Introduction: TBO-309 is a novel, selective PI3Kβ inhibitor currently in Phase II clinical trials for acute ischaemic stroke (AIS). It is designed to suppress thrombosis without significantly impairing physiological haemostasis. Multiplate impedance aggregometry enables rapid assessment of platelet function using whole blood, allowing for effective evaluation of a patient’s level of platelet inhibition.
Method: Hirudin-anticoagulated blood was collected from healthy donors (n=10) and treated with TBO-309 (1 µM), aspirin (soluble), or in combination, for 10 minutes. Platelet aggregation was measured using the Roche Multiplate Analyzer across ADP, TRAP, and ASPI tests. Inter-individual variability was calculated and also intra-individual variation across four timepoints (n=1). A subset (n=3) was also evaluated using Light Transmission Aggregometry (LTA) for comparative analysis.
Results: The combination of TBO-309 and aspirin produced the highest inhibition across all tests with impedance aggregometry percentage inhibition from TBO-309 + aspirin being 42.0%, 14.8% and 95.6% for ADP, TRAP and ASPI tests respectively. LTA demonstrated higher percentage inhibition with ADP reaching 94.6% for combined TBO-309 + Aspirin. Inter-individual variability showed a coefficient of variation (CV) of 22.7% for control ADP test, compared to 30.2% for TBO-309 + Aspirin. Intra-individual variability showed CVs of 20.6% (control) and 18.0% (TBO-309 + aspirin).
Conclusion: The Multiplate Analyzer consistently measured platelet inhibition by TBO-309, which increased in combination with Aspirin, though inter-individual variability was moderate to high and the extent of inhibition with impedance aggregometry was less sensitive compared to LTA.
Relevance to clinical practice or patient experience: The use of Multiplate Analyser within the hyperacute stroke clinical setting could provide Neurointerventionalists with valuable real-time insight into patients’ platelet inhibition levels, helping to aid in clinical decisions during the application of novel treatments.