1. Implementing pharmacogenetics with CIPHER™ Personalized Medicine Program Property of PGxl Laboratories Kristen K. Reynolds, PhD VP Laboratory Operations 11-20-14

2. Polypharmacy Diabetes Hyperlipidemia Coronary Artery Disease Hypertension Thrombosis Stroke Depression Psychosis ADHD Arrhythmia Chronic Pain CIPHER manages the whole patient Property of PGxl Laboratories

3. CIPHER interpretive support: Drug-Gene Pilot Enhanced interpretive report format incorporating patient’s current med list

4. Drug-Drug Interactions Property of PGxl Laboratories Medications not metabolized or otherwise not accounted for in current genetic testing profile: ASPIRIN CARBIDOPA/LEVODOPA CLONIDINE CLOTRIMAZOLE FUROSEMIDE LEVOTHYROXINE LYRICA SULFASALAZINE

5. Drug-Gene Pilot Stats (Feb-Sept 2014) General Cohort Statistics Physicians participating (GP, psychiatry, cardiology, pain management, gerontology) 27 Patients included (Feb-Sept 2014)703 Total medications8090 Total drug-drug interactions found (excluding minor)3113 Total meds with a genetic link2955 psychotropics28% cardiovascular32% analgesics20% Other (allergy/asthma, cough, nausea, etc)20% Avg number meds/patient12 Avg meds/patient with a genetic link4

6. 44% of medications with a potential gene link had a variant genotype identifying a Drug-Gene Conflict 87%

7. PRODRUG OPIOIDS 43% of opioids had CYP2D6 contraindication

8. SSRI ANTIDEPRESSANTS single gene conflict CYP and SLC6A4 conflict 87% of SSRIs had one or more gene conflicts

9. CARDIOVASCULAR MEDICATIONS

10. Drug-Gene Pilot feedback surveys Questions (511 patients to date) % of the cases General comments Overall % of patients for whom decisions changed based on report 52% User friendly; easier to understand; like the colored symbols and alternative meds to consider Useful antidepressants, antipsychotics, anticoagulants, opioids “Drug-drug interactions were an eye-opening experience” “Overall reduction in total Rx meds was significant, 15- 25%” Used drug-drug interaction section65% Switched a medication57.5% Added or D/C medication without switch 50% Avoided an entire class52.5% Focused on an entire class47.5% Adjusted dose of current medication50% Made no regimen changes at all45% Saw improvements in outcomes and/or patient satisfaction 67.5%

11. Summary Many factors influence drug safety and efficacy CIPHER identifies significant risks across medication classes Genotyping a patient for a single indication, drug, or gene is unlikely to reveal the patient’s true risk burden based on their co-morbidities and polypharmacy Panel-based approach with drug-gene and drug-drug interactions improves sensitivity –ID high-risk drugs, safer doses and/or better alternatives –different decisions 52% of the time resulting in improved outcomes and satisfaction in 67% of cases

12. Do you have 1 or of these goals? What is the cost of not having Personalized Medicine Program? What are initiatives are you pursuing to reach these goals? What would success look like for each of these goals? What would achieving 1 or more of these goals mean? Personalized Medicine Program Outcome Goals Reduce Risk of ADRs Reduce Cost of ADRs Improve odds of reaching therapeutic goals Reach therapeutic goals faster Improve patient adherence to prescribers instructions Improve patient satisfaction Reduce regulatory and/or legal risk Innovative, Center of Excellence Decrease LOS Decrease readmissions

13. Thank you!