PhenGene P2Y12 Test

CLOPIDOGREL METABOLISM AND ACTION OF CLOPIDOGREL A second-generation thienopyridine antiplatelet agent, an antagonist of platelet P2Y12 receptor Inhibits the formation of blood clots in the coronary, peripheral & cerebrovascular arteries METABOLISM AND ACTION OF CLOPIDOGREL

Clopidogrel is not effective in about 1/3 of individuals Problem – limited effectiveness of clopidogrel Pharmacodynamic evidence recognized by the FDA, American College of Cardiology, American Heart Association, and European Society of Cardiology suggests that clopidogrel has a suboptimal effect in a substantial proportion (“about one third”) of patients and that increasing the dose has limited efficacy in selected patients. Clopidogrel is not effective in about 1/3 of individuals One of the most prevalent reasons for reduced response to CLOPIDOGREL is inefficient conversion of the drug into its active metabolite due to genetic variability in liver enzymes

No easy-to-use test for clopidogrel effectiveness Clopidogrel effectiveness is not routinely measured due to current assessment of platelet function requiring testing within a limited time of taking the blood sample specialised equipment and technical expertise requirements on site Ineffective treatment can increase the risk of a recurrent cardiac event or stroke Overly effective treatment can lead to excessive bleeding

Our Solution To identify patients who are not responding to Clopidogrel using PhenGene P2Y12 Test that includes: Genotyping: CYP2C19 enzyme Involved in the metabolism of clopidogrel Every individual has two CYP2C19 alleles Depending on the combination of alleles in an individual, drug- metabolizing phenotypes associated with the CYP2C19 enzyme can vary Phenotyping: assessing platelet reactivity in response to stimulation with agonists High on-treatment platelet reactivity correlates with recurrent thrombotic events Blood samples are collected, processed using simple kit and are sent for analysis at a central laboratory – no need for specialised equipment on site and no time limitations to perform the analysis

Supporting Studies

Importance of CYP2C19 Genotyping In 2009, the US Food and Drug Administration (FDA) issued a boxed warning, recommending “consideration of CYP2C19 genotype” prior to prescribing clopidogrel.

Sample Collection & Processing OUR WORKFLOW Assess anywhere Patient on antiplatelet therapy can be assessed in primary care or home setting Sample Collection & Processing Blood sample taken and processed using simple, drug-specific kit Sample Shipment Processed sample is shipped to a central processing lab in the UK Sample analysed Laboratory staff analyse sample for P-selectin using flow cytometry and CYP2C19 using Luminex Platform Electronic reporting Complete test results are reported back electronically

Advantages of this combined testing Identify at risk patients with sub-optimal response to Clopidogrel using both genotyping and phenotyping approaches Results allow healthcare providers tailor the prescription of antiplatelet agents for their patients accordingly to reduce the risk of myocardial infarction, stent thrombosis or stroke No capital investment is required on site to setup the testing – all that is needed is an easy-to-use testing kit to process and stabilise the blood sample, which is then sent for expert analysis to a central laboratory