacokinetics and Selectivity
• Potent In Vitro Activity Against Resistant
  Strains
  
• No Drug-Drug Interactions

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Torcetrapib/Atorvastatin

• Candidate
• CETP inhibitor/HMG CoA reductase inhibitor for
  atherosclerosis
  
• Complementary mechanisms for ?HDL and ?LDL
• Comments
• Phase 3 development underway solid enrollment
  performance in multiple trials during 2004.
  Imaging program on critical path
  
• Numerous additional pivotal trials to initiate
  during 2005
  
• Resourced to support aggressive development
  program

12
Torcetrapib/AtorvastatinTwo Molecules Two
Complementary Mechanisms
Atorvastatin ? LDL
Torcetrapib ? HDL
13
Torcetrapib/Atorvastatin
Comprehensive Phase 3 Development Program

• Imaging Studies to Investigate Atherosclerosis
  Effects
  
• Lipid Studies to Support Dyslipidemia Claims
• Treatment Comparator Studies
• Scientific Development Program
• Morbidity and Mortality Study

40 Studies, 25,000 Subjects
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SutentU.S. Approval Received January, 2006
Multi-Targeted Kinase Inhibitor
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TicilimumabOncology Metastatic Melanoma

• Cyctotoxic T-Lymphocyte-associated Antigen-4
  (CTLA-4) Antibody
  
• CTLA-4 Blockade with CP-675,206 May Break
  Peripheral Immunological Tolerance and Induce
  Anti-tumor Activity
  
• Currently Conducting Phase II Study Using
  Multiple Doses
  

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Ticilimumab
Enhances the Immune Response
Immune Cells
CP-675,206
Immune Brake Off
Immune Cells Multiply and Attack the Cancer
Immune Brake On
Tumor Cells
Tumor Growth
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Ticilimumab Metastatic Melanoma
All 6 High-Dose Patients Benefited
Patients
15 mg/kg
18
TicilimumabCTLA4 Monoclonal Antibody - Cancer
07-30-03
01-07-03
Tumor Cleared
Abdominal Cavity Tumor
Efficacy in Metastatic Melanoma
19
Exubera Diabetes
Received U.S. and E.U. Regulatory Approval
January 2006

• First inhaled form of insulin to be approved
• Approved for Type 1 and 2 Diabetes (adults)
• Product launch expected in 2nd-3rd Q06

