Personalized Medicine – From Theory to Practice as presented by keynote speaker Ralph Snyderman, MD; Director of the Center for Research on Prospective Health Care, James B. Duke Professor of Medicine, Chancellor Emeritus, Duke University

2. Science and Medicine 1900s Germ Theory Chemistry Physiology Pathology Physics 2000s Genomics Proteomics Metabolomics Systems Biology Informatics Micro/Nano Processing Find It Fix It Predict It Personalize It Understanding Disease Understanding Health, Disease and Complexity ©2010 RALPH SNYDERMAN

3. Concepts of Disease Emergence: Multiple factors Reductionism: Single factor Baseline Risk Environmental Factors Preclinical Progression Disease Initiation Disease Progression Irreversible Damage Causative Factor Enhance Health and Well-Being Disease ©2010 RALPH SNYDERMAN

5. Paradigm Shift to Personalization Traditional Medical Evaluation and Record Chief Complaint History of Illness Past Medical History Family History Social History Physical Exam Diagnostic Tests Assessment and Plan Personalized Health Plan Current Health Status Clinical Risk Assessment Tracking Wellness and Pathogenesis Clinical Event Prediction Therapeutic Plans ©2010 RALPH SNYDERMAN

6. Evolution of Understanding Disease Pre 1850 Pre 1900s Pre 2000 2000s Post 2010 Humoral imbalance Consumption Lung cancer; Stage II a, etc.; treatment by guidelines Lung cancer; Stage II a; oncogenic pathways; advanced guidelines Lung cancer; Stage II a; oncogenic pathways; theranostics; targeted therapies; consideration of associated risks and support systems; personalized Dx, Rx and health plan Metaphysical Phenotypic Phenotypic, refined Mechanistic Personalized, holistic Period Approach Clinical Description ©2010 RALPH SNYDERMAN

9. ©2009 RALPH SNYDERMAN Consider a 28 year old man with a mass in his neck Personalizing Cancer Care

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13. Companion Diagnostics Diagnostic Testing Overview Source: Company websites, L.E.K. analysis ©2010 RALPH SNYDERMAN

15. Clinical Decision Support at the Point of Care EHR Clinical Decision Support Clinical Risk Predictors Diagnostics Selectors Therapeutic Predictors Payer Adjudication CPOE New Model Validation Biocausality Engine proventys CDS TM PDx TM ©2010 RALPH SNYDERMAN Personalized Diagnostic and Therapeutic Plan

16. Pending 510(k) for Proventys PDx Oncology; not available for sale in the United States. Proventys, Inc. 2010 - Business Presentation Only Main risk assessment results page for an individual patient Proventys PDx The FN PDx for febrile neutropenia risk ©2010 RALPH SNYDERMAN

18. “ It is not the strongest of the species that survives, but rather the one most responsive to change.” Charles Darwin ©2010 RALPH SNYDERMAN