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Athenagen Inc. plans to use $50 million raised in its Series B financing to push the Phase I/II-ready Alzheimer's disease drugs gained in the merger with Zapaq Inc., as well as the firm's own compounds for age-related macular degeneration and enhancement of cognition.

The financing will take South San Francisco-based Athenagen into the middle of 2008, said Scott Harkonen, president and CEO.

By then, the firm should have Phase II efficacy data for its AMD eye drop therapy, known as ATG003, and the same for GTS-21 against multiple cognitive disorders, as well as Phase I/II proof-of-concept results from the beta-secretase inhibitor program acquired from Oklahoma City-based Zapaq last month.

The enzymes beta- and gamma-secretase have been subjects of much interest for Alzheimer's drug developers. In the brains of people with the disease, characterized by the buildup of amyloid plaques, a protein known as amyloid precursor is cleaved by the b-secretase and then by g-secretase, to form amyloid beta peptide.

"I think a lot of interest has shifted toward beta, over the last two or three years," Harkonen told BioWorld Today, noting that evidence from knockout mice suggests inhibiting b-secretase is safer, and published studies show a rebound effect, whereby patients had a buildup of precursor protein after g-secretase inhibitor therapy stops.

"But they're both viable targets," Harkonen said.

Torrey Pines Therapeutics Inc., of San Diego (recently merged with New York-based Axonyx Inc.) has early stage NGX555, a g-secretase modulator. In May, Eisai Medical Research Inc., a subsidiary of Eisai Co. Ltd., of Tokyo, kicked off a Phase I trial with E2012, a compound in the same class.

This spring, Ortho-McNeil Pharmaceutical Inc., a unit of Johnson & Johnson, exercised its option to license and develop Boston-based Cellzome Inc.'s g-secretase modulator program, under the terms of the collaboration signed two months earlier.

In the b-secretase area, Astex Therapeutics Ltd., of Cambridge, Mass., is working with London-based AstraZeneca plc, and Elan Corp. plc, of Dublin, Ireland, has Alzheimer's programs investigating both enzymes.

Athenagen's ATG003 (mecamylamine) could offer a more convenient alternative to Lucentis (ranibizumab), the AMD therapy from South San Francisco-based Genentech Inc., approved this summer. (See BioWorld Today, July 5, 2006.)

"It's also a separate but parallel mode of action, in terms of suppressing new blood vessel growth," Harkonen said. Blocking VEGF (as Lucentis does) may not be enough, and AT5003 works through a separate anti-angiogenic pathway.

"One very attractive idea would be to use the eye drops as a maintenance therapy after several injections with Lucentis," he said.

Mecamylamine inhibits endothelial nicotinic acetylcholine receptors and is marketed in systemic form by Winston-Salem N.C.-based Targacept Inc. as Inversine. Labeled for the management of moderately severe to severe essential hypertension, Inversine gets prescribed instead mostly for neuropsychiatric disorders, and has been used to help patients quit smoking.

Athenagen's oral small molecule GTS-21, a selective alpha-7 nicotinic acetylcholine agonist to boost cognitive ability, will back up the beta-secretase inhibitors for Alzheimer's. The company added GTS-21 to its pipeline in April, by acquiring the assets of Osprey Pharmaceutical Co., of Ponte Vedra Beach, Fla., for undisclosed financial terms.

Harkonen cited "growing interest in the alpha-7 pathway" and said GTS-21 could be complementary to a b-secretase inhibitor for Alzheimer's, but the drug has plenty of other potential.

"We're going to have clinical results from a second Phase II trial in schizophrenia by the end of this year, and we're setting up a Phase II trial in Alzheimer's," with results from the latter due in the second quarter of next year, he said. A pilot study is planned in attention deficit hyperactivity disorder, too.

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