Vesper Bio has announced the successful completion of its Phase 1 clinical trial for VES001, a potentially disease-modifying treatment for frontotemporal dementia (FTD) caused by GRN mutations. The trial, involving 78 healthy volunteers, demonstrated excellent safety and tolerability of the orally administered drug. Data also showed a substantial normalization of progranulin levels in participants dosed with VES001. These findings suggest that VES001 could address a critical unmet need in FTD treatment by increasing levels of the neuroprotective protein progranulin.
Mechanism of Action
In FTD caused by inherited GRN mutations, the production of progranulin is suppressed. Sortilin, another protein, binds to progranulin and directs it for degradation, further reducing progranulin levels. Reduced levels of progranulin are associated with neuronal dysfunction and the abnormal accumulation of TDP-43. VES001 is designed to selectively inhibit sortilin, preventing it from binding with progranulin and thereby increasing progranulin levels in individuals with GRN mutations.
Phase 1 Trial Results
The Phase 1 trial evaluated the safety and tolerability of VES001, as well as its absorption, distribution, and metabolism. The study included single and multiple ascending dose stages. The company reported that VES001 met all study goals, with data from the multiple ascending dose stage reaffirming earlier findings of high safety and tolerability. The multiple ascending dose stage also demonstrated a substantial normalization of progranulin levels in participants who received once or twice daily doses of VES001.
Future Directions
Vesper Bio has completed a clinical trial application to begin a Phase 2a trial with VES001, which will aim to determine the optimal dose. This phase will be a precursor to Phase 2b studies, which will evaluate the efficacy of the drug against FTD. "The data generated in our phase 1 trial of VES001 demonstrate the potential of sortilin inhibition as a therapeutic approach to the treatment of frontotemporal dementia, and potentially other neurodegenerative diseases," said Mads Fuglsang Kjølby, MD, PhD, chief medical officer at Vesper Bio.
"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 CEO Paul Little, PhD, CChem FRSC. "These promising clinical data coupled with VES001’s patient-friendly profile bring us one step closer to transforming patient outcomes in frontotemporal dementia."
