NEW YORK – Vesper Bio on Thursday said it has dosed the first patient in a Phase I trial of VES001, a candidate therapy for patients with frontotemporal dementia due to loss-of-function mutations in the progranulin gene (FTD-GRN).
Roughly 5 percent to 10 percent of FTD cases stem from mutations in the GRN gene, which codes for the progranulin protein. GRN mutations cause lower levels of circulating progranulin, which plays a key role in the survival of neurons, regulating cell growth and repair, and modulating inflammation.
VES001 aims to maintain higher levels of circulating progranulin by crossing the blood-brain barrier and binding to the vps10p receptor on the sortilin membrane protein to block progranulin's cellular reuptake.
The first patient dosed with VES001 is enrolled in a randomized, double-blind, single and multiple ascending dose Phase I study in healthy volunteers that is designed to assess the safety, tolerability, and pharmacokinetics of the drug, as well as its engagement with target biomarkers.
The trial will involve 48 participants in the single ascending dose arm and 30 volunteers in the multiple ascending dose arm. After establishing VES001's safety, Vesper plans to do a Phase Ib proof-of-concept study in GRN mutation carriers and move into registrational Phase II/III trials after that.
"We have taken a significant step forward in bringing VES001 closer to treating patients suffering from FTD-GRN," Vesper CEO Paul Little said in a statement. "This is a devastating disease for both patients and their families, and we hope to show that this is a potentially game-changing treatment. The role of progranulin is becoming better understood, with clinical validation using antibody approaches, and preclinical trials with our small molecule, VES001, have shown the effectiveness of targeting the uptake of progranulin in this way."
The company is also preparing a Phase I trial for a second molecule, VES002, focused on a separate and currently undisclosed central nervous system indication.