By Brady Huggett

Collateral Therapeutics Inc. and its development partner, Schering AG, plan to initiate two Phase IIb/III trials for their product candidate Generx, and will evaluate the data from the trials for regulatory approval filings in both the United States and the European Union.

Schering, of Berlin, will shoulder the financial burden for the Generx trials, if they are approved by regulatory authorities. Generx is a nonsurgical angiogenic gene therapy designed for the treatment of patients with stable exertional angina due to coronary artery disease. The companies entered their collaborative agreement in May 1996.

Schering, through subsidiary Berlex Laboratories Inc., of Wayne, N.J., submitted an application to the FDA for the U.S.-based Phase IIb/III study of Generx in patients with stable exertional angina due to coronary artery disease early this year. (See BioWorld Today, Jan. 11, 2001.)

The U.S.-based and European versions of the trial should be of similar size, said Christopher Reinhard, president and chief operating officer of Collateral, and overall, the trials should enroll about 1,000 patients.

¿It¿ll be in about 100 sites in the U.S.,¿ Reinhard said. ¿I would suspect it would be on the same order of magnitude in Europe, although [the trial] may be a little different there.¿

The European trial would have a slightly different focus than the U.S. version, Reinhard said, thus the caveat on size. The study in Europe would evaluate patients with advanced coronary artery disease who are not considered candidates for interventions such as angioplasty and bypass surgery or are unlikely to have positive outcomes from such interventions. The variations in the trials could open up regulatory doors for Collateral.

Reinhard said the idea behind Generx is to provide an alternative to the three options coronary artery disease patients normally have: drug therapy, interventional treatment such as angioplasty and stents, and bypass surgery. By testing Generx in opposing patients ¿ those with options and those with fewer choices ¿ Collateral hopes to get its product candidate into both markets, Reinhard said.

Generx (Ad5-FGF4) is designed to stimulate angiogenesis. It is a one-time nonsurgical administration of an adenoviral gene therapy vector containing the human fibroblast growth factor 4 angiogenic gene that is given through a catheter into the coronary arteries. Reinhard said it can be administered at the same time an angiogram is performed. And while Generx is given through a catheter, this is pure biotechnology, Reinhard said.

¿This is not a device-driven approach,¿ he said. ¿This is molecular biology at its finest.¿

San Diego-based Collateral was founded in 1995 by five individuals, including Reinhard. Its company development path is unique in that it never received venture funding.

¿Schering made a courageous investment at the embryonic level,¿ Reinhard said. ¿We went public in 1998 and the State of Wisconsin [Investment Board] came in and they own 19 percent of the company now. This is not a venture-funded company.¿

Collateral raised about $15.9 million through the sale of 2.2 million shares at $7.25 per share in its 1998 initial public offering. It had filed to sell 3.3 million shares in the price range of $11 to $13, which would have brought in about $40 million if it had priced in the middle at $12. (See BioWorld Today, April 28, 1998 and July 6, 1998.)

Collateral¿s stock (NASDAQ:CLTX) gained 4 cents Monday to close at $7.05.

Reinhard said Schering owns about 10 percent of Collateral and management owns somewhere between 30 percent and 35 percent.

¿We decided to focus on the cardiovascular field and bring all our efforts,¿ he said. ¿Some would say it¿s more risky that way, but we say it¿s less risky because we are very focused on one field.¿

The primary endpoint of the study would be measured by exercise time on a treadmill at 12 weeks following Generx administration with a maximum exercise time of 12 minutes or less at baseline. Other endpoints would include quality of life, anginal frequency and medication usage.

Schering also is responsible for four European Phase I/II trials to evaluate Collateral¿s angiogenic gene therapy product candidate designed as a nonsurgical treatment for patients with peripheral vascular disease and is preparing for the trials now. Reinhard said Schering¿s strong backing has given credence to the effort Collateral has exerted since its inception.

¿We¿ve come a long way since 1995 and we¿re very excited about it,¿ he said.