EntreMed Commences Leukemia Clinical Trial For MKC-1 In Canada

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Blood / Hematology;  Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 25 Jul 2007 - 0:00 PDT

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EntreMed, Inc. (Nasdaq: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced that it has commenced a Phase 1 study of MKC-1 in leukemia patients at the Princess Margaret Hospital, University Health Network (UHN), Toronto, Canada. Dr. Karen Yee, Assistant Professor, University of Toronto, is the principal investigator for the clinical trial. EntreMed received a No Objection Letter (NOL) from the Therapeutic Products Directorate of Health Canada on its Clinical Trial Application to conduct the clinical trial in leukemia patients. A Canadian Clinical Trial Application (CTA) is similar to a United States (US) Investigational New Drug (IND) application.

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, including tumor growth inhibition or regression in multiple preclinical models, even in 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.

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.

Carolyn F. Sidor, M.D., M.B.A., EntreMed's Vice President and Chief Medical Officer, commented, "This is a significant milestone for EntreMed and the MKC-1 clinical development program. The CTA represents our first regulatory submission to Health Canada and provides us with the opportunity to expand clinical studies with MKC-1 to institutions outside the United States."

Dr. Sidor further commented, "We have demonstrated in preclinical studies that MKC-1 disrupts multiple survival pathways in tumor cells, including the PI3-Kinase and mTOR signaling pathways. MKC-1 causes cell cycle arrest and induces apoptosis both in leukemia cell lines and in leukemia patient samples. MKC-1 is currently in two U.S. Phase 2 studies in breast cancer and non-small cell lung cancer. Additional studies in pancreatic and ovarian cancer are planned for later this year."

About Hematological Malignancies

Hematological malignancies are cancers that affect blood, bone marrow and lymph nodes. As the blood, bone marrow and lymph nodes are intimately connected through the immune system, a disease affecting one of the three will often affect the other. Chromosomal translocations are a common cause of these diseases, which leads to a different approach in diagnosis and treatment. Diseases characterized as hematological malignancies include leukemia, lymphoma and multiple myeloma.

About EntreMed

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. Additional information about EntreMed is available on the Company's web site at http://www.entremed.com and in various filings with the Securities and Exchange Commission.

Forward Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act with respect to the outlook for expectations for future financial or business performance (including the timing of royalty revenues and future R&D expenditures), strategies, expectations and goals. Forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Forward-looking statements speak only as of the date they are made, and no duty to update forward-looking statements is assumed. Actual results could differ materially from those currently anticipated due to a number of factors, including those set forth in Securities and Exchange Commission filings under "Risk Factors," including risks relating to the need for additional capital and the uncertainty of additional funding; variations in actual sales of Thalomid(R), risks associated with the Company's product candidates; the early-stage products under development; results in preclinical models are not necessarily indicative of clinical results, uncertainties relating to preclinical and clinical trials; success in the clinical development of any products; dependence on third parties; future capital needs; and risks relating to the commercialization, if any, of the Company's proposed products (such as marketing, safety, regulatory, patent, product liability, supply, competition and other risks).

EntreMed, Inc.
http://www.entremed.com