Optimizing Pfizer Inc’s New Product Development Process 4/4/00 Optimizing Pfizer Inc’s New Product Development Process Transforming Molecules to Medicines AM X50.9252: Mastering New Product & Service Development Sunday, November 19, 2006

Key Questions WHO WHAT WHERE WHEN WHY HOW Pfizer Inc 4/4/00 WHO Pfizer Inc WHAT In Dire Need of a New Product Development Process WHERE Throughout the Entire Organization WHEN Within the Next 5 Years WHY Industry Challenges / Pipeline Concerns: PFE is struggling to maintain its growth in the face of increased competition and the expiration of key patents. HOW By Leveraging Internal Insights & Implementing a New Product Development Process Incorporating the Stage-Gate™ Process

An Introduction to Pfizer 4/4/00 OUR MISSION We will become the world's most valued company to patients, customers, colleagues, investors, business partners, and the communities where we work and live. OUR PURPOSE We dedicate ourselves to humanity's quest for longer, healthier, happier lives through innovation in pharmaceutical, consumer, and animal health products.

Pfizer Research and Development: Commitment 4/4/00 DID YOU KNOW ? Pfizer invests more in pharmaceutical research than any other private institution in the world. 1 This research is aimed at a single goal: to develop new medicines that will enable people to lead healthier, longer and more productive lives. 1 The Department of Trade and Industry (U.K.) The 2005 R&D Scoreboard. Page 96. Available at: http://www.innovation.gov.uk/rd_scoreboard/. Accessed on Oct. 26, 2005.

Pfizer Research and Development: Key Points 4/4/00 The discovery of new drugs and their development into useful pharmaceuticals is central to the concept of medical progress. The U.S. pharmaceutical and biotech industries invested nearly $39 billion in research and development in 2004, with Pfizer leading the way with $7.7 billion and 12,500 scientists. 2,3 Years to create a new drug: 12-15 years Probability of Success: <1% Costs to create a new drug: Between $800 million and $1.7 billion 2 PhRMA. Press Release. Feb. 18, 2005. Available at: http://www.phrma.org/mediaroom/press/releases/18.02.2005.1128.cfm. Accessed on Oct. 26, 2005. 3 Pfizer 2004 Annual Report. Available at: /pfizer/annualreport/2004/financial/p2004fin08.jsp. Accessed on Oct. 26, 2005. Also see Pfizer.com Research and Development website, available at: /pfizer/help/index.jsp.

Pfizer Research and Development: Risky Business 4/4/00 Only one in five medicines that enter clinical trials testing in humans is eventually approved for patient use by the U.S Food and Drug Administration (FDA). 6 That's part of the risk involved in Pfizer's business of seeking out new and innovative health solutions. 6 Stanford Medical School's Academic Consortium for Clinical Excellence in Scientific Studies. Clinical Trials FAQ. Available at: http://clinicaltrials.stanford.edu/patients/ctfaq.html. Accessed on Oct. 26, 2005.

Seven Goals of a New Product Process 4/4/00 Goal #1: Quality of Execution Goal #2: Sharper Focus, Better Prioritization Goal #3: Fast-Paced Parallel Processing Goal #4: A True Cross-Functional Team Approach Goal #5: A Strong Market Orientation with the Voice of the Customer Built In Goal #6: Better Homework Up-Front Goal #7: Products with Competitive Advantage Source: Winning at New Products by Robert G. Cooper, p.115

Project enters the NP Process at Gates 1, 2, or 3 With Such High Risks and the Vital Importance of New Medicines - New Product Development Systems Must Be Optimized 4/4/00 Robert G. Cooper’s Two-Stage Model Research and Technical Development Gate 1: Idea Screen Stage 1: Technical Assessment Gate 2: Second Screen Stage 2: Detailed Investigation Gate 3: Application Path Gate New Product Development Gate 1: Idea Screen Stage 1: Scoping Gate 2: Second Screen Stage 2: Building Business Case Gate 3: Go to Development Stage 3: Development Gate 4: Go to Testing Stage 4: Testing and Validation Gate 5: Go to Launch Stage 5: Launch Post-Launch Review Project enters the NP Process at Gates 1, 2, or 3

