EntreMed’s ENMD-2076 Demonstrates Antitumor Activity in Multiple Myeloma Model

Preclinical Data Support Rationale for Clinical Study

ROCKVILLE, MD, June 2, 2008 – EntreMed, Inc. (NASDAQ: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced the presentation of preclinical data for its Aurora A/angiogenesis kinase inhibitor, ENMD-981693, the free base of ENMD-2076. The data were presented by Dr. Xiaojing Wang,
postdoctoral fellow of EntreMed collaborator Dr. Sherif S. Farag, Division of Hematology and Oncology, Indiana University School of Medicine, at the American Society of Clinical Oncology Annual Meeting being held this week in Chicago, Illinois.
ENMD-2076 free base exhibited dose-dependent cytotoxicity towards multiple myeloma (MM) cell lines, and was shown to induce cell death in vitro following relatively short (6 hour) exposures through apoptosis via a mitochondrial pathway. Consistent with the effect of ENMD-2076 free base on several receptor tyrosine kinases, inhibition of phosphorylation of proteins in the oncogenic PI3-kinase/Akt pathway including p-BAD, p-FOXO1a, and p-GSK3β was observed. Longer incubations of MM cells (24-48 hours) with ENMD-2076 free base elicited increased cell death with concomitant inhibition of Aurora A autophosphorylation, induction of cell cycle arrest, and downregulation of cyclins A and B1. ENMD-2076, administered either on a daily or weekly schedule, elicited complete inhibition of tumor growth towards a xenograft of the human myeloma cell line H929 in vivo.
ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to Aurora A kinase and other oncogenic proteins. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. Inhibition of Aurora A has been shown to induce cell death in preclinical multiple myeloma cell lines. In addition, ENMD-2076 is selective for the Aurora A isoform in comparison to Aurora B.
Dr. Mark R. Bray, Vice President Research at EntreMed commented on the presentation, “The research of Dr. Farag and his co-workers has yielded important insights into the mechanism of cell death induced by ENMD-2076. These data support EntreMed’s clinical rationale for this compound and provide further validation for its potential clinical utility in hematological cancers, including multiple myeloma. ENMD-2076 is currently in a Phase 1 study in solid tumors and the company plans to initiate a second Phase 1 study in patients with hematological malignances later this year.”

About EntreMed
EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. MKC-1 is currently in multiple Phase 2 clinical trials for cancer. MKC-1 is an oral cell-cycle regulator with activity against the mTOR pathway. ENMD-1198, a novel antimitotic agent, and ENMD-2076, a selective kinase inhibitor, are in Phase 1 studies in advanced cancers. The Company also has an approved IND application for Panzem® in rheumatoid arthritis. EntreMed’s goal is to develop and commercialize new compounds based on the Company’s expertise in angiogenesis, cell-cycle regulation and inflammation – processes vital to the treatment of cancer and other diseases, such as rheumatoid arthritis. Additional information about EntreMed is available on the Company’s web site at www.entremed.com and in various filings with the Securities and Exchange Commission.

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