ROCKVILLE, Md., April 3 /PRNewswire-FirstCall/ -- EntreMed, Inc. today announced the presentation of preclinical results for its lead clinical-stage compound, Panzem(R) (2-methoxyestradiol or 2ME2), and tubulin binding agent, ENMD-1198. The results from these studies were presented at the 97th Annual Meeting of the American Association for Cancer Research being held this week in Washington, DC.
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Preclinical studies demonstrate that 2ME2 can be combined with maximally tolerated doses (MTD) of standard chemotherapeutic agents without additive toxicity, resulting in greater antitumor activity than either agent alone. In one preclinical study, daily oral administration of 2ME2 in combination with a maximally tolerated course of Temodar(R) (temozolomide) resulted in 87% growth inhibition of advanced glioblastoma (brain cancer). Treatment with either 2ME2 or Temodar(R) alone was only marginally effective in slowing tumor growth.
In a separate preclinical study, 2ME2 was used in combination with a maximally tolerated course of 5-fluorouracil (5FU) in colon carcinoma. Daily oral administration of 2ME2 with 5FU resulted in 84% growth inhibition of established tumors, while treatment with either agent alone was only minimally effective in arresting tumor growth.
Taken together, these preclinical results suggest that incorporating 2ME2 into maximally tolerated courses of temozolomide or 5FU for cancer treatment may provide the ability to maximize the therapeutic potential of each agent. In addition, reduced doses of temozolomide or 5FU are not required when combined with 2ME2. These results support further evaluation of 2ME2 in combination therapy with approved standard-of-care cytotoxic agents.
In an additional AACR presentation, preclinical results were also presented for ENMD-1198, a novel tubulin binding agent. Oral administration of ENMD-1198 showed pronounced in vivo antitumor activity in three preclinical models of human cancer. Daily oral treatment with ENMD-1198 in an orthotopic MDA MB 231 breast cancer model led to the disruption of microtubules within tumor cells and a substantial decrease in HIF-1alpha, a tumor cell survival protein over-expressed in more than 70% of human tumors. HIF-1alpha over- expression correlates with tumor aggressiveness, metastases and poor prognosis. Activation of two additional transcription factors, NFkappaB and Stat3, known to modulate HIF-1alpha protein levels in vitro and promote tumorigenesis, were also reduced following daily oral ENMD-1198 treatment. All three transcription factors are known to regulate multiple genes and their proteins that contribute to tumor growth, angiogenesis and progression.
In a separate preclinical orthotopic breast cancer model, serum proteins regulated by HIF-1alpha, NFkappaB and Stat3, were also reduced substantially following oral administration of ENMD-1198. Results from several studies demonstrate that treatment with ENMD-1198 decreased plasma or serum levels of the human proangiogenic growth factor VEGF (secreted by tumor cells) substantially (40-100%). Serum levels of human IL-6, which is modulated by NFkappaB, were also decreased significantly (62-96%) following ENMD-1198 treatment. Over-expression of IL-6 is associated with higher morbidity in breast cancers, bone metastases, and increased cancer drug resistance.
Carolyn F. Sidor, M.D., EntreMed Vice President and Chief Medical Officer, commented on the presentations, "These studies continue to support the potential for 2ME2 in combination cancer therapy. We believe 2ME2's safety profile provides multiple opportunities for combining it with conventional chemotherapies to increase the effectiveness of both anticancer drugs. EntreMed is currently evaluating Panzem(R) NCD in Phase 1 and 2 clinical oncology studies, as well as preclinical studies of 2ME2 in rheumatoid arthritis."
Dr. Sidor continued, "Preclinical results for ENMD-1198 continue to be impressive. ENMD-1198 is a novel molecule with potent antitumor and antiangiogenic properties. These data provide valuable information regarding the potential importance of HIF-1alpha inhibition in the treatment of human cancers. We have an active IND for this compound and anticipate commencing Phase 1 oncology studies during the second quarter of 2006."
About EntreMed
EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem (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, recently acquired through the Company's acquisition of Miikana Therapeutics, is also in Phase 2 studies 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 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, 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; 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).
CONTACT: Ginny Dunn EntreMed, Inc. Associate Director Corporate Communications & Investor Relations (240) 864-2643
Photo: Newscom: http://www.newscom.com/cgi-bin/prnh/20010620/ENMDLOGOAP Archive: http://photoarchive.ap.orgPRN Photo Desk photodesk@prnewswire.comEntreMed, Inc.CONTACT: Ginny Dunn Associate Director, Corporate Communications &Investor Relations, of EntreMed, Inc., +1-240-864-2643
Web site: http://www.entremed.com/
