Six months after yanking a proposed initial public offering due to market conditions, Amicus Therapeutics Inc. is trying again.

The Cranbury, N.J.,-based company filed for an IPO, seeking $86.3 million to fund ongoing development of its lead drugs against lysosomal storage disorders, though it has not yet determined the share price or number of shares to be offered.

If successful this go-around, Amicus' stock would be listed on Nasdaq under the ticker "FOLD," which reflects the company's therapeutic focus: the development of small-molecule pharmacological chaperones that bind to misfolded proteins to help them form correct functional shapes. Though the company has said pharmacological chaperones could have applications in a number of diseases, its initial focus has been on chronic genetic diseases known as lysosomal storage disorders.

Its lead products are targeting Fabry's, Gaucher's and Pompe diseases. Existing therapy for those conditions involves enzyme replacement therapy - namely Cambridge, Mass.-based therapies Fabrazyme, Cerezyme and Myozyme - but Amicus' approach is designed to work by restoring enzyme function.

The company recently finished enrolling patients in all ongoing Phase II studies of its Fabry's disease candidate, Amigal (migalastat hydrocholoride). Those studies are evaluating dose levels and frequencies of the drug to determine the safety and tolerability, as well as pharmacodynamic measures of treatment, such as the effects on alpha-galactosidase A and globotriaosylceramide levels in various cells and tissues. Data are expected by the end of the year.

Its Gaucher's disease product, Plicera (isofagomine tartrate) is in two Phase II trials, with preliminary results by year-end. Characterized by a lysosomal accumulation of glucocerebrosideinside cells, Gaucher's disease is caused by a deficiency in the GCase enzyme. Plicera aims to facilitate proper trafficking of the enzyme to the lysosomes to break down the glucocerebroside.

Amicus' third product, AT2220, is in a Phase I trial for Pompe disease, a disorder caused by an inherited mutation of the alpha-glucosidase enzyme. Pending a successful outcome of that study, the company intends to initiate Phase II testing by the end of the year.

Funds from the IPO would be used to fund continuing development of those programs, plus additional research and development activities and for general corporate purposes. The company, which retains all rights to its compounds, plans to fund them all the way through development before establishing its own commercial operations and sales force to market at least some of the products.

Amicus first filed for an IPO in May 2006, again seeking $86 million. But the possibility of pricing its shares much lower than anticipated prompted the company rethink its options. In September, six weeks after withdrawing its filing, Amicus pulled in $60 million in a Series D round to support drug development. (See BioWorld Today, May 18, 2006, and Sept. 15, 2006.)

The company, which reported a net loss of $46.3 million for 2006, ended the year with about $79.1 million in cash.

Prior to the offering, its principal stockholders include entities associated with: Baltimore-based New Enterprise Associates, which holds 33.7 million shares, or 26.3 percent of the company; Seattle-based Frazier Healthcare Ventures, which holds 19.5 million shares, or 15.2 percent; Palo Alto, Calif.-based Prospect Venture Partners II LP, with 16.9 million shares, or 13.2 percent; Stamford, Conn.-based CHL Medial Partners, with 15.8 million shares, or 12.4 percent; Westport, Conn.-based Canaan Partners, with 15.4 million, or 12.1 percent; and Philadelphia-based Quaker BioVentures, with 10.6 million shares, or 8.3 percent.

Morgan Stanley & Co. Inc. and Merrill Lynch & Co. are serving as joint bookrunners, and J.P. Morgan Securities Inc., Lazard Capital Markets LLC and Pacific Growth Equities are acting as co-managers.

NovaCardia's IPO To Fund CV Drugs

Cardiovascular company NovaCardia Inc. also is looking to raise $86.3 million in its proposed IPO to fund ongoing clinical development of its two lead products: KW-3902 in congestive heart failure (CHF) and K201 for atrial fibrillation (AF).

The San Diego-based firm has not yet determined the number of shares or share price, but said in its prospectus that it hopes to on Nasdaq under the ticker "NCAR." In addition to clinical trial work, proceeds from the offering also will support general corporate purposes.