20
PGRD Conducts RD Globally13,000 Colleagues
7.8 Billion RD Budget
La Jolla, CA, U.S.A.
Amboise, FRANCE
St. Louis, MO, U.S.A.
Sandwich, ENGLAND
Ann Arbor and KalamazooMI, U.S.A.
Brussels, BELGIUM
Cambridge, MA, U.S.A.
Madrid, SPAIN
New Haven, CT, U.S.A.
Singapore
RD CRU
Nagoya Tokyo, JAPAN
New London andGroton, CT, U.S.A.
21
Global RD Therapeutic Areas
Allergy Respiratory Cardiovascular, Metabolic
Endocrine Diseases Cancer Dermatology Gastroi
ntestinal and Hepatology Genitourinary Infectiou
s Diseases Inflammation Neuroscience Ophthalmol
ogy Pain
22
RD Expenditures as a Percentage of Annual
Revenues
Pharmaceutical vs Other Industries
17
10.5
8.4
7.8
5.3
4.7
3.9
3.8
1.2
0.73
3.9
Source PhRMA, 2001, based on data from PhRMA
Annual Survey and Standard Poors Compustat, a
division of McGraw-Hill
23
Attrition is High in the RD Process
Millions of Compounds Screened
100 Discovery Approaches
High Risk Process 12-15 years, 800MM
Preclinical Pharmacology
Preclinical Safety
1 2 Products
Clinical Pharmacology Safety
Discovery
Exploratory Development
Full Development
Phase I
Phase II
Phase III
0
15
10
5
Idea
Drug
11 - 15 Years
24
Development Process Starts with Many Hypotheses
Prevent Amyloid Plaques
Attenuate Neuro-Inflammation
Block Glutamate Neurotoxicity
Stabilize Neuronal Infrastructure
Stop Programmed Cell Death
Alzheimers Disease
25
The Long Road to a New Medicine
NDA/MMA
Clinical Data Analysis
Full Development
Registration
Studies in 100-300 Patients (Phase II)
Candidate Medicine Tested in 3-10,000 Patients (P
hase III)
Extensive Safety Studies
Large Amounts of Candidate Medicine Synthesize
d
Studies in Healthy Volunteers (Phase I)
Candidate
Formulations Developed
Exploratory Development
Early Safety Studies
Synthesis of Compounds
Project Team and Plans
Screening
Discovery
26
Evolution of Drug Screening
27
Drug Molecule Binding to Protein Target
28
The Long Road to a New Medicine
NDA/MMA
Clinical Data Analysis
Full Development
Registration
Studies in 100-300 Patients (Phase II)
Candidate Medicine Tested in 3-10,000 Patients (P
hase III)
Extensive Safety Studies
Large Amounts of Candidate Medicine Synthesize
d
Studies in Healthy Volunteers (Phase I)
Candidate
Formulations Developed
Exploratory Development
Early Safety Studies
Synthesis of Compounds
Project Team and Plans
Screening
Discovery
29
Ann Arbor Labs Mortar and Pestle
30
The Long Road to a New Medicine
NDA/MMA
Clinical Data Analysis
Full Development
Registration
Studies in 100-300 Patients (Phase II)
Candidate Medicine Tested in 3-10,000 Patients (P
hase III)
Extensive Safety Studies
Large Amounts of Candidate Medicine Synthesize
d
Studies in Healthy Volunteers (Phase I)
Candidate
Formulations Developed
Exploratory Development
Early Safety Studies
Synthesis of Compounds
Project Team and Plans
Screening
Discovery
31
Worldwide Clinical Trial Sites for Pregabalin
32
The Long Road to a New Medicine
NDA/MMA
Clinical Data Analysis
Full Development
Registration
Studies in 100-300 Patients (Phase II)
Candidate Medicine Tested in 3-10,000 Patients (P
hase III)
Extensive Safety Studies
Large Amounts of Candidate Medicine Synthesize
d
Studies in Healthy Volunteers (Phase I)
Candidate
Formulations Developed
Exploratory Development
Early Safety Studies
Synthesis of Compounds
Project Team and Plans
Screening
Discovery
33
New Drug Application for Lipitor
34
Innovation Process Difficult
Complex Disease Targets Too Long in
Body Adverse Reactions Poor Absorption
Low Levels in Body Not Effective Enough
Not Sufficiently Selective Side Effects
Unsafe Unstable Competition Impractical To
Make
Most Compounds Do Not Become Medicines
35
Attrition is High in the RD Process
Millions of Compounds Screened
100 Discovery Approaches
High Risk Process 12-15 years, 800MM
Preclinical Pharmacology
Preclinical Safety
1 2 Products
Clinical Pharmacology Safety
Discovery
Exploratory Development
Full Development
Phase I
Phase II
Phase III
0
15
10
5
Idea
Drug
11 - 15 Years
36
Only 3 in 10 Medicines Return Development Costs
3,000
New Chemical Entities 1990-1994
2,500
2,000
1990 Dollars (Millions)AfterTax Present Value
1,500
1,000
Average RD Cost
500
0
1
2
3
4
5
6
7
8
9
10
Present Values by Decile
(n 67, Excludes Oncology and Selected Other
Categories)
Source PhRMA Industry Profile 2002, Grabowski
and Vernon.
37
High RD Risks High Market Risks

• Much Shorter Practical Exclusivity
• Most Marketed Medicines Do Not Show Positive
  Return on Invested Capital
  
