NicOx S.A. reported positive Phase I/IIa clinical results for NCX 4016, its nitric oxide donating derivative of aspirin in development for the treatment of cardiovascular diseases. In light of the data, the company also announced the initiation of a Phase II trial in symptomatic peripheral arterial disease.

The data presented reported demonstrated inhibition of vascular inflammation and platelet activation in a human Phase I/IIa clinical model and summarized excellent overall safety in seven separate Phase I clinical trials. The data were disclosed in four communications as part of 13 scientific presentations on NicOx's novel nitric oxide donating compounds at the "Nitric Oxide Based Drug Therapy Conference" organised by the William Harvey Research Institute in Porto, Portugal, on April 10-12, 2002.

NCX 4016 was tested in a well standardised human clinical model of vascular inflammation, platelet activation and coagulation induced by lipopolysaccharide (LPS) infusion. NCX 4016 appeared to differ from aspirin in the way it reduced platelet activation without affecting parameters related to bleeding risk. NCX4016 in contrast to aspirin exhibited a broad activity indicating inhibition of vascular and endothelial inflammation. NCX4016 was also active in inhibiting COX2 enzyme expression, cytokine inflammatory mediators and procoagulant factors while aspirin, in this model, was proinflammatory and procoagulant. No serious or severe adverse drug reactions were observed in the study, and the overall safety of NCX 4016 was excellent.

The unique effectiveness of NCX4016 in combining reduction of endothelium inflammation together with antithrombotic effects could provide a basis for therapeutic benefit in the treatment of cardiovascular diseases related to endothelium dysfunction and vascular inflammation, including atherosclerosis, vascular restenosis, and cardiovascular complications of diabetes. The results confirm that NCX4016 has a novel pharmacological activity different from aspirin through its nitric oxide donating properties. These clinical data support the previously published results of NCX 4016 in animal models showing that NCX 4016 was effective in treating endothelium dysfunction and vascular impairment.

In addition, at the scientific meeting in Porto, clinical results were summarized from seven Phase I clinical trials involving a total of with 173 healthy subjects where NCX 4016 showed an excellent overall safety profile, not substantially different from placebo. 128 human volunteers received doses of up to 1600 mg in single dose studies and up to 800 mg twice daily for seven days in repeated dose studies. Safety and tolerability were investigated in all studies by standard haematology and biochemistry examinations, blood pressure monitoring and by reporting of adverse events.

Michele Garufi, chairman and CEO of NicOx, commented: " We are very satisfied these data provide a clear to have confirmation in man of the unique pharmacological profile and safety of NCX 4016. It is well known that the deficiency of nitric oxide is a contributing factor in endothelium dysfunction- related diseases and collectively, these new clinical data confirm that NCX 4016 has significant therapeutic potential in the treatment of cardiovascular and metabolic diseases. Based on these promising clinical results, NicOx is aggressively pursuing its ambitious development programs for NCX 4016."