Washington Editor

Encysive Pharmaceuticals Inc. expects to net $30.8 million through the sale of 4 million shares of common stock at $7.76 apiece.

Proceeds from the sale will be used for clinical development, marketing and pre-launch activities related to Thelin; research and development of Encysive's other product candidates; and general corporate purposes, including capital expenditures and other working capital requirements.

Due to an SEC-imposed quiet period, officials from Houston-based Encysive were unable to comment. The firm expects the offering to close Sept. 13. The company sold the shares from a mixed shelf registration it filed in June for the sale of up to $150 million in debt securities, common stock, preferred stock, depository shares, warrants, purchase contracts and units.

Encysive has granted its underwriter, Wachovia Securities, of Baltimore, a 30-day option to purchase up to 600,000 shares of common stock to cover overallotments. As of June 30, Encysive reported about $60.6 million in cash, cash equivalents and investments, compared to about $85.5 million on Dec. 31.

Thelin (sitaxsentan), Encysive's lead drug candidate, is an endothelin receptor antagonist in late-stage development as a treatment for pulmonary arterial hypertension (PAH). Enrollment in a 240-patient Phase III trial called STRIDE-2 is expected to be completed during the third quarter. STRIDE-2 is a randomized, double-blind, placebo-controlled safety and efficacy study of Thelin with an open-label bosentan arm in PAH patients.

Company officials just presented data on Thelin at the European Respiratory Society's 14th annual congress in Scotland suggesting that the candidate might offer an alternative for PAH patients whose conditions are worsening on bosentan. (Encysive officials said one-third of patients come off bosentan because of lack of efficacy or liver toxicities. Bosentan is a nonselective endothelin receptor antagonist.)

Encysive said Thelin might have value for newly diagnosed PAH patients. Data from a study entitled "Sitaxsentan Sodium for the Treatment of Pulmonary Arterial Hypertension in Patients Failing Bosentan: Preliminary Single Center Data," showed that 10 of 11 patients who had failed on bosentan due to clinical deterioration or liver toxicities improved or stabilized when given Thelin oral therapy. All 10 patients are continuing on Thelin today, some as long as 10 months.

Eight patients who had deteriorated on bosentan were given Thelin 100 mg and followed for up to 12 weeks. Seven patients stabilized or experienced improvement in the six-minute walk test (6MW), a standard measurement of function in patients with PAH. One patient in the study discontinued Thelin treatment due to continued disease progression and had no evaluable 6MW measurements. Three other patients were enrolled after failing bosentan therapy due to liver toxicity. All three improved on Thelin without recurrence of liver abnormalities.

One patient who had clinically deteriorated on bosentan experienced a single occurrence of an abnormal liver function test. That patient has continued on Thelin without a recurrence, the company said. Meanwhile, the company presented data from two other abstracts, the first, "Long-Term Sitaxsentan Therapy in PAH," showed that Thelin was similarly effective in improving symptoms at doses of 100 mg and 300 mg.

Given the better safety profile for the 100-mg dose, the data support the selection of 100 mg as the maximum dose. The last abstract, titled, "Efficacy of Sitaxsentan, an Endothelin-A Receptor Antagonist in PAH in Traditional Versus Expanded Study Populations," contains data that support the existence of a "ceiling effect," as provided for in traditional PAH trial designs. Frequent exclusion of patients with milder PAH, in order to increase treatment effect sizes and statistical power, is customary when using 6MW as the endpoint, the company said.

STRIDE-1 (Phase IIb/III), a 12-week, randomized, double-blind, 178-patient trial employing placebo and Thelin at 100-mg or 300-mg doses, included patients with NYHA functional Class II, congenital heart disease and a baseline 6MW > 450 m-groups often excluded from previous trials.

For patients meeting traditional enrollment criteria (NYHA Class III or IV and 6MW less than or equal to 450 m at baseline with idiopathic PAH or PAH related to connective tissue disease), Thelin produced a robust increase in 6MW of 65 meters (p=0.0002) vs. 34 meters (p=0.0005) in the intent-to-treat patient group. PAH is a condition that involves high blood pressure and structural changes in the walls of the pulmonary arteries.

Primary and secondary PAH are estimated to afflict about 80,000 to 100,000 people worldwide, many of whom are children and young women, the company said.

No Comments