National Editor

Wading into the turbulent waters of treatments for lysosomal storage disorders - in which other companies have clashed over patent holdings - Amicus Therapeutics Inc. raised $31 million in a Series B financing to advance its candidate for Fabry's disease to the clinic.

But New Brunswick, N.J.-based Amicus has reason to expect smoother sailing for its Fabry's disease therapy. Unlike other therapies for the disease, which aim to replace the alpha-galactosidase A enzyme that Fabry's patients lack, Amicus' AT1001 is a small-molecule, oral drug to enhance the patient's own enzyme activity.

The money gives New Brunswick, N.J.-based Amicus enough cash to operate until early 2006, "by which time we'll be well into pivotal trials, and we should be in the clinic with our second product by then," said Ronald Hardman, CEO.

"We will probably need more financing to get to final approval, but assuming we deliver for these new investors, we think we can go back to them and get whatever additional amount we need to get us to the market," he added.

With the proceeds, Amicus plans to get AT1001 into the clinic by the third quarter and further develop a research program for Gaucher's disease, another enzyme-shortage illness. The FDA has granted AT1001 orphan drug status.

Founded in April 2002 by the Mount Sinai School of Medicine in New York and CHL Medical Partners, of Stamford, Conn., Amicus - the name is Latin for "friend" - has 10 employees working on oral small molecules that restore normal function to malformed proteins.

Hardman noted that many diseases of genetic origin are caused by missense mutations and other rescuable changes that result in misfolding of a protein or enzyme, which become targeted for degradation before reaching their normal site of action. That, in turn, leads to the disease phenotype.

"It's like a string of beads, and it folds into three dimensions," Hardman explained. "The folding is an integral part of the maturation process, but nature has not made it perfect. A significant part of the time it goes wrong."

Pharmacological Chaperones, developed by Amicus, are designed to help the mutant protein fold correctly into three dimensions, getting back the normal processes and letting biology takes its healthy course.

Ironically, Hardman said, "the molecules that are able to do that turn out to be reversible enzyme inhibitors." Used at lower concentrations, they act not as inhibitors but as templates for folding.

The technology is based on research conducted by Jian-Qiang Fan, founder of Amicus and vice president of research. He was formerly assistant professor in the Sinai school's department of human genetics.

Fabry's disease was most recently in the news when Cambridge, Mass.-based Transkaryotic Therapies Inc. gave up its struggle to win FDA approval of Replagal, an enzyme replacement therapy for Fabry's disease that would have competed in the U.S. with Fabrazyme, from Genzyme Corp., also of Cambridge. (See BioWorld Today, Jan. 14, 2004.)

"It was definitely a clash of the titans," Hardman acknowledged, but Amicus will avoid such skirmishes with its small-molecule approach, which he said is protected by patents that cover not only the rescue of any mutant enzyme but also, interestingly, enhancement of a normal one - which could mean applications in diseases that involve enzymes at key points in metabolic pathways.

Age-related disease could be a promising area, too.

"What happens if you get older, and you lose the ability to make an enzyme? It's blue-skies thinking at the moment, but we have protected that intellectual property," Hardman said.

Meanwhile, the focus is on Fabry's disease first and then Gaucher's. Hardman said the company is on the fence about partnering.

"The answer is, it's a possibility but it's not mandated," he told BioWorld Today, noting that Amicus has brought its lead drug candidate to the door of the clinic "in three years with relatively modest financial resources," thanks to a "relatively low-risk" development - AT1001 is a molecule that was in the public domain already - with a somewhat faster path, since those who need the drug are identified.

"It's a classic pharmacogenomics development play," Hardman said.

Investors liked it, and Hardman said he was "extremely pleased about the quality of that group. Collectively, they have a very good reputation for moving breakthrough technologies into the marketplace, [which] gives us even more confidence than we had before."

Canaan Partners LP, of Rowayton, Conn., led the round with participation from other new investors Frazier Healthcare Ventures LP, of Seattle; New Enterprise Associates LP, of Menlo Park, Calif.; Prospect Venture Partners LP, of Palo Alto, Calif.; and Radius Venture Partners LP, of Boston. CHL Medical, the founding investor, also took part.

Joining the board are Stephen Bloch of Canaan, James Topper of Frazier, Mike Raab of New Enterprise and Alex Barkas of Prospect, sitting alongside existing board members Hardman and Gregory Weinhoff of CHL.