PB2452: A ticagrelor reversal agent

Ticagrelor is a direct-acting P2Y12 receptor antagonist that works by inhibiting platelet activation and has been shown to reduce the rate of atherothrombotic cardiovascular (CV) events, such as heart attack or CV death, in patients with acute coronary syndrome (ACS).

Ticagrelor is unique among P2Y12 antagonist antiplatelet agents due to its ability to reversibly bind to the P2Y12 receptor, whereas other P2Y12 antagonists bind permanently. Ticagrelor, co-administered with aspirin (also known as acetylsalicylic acid [ASA]) is indicated for the prevention of atherothrombotic events in adult patients with ACS, or for patients with a history of myocardial infarction and a high risk of developing an atherothrombotic event.

PB2452 is an investigational intravenous Fab antibody fragment that has a very high affinity for ticagrelor and its active metabolite, and is intended to rapidly reverse the antiplatelet effects of ticagrelor. In preclinical studies, PB2452 was shown to reverse ticagrelor-mediated inhibition of platelet aggregation and normalize bleeding.

By administering the PB2452 reversal agent to patients on ticagrelor therapy in rare emergency situations, we hope to achieve a rapid reversal of the P2Y12 antagonist antiplatelet activity to curtail severe bleeding or reduce the waiting period ahead of urgent surgery.

PhaseBio is conducting a Phase 1 single ascending dose trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous PB2452 in healthy volunteers.

PB2452 was originally developed by MedImmune, the global biologics research and development arm of AstraZeneca, as MEDI2452. PhaseBio exclusively licensed PB2452 from MedImmune in November 2017.