Robert G. Cooper’s Two-Stage Model 4/4/00 Research and Technical Development GATE 1 GATE 2 GATE 3 STAGE 1 STAGE 2 Technical Assessment Detailed Investigation Application Path Gate GATE 1 Project enters the NP Process at Gates 1, 2, or 3 New Product Development GATE 2 GATE 3 GATE 4 GATE 5 STAGE 1 STAGE 2 STAGE 3 STAGE 4 Scoping Build Business Case Testing & Validation Development STAGE 5 Review probable execution Revised financials Quality = original def. Work reviewed Go to test Decision to spend Confirm case POST LAUNCH REVIEW Legal Technical Sales Involved Marketing Involved Payback period LAUNCH Review costs Review profits Review strengths Review weaknesses Review what learned

Transforming Molecules to Medicine 4/4/00 Finding the Right Lead Molecule Preclinical CH 3 C 1 R 1-10 CH 3 C 1 R 4 + + Establishing the Safety of a New Molecule for Human Testing File IND Discovery Research Team Many Compounds In vitro & in vivo Screening Drug Candidate Selection Scale Up & Animal Tox Testing the Experimental Drug in People Clinical Establishing the Safety and Efficacy of a New Medicine for Patients n = 10 - 30 n = 20 - 200 n = 500 - 10,000 Phase I Phase II Phase III From Laboratory to the Doctor Regulatory Review Phase IV File NDA Regulatory Review & Commercialization Regulatory Approval & Launch Research and Technical Development  New Product Development

Transforming Molecules to Medicine 4/4/00 Average Years Compound Success 2 4 6 8 10 12 14 16 Rates by Stage Discovery 5,000 – 10,000 Screened Preclinical Phase I Phase II 250 Enter Preclinical Phase III Registration Postmarketing 5 Enter Clinical 1 Approved Medicine Research and Technical Development  New Product Development

Reasons Why Medicine Candidates Fail 4/4/00 It takes 12 CANs to yield 1 marketed drug on average 2 4 6 8 10 12 animal toxicity, PK chemical stability, superior compound human PK, safety/toleration, formulation No. candidates efficacy/safety, differentiation, dose/cost of goods efficacy, long-term safety non-approval 1 2 3 4 5 6 7 8 9 Years Preclin. Phase I Phase II Phase III Registration Research and Technical Development  New Product Development

The Drug Discovery and Development Process 4/4/00 Registration Full Development Exploratory Development Discovery Research and Technical Development  New Product Development

Drug Discovery: The Overarching Questions 4/4/00 Voice of Customer Research Is there a medical need? What is prevalence of the disease? What is the market potential? Do we have a biochemical target? Can we synthesis compounds that are target selective, potent in vivo, and bioavailable? Are the compounds efficacious in disease models, show dose response, and are not toxic? Building Business Case Technical Assessment Detailed Investigation Research and Technical Development  New Product Development

Where Do Potential Leads Come From? 4/4/00 Ideation Acquisition Compounds Natural Sources GlaxoWellcome AstraZeneca Merck Endogenous Ligand Newly Synthesized LEAD e.g. Natural peptide, hormone, etc. Random Screening of Existing Compounds Combinatorial Chemistry Libraries Research and Technical Development

Discovery (3–4 Years) Ideation, Gate 1, Stage 1 Gate 2 Go / Kill 4/4/00 Ideation, Gate 1, Stage 1 Gate 2 No Basic Science Go / Kill Medical Literature + Activity + Yes Disease Intervention Hypothesis Target Characterization Synthesis of Molecules Screening Medical Need Refinement Voice of Customer Research Improved Activity Nomination of Lead Molecule for Additional Investment Initial Safety Testing of Lead Molecule Detailed Investigation: Stage 2 Research and Technical Development

