NicOx To Move NCX 4016 Forward In Phase 2 For Diabetes

Main Category: Diabetes
Also Included In: Clinical Trials / Drug Trials
Article Date: 27 Jul 2006 - 0:00 PDT

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NicOx S.A. (Eurolist: NICOX) today announced its decision to move NCX 4016 forward in clinical development as a novel insulin sensitizing agent for the treatment of type 2 diabetes. The Company expects to initiate two phase 2 studies within the next 6 months. These trials will have the goal of confirming the mechanism of action of NCX 4016 as an insulin sensitizer and demonstrating a clinical benefit in the treatment of type 2 diabetes. The decision to initiate this clinical program follows the encouraging results obtained in type 2 diabetes patients in three previously announced trials for NCX 4016 in the cardiometabolic setting. A good safety and tolerability profile has also been demonstrated in long-term treatment. NicOx has no current plans to develop NCX 4016 further in Peripheral Arterial Obstructive Disease (PAOD).

"In light of the type 2 diabetes pandemic that is appearing in the developed world, there is a clear need for a new class of oral treatments which could counteract insulin resistance through an alternative mechanism," said Maarten Beekman, Vice President of Clinical Development at NicOx.

"There is a solid scientific rationale supporting the development of NCX 4016 as an insulin sensitizing agent, based on the known effects of nitric oxide and salicylate and the recent finding that NCX 4016 releases higher and more sustained levels of salicylate than previously thought. Clinical results also suggest these mechanisms may benefit the vascular complications of type 2 diabetes and we hope to develop NCX 4016 as a new oral treatment for this very serious and prevalent disease."

NicOx has decided to conduct two phase 2 studies for NCX 4016, which are expected to be initiated within the next 6 months. The first study is projected to be a single-center, cross-over trial, designed to confirm the mechanism of action of NCX 4016 as an insulin sensitizing agent using a hyperinsulinemic euglycemic clamp, the same technique used in the 13 patient, phase 2a trial presented at the 2005 American Heart Association (AHA) meeting (see press release of November 16, 2005). The results presented at AHA showed a statistically significant improvement in insulin sensitivity following treatment with NCX 4016, as compared to baseline (p<0.05). The second trial is projected to be a placebo and active controlled, double blind, parallel study, aiming to demonstrate a clinical benefit for NCX 4016 through the measurement of HbA1c (glycosylated hemoglobin, the gold standard test for glycemic control in diabetics) and blood glucose in the fasting state and after meals.

The Company's decision to move forward in type 2 diabetes is supported by the recent data showing that NCX 4016 is metabolized to release higher and more sustained levels of salicylate than previously thought, in addition to a nitric oxide-donating moiety. There is considerable scientific evidence suggesting that salicylate and nitric oxide could have synergistic effects in improving insulin sensitivity in diabetes. In particular, both of these compounds exert a direct effect on IKK beta, a signaling molecule which regulates intracellular glucose uptake and therefore insulin sensitivity. Furthermore, nitric oxide has been shown to be involved in regulating blood flow and insulin secretion and inhibiting pro-inflammatory signaling molecules, all of which are believed to become dysfunctional in type 2 diabetes.

It has been known for a number of years that high dose aspirin treatment, through the release of salicylate, can have a beneficial effect in diabetes management by lowering plasma glucose levels. This has been shown to be due to improved insulin sensitivity and decreased insulin clearance. High dose aspirin or salicylate cannot be used chronically due to safety and tolerability issues. However, the salicylate levels generated by NCX 4016 have not caused tolerability issues in clinical studies to date and it appears that a synergistic effect with nitric oxide may reduce the salicylate concentration needed to have a clinically meaningful effect. This hypothesis is supported by the positive results obtained for NCX 4016 in type 2 diabetes patients.

Michele Garufi, Chairman and CEO of NicOx, commented: "We are very aware of the importance of choosing the right clinical development program to demonstrate the benefits of our technology. This not only involves identifying diseases where there is a strong scientific rationale for a positive nitric oxide effect but also where a meaningful clinical benefit can be reasonably demonstrated. The evidence we have identified suggests NCX 4016 represents a strong, innovative candidate for the oral treatment of type 2 diabetes and we believe a clinical program demonstrating an insulin sensitizing effect offers a clear route to market."

NicOx S.A. (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven biopharmaceutical company dedicated to the development of nitric oxide-donating drugs to meet unmet medical needs.

NicOx is targeting the therapeutic areas of pain and inflammation and cardio-metabolic disease. Resources are focused on two lead compounds, naproxcinod (formerly HCT 3012), in phase 3 development for the treatment of osteoarthritis, and NCX 4016, in phase 2 for cardiometabolic disorders. NicOx has strategic partnerships with some of the world's leading pharmaceutical companies, including Pfizer Inc. and Merck and Co., Inc.

NicOx S.A. is headquartered in Sophia-Antipolis, France, and is a public company listed on the Eurolist of Euronext Paris (segment: Next Economy).

The elements included in this communication may contain forward-looking statements subject to certain risks and uncertainties. Actual results of the company may differ materially from those indicated in the forward-looking statements because of different risks factors described in the company's document de reference.

NicOx S.A.
http://www.nicox.com