The Medical Challenge –
treating inflammation in vascular disease
The treatment and prevention of vascular disease, including diseases and conditions affecting the heart as well as blood vessels in the brain, legs and other organs, have improved significantly, but morbidity and mortality remain high. More than 500 million worldwide suffer from various types of vascular disease, which is the leading cause of death in the world (WHO 2017). Several of the most prescribed drugs are directed against vascular disease, with sales of $130bn in 2015 (GBI Research, 2016).
Inflammation is a recognized component of vascular disease but is not specifically addressed.
A treatment that effectively inhibits vascular inflammation could greatly improve survival and reduce morbidity.
The Solution –
ATH3G10 fully human therapeutic antibody
ATH3G10 is a fully human monoclonal antibody that binds to oxidized phospholipid, OxPL. The specific chemical target is called Phosphoryl choline (PC).
This drug target is exposed in blood vessels in vascular disease such as atherosclerosis or when injuries occur in the blood vessels, for example in a surgical procedure.
|In the ‘Cryptic Epitope’, phosphorylcholine, PC (shown in blue) is hidden inside viable cells or native LDL and is inactive and harmless.
In the ‘Exposed Epitope’, modified or damaged cells where membranes have been disrupted, or oxidized lipid particles, carry OxPL as PC (in red) on the outside. Exposed PC is the Danger Associated Molecular Pattern (DAMP) or ”eat-me”-signal for the immune system to clear out the damaged cells and oxidized lipid particles.
Endogenous or natural antibodies to PC act to clear out damaged cells from the body, through the inflammatory challenge caused by exposed PC. Our therapeutic antibody ATH3G10 is designed to mimic the anti-inflammatory role of endogenous antibodies against PC and further support the immune response to vascular inflammation challenges, thereby reducing the risk for complications in vascular disease.
Promising Clinical Trials and Excellent Patent Protection
Three Phase 1 studies in healthy volunteers and patients have delivered positive data. Key patents have been secured for ATH3G10. New patent applications have been filed for further therapeutic innovations.
Blocking PC reduces inflammation
Damaged cells with disrupted membranes exposes PC, thereby causing inflammation of the vessels. This results in impaired cardiovascular function, i.e. increased risk of complications in vascular disease. If PC exposure can be blocked then inflammation in vessels can be reduced and the vascular function improved.
Endogenous anti-PC is anti-inflammatory
There are natural antibodies in healthy individuals that bind to PC, thereby clearing out damaged cells and suppressing inflammation. Clinical research has shown that low levels of natural antibodies to PCs are linked to a faster development of inflammation-related vascular disease, as well as increased complications of vascular disease.
ATH3G10 acts to support the immune
response to vascular inflammation
ATH3G10 is designed to mimic the anti-inflammatory role of endogenous antibodies against PC. ATH3G10 binds to, and thus blocks, PC. This reduces the inflammation of the blood vessels and lessens the consequences of vascular disease. The therapeutic antibody ATH3G10 supports the immune response to vascular inflammation challenges, thus reducing the risk of developing complications of vascular damage driven by exposed PC. The therapeutic approach has proven efficacy in preclinical studies, as ATH3G10 has been effective in several models of vascular disease and inflammation.
Evidence that anti-inflammatory drugs
could reduce risk of second heart attack and stroke
A recent study has shown that treatment with an anti-inflammatory drug could lower the risk of secondary cardiovascular events after heart attack and have effect in addition to conventional treatment. The study, CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study), involved 10,000 patients who had had a heart attack and a positive blood test for an inflammatory marker, hsCRP. Treatment with the human monoclonal antibody canakinumab over four years reduced their risk of an additional cardiovascular event by 15%.