West Coast Editor

Despite serious, well-entrenched competition from Genzyme Corp. for its Phase II Fabry's disease drug candidate, Amicus Therapeutics Inc. pulled down $60 million in a Series D financing to boost Amigal, as well as earlier-stage products for other lysosomal storage disorders (LSDs), including Gaucher's and Pompe.

Combined with cash already in the bank, the financing gives Amicus about $100 million, enough to operate "at least into 2009," said John Crowley, president and CEO. By then, Amicus likely will have filed new drug applications for Amigal (migalastat hydrochloride) as well as AT2101 for Gaucher's disease, now in Phase I trials.

Behind those, Amicus has AT2220 targeting Pompe, due for an investigational NDA filing in the second half of this year.

The firm withdrew about six weeks ago its plan for an initial public offering, but Amicus might have gained more cash through the Series D than the IPO could have garnered, and Crowley credited "well understood diseases, validated targets, and multiple proof of concepts" for the interest in the Amicus approach.

"It all came together inside of a month," he said.

Late-August publication of a book about Crowley probably didn't hurt the Series D, either. The Cure: How a Father Raised $100 Million - And Bucked the Medical Establishment, by The Wall Street Journal reporter Geeta Anand, describes how Crowley quit his job as a financial consultant and went into biotechnology in a quest to save his two children, afflicted with Pompe disease.

Crowley put his life savings into co-founding Novazyme Pharmaceuticals Inc., of Oklahoma City, which Cambridge, Mass.-based Genzyme bought during the fall of 2001 in a stock deal originally valued at about $137.5 million. (See BioWorld Today, Aug. 8, 2001.)

He worked at Genzyme for about a year and a half, then went on to found the obesity firm Orexigen Therapeutics Inc., of San Diego. Crowley left the CEO job there in 2005 to assume his current post at Amicus, having served as a director since 2004.

Rather than simply replace missing lysosomal enzymes, Amicus makes oral small molecules to restore the function of a patient's own, using a pharmacological chaperone that binds to the target protein, for a correct fold that boosts activity.

"It's a broad platform, applicable to a whole range of human genetic proteins," Crowley said. "Misfolded proteins are the core pathology in Lou Gehrig's disease and even Type II diabetes." The chaperone technology came from Mt. Sinai Medical Center in New York. Scientists there focused first on LSDs.

Amigal, if approved, would go up against Genzyme's drug for Fabry's, Fabrazyme (agalsidase beta), which sold $89 million in the second quarter.

"Based on what we know from early clinical data, we think we can do at least as much as an enzyme-replacement therapy," Crowley said - and might do so in a pill, given once per day or once every other day. Amicus' method won't work for everyone, and efficacy depends on the LSD in question, he conceded.

"It's not for all patients; we think it's for most," Crowley said. "We're stabilizing the patient's own protein at the source of the problem, where they're synthesized in the cell." In certain patients, combination therapies might get the best results.

Genzyme also has a Type I Gaucher's therapy, Cerezyme (imiglucerase), chalking up $254 million in the quarter. In April, Genzyme gained FDA approval for Myozyme (alglucosidase alfa), an enzyme-replacement therapy for Pompe disease, which sold $6.5 million in the second quarter.

The enzyme-replacement therapy Aldurazyme (laronidase), for patients with MPS I, is marketed by Genzyme through a joint venture with Novato, Calif.-based BioMarin Pharmaceutical Inc., and second-quarter sales for Aldurazyme jumped 23 percent over the same period last year, totaling $23.5 million.

Also exploring the LSD space is Zystor Therapeutics Inc., of Milwaukee, Wis., which deploys what the firm calls Glycosylation Independent Lysosomal Targeting technology licensed from St. Louis-based Symbiontics Inc. Zystor's approach enhances the binding ability of replacement enzymes by attaching to the enzyme a peptide tag that targets receptors on cell surfaces.

The method is carefully targeted, Zystor's president and CEO Loren Peterson told BioWorld Today, noting that Crowley served briefly on his firm's board.

"A lot of what Genzyme does with their Pompe drug is just put a lot of it into the body and hope some of it gets taken up by cells," Peterson said.

The appeal of LSDs, despite Genzyme's established products and sales force, has to do with relatively low cost of developing a drug for a well-identified niche patient population, Peterson said.

"I could get [a drug candidate] into the clinic on another $15 million," he said. "You're not talking about huge sums of money, and pivotal trials are done with as few as 43 patients."

Zystor would not need a partner to push the Pompe drug along, said Peterson, fresh from a board meeting Wednesday, but the company is "looking at the possibility" and discussing alternatives. The Midwest headquarters has not kept Zystor from attracting funds from a syndicate of venture capitalists, he noted.

"We're on to something here," Peterson said.

Amicus' latest round was led by New Enterprise Associates, of Menlo Park, Calif., joined by current investors Canaan Partners, of Rowayton, Conn.; CHL Medical Partners, of Stamford, Conn.; Frazier Healthcare Ventures, of Seattle; Palo Alto Investors, of Palo Alto, Calif.; Prospect Venture Partners, also of Palo Alto; Quaker BioVentures, of Philadelphia; and Radius Ventures, of Boston. Affiliated investment funds of Och-Ziff Capital Management Group in New York took part as a new investor.