Vesper Bio achieves enrolment milestone in Phase Ib/IIa trial of lead candidate VES001 for frontotemporal dementia

Vesper Bio achieves enrolment milestone in Phase Ib/IIa trial of lead candidate VES001 for frontotemporal dementia

• Phase Ib/IIa trial is to evaluate the efficacy of VES001 in asymptomatic patients with gene mutations that cause frontotemporal dementia
• A total of six participants have been enrolled in the trial across two sites – one in the Netherlands and one in the United Kingdom

Copenhagen, Denmark, 09 May 2025 – Vesper Bio ApS (“Vesper” or “the Company”), a clinical stage biotech developing an oral therapy for frontotemporal dementia, today announces it has reached an important enrolment milestone in the Ib/IIa phase of its ongoing SORT-IN-2 study of its lead candidate VES001. This Phase Ib/IIa trial is in asymptomatic carriers of a mutation in the progranulin-coding gene (GRN), which causes a leading genetically-determined type of frontotemporal dementia (FTD), called FTD-GRN.

Six volunteers who carry the GRN mutation, but who are asymptomatic, have now been enrolled across the two sites, one in the Netherlands and the other in the UK. Although this enrolment milestone has been reached, the trial is still accepting participants.

FTD is the most common dementia in those under the age of 60, but is often misdiagnosed as Alzheimer’s disease. VES001 – a first-in-class, oral, brain-penetrant, small molecule sortilin inhibitor – is being developed as a disease-modifying treatment for FTD-GRN, which is thought to account for around 25% of familial FTD cases.

Mads Fuglsang Kjølby, Chief Medical Officer at Vesper Bio, said: “Meeting this important enrolment milestone is a sign of the strong progress that Vesper is making towards its objective of producing a potentially transformative treatment for frontotemporal dementia. Vesper has strong momentum and is on track to deliver primary readouts for this Phase Ib/IIa trial in the second half of 2025. We would like to thank the participants for enrolling and the clinical teams for ensuring the timely and efficient execution of this trial.”

Paul Little, Chief Executive Officer at Vesper Bio, said: “There is a pressing need for a safe, effective and easy-to-administer treatment for people with frontotemporal dementia, a seriously debilitating condition for which there is currently no treatment available. The rapid advancement of our VES001 clinical development programme brings us one step closer towards meeting that significant need.”

The Phase Ib/IIa trial, part of Vesper’s ongoing SORT-IN-2 study, is an open-label trial assessing the clinical efficacy, safety and tolerability of VES001 in asymptomatic carriers with the GRN mutation. The trial will examine changes in levels of progranulin – a protein that plays a key role in cell growth, function and survival – in participants’ plasma and cerebrospinal fluid, at specific periods after they have received VES001 compared to baseline. Previous FTD natural history studies have shown that asymptomatic individuals with this GRN mutation have progranulin levels in both plasma and cerebrospinal fluid that are around 50% lower than those without the mutation. Similarly, those with symptomatic FTD-GRN also have progranulin levels that are around 50% lower than normal.

VES001 is designed to normalise and maintain progranulin levels by preventing sortilin-associated progranulin degradation. It does this by blocking sortilin, a neuronal surface receptor that would otherwise bind to progranulin and degrade it.

Last September, Vesper announced positive clinical data from its first-in-human Phase Ia trial of VES001, in healthy volunteers. Safety and tolerability were established, with no serious adverse events reported. VES001 also exhibited excellent pharmacokinetic properties, distributing to both plasma and CNS compartments, as well as strong target engagement, evidenced by an increased level of progranulin in both compartments.

The ongoing SORT-IN-2 study is based in two clinical centres: the Erasmus University Medical Centre, Rotterdam, in the Netherlands; and the Leonard Wolfson Experimental Neurology Centre Clinical Research Facility at the National Hospital for Neurology and Neurosurgery, University College London, in the UK. It is under the direction of esteemed professors Dr. Harro Seelaar (Netherlands) and Dr. Jonathan Rohrer (UK).

The Phase Ib/IIa trial is on track to read out during the second half of 2025. For more information about the trial (NCT06705192), please visit www.clinicaltrials.gov.

For further information, please contact:

Vesper Bio

Paul Little, CEO

Email: info@vesperbio.com

Optimum Strategic Communications

Nick Bastin, Stephen Adams, Joshua Evans, Aoife Minihan

Phone: +44 203 821 6420

Email: vesper@optimumcomms.com

About Vesper Bio

Vesper Bio is a clinical stage biotech and world leader in sortilin receptor biology. Its lead programme uses a sortilin inhibitor to rebalance levels of progranulin in patients where the sortilin receptor would otherwise reduce circulating and extracellular progranulin, contributing to disease. Progranulin is a protein that the body uses to regulate cell growth, survival, repair and avoid inflammation. Low progranulin levels are believed to be a factor in cell dysfunction and damage in a range of indications across neurology. By normalising progranulin levels, Vesper believes its compounds will have a disease modifying effect, protecting and preserving the remaining cells.

Its lead compound, VES001, is a patient friendly, first-in-class, brain penetrant, oral treatment which targets progranulin deficiency, a major underlying cause of frontotemporal dementia (FTD). As an orally delivered small molecule, VES001 is able to cross the blood-brain barrier and is an ideal dosing method among these patients due to their rapidly declining mental state.

About frontotemporal dementia (FTD)

Frontotemporal dementia (FTD), also known as frontotemporal lobar degeneration (FTLD), is a group of brain disorders that cause degeneration in the frontal and temporal lobes of the brain. FTD impacts a person’s behaviour, judgement, communication and ability to participate in all activities of daily living. It is the most common cause of dementia in people under the age of 60 and is often misdiagnosed as Alzheimer’s disease. FTD-GRN is a form of FTD caused by mutations of the progranulin gene (GRN), resulting in low progranulin levels. FTD-GRN is thought to account for a quarter of familial FTD cases. Low levels of progranulin are associated with cellular dysfunction, neuroinflammation and other neuronal damage across a variety of neurological indications.

For further information please visit, https://www.vesperbio.com/