Vandria has presented new data from the multiple ascending dose part of its phase 1 study of VNA-318.
The data, presented at the Alzheimer’s Association International Conference (AAIC) in London, show that VNA-318’s mechanism of action translates from preclinical models into human biology and that the candidate exerts a clear pharmacodynamic effect on the human brain, suggesting the potential for therapeutic benefit in patients.
“The translation of biology into humans and the effects on brain function mark a key inflection point for VNA-318 as a potential new therapy with once-daily oral dosing,” said Klaus Dugi, CEO of Vandria.
“Together with the previously reported human safety, pharmacokinetic, and target engagement data, these findings strengthen our conviction in VNA-318 and support further clinical development, with Alzheimer’s disease as the initial indication.”
The newly presented results for pre-specified endpoints include pharmacodynamic effects in the human brain following 12 days of dosing with VNA-318, assessed using quantitative electroencephalography (qEEG), and direct measurement of VNA-318 concentrations in cerebrospinal fluid (CSF), confirming brain penetration and activity consistent with preclinical studies.
“The observed reduction in alpha-band activity in quantitative EEG provides robust evidence of a pharmacodynamic engagement of the compound in the human brain,” said Daniel Mathalon, professor of Psychiatry and Behavioral Sciences, University of California San Francisco.
“Importantly, these signals may be linked to changes of attention, inhibitory control, and cognitive state.”
In addition, new post-hoc analyses of plasma and intracellular metabolite biomarkers linked to energy metabolism and fatty acid oxidation observed in peripheral blood mononuclear cells are consistent with those seen in preclinical models of neurodegenerative disorders. Together with the qEEG findings, these data provide converging evidence that VNA-318’s mechanism of action translates into human biology.
The findings presented at AAIC build on the positive topline results of this first-in-human phase 1 study of VNA-318, reported previously at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) conference, held in San Diego in December 2025.
The results showed a favourable safety and tolerability profile of VNA-318, with no serious adverse events and no adverse events leading to trial discontinuation. Pharmacokinetic data demonstrated a half-life supportive of once-daily oral dosing and a predictable, dose-linear increase of exposure with low to moderate variability.
Pharmacokinetic data showed exposure to VNA-318 at concentrations predictive of therapeutic efficacy based on preclinical models in both acute pro-cognitive and long-term disease-modifying models of Alzheimer’s disease pathophysiology.
The phase 1 trial, VNA-318-01, was a randomised, double-blind, single- and multiple-ascending-dose (SAD/MAD) study designed to assess safety, tolerability, pharmacokinetic, and pharmacodynamic parameters in 92 healthy male subjects.