By Kim Coghill

Washington Editor

Collateral Therapeutics Inc.'s development partner, Schering AG, submitted an application to the FDA for a U.S.-based pivotal Phase IIb/III clinical study of GENERX (Ad5FGF4), a nonsurgical angiogenic gene therapy product for treatment of patients with stable exertional angina due to coronary artery disease.

The application was submitted through Schering's U.S. affiliate, Berlex Laboratories Inc., of Wayne, N.J.

GENERX therapy is designed to enhance the growth of new blood vessels supplying the heart in order to alleviate the ischemia - lack of oxygen - associated with cardiovascular disease. The gene therapy approach, which is delivered during a standard heart catheterization, offers a nonsurgical way to get more oxygen to the heart muscle. GENERX is an adenoviral gene therapy vector containing the human fibroblast growth factor-4.

In March the company's stock jumped 56 percent to close at $40.18 when the Phase I/II GENERX study produced positive results. The shares (NASDAQ:CLTX) closed Wednesday at $15.312, up $1.062 or 7.5 percent. (See BioWorld Today, March 21, 2000.)

"Based on the data from the Phase I/II study, our development partner and Collateral Therapeutics have concluded that selected tested doses of Ad5FGF4 appear to be appropriate for larger-scale Phase IIb/III clinical studies. Clinical investigators are in the process of preparing a presentation and manuscript on the Phase I/II study, and we expect information to be available to the scientific and medical community during the first part of this year," Jack Reich, Collateral Therapeutics' chairman and CEO, said in a prepared statement.

Company officials were not available for comment Wednesday.

The Angiogenic Gene Therapy (AGENT) Phase I/II clinical trial included 70 patients who suffered from stable, chronic, exertional angina, or chest pain, caused by a lack of oxygen in the heart muscle triggered by emotional stress or physical exertion. The study was a placebo-controlled, double-blind trial testing four doses of GENERX.

In other developments, Collateral Therapeutics and Schering in October filed regulatory applications with six European health authorities for initiating clinical trials of Gevascor, a nonsurgical angiogenic gene therapy candidate for treatment of patients with peripheral vascular disease. The product is designed to promote new blood vessel growth and could restore blood flow to ischemic regions of the leg. The Phase I/II trials are designed to enroll up to 130 patients at 10 European sites.

In September, Collateral Therapeutics reached an agreement with the University of Texas to exclusively license certain human genes discovered by UT researchers and to sponsor additional gene discovery research focused on cardiac cell differentiation.