Staff Writer

In a deal that could top $440 million, Amicus Therapeutics Inc. teamed up with Shire Human Genetic Therapies Inc. on the ex-U.S. development and commercialization of Amicus's three lead pharmacological chaperone compounds for lysosomal storage disorders (LSDs): Amigal, Plicera and AT2220.

Although the deal came ahead of Phase II data expected by the end of the year for Amigal and Plicera, Amicus President and CEO John Crowley said during a conference call that Shire "was privy to all the data" that Amicus itself has seen in those open-label trials.

Lazard Capital Markets LLC analyst Matthew Osborne said in a report that the "timing and terms of the deal likely indicate Shire's comfort level with the Amicus chaperone technology." Even so, investors seem to be waiting to see the data for themselves: they pushed Amcius's stock up just 4 percent on news of the deal.

Under the terms of the agreement, Amicus stands to get $50 million up front as well as up to $150 million in clinical and regulatory milestones and $240 million in sales milestones. Crowley said several of the clinical milestones are achievable within the next 12-18 months.

In exchange, Shire gets ex-U.S. development and commercialization rights to the Phase II Fabry disease drug Amigal (migalastat hydrochloride), the Phase II Gaucher disease drug Plicera (isofagomine tartrate) and the Phase I Pompe disease drug AT2220 (deoxynojirimycin). The two companies will split equally development costs supporting global approval, with Amicus taking the lead through the completion of Phase II trials for each compound and a joint steering committee delegating Phase III responsibilities. Amicus retains all U.S. commercialization rights and will get tiered double-digit royalties on ex-U.S. sales.

Crowley said Amicus has been in partnering discussions with multiple parties since its initial public offering earlier this year, and that it reviewed multiple term sheets before closing the deal with Shire. (See BioWorld Today, June 1, 2007.)

Although Amicus's drugs target orphan genetic diseases, Genzyme Corp. has proven that these small markets can be a big business. In the third quarter of 2007, Genzyme's Fabry disease drug Fabrazyme (agalsidase beta) brought in $104.6 million, while its Gaucher disease drug Cerezyme (imiglucerase for injection) brought in $286.1 million and its Pompe disease drug Myozyme (alglucosidase alfa) brought in $53.6 million.

Shire also is no stranger to the rare genetic disease market. Its Fabry disease drug Replagal (agalsidase alfa) brought in $40.7 million in the third quarter, while its Hunter syndrome drug Elaprase (idursulfase) brought in $55.1 million. Shire also is conducting Phase III trials with GA-GCB for Gaucher disease.

But while Genzyme and Shire's drugs are enzyme replacement therapies, Amicus's pharmacological chaperones are small molecules designed to bind and stabilize the patient's own enzyme, resulting in improved protein folding and increased activity.

"Instead of artificially replacing the enzyme . . . we fix the problem at its source," Crowley said. He added that Amicus's drugs are pills rather than multi-hour infusions and that they could provide safety and efficacy benefits, as evidenced by preclinical biodistribution data and a "clean" profile in Phase I trials.

Phase I data on AT2220 presented last month showed that the drug was well tolerated with good oral bioavailability and pharmacokinetic parameters. Ongoing Phase II trials of Amigal in Fabry disease will evaluate safety; dose regimen; pharmacodynamic measures; and cardiac, renal and central nervous system function. The ongoing Phase II study of Plicera in Gaucher disease involves switching patients from enzyme replacement and then analyzing safety and pharmacodynamic effects after four weeks.

In a research report, Robert W. Baird & Co. analyst Christopher Raymond said that the Amicus deal with Shire "steps up the competitive pressure on Genzyme's LSD franchise," but added that he will "reserve judgment" until he sees the final data.

Shares of Cranbury, N.J.-based Amicus (NASDAQ:FOLD) closed up 67 cents at $16.75 on Thursday. Shares of Basingstoke, UK-based Shire plc (NASDAQ:SHPGY) closed down 20 cents at $70.65.

Amicus reported cash, equivalents and marketable securities of $119.4 million as of Sept. 30 after burning through $11.8 million in operating expenses during the quarter.