1. PK/PD Reporting and Analysis Services (RAS) January 2009 Mark L.J. Reimer, PhD Senior Director Reporting and Analysis Services Pharsight Corporation [email_address]

2. What Are Pharsight Capabilities? One theme: Efficient Drug Development Software Enterprise and desktop products for analyzing, presenting and storing drug development data. Improve productivity and compliance Strategic Consulting Services (SCS) Consulting expertise in model-based drug development and decision-making. Quantify your decision-making Metadata Modeling-ready data sets complied by experts from public source medical & scientific literature. Understand the competitive landscape PK/PD Reporting and Analysis Services (RAS) High quality NCA, Population PK/PD Analysis and Reporting. Outsource PK/PD Analysis and Clinical Study Report Writing Training A variety of courses teaching Pharsight software tools and model-based drug development skills. Build your capabilities

3. Who Are Pharsight Customers? This is a sample from Pharsight's customer base which includes all Top 50 Pharmaceutical companies.

4. Where Is Our Strategic Focus? We provide tools and services that help our customers increase drug development efficiency, with a particular focus on the decisions occurring within the FDA’s “critical path.” 5000 250 5 1 Discovery Pre-Clinical Clinical Approval $23B 1 Dimasi, et al, "The price of innovation: new estimates of drug development costs," Journal of Health Economics, 22:2, March 2003 2 2005 PAREXEL R&D Statistical Sourcebook from Bain and In Vivo 3 2002 Estimated Global Pharma and Biotech R&D Spending by Category: BioPharm International, March 2003 4 PhRMA 2003 Industry Profile, March 2003 $48B The Critical Path except where noted all numbers are estimates for industry totals per year 3,4 Average time and cost per approved compound:8 years and $524M 1,2

5. PK/PD Expertise in Early Drug Development

11. WinNonlin AutoPilot™ - High Throughput Analysis to Save Time and Money

15. Efficiency of Working with RAS & AutoPilot 3 day gain ~75% gain (3/4) in efficiency Preclinical Example 1 day 4 days Total Not Required 1.0 day QA Audit of Tables and Figures 0.5 day 0.5 day QA Audit of WinNonlin Analysis QA Instantaneous 2 days Generation of Tables and Figures 0.5 day 0.5 day Calculation of PK parameters in Monkeys WinNonlin and AutoPilot WinNonlin and Manual Creation of Tables and Figures Activities

16. Efficiency of Working with RAS & AutoPilot 15 day gain ~75% gain (15/20) in efficiency Clinical Example 5 days 20 days Total Not Required 4 days QA Audit of Tables and Figures 1 day 1 day QA Audit of WinNonlin Analysis QA 0.25 day 4 days Urine Data – Metabolite 0.25 day 4 days Urine Data – Parent 0.25 day 2 days Plasma Data – Metabolite 0.25 day 2 days Plasma Data – Parent Generation of Tables and Figures 1 day 1 day Urine Data – Metabolite 1 day 1 day Urine Data – Parent 0.5 day 0.5 day Plasma Data – Metabolite 0.5 day 0.5 day Plasma Data – Parent Calculation of PK parameters WinNonlin and AutoPilot WinNonlin and Manual Creation of Tables and Figures Activity

17. Automated TFLs, Executive Summary & Review Non-Automated NCA and TFLs Approach AutoPilot TFLs 20% 2- Distribution and Review of Executive Summary Distribution of TFLs 1- Distribution of TFLs Executive Summary 20% 60% 1-Typical Non-Automated NCA and TFLs 2- Automated TFLs, Executive Summary & Review Decision-Making 20% 20%

18. Applications of Modeling and Simulations

19. Modeling and Simulations: Structural Model Discrimination 1-Compartment 2-Compartment 3-Compartment Various compartmental models will be constructed (e.g., 1-, 2-, 3-compartment models) and their performance will be evaluated statistical estimator to assess their goodness-of-fit.

21. Structural Model Discrimination: Visual Tool

26. Optimal Sampling Strategy CL Vc CLd Vp