In its sixth collaboration to date, NicOx SA entered a potential 54.9 million (US$66.6 million) deal with Topigen Pharmaceuticals Inc. for rights to NicOx's Phase IIa compound, NCX 1020, in chronic obstructive pulmonary disease (COPD) and other respiratory disorders.

NicOx initially granted Topigen North American rights to the drug, in exchange for a 2 million up-front payment, with an option to gain rights for the rest of the world. If Montreal-based Topigen exercises the option, then total development and regulatory milestones could bring NicOx an additional 52.9 million, plus royalties.

Michele Garufi, chairman and CEO of NicOx, said that "Topigen will be funding 100 percent of the development, including the supply of the drug's active ingredient."

The agreement also allows Topigen sublicensing rights, in which case NicOx would be entitled to receive a share of those license fees and milestone payments, as well as the royalties.

NCX 1020 is a nitric oxide-donating derivative of budesonide, an inhaled corticosteroid for respiratory diseases. The product has just started clinical development, and recently completed a study in 12 asthma patients that compared the product to budesonide. Results of that trial showed that NCX 1020 could more effectively protect against bronchoconstriction.

Though preliminary, those results also indicated "a signal that it might have a longer retention time in the airway, giving it a longer duration of action," Garufi told BioWorld Today. "Topigen also conducted animal studies in its own laboratory, and our product showed the capability to inhibit neutrophil infiltration in the airways."

Garufi said Topigen indicated that it would begin testing NCX 1020 in COPD, the fourth-leading cause of death in the U.S., which is characterized by a progressive decline in lung function. Existing treatments for the disease include inhaled corticosteroids, beta 2-adrenergic agonists and muscarinic antagonists, but those products do not treat the damage that typically occurs before symptoms begin appearing.

NicOx's drug, developed in house, aims at targeting the underlying inflammatory processes. The nitric oxide donation has been shown to cause bronchial relaxation and could improve efficacy of steroids used to treat disorders such as COPD and asthma.

In addition to NCX 1020, the company has several other products in development, including HCT 3012, an anti-inflammatory in a class of CINOD (COX-inhibiting nitric oxide-donating) drugs.

"We just completed Phase II, and are planning to enter Phase III within the first quarter of 2006," Garufi said.

Unlike the non-steroidal anti-inflammatory drug (NSAID) class - such as COX-2 inhibitors like Whitehouse Station, N.J.-based Merck & Co. Inc.'s Vioxx - NicOx's HCT 3012 has shown a safe profile in hypertensive patients, Garufi said.

NicOx intends to seek a partner for HCT 3012, though the company might keep marketing rights for itself in some areas. Funds from its collaboration with Topigen, as well as other collaborations, will be used for ongoing development of the product and NicOx's second lead product, NCX 4016, in peripheral arterial obstructive disease.

That drug met its primary efficacy endpoint in a Phase IIa study, and now is being evaluated in a large Phase II trial, set to be completed by the end of the year.

"Those two products are the focus of our internal human and financial resources," Garufi said. "We decided to partner out products where we could not focus our efforts."

In 2002, the company signed a co-development and license agreement with Axcan Pharma Inc., of Mont Saint-Hilaire, Quebec, for NCX 1000 in liver diseases such as portal hypertension. In that deal, NicOx is entitled to milestones up to $18.5 million, plus royalties. Both companies share the costs of development through Phase II studies. The compound is expected to begin Phase IIa proof-of-concept study within the first quarter of next year.

NicOx has ongoing research agreements with Merck, for an undisclosed target, and with New York-based Pfizer Inc. for an ophthalmology compound. Both of those collaborations are progressing "successfully, from a scientific point of view," Garufi said "and we hope that both companies will prolong those collaborations in the future."

The company has a collaboration with Barcelona, Spain-based Grupo Ferrer Internacional SA for the research, development and marketing of nitric oxide-donating corticosteroids in dermatology, and another collaboration with Stockholm, Sweden-based Biolipox AB to develop compounds in the respiratory field.

Based in Sophia Antipolis, France, NicOx currently is listed on the Eurolist markets, though Garufi said the company hopes to post on the Nasdaq market after its lead program begins Phase III, in hopes of broadening its exposure to investors and industry experts.

Privately held Topigen, which is developing classes of drugs specifically for respiratory diseases using its DNA/RNA chemistry platform, has several drugs in preclinical and early clinical development to treat asthma, allergic rhinitis and other topical diseases.