Staff Writer

Gilead Sciences Inc. added another cystic fibrosis drug to its pipeline by licensing the preclinical epithelial sodium channel (ENaC) inhibitor P-680 from Parion Sciences Inc.

Foster City, Calif.-based Gilead will pay Durham, N.C.-based Parion up to $156 million for the drug, including a $5 million license fee, a $5 million equity purchase, research funding and potential milestone payments. Parion would also receive double-digit royalties on future sales.

In exchange, Gilead gets exclusive worldwide commercialization rights to P-680 in the treatment of pulmonary diseases including CF, chronic obstructive pulmonary disease (COPD), and non-CF bronchiectasis. Parion will complete preclinical and some Phase I development of the drug, with Gilead taking over further development. The two companies also will collaborate on a research program to identify other ENaC inhibitors.

The purpose of ENaC inhibitors, including P-680, is to block sodium channels that regulate hydration in the mucus membranes. This blockage prevents the absorption of liquid and keeps the mucosal surfaces hydrated. In the case of CF, the approach is intended to inhibit the development of thick mucus that results in infections and lung damage.

Parion's ENaC program was spun out of the University of North Carolina at Chapel Hill by Richard Boucher, UNC chief of pulmonary medicine and founder of Inspire Pharmaceuticals Inc. Boucher teamed up with former Trimeris Inc. CEO Ross Johnson to found Parion, which was originally named CyFi Pharmaceuticals.

Since its founding in 2000, Parion has remained under the radar while quietly advancing its lead ENaC inhibitor, P-552, through Phase II programs in CF and xerostomia (dry mouth) associated with Sjogren's syndrome. Trials in more than 150 patients have shown P-552 to be well-tolerated and to cause mucus clearance in CF patients, according to Parion Director of Operations Paul Boucher.

P-552 is now slated for a Phase IIb trial in CF and additional trials in Sjogren's syndrome, but Boucher said the timelines and details are still being planned.

Since ENaC is found on the mucosal surfaces of the lung, mouth, nose, eye and gastrointestinal tract, Parion's ENaC inhibitors may have broad utility in COPD, bronchiectasis, dry eye and many other conditions, including biodefense applications against inhaled pathogens like anthrax and plague. Boucher said the company has a "vast library" of ENaC inhibitors, some of which may be possible partnering candidates. He added that the company also has "very extensive" intellectual property in the space.

Thus far, Parion has advanced its pipeline without any venture funding, instead relying on grants from the NIH and Cystic Fibrosis Foundation Therapeutics Inc. (CFF). Earlier this week, CFF signed a $20 million venture philanthropy deal with FoldRx Pharmaceuticals Inc., bringing the foundation's total in committed biotech funding for CF programs to about $250 million since 1998. (See BioWorld Today, Aug. 14, 2007.)

For Gilead, the P-680 license represents another step in the effort to increase its footprint in respiratory therapeutics. To date, most of Gilead's success has come from antiviral products like Atripla (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) and Truvada (emtricitabine and tenofovir disoproxil fumarate), but Gilead spokesperson Nathan Kaiser said the company is "very committed" to building out its respiratory franchise.

As of now, that franchise consists solely of Tamiflu (oseltamivir phosphate), on which Gilead gets royalties from F. Hoffmann-La Roche Ltd.. Yet a new drug application filing is planned before the end of the year for CF drug aztreonam lysine for inhalation, which met its endpoints in two Phase III trials. (See BioWorld Today, May 31, 2007.)

Kaiser noted that P-680 and inhaled aztreonam lysine "address different aspects of the disease." P-680 improves mucosal clearance, while inhaled aztreonam lysine addresses Pseudomonas aeruginosa infection, a significant cause of morbidity and mortality among CF patients. The two drugs "theoretically could be used in combination," Kaiser said.

Another target indication for Gilead, according to Kaiser, is cardiovascular disease. The company markets hypertension drug Flolan (epoprostenol sodium) and gained approval in June for pulmonary arterial hypertension drug Letairis (ambrisentan). Another hypertension drug, darusentan, is in Phase III. (See BioWorld Today, June 19, 2007.)

Gilead acquired inhaled aztreonam lysine through its buyout of Corus Pharma Inc. and all three hypertension drugs through its buyout of Myogen Inc. With about $2 billion in cash, equivalents and marketable securities as of the end of the second quarter, the company certainly has the money to buy more companies if it so chooses, but Kaiser was mum as to any acquisition plans. (See BioWorld Today, July 31, 2006 and Oct. 3, 2006.)

Shares of Gilead (NASDAQ:GILD) dipped 21 cents to close at $37.60 on Thursday.