EntreMed, Inc.
(Nasdaq: ENMD), a clinical-stage pharmaceutical company developing
therapeutics for the treatment of cancer and inflammatory diseases,
announced the presentation of results for its cell cycle inhibitor, MKC-1,
in preclinical renal cell carcinoma (RCC) models. The results were
presented at the AACR-NCI-EORTC International Conference on Molecular
Targets and Cancer Therapeutics in San Francisco, California.
Activation of the oncogenic kinase Akt and the mTOR pathway are known
to be adverse prognostic factors and contributors to the pathology of
metastatic RCC, therefore inhibitors of these pathways are of significant
interest for treatment of this disease. Human RCC cell lines in vitro were
shown to have marked sensitivity to MKC-1. MKC-1 inhibited both Akt and
mTOR pathway activation in vitro, and was further evaluated in a
preclinical model consisting of a xenograft of the human RCC cell line,
Caki-1. Orally- administered MKC-1, but not sunitinib malate (Sutent(R)),
significantly increased survival of tumor-bearing animals in this model.
Examination of tumors following five days of oral treatment with MKC-1
revealed inhibition of the Akt-mTOR pathway, as well as decreased
angiogenesis and cell proliferation within the tumors. These preclinical
results support further evaluation of MKC-1 for the treatment of renal cell
carcinoma.
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. Data from previous studies with
MKC-1 demonstrate 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. Furthermore, MKC-1 inhibits the
Akt-mTOR signaling pathways, which may occur through inhibition of the
mTOR/rictor pathway. The Akt-mTOR pathway is the most frequently mutated
pathway in human tumors and mutations have been shown to promote tumor
progression and decrease survival in cancer patients.
Mark R. Bray, Ph.D., EntreMed Vice President, Research, commented on
the results, "Data from preclinical studies with MKC-1 continue to support
its therapeutic potential in a variety of tumor types. The data are
consistent with MKC-1 targeting the mTOR pathway by a mechanism that is
distinct from rapamycin-like agents, such as Temosirolimus. These results,
along with the recent success of agents that target the mTOR pathway,
provide validation that clinical studies with MKC-1 in cancers such as
renal cell are warranted. MKC- 1 is currently in clinical trials in
metastatic breast cancer, non-small cell lung cancer, and leukemia."
To view the poster presentation, visit the Company's web site at
entremed.
Sutent(R) is a registered trademark of its owner and is not a
registered trademark of EntreMed, Inc.
About EntreMed
EntreMed, Inc. is a clinical-stage pharmaceutical company developing
therapeutic candidates primarily for the treatment of cancer and
inflammation. Panzem(R) NCD (2-methoxyestradiol or 2ME2) is currently in
multiple Phase 2 clinical trials for cancer. MKC-1, an oral cell-cycle
regulator, is in multiple Phase 1 and 2 studies for cancer. ENMD-1198, a
novel tubulin-binding agent, is in Phase 1 studies in advanced cancers.
Panzem(R) is also in preclinical development for rheumatoid arthritis, and
ENMD-2076, a dual-acting Aurora-angiogenesis inhibitor, is in preclinical
development for cancer. 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
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 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.
entremed