Vesper Bio has announced positive data from its Phase I clinical trial of VES001, a novel treatment for frontotemporal dementia (FTD) targeting progranulin gene mutations (GRN). The trial, involving 78 healthy volunteers, assessed the safety, tolerability, pharmacokinetics, and target engagement of VES001.
The study met all primary endpoints, with data from the multiple ascending dose (MAD) stage confirming earlier single ascending dose (SAD) findings. VES001 exhibited a high safety and tolerability profile, with no serious or treatment-emergent adverse events reported.
Pharmacokinetics and Target Engagement
Pharmacokinetic data indicated that VES001 is effectively distributed to both plasma and the central nervous system following oral administration. Furthermore, the treatment demonstrated significant target engagement, increasing progranulin levels in participants receiving daily doses. The data suggest that VES001 could substantially normalize progranulin concentrations in patients after seven days of dosing.
Mechanism of Action
VES001 is a brain-penetrant, small-molecule sortilin inhibitor designed to modify the course of FTD. It functions by inhibiting the sortilin receptor, which competes with progranulin receptors and contributes to neuronal damage when progranulin binds to it. By preventing this binding, VES001 aims to maintain and normalize progranulin levels, offering a convenient, orally administered treatment option.
Next Steps
Based on these promising Phase I results, Vesper Bio has submitted a clinical trial application (CTA) to initiate a Phase IIa proof-of-concept study. Patient dosing is expected to begin in the fourth quarter of 2024.
Management Commentary
"At Vesper, we are motivated by our patients and their relatives, who inspire our mission to develop innovative therapies that can help fight this awful disease," said Vesper Bio CEO Paul Little. "These promising clinical data coupled with VES001’s patient-friendly profile bring us one step closer to transforming patient outcomes in frontotemporal dementia."
