PB0027 - Glenzocimab does not impact bleeding severity in two different mouse models of intracranial hemorrhage

Background: Because of the potential risk of worsening bleeding in case of hemorrhagic stroke, administration of antiplatelet drugs at the acute phase of ischemic stroke cannot be envisioned until the diagnosis of stroke and its ischemic nature have been confirmed by imaging. Reducing the delay between acute ischemic stroke (AIS) onset and treatment initiation is however critical for treatment efficacy. Glenzocimab, a novel antiplatelet drug targeting GPVI currently in phase 2 evaluation for AIS, has been shown to have no impact on hemostasis following traumatic injury or at sites of inflammation. Whether Glenzocimab treatment remains safe in the context of intracranial hemorrhage remains however unknown.

Aims: Here, we investigated and compared the safety of GPVI or GPIIbIIIa targeting in 2 mouse models of intracranial hemorrhage.

Methods: The severity of intracranial bleeding was compared between wild-type, GPVI-/-, integrin beta3-/-, and mice humanized for GPVI (hGPVI) treated or not with glenzocimab or eptifibatide, in a model of hemorrhagic stroke caused by unilateral striatal injection of collagenase type VII, as well as in a model of hyperglycemia-induced hemorrhagic transformation of cerebral ischemia-reperfusion injury.

Results: GPVI deficiency or pharmacological inhibition with glenzocimab had no impact on bleeding severity in either model of intracranial hemorrhage. Conversely, GPIIbIIIa deficiency and eptifibatide treatment caused a significant increase in intracranial bleeding in both models and were associated with increased mortality in the model of hyperglycemia-induced hemorrhagic transformation of cerebral ischemia-reperfusion injury.

Conclusion(s): In contrast to eptifibatide, glenzocimab does not increase bleeding severity in case of intracranial hemorrhage. The safety of glenzocimab in the context of intracranial hemorrhage suggests that it could be administered in patients with suspicion of stroke, before assessment of its ischemic nature, thus allowing a drastic reduction in treatment initiation.