Antoxis Limited Targeting Free Radicals in Disease

Our Market Focus

The ubiquitous nature of free radical involvement in disease is such that many clinical conditions may be amenable to treatment using a targeted antioxidant approach. In a market assessment commissioned by Antoxis 36 indications were found to merit appraisal. In a broad-ranging, decision process that encompassed: Feedback from clinicians and industry; Unmet medical need; Suitable disease-state models; Competitor evaluation; Time to market and EU/US annual sales, it was decided that Antoxis would focus initially in neurodegeneration and in particular, stroke and Alzheimer's disease.

Stroke

Stroke is the third most common cause of death in the US and EU and the major cause of serious, long-term disability in adults. Major stroke is estimated to cost the UK economy £ 76,000 per patient.

Stroke is clinically defined as a vascular event in the brain which causes loss of normal neurological function lasting for more than twenty four hours. It occurs either when there is a sudden occlusion of a cerebral artery (usually by clot or embolus) leading to cerebral ischaemia and infarction, or cerebral haemorrhage arises causing brain damage.

At present clot-dissolving drugs are the only pharmacological approach approved by the FDA and EU for ischaemic stroke. However, this is considered a high-risk treatment and can only be used in accordance with strict guidelines, otherwise patient outcomes can worsen. In particular, these agents cannot be administered to the estimated 20% of patients presenting with haemorrhagic stroke. Thus a differential diagnosis of stroke type is required pre-treatment which limits the number of patients that can be treated within the effective post-stroke window-of-opportunity. Consequently, there is exceptional unmet medical need for new therapeutic approaches that carry lower risk to the patient and can be administered irrespective of stroke type.

Free radicals are generated during brain ischaemia and especially at the point of tissue re-oxygenation following clot dissolution and restoration of blood flow. This severe oxidative stress is implicated in triggering a cascade of events that contributes to brain damage and is known as reperfusion injury. Antoxis technologies are aimed at disrupting this cascade therebye reducing brain damage and enhancing functional recovery after stroke.

It is estimated that for a clinically-effective time window of six hours with valuation based on 50% of the US acute care costs, a new class of drug could compete for a share of a £ 242 M annual US/EU market. These are conservative figures and where effectiveness extends to 24 hours and there is extensive savings on long-term care, a figure of £ 1.2 B is feasible.

Alzheimer's Disease

Alzheimer’s disease is the most common form of dementia accounting for 57% of all dementia cases in the US. Despite the introduction of anticholinesterase inhibitors, management of this progressive illness is still inadequate. There is a considerable social and health resource burden with great reliance on relatives, nursing and supportive care for these patients.

There is significant unmet need for new treatment regimes that will improve memory and slow, or arrest, progression of the condition. The processes underlying the pathophysiology of Alzheimer’s disease are complex and poorly understood. However, free radical processes are thought to be a significant factor. The Clinical Trials arm of the US National Institutes of Health are currently undertaking a long-term study to determine if supplementation by vitamin E in combination with selenium (a cofactor of antioxidant enzymes) can afford protection.

Antoxis technologies are aimed at increasing the potency of natural plant antioxidants and imparting drug-like characteristics to enhance cell delivery and transport across the blood-brain barrier. Such approaches will help maximise clinical benefit by selectively targeting areas most vulnerable to oxidative stress.

The incidence of dementia increases with age such that 26% of women and 21% of men over 85 years of age have some presentation of the condition. In the USA and Europe, the combined prevalence of dementia attributable to Alzheimer’s disease is estimated at 11.9 M with an annual incidence of 590,000. As life expectancy increases, incidence and prevalence of the condition is anticipated to rise significantly.

Benchmarking costs against anticholinesterase inhibitors (a drug class that therapeutic antioxidants are likely to complement, rather than displace), it is estimated that a successful product aimed at mild-to-moderate disease would compete for a market valued at £ 2.1 B / annum.