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EntreMed Presents Multi-Mechanism Antitumor Data for ENMD-1420 in,Preclinical Models

Tumor Inhibition Demonstrated in Lung and Colorectal Cancers

ROCKVILLE, Md., April 16, 2007 /PRNewswire-FirstCall/ -- EntreMed, Inc. , a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, announced the presentation of results for its preclinical tubulin inhibitor compounds. The data were presented by EntreMed scientists at the American Association for Cancer Research (AACR) Annual Meeting in Los Angeles, California.

Results of the studies presented at the AACR meeting demonstrated a potent, dose-dependent inhibition of tumor growth following the administration of ENMD-1420 (previously CC-5079) in two distinct preclinical models of metastatic lung and colorectal carcinoma. At maximally tolerated doses, tumor growth inhibition ranged from 80-90%. ENMD-1420 can exist in two chemical configurations termed the Z or E isomer. In vivo studies with each configuration further demonstrated the Z isomer (ENMD-1427) to be significantly more potent than the E isomer (ENMD-1916) for antitumor activity.

Part of the mechanism by which ENMD-1420 exerted an antitumor effect involved the inhibition of angiogenesis, in addition to its antiproliferative activity. In vivo angiogenesis assays showed that the administration of ENMD- 1420 at maximally tolerated doses led to the disruption of established blood vessels. Previous studies showed that ENMD-1420 inhibits tubulin polymerization and TNF-alpha production, contributing to its antiproliferative activity through apoptosis. Collectively, these data suggest that both ENMD- 1420 and its Z isomer have potent antitumor and antiangiogenic activity. Furthermore, a synthetic strategy targeting a particular isomer can be used to optimize antitumor and antiangiogenic activity for purposes of lead compound identification.

Carolyn F. Sidor, M.D., M.B.A., EntreMed Vice President and Chief Medical Officer, st
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