Study to focus on asymptomatic individuals with gene mutations linked to a deadly form of frontotemporal dementia.
Danish biotech Vesper Bio has commenced a Phase 1b/2a proof-of-concept study to evaluate its investigational small molecule drug in patients with genetic mutations that lead to frontotemporal dementia (FTD). The SORT-IN-2 trial focuses on asymptomatic individuals with progranulin gene (GRN) mutations, a causal factor in FTD(GRN), a fatal version of the neurodegenerative disease.
FTD is a degenerative condition affecting the frontal and temporal lobes of the brain, impairing behavior, judgment, and communication. It is the leading cause of dementia in individuals under 60 and is frequently misdiagnosed as Alzheimer’s disease. Cases of FTD(GRN) are characterized by a deficiency in progranulin, a key protein responsible for cell growth, survival, and repair. Deficiency in this protein contributes to cellular dysfunction and neurodegeneration.
Vesper’s lead compound, VES001, is a brain-penetrant, orally administered small molecule designed to inhibit sortilin, a neuronal receptor responsible for degrading progranulin. By preventing sortilin from binding to and internalizing progranulin, VES001 preserves and normalizes progranulin levels, potentially slowing or halting the progression of FTD(GRN). This treatment approach is intended to protect remaining neurons, addressing the underlying cause of the disease rather than simply managing symptoms.
“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 co-founder Mads Fuglsang Kjølby. “Based on the data from our successful First-in-Human trial, we believe VES001 will normalise progranulin levels, and thus has great potential to slow or even arrest FTD(GRN) disease progression.”
The SORT-IN-2 study is an open-label trial conducted at Erasmus University Medical Centre in Rotterdam and the Leonard Wolfson Experimental Neurology Centre at University College London. The trial targets asymptomatic individuals with GRN mutations, aiming to assess VES001’s safety, tolerability, and its ability to elevate progranulin levels in cerebrospinal fluid and plasma. Vesper has initiated dosing after receiving clinical trial authorization from regulatory bodies in the Netherlands and the United Kingdom, and anticipates completing dosing by mid-2025.
“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 CEO Paul Little. “We are committed to bringing this important new oral treatment option to families living with FTD, where there is no approved therapy available today.”
The decision to advance to this phase follows encouraging results from a Phase 1a study of VES001 in healthy volunteers. In the trial, VES001 was distributed effectively to both plasma and the central nervous system, resulting in increased progranulin levels without serious adverse events.
