By Mary Welch

EntreMed Inc. raised more than $25 million in a private placement that will be used to support clinical development of its angiogenesis inhibitors, one of which, Endostatin, is poised to start Phase I trials within 60 days.

A company spokeswoman said the shares sold at just under $21 apiece. The shares were issued at a 7.5 percent discount to a five-day average market price. Investors also received two series of warrants that included an exercise price at a "significant premium" and company call options. Specifics were not disclosed. First Security Van Kasper, of San Francisco, acted as placement agent.

EntreMed's stock (NASDAQ:ENMD) closed Wednesday at $22.375, down 25 cents per share. EntreMed now has 13.1 million shares outstanding.

"The proceeds will be used to pay for Endostatin through clinical trials but also to support INDs [investigational new drug applications] for 2-methoxyestradiol and Angiostatin protein," said Mary Sundeen, the company's senior director of corporate communications and investor relations. "We think these other two drugs warrant a lot of attention that they haven't received yet in the newspapers."

The Phase I trial of Endostatin will involve between 15 to 30 patients at each of the three sites. The participating sites are the Dana-Farber/Partners CancerCare, the joint venture between Dana-Farber Cancer Institute in Cambridge, Mass., and Brigham and Women's and Massachusetts General hospitals in Boston. Other sites are the University of Texas M.D. Anderson Medical Center in Houston, and the University of Wisconsin Comprehensive Cancer Center in Madison. Work at the latter two sites is being sponsored by the National Cancer Institute.

The trial will be open to patients with all forms of solid tumors as well as lymphomas and should last at least 12 months. "Patients with prostate cancer are as eligible as those with bone cancer, assuming they meet the other criteria," Sundeen said.

The Endostatin protein is a naturally occurring fragment of collagen 18a. In tests in mice, the protein repeatedly inhibited the growth of metastatic and primary cancerous tumors with no drug resistance or toxicity noted. EntreMed is in the second year of a five-year development agreement with the National Cancer Institute.

"We filed the IND for Endostatin three months ahead of schedule and we anticipate filing another one in the fourth quarter of this year for the Angiostatin protein and a third for 2-methoxyestradiol in the second half of this year," Sundeen said, "We have a very aggressive schedule of clinical trials for a company of only 73 people."

Angiostatin is a naturally occurring antiangiogenic agent designed to block the growth of tumors by depriving them of their blood supply. The company said the protein could be of particular use in patients with multiple tumors. When a primary tumor is removed, secondary metastatic tumors often rapidly occur. It is theorized that the Angiostatin protein could treat all tumors effectively and simultaneously.

In addition to being used for cancer indications, EntreMed said the three drug candidates have potential for treating progressive macular degeneration as well as progressive arthritis.