Pipeline
Vesper Bio is developing a rich pipeline of first-in-class small molecule sortilin modulators for a number of critical unmet medical needs. Alongside our lead program, VES001 for FTD, we are leveraging our deep domain expertise in sortilin biology to explore multiple additional targets with high disease relevance in a number of therapy areas and indications.
Discovery
IND/CTA-enabling studies
Phase 1
Phase 2
VES001
(Frontotemporal Dementia)
Eye diseases
VES002 (undisclosed)
VES001:
A novel sortilin antagonist for FTD(GRN)
Our 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 normalizing progranulin levels, Vesper believes its compounds will have a disease modifying effect, protecting and preserving the remaining cells.
VES001 is a patient friendly, first-in-class, brain penetrant, oral treatment that could bring meaningful disease modifying benefit to patients suffering from Frontotemporal Dementia (FTD), where there is a clear, critical unmet need.
VES001 selectively binds sortilin and disrupts protein-protein interaction with progranulin at the cell membrane. This means that VES001 acts as a progranulin uptake inhibitor. Vesper Bio has demonstrated dose-dependent elevation in extracellular progranulin in a manner that does not disrupt the intracellular milieu.
About FTD(GRN)
FTD(GRN) is a genetic disease, where family history accounts for between 20%-40% of all cases. The GRN mutation in FTD patients is one of several mutations and is associated with a 50% reduction in circulating progranulin compared to healthy individuals. There are c.17,400 patients with FTD(GRN) in the seven major markets and c.140,000 carriers at risk who will go on to develop FTD. With no disease-modifying treatments available, there is a clear, critical unmet need.
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Symptoms of FTD include:
Behavioural/personality changes (impulsiveness, apathy, compulsiveness)
Primary progressive aphasia
Semantic dementia
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In many cases, FTD patients display abnormal motor function and coordination including parkinsonism and motor neuron disease. Symptom onset is typically before age 60 and in most cases is associated with a life expectancy of 7-10 years post symptom onset.
There are no FDA-approved treatments for FTD, with the only available treatments targeting behavioural symptoms of the disease.
FTD(GRN)
Genetic analysis of chromosome 17q21 led to the identification of 70 pathogenic mutations within progranulin that cause FTD. These mutations essentially result in a haploinsufficiency of the protein. The frequency of GRN mutations is estimated to be up to 11.7% of the total FTD population, and up to 25% of familial cases. FTD-GRN has an incidence of 3 to 15 per 100,000 of population aged 45-64.
Other indications
Sortilin protein interactions at the cell surface are well understood and Vesper Bio has demonstrated that our compounds disrupt apoptotic signals associated with disease states.