ROCKVILLE, MD, April 19, 2007 – 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 results for MKC-1, its novel cell cycle inhibitor. The data were presented by EntreMed scientists at the American Association for Cancer Research (AACR) Annual Meeting being held this week in Los Angeles, California.
MKC-1 is a novel, orally-active cell cycle inhibitor with in vitro and in vivo efficacy against a broad range of human solid tumor cell lines, including multi-drug resistant cell lines. In previous studies, MKC-1 demonstrated broad-acting antitumor effects, showing tumor growth inhibition or regression in multiple preclinical models, including paclitaxel-resistant models. MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M-phase (mitosis) of the cell cycle, and induce apoptosis. These effects are consistent with mechanisms resulting from MKC-1 binding to multiple intracellular targets, including tubulin and the importin-β proteins. The importin-β family of proteins plays a critical role in nuclear transport and cell division.
In these studies, MKC-1 showed potent, dose-dependent activity against a variety of cell lines derived from cancers of human blood cells, and inhibited growth of primary cells derived from acute and chronic myelogenous leukemia (AML and CML) patients in vitro. MKC-1 was also shown to inhibit PI3-Kinase and mTOR pathways by inducing a dose-dependent reduction in the levels of the activated forms of the oncogenic kinases Akt and p70S6K. These signaling pathways are strongly linked to cancer proliferation and survival.
Additionally, MKC-1 showed enhanced activity with cytosine arabinoside (Ara-C) in combination studies in vitro when added either simultaneously or sequentially in an AML cell line. MKC-1, therefore, induces apoptosis in hematopoietic cell lines and patient samples through a complex mechanism involving arrest of the cell cycle and disruption of multiple oncogenic survival pathways.
Mark R. Bray, Ph.D., EntreMed’s Vice President Research, commented on the results, “These data provide further evidence that MKC-1 disrupts multiple survival pathways in tumor cells, including the PI3-Kinase and mTOR signaling pathways. Our results indicate that MKC-1 causes cell cycle arrest and induces apoptosis both in leukemia cell lines and in leukemia patient samples.”
Dr. Bray also commented, “These findings further support our plans to evaluate MKC-1 in leukemia patients, either as a single agent or in combination with other chemotherapeutic agents. MKC-1 is currently in Phase 2 trials for metastatic breast cancer and non-small cell lung cancer, as well as a Phase 1 clinical trial for leukemia. We plan to continue evaluating the clinical potential for MKC-1 in both solid and hematological tumors.”
To view the poster presentation, visit Scientific Presentations under the Therapeutic Pathways section of the Company’s web site at www.entremed.com.
EntreMed, Inc. (NASDAQ: ENMD) is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem® (2-methoxyestradiol or 2ME2), the Company's lead drug candidate, is currently in Phase 2 clinical trials for cancer, as well as in preclinical development for rheumatoid arthritis. MKC-1, an oral cell cycle regulator, is in Phase 2 studies for cancer. ENMD-1198, a novel tubulin binding agent, is also 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. Additional information about EntreMed is available on the Company’s website at www.entremed.com and in various filings with the Securities and Exchange Commission.
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