Vesper Bio has reached a key enrolment milestone in its Phase 1B and 2A trials evaluating VES001, a novel oral therapy for frontotemporal dementia (FTD) linked to GRN gene mutations.

Six asymptomatic participants carrying the mutation have been enrolled across two sites in the UK and Netherlands, marking a significant step in the company’s ongoing SORT-IN-2 clinical program.

The study focuses on individuals who carry a mutation in the progranulan-coding gene (GRN), a known cause of a hereditary subtype of FTD known as FTD-GRN. Although participants show no clinical symptoms, their reduced progranulin levels put them at high risk of developing the disease. The trial remains open to further enrolment.

Frontotemporal dementia is a neurodegenerative condition and the most common form of dementia in individuals under 60. It is often misdiagnosed due to overlapping symptoms with other types of dementia, particularly Alzheimer’s disease. In familial cases, around a quarter are associated with GRN mutations.

VES001 is described as a first-in-class, brain-penetrant small molecule that inhibits sortilin – a neuronal surface receptor involved in progranulin degradation. By blocking this mechanism, VES001 is designed to restore and maintain progranulin levels in both plasma and cerebrospinal fluid.

The current trial is open-label and aims to evaluate the safety, tolerability, and pharmacodynamic effect of VES001 in this pre-symptomatic group. Key endpoints include changes in progranulin concentration in both plasma and CSF after treatment, compared with baseline values. Previous observational studies have shown that GRN mutation carriers exhibit approximately 50% lower progranulin levels than non-carriers, even before symptoms appear.

Vesper Bio previously reported positive results from a Phase 1A trial in healthy volunteers, where VES001 showed good tolerability and pharmacokinetics, with no serious adverse events. The candidate demonstrated dose-dependent increases in progranulin levels, providing early signs of target engagement.

The SORT-IN-2 study is being conducted at two leading neurology centers: Erasmus University Medical Centre in Rotterdam, and University College London’s Leonard Wolfson Experimental Neurology Centre. The trial is led by Professors Harro Seelaar and Jonathan Rohrer, respectively.

The company expects primary readouts from the trial in the second half of 2025. While recruitment continues, the early progress reflects growing momentum toward a disease-modifying approach to FTD, which currently lacks any approved treatment options.