EntreMed Presents Multi-Mechanism Antitumor Data for ENMD-1420 inPreclinical ModelsTumor Inhibition Demonstrated in Lung and Colorectal Cancers
ROCKVILLE, Md., April 16, 2007 /PRNewswire-FirstCall/ -- EntreMed, Inc. , a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, announced the presentation of results for its preclinical tubulin inhibitor compounds. The data were presented by EntreMed scientists at the American Association for Cancer Research (AACR) Annual Meeting in Los Angeles, California.
Results of the studies presented at the AACR meeting demonstrated a potent, dose-dependent inhibition of tumor growth following the administration of ENMD-1420 (previously CC-5079) in two distinct preclinical models of metastatic lung and colorectal carcinoma. At maximally tolerated doses, tumor growth inhibition ranged from 80-90%. ENMD-1420 can exist in two chemical configurations termed the Z or E isomer. In vivo studies with each configuration further demonstrated the Z isomer (ENMD-1427) to be significantly more potent than the E isomer (ENMD-1916) for antitumor activity.
Part of the mechanism by which ENMD-1420 exerted an antitumor effect involved the inhibition of angiogenesis, in addition to its antiproliferative activity. In vivo angiogenesis assays showed that the administration of ENMD- 1420 at maximally tolerated doses led to the disruption of established blood vessels. Previous studies showed that ENMD-1420 inhibits tubulin polymerization and TNF-alpha production, contributing to its antiproliferative activity through apoptosis. Collectively, these data suggest that both ENMD- 1420 and its Z isomer have potent antitumor and antiangiogenic activity. Furthermore, a synthetic strategy targeting a particular isomer can be used to optimize antitumor and antiangiogenic activity for purposes of lead compound identification.
Carolyn F. Sidor, M.D., M.B.A., EntreMed Vice President and Chief Medical Officer, stated, "We continue to make good progress on our tubulin inhibitor program. The results of these studies will help us to further identify a lead molecule for evaluation in additional tumor models. ENMD-1420 and multiple compounds of a similar class are licensed exclusively from Celgene Corporation for development in oncology. These compounds have proven to be potent inhibitors of tumor growth and have both antiproliferative and antiangiogenic activities. We continue to evaluate ENMD-1420 and related compounds with the goal of identifying a lead molecule within the next twelve months."
About Tubulin Inhibitors
Tubulins are the proteins that form microtubules, which are key components of the cellular cytoskeleton (structural network). Microtubules are necessary for cell division (mitosis), cell structure, transport, signaling and motility. Given their primary role in cell division, microtubules have been an important target for anticancer drugs -- often referred to as tubulin inhibitors or microtubule targeting agents. These compounds bind to tubulin protein, either in the monomer form or polymerized in microtubules, and prevent cancer cell proliferation by interfering with the microtubule dynamics required for cell division. This interference blocks the cell cycle sequence, leading to cell death (apoptosis).
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 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.
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).
Posted: April 2007