Presentation given at MDL User Group Meeting in April 2007

1. Chemistry Informatics at Pfizer: Past, Present, and Future Chris L. Waller, Ph.D. World Wide Chemistry Informatics Pfizer Global Research and Development [email_address]

3. Factoids

4. R&D: Long, Expensive and Risky 16 14 12 10 8 6 4 2 0 Years Cost = $1.3B/new drug Target Selection Chemical Selection Clinical Trials Launch Discovery (2-10 years) Pre-clinical Testing Laboratory and animal testing Phase 1 20-80 healthy volunteers - safety and dosage Phase 2 100-300 patient volunteers efficacy & safety Phase 3 3,000-5,000 patient volunteers used to monitor adverse reactions to long-term use FDA Review/ Approval

5. Productivity is Decreasing Source: PhRMA, FDA, Lehman Brothers; The 2004 Industry R&D Expense is an estimate Annual NME Approvals Industry R&D Expense ($ Billions) R&D Investment NME Approvals

8. Service Oriented Architecture

9. Service Oriented Architecture

10. Service Oriented Architecture workflow solution Web services orchestrate composite applications pipelines activity modular reuse Business process capabilities

11. SOA – WW Chemistry Informatics workflow solution capabilities Presentation Component Enumeration Service Registration Service Uniqueness Checking Service Search Service Validation Service Design Component Property Calculation Service Enumerate Search Design Register Identify Display Validate Compute

12. SOA – WW Chemistry Informatics Enumeration Service Registration Service Uniqueness Checking Service Search Service Validation Service Design Component Property Calculation Service Presentation Component Components Services

13. SOA – WW Chemistry Informatics Components Services GUI Interface Wrapper Calculator Interface

15. From Capabilities to Workflow Presentation Component Enumeration Service Registration Service Uniqueness Checking Service Search Service Validation Service Design Component Property Calculation Service Enumerate Search Design Register Identify Display Validate Compute “ Register” - Commit capabilities Workflow

16. Tool Integration Registration Service Uniqueness Checking Service Search Service Validation Service “ Register” - Commit Register Presentation Component Accord SDK Accord SDK Workflow Accord Structure Checker / Accord Chemistry Cartridge Accord Chemistry Cartridge Accord Chemistry Java Object MN.Tautomer /

17. Application Integration

19. Drug Discovery Lead Series Synthesis & Purification GAPS Sample Characterization AP-3 ACDLabs SpecMan Biological Testing Biology eNotebook Sample Registration CombiChem Registration MedChem Registration Synthetic Strategy Reagent Selector Chemistry eNotebook SMART ACD Hypothesis Generation Beilstein Crossfire (e-)Literature SciFinder Interpretation of Results ISISBase (ISIS for Excel) Spotfire Computational Chemistry Tools

20. Typical Desktop Footprint

23. One Possible Solution?

24. User-centered Design

25. Composite Applications

26. Putting it all Together

27. 2006: Legacy of The Lipitor Years Comp Chem Toolkit Compound Search Service Compound Lookup Service Common Services PLP Web Services Molecule Databases SARMart Registration Manager Query Engine Enumeration Service Prop. Calc. Engine Adapters Structures PGVL GCSW RGate Adapters Reaction Databases PCAT AP-3 GAPS CeN MoViT Pipeline Pilot Spotfire ISISDraw ChemDraw MarvinDraw ChimePro ACJO Uniqueness Checker Verify and Validate Marvin

28. 2007: Thinning the Herd Comp Chem Toolkit Compound Search Service Compound Lookup Service Common Services PLP Web Services SARMart Registration Manager Query Engine Enumeration Service Prop. Calc. Engine Structures PGVL GCSW RGate PCAT AP-3 GAPS CeN MoViT Pipeline Pilot Spotfire ISISDraw* ChimePro ACJO Uniqueness Checker Verify and Validate Discovery Gate MDLDraw Discovery Gate Beilstein MDL External CSS Database Discovery Gate ACD Adapters *ISISDraw is declining technology – MDLDraw is emerging

29. Future State Analysis Workbench Innovation Sandbox Synthesis Workbench Data Access Workbench Design Workbench Comp Chem Toolkit Compound Search Service Compound Lookup Service Common Services PLP Web Services SARMart Registration Manager Query Engine Enumeration Service Prop. Calc. Engine Structures Research Gateway (RGate) Chemistry eNotebook (CeN) Integrated Design Desktop (IDD) Spotfire MDLDraw Uniqueness Checker Verify and Validate MDL External Prous, IBM, etc. Discovery Gate ACD Adapters Pipeline Pilot Internal Other External CSS Database

30. Conclusions

33. Questions