EntreMed's Aurora Kinase Inhibitor Induces Tumor Regression In Preclinical Models

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Tumor Regression

EntreMed, a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, announced the presentation of preclinical results for its Aurora kinase - angiogenesis inhibitor, ENMD-981693.

The data were presented during oral and poster presentations by EntreMed scientists at the 2nd Protein Kinases in Drug Discovery Conference being held May 31 - June 1, 2007 in Boston, Massachusetts.

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ENMD-981693 is an oral, dual-acting kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. In preclinical studies, ENMD-981693 has been shown to inhibit a unique profile of angiogenic tyrosine kinase targets in addition to the Aurora kinases. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-981693 is selective for the Aurora A isoform in comparison to Aurora B.

Results from in vitro studies demonstrate ENMD-981693's potent activity against oncogenic receptor tyrosine kinases, including FLT3, c-Kit and CSF1R, which are involved in the pathology of hematological cancers. Additionally, ENMD-981693 demonstrated potent inhibition of a spectrum of targets linked to angiogenesis, including KDR (VEGFR2) and FGFR1. The compound was also shown to induce apoptosis and cell cycle arrest in a broad range of cell lines.

ENMD-981693 exhibited antiangiogenic activity in in vivo animal models by preventing the formation of new blood vessels and inducing regression of formed vessels at well-tolerated doses. Orally-administered ENMD-981693 induced tumor regression with minimal toxicity in a preclinical xenograft model of human leukemia. This activity is consistent with tumor regression induced by ENMD-981693 in preclinical models of human tumors derived from colon, leukemia, and breast cancer cell lines.

Mark R. Bray, Ph.D., Vice President, Research at EntreMed, commented on the presentations, "Results from these preclinical studies highlight the tremendous progress we have made with this compound and further support our selection of ENMD-981693 as the lead for our Aurora kinase program. ENMD-981693 has been shown to induce tumor regression in multiple preclinical models, which demonstrates the compound's potential clinical utility in a broad variety of cancers. IND-directed studies are currently underway and we anticipate the filing of an IND for ENMD-981693 in the fourth quarter of 2007."

EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem(R) (2-methoxyestradiol or 2ME2), the Company's lead drug candidate, is currently in multiple Phase 2 clinical trials for cancer, as well as in preclinical development for rheumatoid arthritis. MKC-1, an oral cell-cycle regulator, is in various Phase 2 studies for cancer. ENMD-1198, a novel tubulin-binding agent, is in Phase 1 studies in advanced cancers. 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.

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