Discovery (3–4 Years) 4/4/00 Ideation, Gate 1, Stage 1, and Gate 2 Identify and Refine a Portfolio of Promising Molecules (“Candidates”) + 1 Thousands of Potential Disease Targets to Consider 3 Synthesis and Testing of Molecules to Bind to Target Disease Intervention Hypothesis Synthesis of Molecules Ideation Gate 1 2 4 Define Target and Structure at Molecular Level Testing Against Target for Biological Effect + Gate 2 Target Characterization Technical Assessment: Stage 1 Screening Go / Kill Research and Technical Development

Early Development (3–5 Years) 4/4/00 Technical Assessment: Ideation, Gate 1, Stage 1, Gate 2 Detailed Investigation: Stage 2 Safety Data IND Application Lead Molecule Endorsed for Additional Investment Manufacture Supplies Required Animal Testing Metabolism Data Formulate Doses for Humans Application Path Gate Is it safe? Is it safe? Is it safe? YES! (Proof of Concept) Phase I: Human Testing in Healthy Volunteers Phase II: Human Testing in Patients Phase II: Human Testing in Patients Building Business Case: Stage 2 How does it behave in the body? Does the drug provide benefit? What is the optimal dose? Research and Technical Development  New Product Development

Early Development (3–5 Years) 4/4/00 Detailed Investigation: Stage 2 Test Safety and Efficacy of “Candidates” Under Controlled Conditions 1 Preclinical Research Requires Testing Candidates in Animals 3 Dose Healthy Volunteers (Absorption, Distribution, Metabolization, and Elimination) Required Animal Testing Phase I Gate 2 2 Determine Dosage Based on Safety and Metabolism Data 4 Dose Patients (Efficacy) Formulate Doses for Humans Phase II Go / Kill Research and Technical Development

Disciplines Involved in Drug Development Research 4/4/00 Product Development Pharmacology Safety Clinical Sciences Clinical Development Development Operations Biostatistics Medical Clinical Pharmacy Operations Library Sciences Chemical Manufacturing Regulatory Affairs Project Management Marketing Biomarkers Informatics Etc …

Full Development (3–5 Years) 4/4/00 Testing & Validation: Stage 4 Full Team Involvement Design Phase III Studies Carcino- genicity Studies Detailed Investigation: Stage 2 Development: Stage 3 Consult FDA Full Development Planning File NDA Formulate, Label, & Ship Recruit 1000s of Patients Conduct Phase III Testing Collect, Verify, & Analyze Data Gate 5 Manufacture Drug Supply Building Business Case: Stage 2 Stability Studies Recruit Investigators Research and Technical Development  New Product Development

Full Development (3–5 Years) 4/4/00 Demonstrate Efficacy and Safety of a Candidate in Patients 1 1 Plan Phase III Studies, Supply, as well as Investigator Recruitment and Education 3 3 Ensure Benefit of Candidate is Clearly Demonstrated in Patient Population Full Development Planning Collect, Verify, & Analyze Data Plan Full Development Program Testing & Validation: Stage 4 Gate 2 2 2 Extensive Safety and Efficacy Testing with Patients under Real World Conditions 4 4 Documented Evidence Concerning the Safety and Efficacy of the new Molecule File NDA Phase III File New Drug Application Gate 4 Gate 5 Research and Technical Development  New Product Development

Registration (1–2 Years) 4/4/00 Gate 5 Other Regulatory Filings Approved New Medicine File NDA Respond to Questions Present to Advisory Committees Regulatory Approvals Label Negotiations POST LAUNCH REVIEW Launch: Stage 5 Review costs Review profits Review strengths Review weaknesses Review what learned New Product Development

Molecules to Medicine: Room for Improvement 4/4/00 NDA/ MAA Approval POC/ R2D2-1 NDA/ IRD Filing Key Commercial Decision Points: Idea CAN DIC-II R2D2-2 Stage: Discovery Pre- Clinical Early Clinical Clinical Late Clinical Post Launch Type of Testing: Laboratory Animals Phase I IIA IIB Phase III Phase IIIB Phase IV Accelerate candidate identification and screening Accelerate development time Improve labels and market access Leverage depth of knowledge from exploratory through loss of exclusivity Ensure global knowledge sharing and collaboration Leverage Internal Resources and Stage-Gate™ Process to Increase R&D Productivity and Maximize Commercial Success