21 st Century CPU The Future of Clinical

21 st Century CPU – The Future of Clinical Pharmacology Units and Early Phase Clinical Research A Panel Discussion 21 st Annual ACPU Meeting NIH Clinical Center April 26, 2012 1

Format of Session Introduction & Background Panelists comments and generation of topics to discuss What has changed, is changing, will change? Panel Discussion on leading topics Identify attributes of ‘ideal’ CPU What would you build with a blank check? Audience questions 2

“Overview of the Phase I Market” Ken Getz, Tufts CSDD; Oct 2010 ACPU Drug Development Landscape Phase I Market Trends Opportunities 3

Ask the Experts Broad perspective of expertise Academia Rob Califf, Carl Peck, [Stephen Spielberg] CROs Oren Cohen, Royce Morrison Pharma, big & small Matt Troyer (John Wagner), Diane Jorkasky Regulatory Stephen Spielberg, [Carl Peck] 4

Drug Development Landscape Commercialization Conditions Restrictive price controls Healthcare reform uncertainty and adverse impact Depressed global markets High-level of revenue at risk R&D Operating Conditions Low success rates Declining levels of innovation Rapidly rising R&D costs Getz, ACPU Oct 2010 Regulatory conservatism Public discontent

“Patent Cliff” 6

Downsizing of Pharma Getz, Overview of the Phase I Market, Oct 2010 ACPU Meeting 7

Declining New Drugs per R&D $ Kaitin, CP&T, 2010; 87(3): 356 -361 8

R&D Cost Drivers Chronic and complex indications Clinical trial size Protocol design complexity Patient recruitment/retention High cost discovery/research tools Regulatory demands Market oriented studies Late-stage attrition Getz, ACPU Oct 2010

Growing Protocol Complexity Getz, Overview of the Phase I Market, Oct 2010 ACPU Meeting 10

Global Phase I Facilities Getz, Overview of the Phase I Market, Oct 2010 ACPU Meeting 11

Phase I CPUs & Number of Beds Getz, Overview of the Phase I Market, Oct 2010, ACPU Annual Meeting 12

Trends in the Phase I Market Heightened safety concerns Emphasis on hospital and in-patient settings Shift to US and Canada for time and cost advantages post EU-Directive Increasing proportion of patients vs. NHV Modified and combination protocol designs Transfer operating risk to CROs Growing entry by for-profit, community-based investigative sites Source: Tufts CSDD interviews

The Times They Are a-changin’ [“you better start swimming or you’ll sink like a stone…”] Greenberg, DIA Global Forum, Feb 2012 14

Pressures in Clinical Research Off shoring clinical trials Transfer operating risk to CROs & partnering with AMCs Personalized medicine – fad or future? Advances in genomics, proteomics, biomarkers, imaging, diseases models, bioinformatics, etc. Regulatory and social pressures on safety for longer term studies Public discontent with Pharma 15

Commercialization Conditions Economic crunch on Pharma productivity Consolidation of Pharma companies Restrictive price controls Healthcare reform uncertainty and its adverse impact Depressed traditional markets & growing emerging markets Patent cliff and revenue at risk 16

R&D Operating Conditions Lower success rates Declining levels of innovation Increase in biologics and biosimilars Rapidly rising R&D costs, and outsourcing demand Regulatory conservatism 17

Trends in the Phase I Market CPUs from Pharma owned and operated to CROs Heightened safety concerns Emphasis on hospital and in-patient settings Shift to US and Canada for time and cost advantages post EU Directive Increasing proportion of patients vs. NHV Combination protocol designs, incl SAD/MAD/POC & adaptive designs Growing role of community-based investigative sites 18

Why these Panelists? Rob Califf: clinical research in AMC Oren Cohen: heads phase I in leading global CRO Diane Jorkasky: duel CPU operations and pharma Royce Morrison: clinician, CPU PI, CRO CMO Carl Peck: FDA CDER, drug development ‘guru’ Stephen Spielberg: academic, pharma, now FDA John Wagner (Matt Troyer): current sponsor view 19

Why these Panelists? Among the 7 panelists: Over 180 years experience in clinical research in over 1000 clinical trials Co-authored over 2000 Publications Given over 3000 Presentations Participated in hundreds of INDs and NDAs in various capacities 20

Thank you Let’s get going …. 21