ROCKVILLE, Md., Nov. 22 /PRNewswire-FirstCall/ -- EntreMed, Inc. , a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for ENMD-1198, a novel tubulin binding agent for which EntreMed intends to pursue clinical development. The Company plans to enter into Phase I oncology clinical studies with the compound in 2006.
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ENMD-1198 is a new chemical entity (NCE) based on a modified chemical structure of 2ME2 designed to increase antitumor and antiangiogenic properties and improve metabolism. ENMD-1198 is characterized by its multiple mechanisms of action, which include inducing apoptosis, binding microtubules, and inhibiting HIF-1alpha. HIF-1alpha is over-expressed in more than 70% of human tumors and its over-expression correlates with tumor aggressiveness, metastases and poor prognosis. Preclinical studies identified ENMD-1198 as an orally active, microtubule disrupting agent that leads to arrest of cell division and apoptosis in tumor cells. Additionally, ENMD-1198 exerts antiangiogenic activity that contributes to its overall antitumor effects.
In preclinical studies, ENMD-1198 has demonstrated pronounced in vivo antitumor activity in models of human cancer. Oral daily treatment with ENMD- 1198 in an orthotopic MDA MB 231 breast cancer model led to a reduction in tumor burden equivalent to the positive control cyclophosphamide, disruption of microtubules within tumor cells, and a substantial decrease in HIF-1alpha. ENMD-1198 also reduced protein levels for two additional transcription factors, NFkB and Stat3, known to modulate HIF-1alpha protein levels in vitro. All three transcription factors are known to regulate multiple genes and their proteins that contribute to tumor growth and progression.
In preclinical tumor studies, serum proteins regulated by HIF-1alpha, NFkB and Stat3, were also reduced substantially following oral administration of ENMD-1198. Results from several studies demonstrate significantly (40-100%) decreased plasma or serum levels of human VEGF (secreted by tumor cells), a major proangiogenic growth factor, compared to control animals following therapy with ENMD-1198. Serum levels of human IL-6 were also decreased significantly (62-96%). Over-expression of IL-6 is associated with higher morbidity in breast cancers, bone metastases, increased aromatase synthesis, and increased cancer drug resistance. Tumor levels of a third tumor protein regulated by HIF-1alpha, carbonic anhydrase IX (CA IX), were also decreased, consistent with HIF-1alpha inhibition.
Carolyn F. Sidor, M.D., M.B.A, EntreMed Vice President and Chief Medical Officer, commented, “We anticipate initiating Phase I oncology studies for ENMD-1198 in 2006. Last week, we announced results from our Phase Ib trials with our lead drug candidate, 2ME2 (Panzem(R) NCD) and the planning of Phase II studies. This means EntreMed will have two drug candidates with antitumor and antiangiogenic properties in the clinic in 2006. Both clinical stage drug candidates, Panzem(R) NCD and ENMD-1198, are multi-mechanism agents that inhibit HIF-1alpha, but with different safety and activity profiles. As such, we have a clear path to developing both compounds.”
About HIF-1
Hypoxia-inducible factor 1 (HIF-1) is a protein composed of two subunits -- HIF-1alpha and HIF-1beta. HIF-1 mediates tumor cell responses to changes in oxygen concentration and belongs to a class of molecules termed transcription (transfer of genetic code) factors. A transcription factor recognizes and binds to specific regions of DNA. In the case of HIF-1, binding results in the activation of greater than 60 genes encoding for proteins involved in cell proliferation and survival, angiogenesis, energy metabolism, and invasion and metastasis. HIF-1 is a mechanism that allows tumor cells to overcome the stress of oxygen deprivation and continue to survive.
About EntreMed
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 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.
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; 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
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CONTACT: Ginny Dunn, Associate Director, Corporate Communications &Investor Relations of EntreMed, Inc., +1-240-864-2643
Web site: http://www.entremed.com/
