By Karen Pihl-Carey

Texas Biotechnology Corp. and ICOS Corp. formed a joint venture that will focus on advancing endothelin-A receptor antagonists.

The agreement could mean as much as $55.5 million in up-front payments and milestones to Texas Biotechnology and involves the Houston-based company's two lead endothelin-A receptor antagonists, sitaxsentan and TBC3711.

The 50-50 joint venture will be called ICOS-Texas Biotechnology Ltd. Partnership.

"This allows us to, most importantly, accelerate the development of these compounds," said Pamela Murphy, vice president of corporate communications at Texas Biotechnology. "Moving them forward as quickly as possible is a real important goal of ours, as well as remaining actively involved in their development. We're very pleased with the establishment of this partnership."

Likewise, ICOS Chairman and CEO Paul Clark said the joint venture is good for both companies. The companies will fund equally the cost of research and development of sitaxsentan and second-generation endothelin antagonist compounds, commercialize resulting products and share equally in worldwide profits. The possible $55.5 million in payments assumes that "multiple indications reach all the way to approval," he said.

Endothelin antagonists are a new class of compounds being developed to treat essential and pulmonary hypertension, chronic heart failure and prostate cancer. The blocking of endothelin-A receptors has been shown to reduce blood pressure in humans. In preclinical testing, endothelin-A antagonists have halted and reversed the pulmonary vascular remodeling that occurs in response to elevated pulmonary vascular pressures.

Clark said his company sees great potential for endothelin antagonists because they address an unmet need. "This is a new class of drug. There are currently no endothelin antagonists on the market," he said.

Bothell, Wash.-based ICOS, Clark said, has had a goal to bring in late-stage products to complement its pipeline, and the company prefers to do so through joint ventures. It already has joint ventures with its two other late-stage products. IC351 is in global Phase III trials to treat male erectile dysfunction and is being developed through a joint venture with Eli Lilly & Co., of Indianapolis. Pafase to treat sepsis is being developed in a joint venture with Suntory Ltd., of Tokyo.

In a Phase IIa study, sitaxsentan, also called TBC11251, showed decreased pulmonary artery systolic pressure and pulmonary vascular resistance in patients with chronic heart failure. It also is being evaluated in a Phase IIa trial in patients with pulmonary hypertension.

The joint venture will focus on moving sitaxsentan into a pivotal Phase IIb/III pulmonary hypertension trial. The trial, which should begin sometime in the second half of this year, will take between 18 months and two years, according to Murphy and Clark.

"These patients are very underserved. There's one IV formulation, Flolan, that's available for them," Murphy said. "So introducing an oral therapy that's available would be a big deal for them."

Flolan is a formulation of the molecule prostacyclin, approved for the treatment of primary pulmonary hypertension.

The other endothelin-A receptor antagonist the joint venture will focus on is TBC3711, a second-generation compound, which Murphy said could move into human testing as early as the fourth quarter of this year. The compound, she said, might be tested in the chronic heart failure indication, but that will be up to the joint venture.

"We just think this is a very good alliance for both companies, and strategically, it allows both companies to evolve a commercial presence with a very strong new class of compounds," Murphy said.

News of the joint venture came Tuesday just as the market closed. Texas Biotech's stock (AMEX:TXB) closed at $11.625, up 50 cents, and ICOS' stock (NASDAQ:ICOS) closed at $41.50, up $1.812.