Dr Klaus Dugi discusses the first-in-human data for VNA-318, the rationale for targeting cellular energy metabolism in Alzheimer’s disease, and how improving mitochondrial function could offer both symptomatic and disease-modifying benefits.
We spoke with Klaus Dugi, Chief Executive Officer of Vandria, at the Alzheimer’s Association International Conference (AAIC) 2026 about the company’s first-in-human study of VNA-318.
In this interview, Klaus Dugi discusses why impaired cellular energy metabolism has emerged as a promising therapeutic target in Alzheimer’s disease, the key findings from the phase 1 study, and the next steps in evaluating VNA-318 as a potential disease-modifying therapy.
Abstract: First-in-class Small Molecule VNA-318, In Development For Alzheimer’s, Inhibits Key Target Engagement Biomarker In First-in-human Trial
touchNEUROLOGY coverage of AAIC 2026
What role does impaired cellular energy metabolism play in Alzheimer’s disease progression, and why has it emerged as an attractive therapeutic target?
Restoring energy production in ageing cells
In 1990, the Human Genome Project began, and we learned an enormous amount about the genetic causes of disease and the potential of gene therapy.
At the same time, we have to remember that we all die with the same genes we are born with. Yet we are healthier when we are young. As we move into our 60s, 70s and 80s, the risk of chronic and neurodegenerative diseases increases dramatically.
There are several hallmarks of age-related diseases, including chronic inflammation and protein misfolding. We believe many of these hallmarks are linked by the reduced ability of cells, tissues and organs to produce energy efficiently.
Generating new proteins requires a great deal of energy, and as we age our cells gradually lose that ability. Our approach is designed to restore that energy production.
Why NAD metabolism matters
There was also a very interesting paper published earlier this year in Cell Reports Medicine. For the first time, researchers showed they could reverse advanced Alzheimer’s disease in the 5xFAD mouse model by improving NAD metabolism. They also demonstrated a significant difference in NAD metabolism between patients with Alzheimer’s disease and age-matched healthy controls. That publication focused a great deal of attention on energy metabolism and NAD biology, which is exactly where our mechanism of action sits.
What is VNA-318’s mechanism of action, and what is the scientific rationale behind this approach?
Improving mitochondrial efficiency
By inhibiting our target, we essentially force cells back towards a much more efficient way of producing energy.
That means increasing oxidative phosphorylation within the mitochondria, as well as fatty acid oxidation, both of which are highly efficient ways of generating the energy cells need to deal with chronic inflammation, protein misfolding and many of the other hallmarks of ageing.
Potential for symptomatic and disease-modifying effects
We discovered how quickly these changes appeared to translate into improvements in cognition in our preclinical models. In aged mice, we saw improvements in cognitive function within weeks.
Over the longer term, we also observed evidence of disease modification, including reductions in brain inflammation and amyloid-beta plaque formation.
The study demonstrated target engagement alongside evidence of CNS penetration. What were the key findings, and what do they tell us about the mechanism of action?
Strong safety and pharmacokinetic profile
The most important objective of any first-in-human study is to demonstrate safety and tolerability. We were very pleased to see that VNA-318 was safe and well tolerated. There were no serious adverse events, no discontinuations due to adverse events, and no concerning findings in vital signs or laboratory safety assessments. The pharmacokinetic data also showed that this is a once-daily oral therapy, which is obviously very convenient for patients.
Translating biology from mice to humans
The exciting part came from the biomarker analyses. One of our goals was to determine whether the biology we had observed in rodents could also be demonstrated in humans. We identified the same time-dependent reduction in a key plasma biomarker that we had previously observed in mice.
We also found statistically significant improvements in biomarkers related to energy metabolism and fatty acid oxidation.
Finally, quantitative EEG demonstrated a significant reduction in alpha band power, suggesting biological activity within the human brain. We do not want to overinterpret those findings because these were healthy volunteers, but they provide encouraging evidence that the drug is reaching the brain and producing measurable pharmacodynamic effects.
How important could the effects of VNA-318 be in slowing Alzheimer’s disease progression?
Balancing optimism with caution
We have to be careful not to overinterpret the findings. We are very encouraged by the preclinical data, where we have demonstrated activity across several models of neurodegenerative disease, including Alzheimer’s disease and Parkinson’s disease. In those studies, efficacy was at least comparable with currently marketed therapies. Now we need to demonstrate similar findings in humans.
A dual therapeutic effect
What differentiates VNA-318 is that it may provide two benefits. Based on our preclinical evidence, we believe there may be an early pro-cognitive effect that could potentially be measured within weeks, followed by longer-term disease modification.
The challenge now is to demonstrate both of those effects in patients with Alzheimer’s disease.
Looking ahead, what are the key questions future clinical trials will need to answer?
Demonstrating safety in patients
As physicians, our first principle is always: do no harm. Although the drug has shown an encouraging safety profile in healthy volunteers, we now need to demonstrate that same safety and tolerability in the more vulnerable Alzheimer’s disease population.
Showing meaningful clinical benefit
We have successfully translated the biology from rodents into healthy volunteers. The next step is to demonstrate similar biological effects in patients with Alzheimer’s disease, who have altered energy metabolism and different EEG patterns.
Ultimately, we need to show not only statistically significant improvements, but clinically meaningful improvements in cognition, memory and learning, benefits that patients notice and caregivers recognize.
One aspect that differentiates our programme is that cognitive improvements may be detectable within four to twelve weeks, rather than after twelve to eighteen months. If that proves to be the case, it would be a unique clinical benefit and may reduce both development timelines and investment risk.
Looking beyond your own research, what have been the most important therapeutic advances presented at AAIC 2026?
New targets beyond amyloid
I was particularly interested in some of the phase 2 data on tau-targeted therapies. I think tau represents one of the next major frontiers in Alzheimer’s disease treatment, so it is exciting to see new therapeutic making significant development progress that may result in clinical benefits for patients.
Moving towards precision medicine
The other area that has really caught my attention is the growing recognition that Alzheimer’s disease is not one single disease. We are beginning to identify different patient phenotypes that may respond differently to different treatments.
If we can better define those subgroups and tailor therapies accordingly, then precision medicine will become an increasingly important part of Alzheimer’s disease care.
I think both of those developments will help bring us closer to more effective treatments for patients.
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Cite: Klaus Dugi. VNA-318 in Alzheimer’s disease: Targeting mitochondrial dysfunction and cellular energy metabolism. touchNEUROLOGY. 16 July 2026.
Abstract: First-in-class Small Molecule VNA-318, In Development For Alzheimer’s, Inhibits Key Target Engagement Biomarker In First-in-human Trial
Editor: Katey Gabrysch, Editorial Director.
Disclosures: Klaus Dugi discloses that he is the CEO of Vandria.
The content was developed and edited by human editors. No fees or funding were associated with its publication. touchNEUROLOGY utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
This content has been developed independently by Touch Medical Media for touchNEUROLOGY in collaboration with Klaus Dugi. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
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