EntreMed`s Panzem(R) Demonstrates Antitumor Activity In Brain Tumor Model
Al Musella's Comments: (This is his personal views and are not necessarily the views of the Musella Foundation!)
Posted on: 12/23/2006
EntreMed's Panzem(R) Demonstrates Antitumor Activity In Brain Tumor Model
Article Date: 22 Dec 2006 - 0:00 PST
EntreMed, Inc. (Nasdaq: ENMD), a clinical-stage pharmaceutical company developing therapeutics primarily for the treatment of cancer and inflammatory diseases, today announced the publication of preclinical results for its lead clinical- stage compound, Panzem(R) (2ME2 or 2-methoxyestradiol), in an orthotopic brain tumor model. The results of the studies, conducted by EntreMed collaborators at Emory University, were published in the December 2006 issue of Cancer Research (Vol. 66, Issue 24).
Using non-invasive imaging and histological evaluation in a preclinical orthotopic glioma tumor model, 2ME2 treatment resulted in a dose-dependent reduction in tumor size. Tumor burden in the brain was reduced by 77% following 2ME2 treatment, as determined by magnetic resonance imaging. Further histological examination of the 2ME2 treated tumors demonstrated a dose-dependent decrease in acetylated tubulin, a marker of microtubule disruption. A decrease in acetylated tubulin is consistent with 2ME2 causing tumor inhibition through interfering with microtubules.
In this preclinical study, 2ME2 also showed a significant improvement in tissue oxygenation, which should result in improved responsiveness to therapy, and a decrease in HIF-1alpha (hypoxia inducible factor-1alpha). HIF-1alpha is a nuclear transcription factor that governs gene expression of proteins involved in tumor cell survival pathways, including angiogenesis.
2ME2 is an orally-active small molecule that attacks tumor cells through multiple mechanisms of action and blocks the development of new blood vessels that feed tumor cells. Panzem(R) NCD, an oral liquid formulation, has been shown to result in enhanced drug levels of 2ME2 in patients and has been shown in preclinical studies to significantly increase the drug's bioavailability and activity. EntreMed is currently conducting Phase 1 and 2 clinical studies with Panzem(R) NCD in cancer patients, including a Phase 2 study in patients with glioblastoma multiforme (GBM) at the Brain Tumor Center at Duke University Medical Center.
Malignant glioma is an aggressive and highly vascularized disease. Previously, EntreMed has presented preclinical data showing that combination treatment with 2ME2 and Temodar(R) (temozolomide) resulted in a marked enhancement in tumor inhibition compared to either agent alone in a glioblastoma model. Collectively, these preclinical studies support the clinical evaluation of Panzem(R) in the GBM patient population.
Carolyn F. Sidor, M.D., M.B.A, EntreMed Vice President and Chief Medical Officer, commented, "We are encouraged by the outcome of this preclinical GBM study, which has resulted from our long-standing collaboration with researchers at Emory University. These tumors are highly angiogenic and frequently harbor PTEN mutations, which result in high levels of HIF-1alpha protein, a pro-survival and pro-angiogenic transcription factor. We are currently evaluating Panzem(R) NCD as a single agent in patients with GBM, with plans to initiate a combination clinical study with Panzem(R) NCD and Temodar(R), an approved anticancer therapy, in this patient population in 2007."
Temodar(R) is a registered trademark of its owner and is not a registered trademark of EntreMed, Inc.
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 1 and 2 clinical trials for cancer, as well as in preclinical development for rheumatoid arthritis. MKC-1, an oral cell cycle regulator, is in Phase 1 and 2 clinical trials 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, signaling pathways, 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 http://www.entremed.com 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 development of 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).
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