BioWorld International Correspondent

PARIS - NicOx SA signed a co-development and licensing agreement with the Canadian pharmaceutical company Axcan Pharma covering NCX 1000, a nitrate derivative of ursodiol7, which NicOx is developing for the treatment of chronic hepatic infections, especially portal hypertension and hepatitis C.

The agreement grants Axcan, of Mont Saint Hilaire, Quebec, an exclusive license to market NCX 1000 in Canada and Poland, as well as an option for an exclusive license to the U.S. market. It would be able to exercise the option on the completion of Phase II proof-of-concept trials.

NicOx retains all commercialization rights for the rest of the world, including the Asia/Pacific region and Europe, with the exception of France, where it will share co-exclusivity rights with Axcan. The companies will share development costs up to the end of Phase II, while Axcan will conduct Phase III trials and handle regulatory filing procedures for NCX 1000 in its licensed areas.

Axcan will pay NicOx license fees, including for the U.S. license if it takes it up, as well as potential milestones at various development stages. The payments could total up to US$19 million, assuming Axcan exercises its option for U.S. rights and if the drug is developed for both indications (portal hypertension and hepatitis C).

In addition, NicOx would receive royalties of 12 percent on Axcan's net sales of the drug in its licensed markets during the entire term of the patent. A patent covering NCX 1000 is pending and is expected to be issued very shortly, the corporate communications manager of NicOx, Corinne Hoff, told BioWorld International. The agreement also gives NicOx the right to produce the active ingredient and supply it to Axcan during both the development and commercialization phases.

The therapeutic potential of NCX 1000 was demonstrated in several preclinical studies in animal models of hepatic inflammation, the results of which NicOx presented at the Digestive Disease Week conference in San Francisco last week. One showed that the drug was efficacious in reducing portal pressure without affecting arterial pressure, while another demonstrated its potential for protecting the liver from the toxicity induced by paracetamol. NCX 1000 was also found to inhibit apoptosis, both in vivo and in vitro, in models where ursodiol (ursodeoxycholic acid) was ineffective, and to inhibit the production of pro-inflammatory cytokines.

NicOx CEO Michele Garufi said Axcan is an "ideal partner" for co-developing NCX 1000 since it is a leader in the field of cholestatic hepatic infections and has considerable experience with ursodiol. The companies agreed to broaden their collaboration in the future to include other treatments for hepatic and gastrointestinal diseases.