Vesper Bio reports successful Phase I trial for frontotemporal dementia treatment

COPENHAGEN, Denmark, Sept. 4, 2024 -- Vesper Bio ApS, a clinical-stage biotech company renowned for its expertise in sortilin receptor biology, has announced the successful completion of the Phase I trial for its leading candidate, VES001. This candidate is being developed as a potentially groundbreaking treatment for frontotemporal dementia (FTD) patients with mutations in the progranulin gene (FTD(GRN)). 

Frontotemporal dementia is the leading cause of dementia in individuals under 60 and is frequently linked to mutations in the progranulin gene (PGRN). This gene is crucial for the regulation of cell growth, survival, and repair. When progranulin levels are low, it can lead to cellular dysfunction, neuroinflammation, and neuronal damage across various neurological conditions. 

VES001 is a pioneering oral, brain-penetrant small molecule that inhibits the sortilin receptor. Sortilin is present on neuron surfaces and competes with progranulin receptors for binding. When progranulin binds to sortilin, it undergoes degradation, which further reduces its levels and causes neuronal damage and cell death. VES001 is designed to cross the blood-brain barrier, inhibit sortilin, and prevent the binding and degradation of progranulin. This action helps maintain and normalize progranulin levels, potentially offering a disease-modifying treatment for FTD(GRN) patients. The convenience of its oral daily dosing makes it an attractive option for patients.

The Phase I trial, conducted in two parts with 78 healthy volunteers, assessed the safety, tolerability, pharmacokinetics, and pharmacodynamic target engagement of VES001 across various dose levels. All endpoints were successfully met. The findings from the 7-day multiple ascending dose (MAD) stage confirmed the results observed in the single ascending dose (SAD) stage reported earlier in May 2024.

Remarkably, VES001 demonstrated a high safety and tolerability profile, with no serious or treatment-emergent adverse events across all tested doses. The data showed that upon oral administration, VES001 had excellent pharmacokinetics and distribution to both plasma and the central nervous system (CNS). Furthermore, strong target engagement was evident, with increased and accumulating levels of progranulin in volunteers dosed once or twice daily during the MAD stage. These results, when modeled on the target patient population, suggest a significant normalization of progranulin levels after just seven days of dosing.

Vesper Bio has now completed a clinical trial application (CTA) to advance VES001 into a Phase IIa proof-of-concept study in a relevant patient population, with the first dose targeted for Q4 2024.

Mads Fuglsang Kjølby, Chief Medical Officer at Vesper Bio, stated, "Our Phase I trial results for VES001 highlight the potential of sortilin inhibition as a therapeutic approach for treating frontotemporal dementia and possibly other neurodegenerative diseases." 

Paul Little, Chief Executive Officer at Vesper Bio, added, "At Vesper, we are driven by the needs of our patients and their families. These promising clinical data and VES001's patient-friendly profile bring us closer to transforming outcomes for frontotemporal dementia patients."

Frontotemporal dementia (FTD), also known as frontotemporal lobar degeneration (FTLD), encompasses disorders that cause degeneration in the frontal and temporal lobes of the brain, affecting behavior, judgment, communication, and daily living activities. FTD is the most prevalent cause of dementia in individuals under 60 and is often misdiagnosed as Alzheimer's Disease. FTD(GRN) is a variant of FTD caused by progranulin gene mutations, leading to reduced progranulin levels and accounting for an estimated 25% of familial FTD cases.

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