• Instantaneous Generic Substitution

38
Shrinking Market Exclusivity
Innovative Drug / Year Introduced
Follower Drug
Lopressor - 1978 Zantac - 1983 Vasotec - 1985 H
ismanal 1989 Videx 1991 Pravachol 1991 Zo
loft 1992 Sporonox 1992 Kogenate 1992 Vio
xx 1999
Inderal - 1965
Tagamet - 1977
Capoten - 1980
Seldane - 1985
AZT - 1987
Mevacor - 1987
Prozac - 1988
Diflucan - 1990
Recombinate - 1992
Celebrex - 1999
0 1 2 3 4
5 6 7 8 9
10
Years
39
Instantaneous Generic Substitution

• August 2, 2001 - Barr Laboratories Cleared to
  Ship Generic Version of Lillys Prozac
  
• By September 2001, 80 of Lillys Sales Were
  Taken by Barr Laboratories Substitute Product

40
Consolidation Trends1988 PMA Members
Abbott Laboratories G.D. Searle Procter
Gamble American Cyanamid Glaxo Rhone Poulenc
A.H. Robins Hoechst Rorer Astra Hoffman-LaRoche
R.P. Scherer BASF ICI Roussel Beecham Laborato
ries Johnson Johnson Sandoz Boehringer Ingelhe
im Knoll Schering Plough Boots Pharmaceuticals E
li Lilly SmithKline Beecham Bristol-Myers Marion
Laboratories Squibb Carter-Wallace Merck Sterli
ng Drug Ciba Geigy Merrell Dow UpJohn Company
Connaught Laboratories Monsanto Warner-Lambert
DuPont Pharmaceuticals Pfizer Wellcome
Fisons Corporations Pharmacia Zeneca
41
Consolidation Trends2006 PhRMA Members
Abbott Laboratories G.D. Searle Procter
Gamble American Home Products Glaxo SmithKline
Rhone Poulenc A.H. Robins Hoechst Rorer Astra
Zeneca Hoffman-LaRoche R.P. Scherer
Aventis ICI Roussel BASF Johnson Johnson San
doz Boehringer Ingelheim Knoll Schering Plough
Boots Pharmaceuticals Eli Lilly SmithKline
Beecham Bristol-Myers Squibb Marion Laboratories
Squibb Carter-Wallace Merck Sterling Drug Cib
a Geigy Merrell Dow UpJohn Company
Connaught Laboratories Novartis Warner-Lambert
DuPont Pharmaceuticals Pfizer Wellcome
Fisons Corporations Pharmacia Zeneca
42
Role of Medicines in Health Care

• Medicines save lives, money (reduced
  hospitalizations, institutionalizations)
  
• Medicines improve quality of life
• Medicines improve length of life
• But these improvements put more pressure on
  health care systems, costs what is the role of
  medicines in resolving this dilemma?

