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Blood brothers
February 2006
by Jeffrey Bouley  | 
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ROCKVILLE, Md.—Although it's no mystery to cancer drug discovery researchers that coagulation and coagulation proteins impact on angiogenesis, trying to make a therapy based on that knowledge has been the tricky part. But EntreMed Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, and Affymax Inc., which works in the area of discovery and development of novel peptide drugs, think they may be on the road to circumventing that problem, based on preclinical data regarding novel peptides they co-developed.
 
Initial findings show that a fragment of tissue factor pathway inhibitor demonstrated antiangiogenic activity in preclinical models and that this activity was modulated through the very low density lipoprotein (VLDL) receptor. The data were recently  presented at the American Society for Hematology Annual Meeting, held mid-December in Atlanta.
 
"It's been known for some time that there is an overlap in coagulation and coagulation proteins with regard to angiogenesis, and we had a program internally already to see if we could separate the bad affects  impacting detrimentally on coagulation mechanisms from its positive effects in terms of anticancer activity," says Dr. Carolyn Sidor, EntreMed's vice president and CMO. "We were pleased by the fact that we were able to accomplish so well what we wanted, which was to develop a therapy without adversely impacting coagulation."
 
"There are many molecules that have come from fragments of coagulation proteins for such treatment. But the interesting thing about our work was in how important the VLDL receptor is," adds Dr. Theresa LaVallee, senior director of cell biology at EntreMed. "The challenge is finding out where the molecule is binding and then figuring out how the receptor is acting—how it is actually mediating the effects of tumors."
 
The companies are now using the VLDL receptor and the antiangiogenic activity for structure-function analysis to identify peptides with similar, but improved properties. The resulting new compounds will subsequently be evaluated in preclinical models for  therapeutic potential in oncology, as well as inflammatory diseases.
 
Code: E020620

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