Vesper Bio starts Phase Ib/IIa study of VES001 for asymptomatic FTD gene mutation patients

Vesper Bio ApS, a clinical-stage biotechnology firm recognized for its leadership in sortilin receptor biology, has embarked on a significant study involving its innovative treatment candidate, VES001. This investigational drug is designed to address frontotemporal dementia (FTD) caused by mutations in the progranulin gene (GRN), known as FTD(GRN). The disorder leads to a significant reduction in progranulin levels, a vital protein for neuronal health. VES001, an orally administered and brain-penetrant drug, aims to elevate these levels, potentially altering the disease's progression.

Vesper has initiated a Phase Ib/IIa proof of concept study named SORT-IN-2, following approvals from regulatory bodies in the Netherlands and the UK. This open-label study will assess the effectiveness of VES001 in asymptomatic patients with GRN mutations and is being conducted at two sites: Erasmus University Medical Centre in Rotterdam and the Leonard Wolfson Experimental Neurology Centre in London. The trial aims to demonstrate VES001's safety and tolerability, alongside its ability to normalize progranulin levels in cerebrospinal fluid and blood plasma. The study is expected to complete its dosing of participants by mid-2025.

The trial represents a significant step forward for Vesper Bio in its mission to combat frontotemporal dementia. Mads Fuglsang Kjølby, the Co-Founder and interim Chief Medical Officer of Vesper Bio, highlighted the importance of verifying VES001's impact on progranulin levels. The company's earlier Phase Ia trial with healthy volunteers indicated high safety and tolerability, with no severe adverse events and excellent pharmacokinetic properties. The results showed promising target engagement, with increased progranulin levels in both plasma and the central nervous system.

Paul Little, CEO of Vesper Bio, expressed pride in the company's rapid progress, emphasizing the urgent need for effective treatments for FTD, for which no approved therapies currently exist. VES001 aims to fulfill this gap by offering a user-friendly oral dosing regimen, crucial for patients suffering from the rapid cognitive decline associated with FTD.

VES001 works by targeting sortilin, a neuronal surface receptor that typically binds and degrades progranulin, leading to decreased levels of this essential protein. By inhibiting sortilin, VES001 helps maintain and normalize progranulin levels, potentially offering a disease-modifying treatment option for patients.

Frontotemporal dementia, or FTD, comprises a range of disorders characterized by the degeneration of brain areas responsible for behavior, judgment, and communication. It is the most prevalent form of dementia in individuals under 60 and is frequently misdiagnosed as Alzheimer's disease. FTD(GRN), a hereditary variant caused by GRN gene mutations, is responsible for approximately 12% of FTD cases, with over 17,000 diagnosed patients in major markets and around 140,000 individuals at risk.

The SORT-IN-2 study, identified as NCT06705192 on clinicaltrials.gov, brings hope to patients and families affected by FTD(GRN). With an innovative approach to treatment, Vesper Bio aims to shift the landscape of neurodegenerative disorder management, offering new hope for a future free from the impact of frontotemporal dementia.