EntreMed, Inc.
(Nasdaq: ENMD), a clinical-stage pharmaceutical company developing
therapeutics for the treatment of cancer and inflammatory diseases,
announced that it has commenced a Phase 1, open-label, continuous dosing
study with its oral cell cycle inhibitor, MKC-1, in patients with advanced
or metastatic solid tumors. The clinical trial will be conducted at the
University of Wisconsin, Paul P. Carbone Comprehensive Cancer Center. Dr.
Glenn Liu, Assistant Professor of Medicine, University of Wisconsin, will
serve as principal investigator.
The purpose of the dose-escalation trial is to determine the maximum
tolerated dose (MTD) of MKC-1 administered orally twice a day continuously
in advanced or refractory solid tumor patients. Response and/or tumor
marker improvement will also be evaluated. Up to 24 patients with
metastatic or unresectable solid tumors for which standard curative
measures do not exist or are no longer effective will be enrolled.
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. To date, MKC-1 has been evaluated in over 400
patients in multiple Phase 1 and 2 clinical trials.
MKC-1 has been shown to induce apoptosis, inhibit mitotic spindle
formation, and prevent chromosome segregation in the M-phase (mitosis) of
the cell cycle. Furthermore, MKC-1 inhibits the PI3K-Akt-mTOR signaling
pathways, which may occur through inhibition of the mTOR/rictor pathway.
The PI3K-Akt- mTOR pathway is the most frequently mutated pathway in human
tumors. Mutations in this pathway have been shown to promote tumor
progression and decrease survival in cancer patients.
"The potential of increasing drug activity by exploiting its inhibitory
effects on the PI3K-Akt-mTOR pathway is exciting and we hope to define this
effect with novel molecular imaging techniques," commented Dr. Glenn Liu.
EntreMed Vice President and Chief Medical Officer, Carolyn F. Sidor,
M.D., M.B.A., commented on the study, "This will be our first continuous
dosing study for MKC-1 in patients with solid tumors. We believe that a
continuous dosing schedule has the potential to improve tolerability and
enhance MKC-1 activity in cancer patients, similar to increased antitumor
activity that sustained exposure has demonstrated in preclinical studies.
Through this Phase 1 study, we expect to determine not only the maximum
tolerated dose of MKC-1 when administered orally twice a day on a
continuous basis, but the pharmacodynamic changes using imaging techniques
as proof of drug effect and assessment of toxicity."
About EntreMed
EntreMed, Inc. is a clinical-stage pharmaceutical company developing
therapeutic candidates primarily for the treatment of cancer and
inflammation. MKC-1 is currently in multiple Phase 2 clinical trials for
cancer. MKC-1 is an oral cell-cycle regulator with activity against the
mTOR pathway. ENMD-1198, a novel antimitotic agent, is in a Phase 1 study
in advanced cancer patients and ENMD-2076, a selective kinase inhibitor, is
expected to begin a Phase 1 study in 2Q08. The Company also has an approved
IND application for Panzem(R) in rheumatoid arthritis. 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