Swiss company Vandria SA has announced topline results from its first-in-human clinical trial of its lead central nervous system (CNS) compound VNA-318.
VNA-318 is a first-in-class, orally bioavailable, and brain-penetrant small molecule targeting a novel protein with a dual mode of action. Initially, VNA-318 is being developed to address the major unmet medical needs facing patients with Alzheimer’s disease: cognitive impairment and the debilitating loss of function associated with it. VNA-318 also has the potential to treat other CNS diseases.
The novel target of VNA-318 has genetic associations with several human diseases including Alzheimer’s disease. In pre-clinical mouse models of neurodegeneration and cognitive impairment, VNA-318’s dual mode of action resulted in both immediate pro-cognitive and long-term disease-modifying benefits. More specifically, VNA-318 showed an immediate improvement in memory, learning, and cognitive function, as well as long-term reduction in neuroinflammation, reduced toxic protein aggregation, and improved mitochondrial function.
Topline results from the first-in-human trial of VNA-318 were being presented at the annual meeting of the 18th Clinical Trials in Alzheimer’s Disease (CTAD) meeting in San Diego.
The phase 1 trial, VNA-318-01, is a randomized, double-blind single and multiple ascending dose study designed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic parameters in 92 healthy male subjects. Interim results show excellent safety and tolerability of VNA-318 with no severe or serious adverse events and no adverse events leading to trial discontinuation. The PK data demonstrate a long half-life supportive of once-daily oral dosing and a predictable, dose-linear increase of exposure with low variability. Already with single dosing, a statistically significant and dose-dependent change in a key target engagement biomarker has been observed. The availability of an easily accessible target engagement biomarker in plasma will be leveraged in VNA-318’s future clinical development.
VNA-318 levels in the cerebrospinal fluid measured during the trial in one cohort confirm that the brain penetration seen in pre-clinical studies translates to humans.
Klaus Dugi, CEO of Vandria, said: “We are very excited about the results of our first-in-human trial of VNA-318, which ticks all the boxes for a phase 1 trial – and more. The statistically significant dose-dependent change in a key target engagement biomarker is a very important finding and will be valuable for our phase 2 clinical development strategy. This, coupled with safety, tolerability and demonstrated brain penetration, as well as pre-clinical data strongly support VNA-318’s advancement in Alzheimer’s disease.
“We believe that VNA-318 has the potential to address unmet medical needs like mild cognitive impairment associated with Alzheimer’s and major depressive disorder, as well as other CNS disorders.”
Vandria is planning to raise a Series B in 2026 to fund proof-of-concept phase 2 trials. The global market for Alzheimer’s alone is estimated at $6bn and is expected to grow at a CAGR of 12% to 2035, driven by an aging population, improved diagnosis, and a growing awareness and understanding of the condition and its implications.
The planned Series B will also be used to progress Vandria’s pre-clinical pipeline of compounds in non-CNS indications such as muscle, lung, and liver disease.
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