1 PGRx: An Interactive Software System for Integrating Clinical Genotyping with Prescription Drug Safety Assurance. Michael D. Kane, Ph.D. Assistant Professor of Computer and Information Technology Lead Genomic Scientist, Bindley Bioscience Center Purdue University Experience: Preclinical R&D Pharmaceutical Industry, VP of R&D in Genomics-Biotechnology Industry. Expertise: Genomics Technology, Bioinformatics, Pharmacology.

2 Emerging Landscape of Clinical Genotyping Enabling Opportunities Human Genome is Complete Genotyping Technologies are “Everywhere” Confirmed Links between Allelic Variants and Clinical Outcomes is Growing Hindrances to Implementation Consumers have Reservations About the Use of Their DNA Limited knowledge about Genomics in Healthcare Professional Practices Cost-Benefit for Disease Prognostics is Uncertain

3 Costs of Adverse Drug Responses (ADR)  According to a survey published in the Journal of American Pharmacists Association in 2001, the cost of drug-related mortality and morbidity in the US was estimated at over $175 billion in  ADRs represents approximately 10% of all health care costs in the US.  It is estimated that adverse drug reactions are the cause of over 200,000 deaths each year and is among the top 10 causes of death in the US.  McKesson is the world’s largest distributor of drugs and the largest healthcare software and IT company, a Fortune 18 company with $93 billion in revenues in THIS IS WHERE THE OPPORTUNITIES EXIST TO INTEGRATE CLINICAL GENOTYPING WITHIN HEALTHCARE

4 What does the PGRx System Do? Utilizes patient-specific genotyping to predict and prevent adverse drug responses. Supports the prescription drug process from physician to pharmacist to consumer. The system behaves similar to a “Drug-drug interaction” system, but can be described as a “Gene-drug interaction” system with detailed training components.

5 Why Pharmacy & Drug Safety? Based on Known Monogenic Traits –Phase-1 oxidative enzymes with known SNPs –Characterization of In vitro (& In vivo?) effects of SNPs is relatively simple Immediate Impact on Point-of-Care Therapeutics –Response to SNP data is easily “translated” to patient drug choice and dosing options –Addresses adverse idiopathic drug responses

6 Why Pharmacy & Drug Safety? Relatively Limited Ethical and Information Security Concerns –Knowledge of a patient's predisposition to altered drug clearance is a financial benefit to consumer, HMO, pharma, etc. –Patient-specific CYP-SNP data is amenable to “low security” web-based access supporting “travel incident” justification. Utilizes Established Information Management Logistics –“Drug-Drug” interactions management augmented with “Gene-Drug” interaction risk. - New Warfarin Label includes SNP-Clearance Data (8/16/07) –Roche (Affymetrix) AmpliChip for 2D6 genotyping (12/23/04) approved by FDA

7 PGRx is both Operational and Educational The software system integrates patient-specific genotypic and physiological information to predict the risk of ADRs. ADRs include: –Inadvertent overdosing due to poor metabolism. –Inadvertent under-dosing due to increased metab. –Inadvertent under-dosing due to decreased pro-drug bioactivation due to poor metab. The software includes a “mock” patient population that represents all clinically relevant genetic alleles relevant to drug metabolism. The software includes all FDA approved drugs and formulations.

8 PGRx is both Operational and Educational (continued) The software system includes detailed training components about each allelic variant (specific DNA changes, effects on protein/enzyme, etc.) The software system includes the ability to alter physiological variables in the “mock” population to allow the user to better understand the relationship between a patients physical status relevant to drug clearance variables (age, weight, volume of distribution, etc.) with allelic variations and ADR risk.

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10 Implementation & Users The practicing pharmacist will likely be the first operational and educational user of the PGRx system, followed by physicians. The value proposition for the PGRx system lies in partnerships with established healthcare software companies, particularly those who support prescription drug dispensing.

11 CONTACT INFO: Michael D. Kane, Ph.D. Department of Computer and Information Technology, Lead Genomic Scientist, Bindley Bioscience Center, Purdue University, West Lafayette, IN (765)