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-beta proteins. The importin-beta 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 entremed.
About EntreMed
EntreMed, Inc. (Nasdaq: ENMD) 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 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 entremed
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 integration of
Miikana and its 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.
entremed