In September 2006, NicOx selected NCX 6560 as a new internal development candidate. NCX 6560 is a nitric oxide-donating derivative of a commonly used statin drug, which has the potential for broadened and increased benefit in cardiovascular disease. Statins represent the most effective and best tolerated drugs for lowering abnormally raised cholesterol and have consequently become the world’s best selling class of pharmaceuticals, with combined global sales of $20.1 billion in 2005.

NCX 6560 has the potential to target atherosclerosis and endothelial dysfunction through a multi-pathway approach. The capacity of the nitric oxide-donating moiety to counteract vascular inflammation and endothelial dysfunction should act in concert with the cholesterol lowering activity of the statin portion, to favorably influence the composition, structure and stability of atherosclerotic plaques.

Atherosclerotic plaques are believed to be the root cause underlying the majority of cardiovascular diseases and their development is a complicated, multi-step process, which is believed to involve both raised cholesterol levels and deficient nitric oxide signaling. The process starts with the formation of fat-containing lesions on blood vessel walls, due to abnormally high plasma cholesterol levels, which has a number of detrimental effects. These include infiltration of immune cells, inflammation and abnormal proliferation of smooth muscle cells, which are all processes which have been linked to abnormally low nitric oxide release from the endothelium. Furthermore, nitric oxide is involved in regulating vascular function and platelet activation and malfunction of these two systems can lead to disruption of the atherosclerotic plaque, clotting and an acute cardiovascular event.

Preclinical results support the rationale for using NicOx’ nitric oxide-donating technology to develop the next generation statins. The nitric oxide released from NCX 6560 appears to markedly increase the non-cholesterol lowering activities of statins. For example, NCX 6560 has demonstrated superiority to a widely used statin in a number of preclinical models, including those related to anti-platelet and anti-thrombotic activity, anti-inflammatory activity and endothelial function. Furthermore, in different models, NCX 6560 has demonstrated either a similar or superior serum cholesterol lowering effect, compared to an equivalent dose of the reference statin.