43
Medicines Extend LivesDrop In Death Rates For
Diseases 1965-1996
Disease
Treatment
Atherosclerosis
Statins, ACE inhibitors, beta blockers, nitrates
Ulcer of Stomach and Duodenum
H2 blockers, proton pump inhibitors
Ischemic Heart Disease
ACE inhibitors, beta blockers, nitrates
Emphysema
Anti-Inflammatories, bronchodilators
Anti-Hypertensives, diuretics
Hypertension
DEATH RATE
Source Lasker/Funding First
44
These Innovations Have Directly Impacted Longevity
300
Centenarians in US Population Number Per Million
250
200
150
100
50
0
1900
1920
1940
1960
1980
2000
2000
1900
Source Caplow, Theodore, et al. The First
Measured Century, Wash DC AEI, 20019
45
U.S. Annual National Health Care Spending
1.6 TRILLION 1.4 1.2 1.0 0.8 0.6 0.4 0.2
0
PRESCRIPTION DRUGS
RESEARCH AND CONSTRUCTION
PERSONAL MEDICAL EQUIPMENT AND NON-PRESCRIPTION
DRUGS
NURSING HOME AND HOME HEALTH CARE
NET COST OF PRIVATE HEALTH INSURANCE,
ADMINISTRATIVE COSTS, AND PUBLIC HEALTH PROGRAMS
HOSPITAL CARE
DOCTORS, DENTISTS, AND OTHER PROFESSIONAL SERVICES
65
70
75
80
85
90
95
00
NOTE 2001 AND 2002 DATA PROJECTED
Source Health And Human Services Department
46
Impact of Drugs on Spending and Mortality for
HIV/AIDS
. . . While Monthly Costs for AIDS Patients
Decreased by 16 after HAART Introduced
HIV Mortality Declined Dramatically after
Introduction of First Expensive
Antiretrovirals . . .
Highly Active Antiretroviral Therapy (HAART)
introduced, 1996-97
Total 1804
First new Drugs Introduced, 1995
Total 1521
Other Costs Decrease by 41
Drug Costs Increase by 34
Source Costs - Bozette et al., New England
Journal of Medicine Vol. 344, No. 11, March 15,
2001 Mortality - Centers for Disease Control
data on drug development from PhRMA and the NIH
Office of Technology transfer.
47
Prescription Drug Spending as an Investment
City of Asheville, NC created a program granting
diabetics free access to prescription drugs and
other services if they enrolled in
acare-management program. After five years,
program is paying significant dividends . . .
7,082
Other Medical
Rx Expense
5,882
5,843
5,394
5,210
4,651
Baseline
14 Months
24 Months
36 Months
48 Months
60 Months
Avg Sick Days 12.6 6.0
8.5 5.7 5.8
5.7
Source Cranor, Bunting and Christenson, The
Asheville Project Long Term Clinical and
Economic Outcomes of a Community Pharmacy Diabete
s Care Program
CPSM 5.3.0
48
Impact of New Hampshire Medicaid Drug
Reimbursement Limits on Schizophrenia Patients
Changes in Per Patient Drug Spending vs. Change
in Hospital and ER Spending, After Monthly Caps
Introduced
1,530
57
Change in Hospital and Emergency Cost
Change in Drug Costs
Source Soumerai S, et al. Effects of Limiting
Medicaid Drug-reimbursement Benefits on the Use
of Psychotropic Agents and Acute Mental Health
Services by Patients With Schizophrenia. New Eng
J Med. Sept. 8, 1994
49
Opportunity to Do Much More
Source Science Magazine Vol. 291 No. 5507, 15
February 2001

50
Implications of the GenomeInsulin Signaling -
1977
Source J.E. Dumont, Cross Signaling, Cell
Specificity, and Physiology. Am. J. Physiology,
Cell. Physiology. Vol. 283, Issue 1, C2-C28, July
2002
51
Glucose Transport and Storage Signaling Pathways
- 2000
Muscle Contraction
PTP-1B
PDK-1
AMPK
Other Ser/Thr kinases
PKB
52
Alzheimers Dilemma We Have a Choice
Emerging Technologies
Nursing Homes
vs.
53
Helping Patients in Need

• Simple Enrollment
• Toll Free and website
• Simple Application
• Our Commitment to Help
• ALL Uninsured Patients
• ALL Medicare Patients

And
54
Getting Medicines to Patients Pfizer Pfriends

• Significant savings for up to a 30 day or up to
  a 90-day supply by mail for most Pfizer products
  
  
• Easy product fulfillment (retail pharmacy or
  mail)
  
• Easy-to-read healthcare information on 16 topics
• Simple Enrollment and Helpline to answer
  questions
  
• Toll Free [phone]
• pfizerhelpfulanswers.com

• Target Population
• Any age
• Any income
• Up to 50 off retail cash price for individual (45,000 for family)
  
• Up to 25 off retail cash price for 30,000
  for individual (45,000 for family)

Represents approximately 300 FPL
55
Responding to ConcernsAligning with
Industry-Wide Activities
Other Pharma Patient Assistance Programs
Public Assistance Programs
56
Improving Access to MedicinesIndustry-Wide
Initiative

• Partnership for Prescription Medicine
• Most comprehensive private sector outreach
  effort
  
• Access to 275 private and public patient
  assistance programs
  
• www.pparx.org
• 1-888-4PPA-NOW (1-888-477-2669)