Antiplatelet therapy is an important strategy for patients with coronary artery disease (CAD) and acute coronary syndromes (ACS) who are at high risk for life-threatening arterial thrombosis, myocardial injury, myocardial infarction, and death. Protease-activated receptor (PAR) 1 inhibition is an emerging approach to target thrombin-induced platelet activation and achieve more comprehensive inhibition of platelet activation when used in combination with current oral antiplatelet agents. Originally discovered by the Kuliopulos and Covic labs at Tufts, PZ-128 is a first-in-class, cell-penetrating ‘pepducin’ antagonist, which blocks downstream of both the thrombin and matrix metalloproteinase 1 (MMP1) pathways of PAR1-dependent arterial thrombosis. I have been managing the clinical phase of PZ-128’s development via the conduct of multiple investigational drug trials across several medical centers. The ultimate goal is to bring forth this new parenterally-administered pharmaceutical drug which provides rapid, specific and reversible inhibition of platelet PAR1 through a novel intracellular mechanism in order to prevent arterial thrombosis and myonecrosis in CAD and ACS patients without an increase in bleeding as compared to slow-acting antagonists which target the outside surface of PAR1.