Horizon Therapeutics Inc., which aims to introduce safer alternatives to the most popular pain-relieving drugs, is gearing up to raise a fourth venture round to conduct Phase III trials and file for U.S. approval of its first product.

Horizon, which has raised $51 million from Essex Woodlands Health Ventures, Scale Venture Partners, Pequot Ventures and Sutter Hill Ventures, hasn't finalized its financing plan, but will likely seek at least as much as it raised for its last financing, a $30 million third round completed in July 2007, according to Chief Executive Timothy Walbert.

In anticipation of the fund-raising, which will begin later this year or early next, Horizon has hired a chief financial officer, Robert J. De Vaere, who until recently held the same position at Walbert's former company, IDM Pharma Inc. De Vaere has more than 28 years of finance experience, according to Horizon. "He brings a great amount of financial, management and business experience," Walbert said.

Unlike most biotech companies approaching investors, Skokie, Ill.-based Horizon is close to putting its first drug on the market. It expects to have Phase III results from its lead product, HZT-501, this year, and intends to file for U.S. approval in the third quarter of 2009. Phase III studies for its second drug, HZT-602, are expected to begin in mid-2009, Walbert said.

The combined peak sales of these two products could reach $1 billion, Walbert said. Non-steroidal anti-inflammatory drugs, or NSAIDs, cause gastrointestinal complications, including ulcers, in 20% or more of patients who use them chronically, and NSAID toxicities cause about 16,500 deaths in the U.S. each year, according to Horizon. Cox-2 inhibitors relieve pain with fewer gastrointestinal complications, but two of the leading Cox-2 inhibitors, Vioxx and Bextra, were withdrawn in 2004 and 2005, respectively, because of safety concerns, though Celebrex remains on the market.

HZT-501 combines an NSAID, ibuprofen, with famotidine, an H2 antagonist. In its Phase III trials, Horizon aims to show that HZT-501 reduces the incidence of ulcers in comparison to patients taking ibuprofen only. There are 27 million ibuprofen prescriptions written in the U.S. each year, Walbert said. If approved, HZT-501 would be prescribed to patients at high risk for gastrointestinal complications, including people age 60 and older, people who take aspirin regularly, and patients with other conditions, such as hypertension.

Horizon's second product is a combination of another NSAID, naproxen, with famotidine. Some 14 million naproxen prescriptions are written in the U.S. annually, according to Walbert.

Horizon intends to market both drugs in the U.S. and to find partners for other markets. A U.S. sales team of 300 to 400 could reach the roughly 40,000 to 50,000 specialists and primary-care physicians who write the most NSAID prescriptions, Walbert said.