Danish biotechnology company Vesper Bio announced in January that its clinical trial for a potentially disease-modifying drug for FTD-GRN is proceeding to phase Ib/IIa.

In FTD caused by an inherited GRN mutation, the production of the neuroprotective protein progranulin is suppressed. The protein sortilin contributes to the loss of progranulin by binding to it and targeting it for degradation. Low progranulin levels are associated with neuronal dysfunction and the abnormal accumulation of the protein TDP-43, a key driver of FTD pathology.

Vesper Bio Evaluating VES001 in People with FTD-GRN

VES001 is a novel, orally administered drug that selectively inhibits sortilin, preventing it from binding with progranulin. VES001 can boost progranulin levels in people affected by a GRN mutation through this process.

In September 2024, Vesper Bio announced that it had completed phase 1 studies of VES001 in people without FTD-GRN, which found that the drug was safe and well tolerated by participants. Crucially, the study found a substantial normalization of progranulin levels in participants dosed once or twice daily.

“Progranulin is vital for maintaining neuronal health; however, progranulin levels in asymptomatic people with GRN mutations are typically half that of people without such mutations,” said Vesper Bio co-founder and interim chief medical officer Mads Fuglsang Kjølby, MD, PhD. “Based on the data from our successful First-in-Human trial, we believe VES001 will normalize progranulin levels, and thus has great potential to slow or even arrest FTD-GRN disease progression.”

In the trial’s next phase, a smaller cohort of people with FTD-GRN will receive the experimental drug. While safety and tolerability data will still be collected during this phase, the main goal is to confirm whether VES001 raises progranulin levels in cerebrospinal fluid and the bloodstream. This type of trial, known as a “proof of concept study,” helps scientists determine whether to continue with a specific compound or move their efforts elsewhere.

“It is an incredible achievement by the Vesper team that we have been able to progress VES001 so quickly into this next clinical trial phase,” said Vesper Bio CEO Paul Little, PhD. “We are committed to bringing this important new oral treatment option to families living with FTD where there is no approved therapy available today. We are all striving for a future free from FTD for patients and their families.”

Clinical trials for FTD are being launched at an increasing pace as companies like Vesper Bio further develop experimental interventions and diagnostic tools. If you are interested in participating in research, the FTD Disorders Registry’s Find a Study page can help you find a trial that is right for you.