Technology

Flavonoids are a large group of naturally-occurring, polyphenolic plant compounds found in many fruits and vegetables as well as teas, wines and coffees. Epidemiological studies have suggested that consumption of  a diet rich in flavonoids is protective against a number of chronic illnesses including cardiovascular conditions, Type 2 diabetes, neurodegenerative disorders, such as Parkinson’s and Alzheimer's diseases, and certain cancers. 

Flavonoids display a wide range of biological activities including antioxidant effects, modulation of enzyme pathways and metal binding properties. Consequently, they have been a source of intense research by many groups world-wide over the last few decades. However, the use of concentrated plant extracts, or individual polyphenolic constituents, to treat disease in a clinical context has, for the most part, proved unsuccessful. 

Whilst dietary consumption throughout life may provide sufficient protection from normal levels of oxidative stress and other disease causing factors, flavonoids do not have ideal pharmacological properties for use in overt clinical conditions where, for example, high levels of oxidative stress may overwhelm the body’s natural defence mechanisms.

Antoxis is addressing this problem through its flavonoid platform technology which is founded on a detailed knowledge of the relationship between chemical structure and the biological activity of major flavonoid families. This has resulted in the rational design and synthesis of entirely new flavonoid-like molecules which demonstrate a step change in activity compared with the natural compounds. 

The company’s novel technology is protected by two comprehensive patents in key territories, including the US, with further filings in progress. The patents cover hundreds of thousands of synthetic variants with alterations to the core flavonoid scaffold to improve physicochemical and drug-like attributes.

Antoxis’ platform technology addresses eight major factors in relation to improving the pharmaceutical properties of natural flavonoids:

Rapid cell uptake; Increased stability; Optimised CLogP; Control of redox balance; Mitochondrial targeting; Improved CNS permeability; Pro-drug options; Increased potency

Extensive studies in a variety of cell-based models, including primary cortical neurons and mouse embryonic stem cells, have demonstrated the effectiveness of Antoxis' compounds, such as AO1530, in providing strong levels of protection against oxidative stress thereby helping to retain cell viability and metabolic function. A number of proprietray molecules in Antoxis' portfolio have also shown potent anti-cancer activity against a broad range of tumour cell lines.

Fluorescence studies, using confocal microscopy, indicate that these novel agents can rapidly cross the cell membrane with the ability to access the mitochondrial compartment. The mitochondria are organelles contained within the cell that have a key role in producing the cell's energy requirements along with other important functions such as cell signalling and differentiation. Mitochondrial dysfunction is observed in a number of human diseases. Consequently, developing compounds that can target and protect the mitchondria has been highlighted in the scientific literature as a potential strategy in the treatment of a variety of clinical conditions.

Antoxis is currently focused on undertaking a range of pre-clinical studies to determine the most appropriate therapeutic areas, involving diseases of the mitochondria, in which to advance candidate molecules from its flavonoid technology platform into clinical trials.