- VES001 is a first-in-class oral, brain penetrant, small
molecule sortilin inhibitor for treatment of FTD(GRN)
- Data demonstrate excellent safety, tolerability profile,
dose-proportionality and target engagement with elevations in
progranulin in both plasma and CNS
- CTA filed for Phase IIa study, first dose targeted for Q4
2024
COPENHAGEN, Denmark, Sept. 4,
2024 /PRNewswire/ -- Vesper Bio ApS ("Vesper" or "the Company"), a clinical
stage biotech and world leader in sortilin receptor biology, today
announces the successful completion of the Phase I study for its
lead candidate, VES001, a potentially disease-modifying treatment
for frontotemporal dementia patients with mutations in the
progranulin gene (FTD(GRN)).
Frontotemporal dementia is the most common cause of dementia in
people under the age of 60. FTD(GRN), which is estimated to account
for a quarter of familial FTD cases, is a form of FTD caused by
mutations of the progranulin gene (PGRN), a protein responsible for
the regulation of cell growth, survival, and repair. Low levels of
progranulin are associated with cellular dysfunction,
neuroinflammation and neuronal damage across a variety of
neurological indications.
VES001 is a first-in-class oral, brain-penetrant, small molecule
sortilin inhibitor rationally designed as a potentially
disease-modifying treatment for FTD(GRN). Sortilin is a receptor
found on the surface of neurons that competes with progranulin
receptors for progranulin binding. Progranulin is degraded when
binding to sortilin through an internalization process, leading to
further reductions in free progranulin and subsequent neuronal
damage and cell death. VES001 is designed to cross the blood brain
barrier and inhibit this process, binding to the sortilin receptor
and stopping progranulin from binding, thereby helping to maintain
and normalize progranulin levels. With its unique mode of action
and convenient oral daily dosing, VES001 is an ideal,
patient-friendly treatment option.
The Phase I study was a two-part trial in 78 healthy volunteers
investigating safety, tolerability, pharmacokinetics and
pharmacodynamic target engagement endpoints across a range of
separate dose levels. All endpoints were successfully met, with the
top line data from the 7-day multiple ascending dose (MAD) stage
re-affirming the findings seen in the single ascending dose (SAD)
stage, announced in May 2024.
High levels of safety and tolerability of VES001 were observed
across the doses tested, with no serious or treatment-emergent
adverse events reported. The data demonstrate that following oral
dosing, VES001 exhibits excellent pharmacokinetics and distribution
to plasma and the targeted Central Nervous System compartment.
Furthermore, VES001 showed strong target engagement evidenced by an
increased and accumulating level of progranulin in the volunteers
dosed once or twice daily in the MAD stage. Data from this study
will be published in due course and when modelled on to the target
population, represent a substantial normalization of progranulin
concentration after 7 days of dosing.
Vesper Bio has completed a clinical trial application (CTA)
seeking to progress VES001 into a Phase IIa proof-of-concept study
in a relevant patient population, with dosing expected to start in
Q4 2024.
Mads Fuglsang Kjølby, Chief Medical Officer at Vesper Bio,
commented: "Vesper Bio is proud of its status as a world
leader in sortilin biology. The data generated in our Phase I trial
of VES001 demonstrate the potential of sortilin inhibition as a
therapeutic approach to the treatment of frontotemporal dementia,
and potentially other neurodegenerative diseases."
Paul Little, Chief Executive
Officer at Vesper Bio, added: "At Vesper, we are motivated
by our patients and their relatives, who inspire our mission to
develop innovative therapies that can help fight this awful
disease. These promising clinical data coupled with VES001's
patient friendly profile bring us one step closer to transforming
patient outcomes in frontotemporal dementia."
Notes to Editors
About Vesper Bio
Vesper is a clinical stage biotech and world leader in sortilin
receptor biology. Its lead program 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 normalizing 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 fronto-temporal
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 behavior, 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 (PGRN), resulting in
low progranulin levels. FTD(GRN) is thought to account for a
quarter of familial FTD cases.
For further information please visit,
https://www.vesperbio.com/.
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SOURCE Vesper Bio