Vesper Bio ApS has initiated a Phase Ib/IIa clinical trial to evaluate VES001, a novel oral treatment, in asymptomatic individuals carrying progranulin (GRN) gene mutations that cause frontotemporal dementia (FTD). The SORT-IN-2 study (NCT06705192) is designed to assess the safety, tolerability, and efficacy of VES001 in elevating progranulin levels, a protein crucial for neuronal health and deficient in FTD(GRN) patients. This trial marks a significant step forward in addressing a disease with no currently approved therapies.
VES001: A Novel Approach to FTD(GRN) Treatment
VES001 is a first-in-class, brain-penetrant, orally administered small molecule designed to inhibit sortilin, a neuronal receptor that binds to progranulin and targets it for degradation. By preventing sortilin from binding and internalizing progranulin, VES001 aims to normalize and maintain progranulin levels, potentially slowing or halting the progression of FTD(GRN). This approach targets the underlying cause of the disease, offering a potential disease-modifying effect.
SORT-IN-2 Trial Design and Objectives
The SORT-IN-2 trial is an open-label, dual-center study being conducted at Erasmus University Medical Centre in Rotterdam, Netherlands, and the Leonard Wolfson Experimental Neurology Centre at University College London, UK. The trial will enroll asymptomatic individuals with GRN mutations. The primary outcome measure is the change in progranulin levels in cerebrospinal fluid (CSF) and plasma. Vesper Bio anticipates completing dosing of all participants by mid-2025.
Mads Fuglsang Kjølby, Co-Founder and interim Chief Medical Officer at Vesper Bio, stated, "The aim of this study is to further demonstrate the safety and tolerability of VES001 and confirm whether VES001 has a positive effect on progranulin levels in the cerebrospinal fluid and blood plasma of these patients... 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."
Prior Clinical Data and Rationale
VES001 has previously demonstrated promising results in a Phase 1a study involving healthy volunteers. The study showed that VES001 was safe and well-tolerated, with no serious or treatment-emergent adverse events reported. Furthermore, the data indicated that orally administered VES001 exhibited excellent pharmacokinetic properties, distributed well to both plasma and CNS compartments, and resulted in a significant increase in progranulin levels, demonstrating target engagement.
Paul Little, Chief Executive Officer at Vesper Bio, commented, "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. We are committed to bringing this important new oral treatment option to families living with FTD, where there is no approved therapy available today."
About Frontotemporal Dementia (FTD)
Frontotemporal dementia (FTD) is a group of brain disorders that cause degeneration in the frontal and temporal lobes of the brain, impacting behavior, judgment, communication, and the ability to perform daily activities. FTD is the most common cause of dementia in people under 60 and is often misdiagnosed as Alzheimer's disease. FTD(GRN) is an inherited form of FTD caused by mutations in the progranulin gene (GRN), resulting in approximately a 50% reduction in progranulin levels. There are an estimated 17,400 patients with FTD(GRN) in major markets, with roughly 140,000 carriers at risk of developing the condition.
