1. Integrative Organs Systems Scientists and Drug Discovery: The Link Between Big Pharma and Academia Glenn A. Reinhart, Ph.D. Senior Group Leader Integrative Pharmacology Global Pharmaceutical Discovery Abbott Laboratories

2. Integrative Organs Systems Scientists in Pharmaceutical Discovery The drug discovery process continues to exploit and develop new, reductionist and high throughput technologies in the search for novel lead molecules for the treatment of new disease targets. To move toward clinical development a compound must demonstrate key in vivo characteristics: –efficacy and specificity in disease state models –safety, safety, safety –adequate pharmacokinetic, pharacodynamic and metabolic profiles

3. Drug Discovery: the Path to Clinical Development Idea Target Identification Target Validation Lead Optimization Drug Development Candidate Clinical Development

4. Molecular Biology Organizational Structure “Matrix” Pharmacology Medicinal Chemistry Project Teams PK / ADMEToxicology Safety Pharmacology

5. Organizational Structure “Project Team” Project Teams PK / ADMEToxicology Integrative Pharmacology Therapeutic Area VP

6. Organizational Structure “Modified Project Team” Project Teams PK / ADMEToxicology Integrative Pharmacology Therapeutic Area VP In Vivo Pharmacology

7. Integrative Scientists: Hallmarks of Success Strong scientific ability Excellent communication skills Critical thinking skills Flexible expertise Depth and Breadth Top tier, well-published, competitive scientists

8. Industry Survey Comparing the Presence of Integrative & Organs Systems vs. Reductionist Scientists: 1991 and 2001 Definitions Integrative & Organs Systems Scientists (IOSS) are functionally defined as scientists focusing on scientific approaches whose aim is to understand how intact biological systems function at the level of whole animals, organs, and organ systems (but not in the clinic) or approaches aimed at identifying or describing potential “clinical’ effects using whole animals, organs, and organ systems. Reductionist Scientists are functionally defined as scientists focusing on scientific approaches whose aim is to identify molecular and cellular events, studied in purified form or in isolated systems and include genomics, proteomics, biochemistry, and cell biology.

9. Industry Survey Comparing the Presence of Integrative & Organs Systems vs. Reductionist Scientists: 1991 and 2001 Distributed via email to > 120 scientists (“Industry Scientists” per EB 2002 registration) AND to members of the Safety Pharmacology Society. 12 respondents: –6-7 companies represented –Big Pharma –CROs –USA, France, Germany Most departments represented likely have an in vivo focus

10. Industry Survey Comparing the Presence of Integrative & Organs Systems vs. Reductionist Scientists: 1991 and 2001 Respondents What title best describes you current position within your Department in 2001? –Vice President1 –Division Chief1 –Department Head/Director6 –Department Manager1 –Group/Team Leader0 –Lab Manager2

11. Number of Employees in Department

12. Numbers of Employees With Degrees

13. Number of Open Positions

14. Length of Employment

16. How many months to find qualified applicants? IOSS Reductionist Others In General

17. Average number of applicants per open position (total applicants)

18. Average number of applicants per open position: IOS Scientists

19. Average number of applicants per open position: Reductionist Scientists

20. Per open IOSS position: qualified vs. unqualified applicants?

21. Are salary adjustments made during recruitment?

22. Industry Survey Comparing the Presence of Integrative & Organs Systems vs. Reductionist Scientists: 1991 and 2001 Based on the Departments represented in the survey, it is suggested that in Industry: A greater number of positions, both filled and open, may exist for BS - MS and Ph.D. level IOS Scientists relative to 1991. A greater number of positions for IOS Scientists remain open compared to 1991. Duration of recruiting is greater for IOSS than Reductionist or other scientists and compared to 1991. Fewer applicants per position. More ‘unqualified’ candidates may be applying for IOSS positions. At present, IOS Scientists appear to have longer duration of employment (same company) than Reductionist or other scientists.