John L. LaMattina, Ph.D.
President, Worldwide Research
Pfizer Global Research and Development
1

 One Pill Must Be Globally Safe and Efficacious
– Across Racial and Ethnic Groups
– Across Age, Weight, and Sex Differences
 One Pill Must Appeal to Global Markets
– Different Cultures, Healthcare systems,
Distribution systems
WPI 3/2002
 One Pill to Pass Global Regulatory Review
– MOST Regulated Industry in the World
– Must meet regulatory requirements in
EVERY country

WPI 3/2002
Broad Portfolio - Number 1 or 2
Major Internally Discovered Products
Products
Neurontin
Accupril/Accuretic
Category
Lipid-Lowering
Hypertension/Angina
Arthritis
Depression/Anxiety
Antibiotic
Erectile Dysfunction
Seizure Disorders
Antifungal
Hypertension/BPH
Alzheimer’s Disease
Allergy
Cardiovascular

A Research-Based Health Care Company
Company
Pfizer
Glaxo/SmithKline
Aventis
Johnson & Johnson
Novartis
AstraZeneca
Roche
Merck
Bristol-Myers Squibb
Eli Lilly
American Home Products
Schering-Plough
WPI 3/2002
4.4
3.8
3.2
2.9
2.0
2.0
1.7
1.3
2.3
2.4
2.6
2.7
2000 Total R&D Spending
($ Billions)

Administrative Support Analytical Chemistry Animal Health Anti-infective Disease Bacteriology
Communication Computer Science Cytogenetics Developmental Planning DNA Sequencing Diabetology
Document Preparation Dosage Form Development Drug Absorption Drug Degradation Drug Delivery
Endocrinology Enzymology Facilities Maintenance Fermentation Finance Formulation
Gastroenterology Graphic Design Histomorphology Intestinal Permeability Law Library Science Medical Services
Natural Products Neurobiology Neurochemistry Neurology Neurophysiology Obesity
Oncology Organic Chemistry Pathology Peptide Chemistry Pharmacokinetics Pharmacology Photochemistry
Project Management Protein Chemistry Psychiatry Public Relations Pulmonary Physiology
Radiochemistry Radiology Robotics Spectroscopy Statistics Sterile Manufacturing Tabletting Taxonomy
Technical Information Toxicology Transdermal Drug Delivery Veterinary Science Virology X-ray Spectroscopy
WPI 3/2002

Development Process Starts with Many
Hypotheses
Prevent Amyloid Plaques
Block Glutamate Neurotoxicity
Attenuate Neuro-inflammation
Stabilize Neuronal Infrastructure Stop Programmed Cell Death
Alzheimer’s Disease
WPI 3/2002

WPI 3/2002
Registration
Clinical Data
Analysis
Full
Development
Studies in 100-300
Patients (Phase II)
Studies in Healthy
Volunteers Phase I
Exploratory Development
Candidate Medicine Tested in
3-10,000 Patients (Phase III)
Large Amounts of
Candidate Medicine
Synthesized
Formulations
Developed
Extensive
Safety
Studies
Candidate
Early
Safety
Studies
Project Team and Plans
Synthesis of Compounds
Screening
Discovery

~100 Discovery Approaches
High Risk Process:
11-15 Years, $800MM+
Millions of
Compounds Screened
Preclinical
Pharmacology
Preclinical Safety
Discovery
Clinical Pharmacology
& Safety
Exploratory Development
Phase I Phase II
Full Development
Phase III
1 - 2
Products
0
Idea
WPI 3/2002
5
11 - 15 Years
10 15
Drug

Complex Disease Targets Not Sufficiently Selective
Too Long in Body
Side Effects
Adverse Reactions
Unsafe
Poor Absorption
Unstable
Low Levels in Body
Not Effective Enough
Competition
Impractical To Make
WPI 3/2002

WPI 3/2002

WPI 3/2002
Nucleus
Cell
Nucleotide Base Pairs
Chromosomes
DNA
Switch
Gene
Protein
Enzymes
Receptors
Hormones

What Are Practical Implications of
Human Genome for Drug Development?
WPI 3/2002
 Increase in targets from ~ 450 to > 4000.
 Can Focus on Human Receptors, Ligands.
 Potentially develop more specific medicines.
 However:
 Exploring New Mechanisms takes time and $
 New Technologies are very expensive
 No guarantee that they will lead to new medicines

WPI 3/2002
Implications of the Genome:
Insulin Signaling - 1977

WPI 3/2002
Glucose transport and storage Signaling pathways - 2000

Myths about Genomic Information
WPI 3/2002
 It will lower the cost of drug development
 Technology is expensive
 Mechanisms poorly understood
 More targets = More Cost

We can use it to develop “magic bullets”
 Chronic disease complicated, multifaceted
 Multiple genes frequently involved
 Environment, behavior remain important
– Sometimes determinative

Ethical Issues of Genomic Information
 Who owns the data?
 Government?
 Individuals?
 Companies?
 Who Collects the data? Who pays?
WPI 3/2002
 How will the data be used?
 Insurance issues
 Privacy issues
 Discrimination

WPI 3/2002
Ethical Issues: Patents
 Diamond v. Chakrabarty, 1980
 Biological organism can be patented
 The Great Sequence Hunt
 Positives - competition pushed sequencing
 Negatives - what value was created?
 Recent Ruling
 Sequence not controlling, must have function

WPI 3/2002
Example of Ethical Issues: SNP’s

Single nucleotide polymorphisms (SNP’s)
 Can identify individual risk profile for various diseases
 Could be used to screen patients for clinical trials - improve safety
 Broad screening can provide important insights into population genetics

Each individual could have “tailored” drugs

Example of Ethical Issues: SNP’s
WPI 3/2002
 Who should pay for the screening?
 Government?
 Private companies?
 Once you have broadly screened the population, what is societal obligation to treat?
 Should you screen for diseases for which there is no cure? (Huntington’s, e.g.).

What about “artificial” selection?

Some Thoughts
 New Area of Ethical Discussion
 Need complete transparency
 HIPPA rules promulgated, now to be implemented

Need “opt-in” system, not “opt-out”
 Presumption of privacy should be preserved
 Education is critical - complex issues with many facets - public good versus private rights
WPI 3/2002
 Different cultural contexts must be respected

 Genomic Technologies show great promise but require enormous resources.
 Ethical Issues Real
 Transparent processes critical to public support
 Support for Research Critical
 Price Control Threats

We Can’t Do it Alone
WPI 3/2002

Extending our Web of Alliances
WPI 3/2002
Washington
Univ.
Gene
Therapy
Mass.
General
X-Ray
Cornell
Univ.
Transgenics
Abgenix
Aurora
Yale
UTHS
Rige l
Rockefeller
Univ.
IBIS
HumAb
Harvard
Xenon
Celera
Genomics
Univ. of
Washington
Chemical
Diversity
Neurogen
ArQule
Combinatorial
Libraries
Chip
Technology
Molecular
Modeling
MIT
Evotec Incyte
Johns
Hopkins

WPI 3/2002
 Genomics will play an important role in developing new medicines
 Costs will increase, at least in the short term
 Ethical issues daunting
 Support for R&D more critical than ever
 Price controls in the US would devastate innovation
 Good public health is expensive, and worth it