By Debbie Strickland

AlphaOne Pharmaceuticals Inc. incorporated October 1997 and moved into office and lab space just last month. Yet the five-employee firm plans to launch its first product, a recombinant version of the proteinase inhibitor alpha-1 antitrypsin (AAT), into clinical trials in 1998, and is aiming to reach the Phase II stage in three indications within two years.

An ambitious timetable? Indeed, but not unrealistic, according to chief operating officer Philip Barr, a founder of LXR Biotechnology, of Richmond, Calif., and the former director of molecular biology for Chiron Corp., of Emeryville, Calif.

The concept of using AAT in pulmonary and dermatological applications has been around since the 1980s, and animal tests and human trials have been conducted. Bayer AG, of Leverkusen, Germany, won FDA approval of a plasma-derived, infusion-delivered version called Prolastin in 1989.

The drug has shown efficacy in emphysema, cystic fibrosis, some dermatological diseases and possibly asthma.

But despite AAT's utility, particularly in emphysema caused by a genetic deficiency of alpha-1 antitrypsin, fewer than 5,000 patients in the U.S. are receiving Prolastin therapy, according to Barr, who estimated that "probably 100,000 should be treated."

Because it is a blood product, Prolastin is both expensive — in many cases, about $65,000 per year — and in short supply, according to Sandra Brandley, executive director of the Alpha1 National Association, in Minneapolis.

"We are indeed experiencing a temporary slowdown at our manufacturing facility in Clayton [N.C.]," said Don Hyman, spokesman for Bayer. "Some of our production will be in short supply or out of stock in some markets during the first quarter."

Bayer is not working on a recombinant version, Hyman said.

"A recombinant product that [could] be proven efficacious, less costly and easier to take would be a boon to the [AAT-deficient] community," said Brandley.

AlphaOne Using Yeast To Produce AAT

AlphaOne's version will be derived from recombinant yeast cells, yielding the possibility of "unlimited quantities" that "will lead to the adequate supply of a pharmaceutical product," Barr said.

"It's a big-dollar product, but it's only making about $60 million annually right now," he said.

In addition to making larger quantities available by a new method, AlphaOne plans to improve on the delivery mechanism by using an aerosol formulation, with technology to be acquired through a partnership with a company specializing in such systems.

The drug, if successfully commercialized, will have been a long time coming. The genetic deficiency was first discovered in the early 1960s.

"I can't think of any other situation where a recombinant version of a protein drug has fallen through the cracks," said Barr, who has ties to the project dating back to his days at Chiron in the 1980s. "We're going to have to do it ourselves or it's not going to get done."

"[AAT] deficiency is a rare disease," said Brandley, "with 100,000 or fewer people affected. Because of that it is very difficult to attract many pharmaceutical companies to look at this population as being a valuable segment."

AlphaOne licensed patent rights to the AAT protein from Protease Sciences Inc., a privately held company based in Tempe, Ariz. (See BioWorld Today, Aug. 1, 1996, p. 1.)

To pay for AAT's development, AlphaOne is in the process of conducting a seed round of financing to raise $2 million, and may hold an initial public offering as early as 1999. *

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