New Phase 1 data show Vandria’s VNA-318 reaches the human brain and produces pharmacodynamic effects supporting further clinical development for Alzheimer’s disease.

Vandria has reported new Phase 1 clinical data showing that its investigational therapy VNA-318 reaches the human brain and produces measurable pharmacodynamic effects, supporting its continued development as a potential treatment for Alzheimer’s disease.

The findings, presented at the Alzheimer’s Association International Conference (AAIC) in London, provide further evidence that the oral small molecule behaves in humans as predicted from preclinical research. The data demonstrated brain penetration, pharmacodynamic activity measured using quantitative electroencephalography (qEEG) and biomarker changes associated with energy metabolism.

Demonstrating that an investigational medicine reaches the brain and produces measurable biological effects is an important milestone in early drug development. Many experimental therapies fail because they either do not adequately penetrate the central nervous system or do not engage their intended biological targets once there.

The new results come from the multiple ascending dose stage of Vandria’s Phase 1 study and build on previously reported findings showing VNA-318 was generally well tolerated, with pharmacokinetic properties supporting once-daily oral dosing.

Researchers measured drug concentrations in cerebrospinal fluid, confirming that VNA-318 crossed the blood-brain barrier. They also observed changes in qEEG recordings after 12 days of dosing, indicating pharmacodynamic activity within the human brain.

Additional biomarker analyses showed changes in plasma metabolites and markers of cellular energy metabolism consistent with those previously observed in preclinical models of neurodegenerative disease. Together, these findings suggest the drug’s proposed mechanism of action translates from laboratory studies into human biology.

Klaus Dugi, chief executive officer of Vandria, said: “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. 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.”

VNA-318 is designed to restore mitochondrial function and reduce chronic neuroinflammation, two biological processes increasingly recognised as contributing to the development and progression of Alzheimer’s disease and other age-related neurodegenerative disorders.

The Phase 1 trial enrolled 92 healthy male volunteers in a randomised, double-blind, single- and multiple-ascending-dose study evaluating the safety, tolerability, pharmacokinetic and pharmacodynamic profile of the investigational therapy.

Daniel Mathalon, professor of psychiatry and behavioral sciences at the University of California San Francisco, said: “The observed reduction in alpha-band activity in quantitative EEG provides robust evidence of a pharmacodynamic engagement of the compound in the human brain. Importantly, these signals may be linked to changes of attention, inhibitory control, and cognitive state.”

Alzheimer’s disease affects millions of people worldwide, yet there remains a significant need for therapies that can modify disease progression. By targeting mitochondrial dysfunction and neuroinflammation, Vandria hopes VNA-318 could offer a novel therapeutic approach alongside existing treatments.

The company said the latest findings support continued clinical development of VNA-318, with Alzheimer’s disease planned as the first therapeutic indication.