EntreMed Presents Mechanism Data for Its Three Lead OncologyCompoundsMultiple Mechanisms for Panzem NCD, MKC-1, and ENMD-1198 Highlighted at Oncology Drug Discovery Conference
ROCKVILLE, Md., March 26, 2007 /PRNewswire-FirstCall/ -- EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced the presentation of comparative mechanism of action data for its three lead clinical stage compounds Panzem(R), MKC-1 and ENMD-1198. These data were presented by Dr. Theresa M. LaVallee, EntreMed's Senior Director, Cell Biology in an oral podium session during the Apoptosis in Drug Discovery Conference, March 22-23, 2007 in San Diego, CA.
Panzem(R), MKC-1 and ENMD-1198 are three orally available agents that exhibit antiproliferative activity through G2/M arrest, apoptosis and antiangiogenesis. In preclinical models, these compounds are not sensitive to multi-drug resistance pumps and show activity in both vinca and taxane resistant tumor cell lines. While these three agents all bind to the colchicine-binding site of tubulin, they have distinct mechanisms of action. Panzem(R) has a well tolerated safety profile that lends itself to combination therapy with many other chemotherapeutic agents. In addition to binding tubulin, MKC-1 binds to importin-beta and inhibits signaling through the PI3K- Akt-mTor pathway. The PI3K-Akt-mTor pathway is frequently activated in cancer and has been shown to promote tumorigenesis. In an orthotopic animal model of human breast cancer, ENMD-1198 led to the disruption of microtubules within tumor cells and a substantial decrease in tumor cell proliferation and angiogenesis. The mechanisms of action of these three tubulin agents was compared and contrasted during the presentation.
Microtubules are key components of the cell structure and are essential for maintenance of cell shape, cellular functions and cell division (growth). These highly dynamic filaments are composed of dimeric tubulin proteins. Microtubule targeting drugs are one of the most successful classes of chemotherapy agents and are used for both solid and liquid tumors. There are three drug binding sites on tubulin: the vinca binding domain, the taxol- binding site and colchicine-binding site. The vinca alkaloids destabilize microtubules. The taxanes bind to the taxol-binding site and stabilize microtubules. While vincas and taxanes are widely used for treating cancer, there is a need to develop orally available molecules that have reduced toxicity and overcome resistance to approved chemotherapeutic agents.
Carolyn F. Sidor, M.D., M.B.A., EntreMed Vice President and Chief Medical Officer, commented on the results, "EntreMed is focused on developing multi- mechanism drugs for the treatment of cancer that have both antiproliferative and antiangiogenic properties. Tubulin binding and subsequent microtubule disruption are common mechanisms of our three lead compounds, yet clinical and preclinical data for these product candidates demonstrate that subtle differences in microtubule dynamics can lead to different approaches to the treatment of cancer. Panzem(R), MKC-1 and ENMD-1198 are all orally-active yet distinct tubulin binding agents, and exhibit a different array of antitumor activity preclinically. Understanding the multiple mechanisms of these drug candidates will help guide our selection of clinical indications and biomarkers. Panzem(R) NCD and MKC-1 are currently in multiple Phase 2 clinical trials for cancer and ENMD-1198 is in Phase 1 trials in advanced cancer patients."
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: March 2007