EntreMed Presents Preclinical Data for Second Generation 2ME2 Compounds
2ME2 Analogs Show Enhanced Antitumor and Antiangiogenic Activity
April 20, 2005
ROCKVILLE, MD, April 20—EntreMed, Inc. (Nasdaq: ENMD) today announced the presentation of preclinical results for its lead 2-methoxyestradiol (2ME2) analogs. Results from these studies, conducted by EntreMed researchers and their collaborators, were presented at the 96th Annual Meeting of the American Association for Cancer Research (AACR) in Anaheim, California.
EntreMed scientists have modified the chemical structure of 2ME2 to develop analogs with increased antitumor and antiangiogenic properties and improved metabolism while retaining 2ME2’s multiple mechanisms of action. These mechanisms include inducing apoptosis, binding microtubules, and inhibiting HIF-1Î±lpha. The Company’s 2ME2 analogs demonstrate improved pharmacokinetic parameters, reduced metabolism, and enhanced antitumor activity in preclinical animal models and represent the next generation of molecules with potential for broad application in cancer and other diseases.
Results from a first preclinical study, conducted by EntreMed collaborators, demonstrated enhanced activity of ENMD-1198 both in vitro and in an orthotopic lung cancer model when compared to 2ME2. Furthermore, a dose-dependent increase in survival was observed, indicating the potential for ENMD-1198 in the treatment of human lung cancers.
In a second preclinical study, EntreMed scientists demonstrated that 2ME2 analogs improved median survival time significantly in a metastatic lung cancer model and reduced tumor volumes significantly in a separate orthotopic cancer model. The study further demonstrated that 2ME2 analogs are microtubule destabilizing agents that cause a reduction in HIF-1Î±lpha protein levels. HIF- 1alpha is over-expressed in more than 70% of human cancers and their metastases, including breast, prostate, head and neck, brain, and lung cancers.
Based on its antitumor activity, enhanced microtubule disruption and HIF- 1alpha inhibition, analog ENMD-1198 is undergoing further preclinical evaluation and IND-directed toxicology studies.
Carolyn F. Sidor, M.D., M.B.A, EntreMed Vice President and Chief Medical Officer, commented on the presentations, “ENMD-1198 retains the mechanisms associated with our lead drug candidate, 2ME2 (PanzemÂ® NCD). This is important, as we believe these molecules represent novel agents. ENMD-1198’s enhanced antitumor activity in multiple models makes it a good candidate for IND-directed studies and we anticipate filing an IND for this compound later in the year.”
To view EntreMed’s poster presentations, visit Scientific Presentations under the Therapeutic Pathways section of the Company’s website at http://www.entremed.com.
EntreMed, Inc. (Nasdaq: ENMD) is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. PanzemÂ® (2-methoxyestradiol or 2ME2), the Company’s lead drug candidate, is currently in clinical trials for cancer, as well as in preclinical development for non-oncology indications. 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.
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