First subjects dosed in first-in-human Phase 1 clinical trial of small molecule central nervous system compound for age-related diseases.
Vandria, a Swiss-based leader in mitochondrial therapeutics, has initiated its first-in-human clinical trial for VNA-318, a novel small molecule designed to induce mitophagy. The trial represents a significant step forward in addressing neurodegenerative and potentially other age-related diseases through mitochondrial health.
Longevity.Technology: Mitophagy is the process of selectively removing damaged or dysfunctional mitochondria from cells to maintain cellular health and energy production. Mitochondrial dysfunction is a hallmark of aging and is implicated in various degenerative diseases, including Alzheimer’s and Parkinson’s. By promoting mitophagy, VNA-318 aims to rejuvenate cells and restore normal function, offering a therapeutic avenue to combat the effects of aging and disease.
The randomized, double-blind Phase 1 trial is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VNA-318 in healthy male participants, and Vandria says early data from preclinical studies have shown VNA-318’s dual mode of action – immediate cognitive benefits and long-term disease modification. The compound improves memory and learning while reducing neuroinflammation, toxic protein aggregation and mitochondrial dysfunction in models of Alzheimer’s and Parkinson’s disease; the trial readout is anticipated by the summer of 2025.
Dr Klaus Dugi, CEO of Vandria, expressed the company’s optimism about the trial: “We are very excited about this pivotal moment as we become a clinical stage company. We believe that VNA-318 has the potential to address unmet medical needs like mild cognitive impairment associated with Alzheimer’s disease, major depressive disorder, other diseases of the CNS, and potentially diseases beyond the CNS.”
Broader implications of mitophagy induction
VNA-318 is not only designed for CNS disorders but may have broader implications for mitochondrial therapeutics. Vandria is exploring the application of mitophagy-inducing compounds in non-CNS conditions, such as muscle, liver and lung diseases. The company’s strategy includes progressing these indications following Phase 2 trials for VNA-318.
Dr Dugi told Longevity.Technology that impaired mitophagy and mitochondrial dysfunction have been implicated in a large number of diseases and that Vandria is exploring links of its molecular targets to age-related diseases outside of the central nervous system and has already generated pre-clinical efficacy data in various diseases.
“We have generated efficacy data for VNA-318 in a number of pre-clinical models of CNS diseases, and are in the process of also generating animal efficacy data on models of muscle, liver, and lung diseases,” he said. “If positive data can be successfully generated, testing VNA-318 in a non-CNS indication in a clinical trial will be explored.” He added that genetic rare mitochondrial diseases are a high hurdle to overcome and are currently not part of Vandria’s focus.
Strength in preclinical studies
The compound’s potential is underpinned by robust preclinical data, with studies demonstrating a wide safety margin and efficacy in reducing neuroinflammation and mitochondrial dysfunction. VNA-318 is protected under a composition of matter patent issued by the US Patent Office.
Professor Li-Huei Tsai, a member of Vandria’s Scientific Advisory Board, was enthusiastic about the company’s progress. “Since my first interaction with Vandria, I have been impressed with the breadth and depth of the preclinical data with VNA-318 which include consistent, dose-dependent efficacy in several models of neurodegenerative disease,” he said. “I am very excited about Vandria taking this important step into clinical development of VNA-318 and thereby bringing it closer to patients who can potentially benefit from it.”
Diversity in clinical trials
While this Phase 1 trial focuses on healthy male subjects, future trials will aim to diversify the participant pool to ensure the compound’s efficacy and safety across broader demographics; such inclusivity is critical for determining VNA-318’s applicability in various stages of neurodegenerative diseases and in patient groups that may metabolize or respond differently to the therapy.
“Subject to positive data from this short Phase I trial, we are planning for two to three parallel Phase 2a studies in patient populations that exhibit cognitive impairment,” Dugi told us. “The underlying disease areas could be Alzheimer’s Disease, major depressive disorder, or others. In these studies, it is planned to include a wider demographic i.e. to include female and also elderly patients.”
Market potential and next steps
The global market for Alzheimer’s therapies, estimated at $6 billion in 2024, is expected to grow at a compound annual growth rate (CAGR) of 12% by 2035, driven by aging populations and improved diagnostics. Vandria’s innovative approach to mitochondrial health could position it to capture a significant share of this growing market.
With $32 million raised in Series A funding, Vandria plans to move into efficacy-focused Phase 1b/2a trials in early 2026. This, combined with the company’s aim to expand its pipeline to include compounds targeting non-CNS indications, positions it strongly as a leader in mitochondrial health innovation. The biotech community will be closely watching the trial outcomes to assess the broader impact of mitophagy-based therapeutics.