According to its prospectus, NovaCardia is set to start two pivotal Phase III trials in May of an intravenous formulation of KW-3902, an adenosine A1 receptor antagonist, in acute CHF in patients with renal impairment and fluid overload. Results from those studies are expected in mid-2008. The company also has an oral formulation of the product aimed at treating chronic CHF and has an upcoming Phase II study in that indication.

In AF, it is planning a Phase II trial of its intravenous form of K201 in acute settings, expected to begin in the second half of this year.

NovaCardia holds all rights to both products in the U.S. and Europe, and intends to establish its own U.S. hospital-based sales force to market the IV versions of both drugs. For marketing outside the U.S., and for further development and commercialization of the oral products, it likely will seek partners.

The company, which was founded in 2001, reported a net loss of $17.9 million for 2006. Since inception, the company's net loss totals about $43 million. As of Dec. 31, NovaCardia had $31.5 million in cash, with 88.1 million shares outstanding.

New York-based J.P. Morgan Securities Inc. and Credit Suisse Securities LLC, also of New York, will act as joint book-running managers, while San Francisco-based Pacific Growth Equities LLC and Albany, N.Y.-based First Albany Capital Inc. will serve as co-managers.

Quark IPO To Advance RNAi Drugs

In its $86.3 million IPO filing, Fremont, Calif.-based Quark Biotech Inc. expects to use proceeds to fund ongoing research and development activities, with funds also going to support general administration, working capital and general corporate purposes.

The company is developing RTP801i-14, a synthetic, chemically modified short-interfering RNA (siRNA) aimed at inhibiting RTP801, a gene believed to be involved in wet age-related macular degeneration. The first cohort of patients has been dosed in a Phase I/II trial, with no drug-related adverse events reported. Quark expects to finish dosing in the second half of this year, and pending, successful results, will initiate a Phase II trial to evaluate the drug's clinical activity.

In September, the company licensed worldwide rights to RTP801i-14 to New York-based Pfizer Inc. for both ophthalmic and non-ophthalmic indications. To date, Quark has received $25.2 million in up-front payments, reimbursements for development work and milestones, and could receive up to $299 million in additional milestones if Pfizer gains approval of a product for two ophthalmic indications and at least one non-ophthalmic indication. In addition, Pfizer agreed to pay royalties on sales and up to $309 million in sales-based milestones.

Behind RTP801i-14, Quark is developing AkIi-5, which is in Phase I testing for the prevention of acute renal failure in patients undergoing major cardiac surgery. AkIi-5 is a synthetic, chemically modified siRNA molecule designed to temporarily inhibit p53 expression. The Phase I trial is expected to conclude in the second half of 2007.

The company also has several programs in preclinical development, including AHLi-11 for hearing loss. Quark expects to file an investigational new drug application later this year for that compound. A second preclinical candidate, CTPi-I, aimed at chronic obstructive pulmonary disease, also targets RTP801 and is included in the Pfizer licensing deal.

Quark's products stem from its BiFAR target discovery platform, which is designed to identify genes and proteins responsible for certain disease traits. Its clinical candidates emerged from using the BiFAR platform to look at diseases associated with oxidative stress.

Since its founding, Quark has funded operations through equity investments totaling $83 million and nearly $90 million earned in licensing and collaboration agreements involving BiFAR. For 2006, the company reported a net loss of $17 million. As of Dec. 31, it had cash and cash equivalents of $19.8 million.

The company principal stockholders include: Tako Venture LLC, of Redwood City, Calif., which holds 16.3 million shares, or 43 percent of the company; Trans-Science Funds, of Tokyo, which has 5 million shares, or 13.1 percent; and Asuka DBJ Investment LPS, also of Tokyo, with 2.9 million shares, or 7.7 percent. As of March 28, 2007, the company had 37.5 million shares outstanding.

The offering will be conducted by JPMorgan, CIBC World Markets, Banc of America Securities LLC and C.E. Unterberg, Towbin LLC.

Upon completion of the IPO, Quark's shares would be listed on Nasdaq under the symbol "QURK."