National Editor

About one year after EntreMed Inc. dealt away its thalidomide analogue program, the company has entered an agreement to transfer away rights to its protein-based, anti-angiogenesis drugs Endostatin and Angiostatin for undisclosed terms - thus sharpening the company's focus even more on its small-molecule cancer pipeline.

Rockville, Md.-based EntreMed's stock (NASDAQ:ENMD) closed Wednesday at $3.67, down 18 cents.

Amy Finan, senior director of corporate communications and industry relations for EntreMed, said the out-licensing of Endostatin and Angiostatin "really is no surprise," since the company has been planning the move for more than a year and providing guidance to investors accordingly.

Under the terms of the three-way agreement, Boston-based Children's Medical Center Corp., from which the compounds originally were licensed by EntreMed, gets rights for the world, excluding Asia. Alchemgen Therapeutics Inc., of Houston, gets exclusive rights in Asia to the compounds, which had gone as far as Phase II trials, Finan said.

EntreMed has protected its interests, she added, noting that the company is in line to receive 20 percent of future proceeds (such as up-front, milestone and royalty payments) resulting from any CMCC licensing activity outside Asia. Further financial details were not disclosed.

CMCC is the business arm of Children's Hospital, and Alchemgen is a gene-therapy firm with an early stage program in anti-angiogenesis.

Angiostatin is a recombinant version of a naturally occurring angiogenesis inhibitor and a component of plasminogen, a protein known to be involved in coagulation. Endostatin targets abnormal blood vessel growth associated with cancer, blindness, arthritis and atherosclerosis, among other diseases.

Since licensing Endostatin in 1996 from CMCC, EntreMed has spent $70.9 million on accumulated direct project expenses, according to the company's financial report from the third quarter of 2003. Costs for Angiostatin, licensed in 1994, totaled $35.2 million.

At the start of last year, EntreMed Inc. entered a deal valued at about $27 million with Celgene Corp., of Warren, N.J., for rights to EntreMed's thalidomide analogue program. (See BioWorld Today, Jan. 3, 2003.)

Then, to bring in more cash, the firm near the end of the year sold common stock and warrants to institutional investors, raising about $22.3 million in gross proceeds, which was described as enough to last "well into 2005."

As of Sept. 30, before the sale, the company had cash and short-term investments of about $20.7 million. (See BioWorld Today, Nov. 4, 2003.)

EntreMed's pipeline is led by Panzem (2-methoxyestradiol), a small molecule with anti-angiogenesis properties being studied in a Phase II oncology program. Trials have been completed in prostate cancer with favorable results, and trials in multiple myeloma trials are ongoing.

At the American Society of Clinical Oncology in 2002, EntreMed reported stabilized disease and declining prostate-specific antigen levels in hormone-refractory prostate cancer patients in the Phase II study. Data also showed that the oral drug was safe, well tolerated and demonstrated signs of inhibiting blood vessel growth.

At the meeting of the American Society of Hematology last December, EntreMed said early data from the multiple myeloma trials show Panzem was well tolerated and stabilized disease in patients with plateau or relapsed forms.

EntreMed has spent $21.5 million on Panzem so far, according to the quarterly report. Finan said the company is reformulating Panzem for greater bioavailability and expects to begin clinical trials with the new version in the first half of this year.