Potentially providing an enhanced therapy for cystic fibrosis patients, Enzon Pharmaceuticals Inc. agreed with Pharmagene plc to collaborate on the development of long-acting PGN0052, a synthetic version of human secretin.

Enzon, of Bridgewater, N.J., will use its PEGylation technology to engineer a molecule with optimized pharmacokinetic properties and an extended duration of action.

"This is just us putting the seeds down for our future pipeline," said Kenneth Zuerblis, Enzon's vice president of finance and chief financial officer.

Enzon will receive an initial fee upon signing the agreement and a milestone payment once the molecule meets certain pre-determined criteria. If the molecule reaches the milestone, the companies might enter a worldwide joint development and commercialization agreement.

Royston, UK-based Pharmagene retains all rights to the original un-PEGylated product. But Enzon has rights, and a share in potential profits, of the PEGylated version, not just in cystic fibrosis, but also in other indications in which it shows potential, including chronic obstructive pulmonary disease and asthma.

"While we continue to develop internal compounds," Zuerblis said, "we also get access to additional very promising compounds that we could also develop for future sales."

Zuerblis estimated it would take the companies about 10 to 12 months to reach the point at which they would decide whether to move forward with a joint development agreement.

Under such an agreement, the companies would equally share the development costs and profits and Pharmagene would be eligible to receive future licensing and milestone payments that could total £26.5 million (US$47.5 million). If the companies choose not to enter the agreement, Pharmagene would be entitled to use the PEGylated molecule for development and commercialization purposes and Enzon would receive certain co-marketing rights and royalties on worldwide sales for all indications.

"They're Peg-Intron-like royalty rates," Zuerblis told BioWorld Today. Peg-Intron is the company's marketed hepatitis C product with Kenilworth, N.J.-based Schering-Plough Corp. Enzon receives between a 7 percent and 8 percent royalty on those sales.

PGN0052, a peptide hormone, has advanced through three Phase I studies and is being evaluated in a Phase IIa proof-of-concept trial. Data have demonstrated favorable safety and tolerability profiles, as well as the compound's ability to be effective in improving airway function following intravenous administration. Researchers believe that by extending the duration of action of PGN0052, they can improve the overall effectiveness and the compound.

"PEGylation benefits are less dosing, a longer circulation life, and a longer exposure to the molecule itself," Zuerblis said.

Phase I data presented in May showed PGN0052 was well tolerated and effective in producing measurable effects on airway function when delivered in the intravenous form. In vitro data show evidence of a relaxant effect on bronchial smooth muscle. The Phase IIa study is designed to assess the impact of the drug on mucociliary clearance, which is the ability of the lining of the lungs to clear the protective mucus secreted by the epithelial cells. Results of the Phase IIa are expected in the fourth quarter.

Cystic fibrosis affects about 30,000 people in the U.S. and about 70,000 worldwide. Their epithelial cells produce a defective form of a protein called cystic fibrosis transmembrane conductance regulator (CFTR), which forms a channel that controls the movement of salt and water into and out of cells. CF is characterized by a disruption in the essential salt and water balance needed to maintain a normal thin coating of fluid and mucus inside the lungs, pancreas and passageways in other organs. That causes the organs to function improperly, and death usually occurs due to pulmonary complications.

Secretin is a 27-amino-acid polypeptide hormone that is about half the size of insulin. It promotes the secretion of electrolytes and water from epithelial cells and stimulates the release of pancreatic juice by the pancreas and bile by the liver.

Aside from the new agreement, Enzon has several marketed and development-stage products. It received its first FDA approval in March 1990 for Adagen, a PEG-modified version of the bovine enzyme adenosine deaminase, which is used to treat ADA-deficient severe combined immunodeficiency disease. Approved in 1994, Oncaspar is a PEG-modified version of the enzyme L-asparaginase that is used as a chemotherapeutic agent for acute lymphoblastic leukemia. Peg-Intron was approved in 2001 as a hepatitis C treatment. Enzon also markets Abelcet, an antifungal acquired from Dublin, Ireland-based Elan Corp. plc, and the chemotherapeutic agent Depocyt through a licensing agreement with SkyePharma plc, of London.

Enzon has four products in the clinic, including its lead cancer drug, Marqibo, which is being developed with Inex Pharmaceuticals Corp., of Vancouver, British Columbia. The companies have submitted a new drug application for Marqibo as a single-agent treatment of relapsed aggressive non-Hodgkin's lymphoma in patients previously treated with at least two combination chemotherapy regimens. Enzon's other products, Pegamotecan and SS1P are in pivotal and Phase I trials, respectively, in various cancers, while ATG-Fresenius S is moving into a pivotal trial for solid-organ transplantation.

Enzon's stock (NASDAQ:ENZN) rose 38 cents Thursday to close at $15.45, while Pharmagene's stock (LSE:PGN) rose $4.50, to close at $62.50.

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