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Preclinical Study of Bentracimab (PB2452)
Preclinical Study of Bentracimab (PB2452)

In an animal study published in 2017, pigs, after pre‐treatment with aspirin, were administered an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a standardized liver injury was induced and a bolus of PB2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 hours. Blood samples for drug plasma exposures and platelet aggregation were collected.

PB2452 eliminated the free concentrations of ticagrelor and ticagrelor active metabolite (TAM) within 5 minutes. ADP‐induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. PB2452 numerically improved ticagrelor‐mediated effects: body-weight-adjusted blood loss in the 15- to 90-minute interval; survival; and median survival time.  In addition, PB2452 significantly attenuated decline in mean arterial blood pressure (MAP) and maintained MAP at a significantly higher level.

The investigators concluded that PB2452 eliminated free ticagrelor and TAM within 5 minutes. This translated into a gradual normalization of ADP‐induced platelet aggregation and significant improvement in blood pressure and numerical but non‐significant improvements in blood‐loss and survival.  This final finding reiterates the concept that bentracimab is not in itself a hemostatic agent, but instead it reverses the anti-hemostatic effects of ticagrelor and TAM, facilitating multimodal resuscitation of the bleeding animal.