Company readies for Phase 2 studies after frontotemporal dementia drug demonstrates key target engagement.
Danish biotech Vesper Bio has successfully completed its Phase 1 study of its lead compound, a small molecule sortilin inhibitor, as a potential treatment for frontotemporal dementia (FTD). All endpoints in the trial were met, with data showing the drug to be safe and well-tolerated along with evidence of target engagement, and the Copenhagen-based company now expects to commence a Phase 2a trial later this year.
The recent trial focused on a subtype of FTD, known as FTD(GRN), which is characterized by low levels of progranulin, a key protein responsible for cell growth, survival, and repair. Progranulin deficiency is associated with cellular dysfunction and neurodegeneration, and stabilizing levels of the protein is thought to have the potential to preserve neuronal health and mitigate the progression of the disease.
Vesper’s drug, VES001, is an orally administered, small molecule sortilin inhibitor designed to address progranulin deficiency by preventing its degradation. Sortilin receptors, found on neuron surfaces, bind to progranulin, causing its breakdown and further lowering progranulin levels, which leads to cell damage and death. VES001 works by inhibiting this process, allowing progranulin levels to be maintained and normalized. The compound is also brain-penetrant, meaning it can cross the blood-brain barrier to exert its effects within the central nervous system, potentially offering a convenient dosing option for patients suffering from rapidly progressing neurological decline.
Vesper Bio’s Chief Medical Officer Mads Fuglsang Kjølby, and Paul Little, CEO.
In the Phase 1 trial, which involved 78 healthy volunteers, VES001 demonstrated positive results across safety, tolerability, and pharmacokinetic measures. The trial was conducted in two parts: a single ascending dose (SAD) phase and a multiple ascending dose (MAD) phase, both of which confirmed VES001’s safety profile with no serious or treatment-emergent adverse events.
Pharmacokinetic data showed that VES001 is well-distributed in the plasma and the central nervous system. Target engagement was evidenced by the elevated levels of progranulin in both plasma and the CNS, with a significant and sustained increase observed after seven days of dosing in the MAD phase. Vesper claims the results indicate that VES001 is effective at preventing the breakdown of progranulin, achieving the intended biological response in healthy subjects.
“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,” said Paul Little, CEO of Vesper Bio. “These promising clinical data coupled with VES001’s patient friendly profile bring us one step closer to transforming patient outcomes in frontotemporal dementia.”
Following the trial results, Vesper has filed a clinical trial application to initiate a Phase 2a study to evaluate VES001 in a patient population affected by FTD(GRN). The company says it plans to begin dosing in this proof-of-concept study by the fourth quarter of 2024.
Earlier this year, Vesper was awarded a grant from The Michael J Fox Foundation to assess the potential impact of sortilin inhibitors in the treatment of Parkinson’s disease.
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