EntreMed Announces Publication Of Preclinical Results For ENMD-2076 In Triple-negative Breast Cancer

ROCKVILLE, Md., Nov. 26, 2012 /PRNewswire/ -- EntreMed, Inc. (Nasdaq: ENMD), a clinical-stage pharmaceutical company developing targeted therapeutics for the treatment of cancer, announced today the publication of favorable results of a preclinical study in breast cancer of its oral Aurora A/angiogenic kinase inhibitor, ENMD-2076. 

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The article, entitled "Predictive Biomarkers of Sensitivity to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Breast Cancer Models" reports evidence that ENMD-2076 exhibited robust anticancer activity against breast cancer cell lines lacking expression of the estrogen receptor (ER), progesterone receptor (PR) and without HER2‑amplification: a particularly difficult to treat subtype termed "triple-negative" breast cancer (TNBC).  TNBC is associated with a shortened disease-free and overall survival at all stages of diagnosis when compared to other breast cancer subtypes.  Candidate predictive biomarkers were also identified which may be useful in selecting patients that are particularly sensitive to this compound, ENMD-2076, in the future. 

In this study, a diverse panel of twenty-nine breast cancer cell lines representative of the clinically defined breast cancer subtypes were exposed to ENMD-2076 and the effects on proliferation, apoptosis, and cell cycle distribution were evaluated.  ENMD-2076 demonstrated more robust activity against cell lines of the TNBC subtype compared to the luminal and HER2-amplified subtypes.  This in vitro activity was confirmed in vivo, in MDA-MB-468 and MDA-MB-231 TNBC xenografts.  Baseline gene expression profiling and pathway analysis of the panel revealed that p53 and G1/S cell cycle pathways were upregulated in the more sensitive cell lines.  Within the TNBC subset itself, cell lines with a p53 mutation and increased p53 expression were more sensitive to the cytotoxic and pro-apoptotic effects of ENMD-2076 exposure than cell lines with decreased p53 expression.  This information provides the basis for a predictive biomarker strategy to explore in future clinical trials with ENMD-2076.

Dr. Jennifer R. Diamond of the University of Colorado School of Medicine, who led the study, commented, "Triple-negative breast cancer is an aggressive breast cancer subtype which carries a high risk of developing metastasis. A major barrier to the successful treatment of metastatic TNBC is the lack of effective targeted anti-cancer agents.  Through this study, we show that ENMD-2076 has activity against preclinical models of breast cancer with more robust activity against TNBC.  The study also supports further clinical investigation of ENMD-2076 in patients with metastatic TNBC with an emphasis on the continued development of p53-based predictive biomarkers."

Ken Ren, Ph.D., EntreMed's Chief Executive Officer further commented, "One of the major challenges for the development of a target therapy for cancer is the identification of a responsive subtype with a predictive biomarker. In our previous Phase 1 study, we observed a patient with TNBC who had failed multiple chemotherapy regimens then had clinically significant stabilization of disease for 41 weeks after ENMD-2076 treatment.  The benchmark of median duration after first line therapy in such patients with metastasis is just 12 weeks. This pre-clinical study illustrated scientific insight into the selective sensitivity of TNBC to ENMD-2076 with direct correlation to p53 mutation and over expression. It provides strong support for the rational of our ongoing Phase 2 TNBC trial. Upon further confirmation clinically, it may also provide guidance on future trials for patient selection, and may increase the probability of success. We are continuing to enroll patients in the ongoing Phase 2 trial and anticipate the initiation of a second site for this trial soon. We remain on track with our clinical development activities and expect our progress to accelerate in the coming months and year."

About EntreMed

EntreMed, Inc. is a clinical-stage pharmaceutical company employing a drug development strategy primarily in the United States and China to develop targeted therapeutics for the global market.  Its lead compound, ENMD-2076, a selective angiogenic kinase inhibitor, has completed several Phase 1 studies in solid tumors, multiple myeloma, and leukemia, and is currently completing a multi-center Phase 2 study in ovarian cancer. EntreMed, Inc. recently initiated a Phase 2 study of ENMD-2076 in triple-negative breast cancer.  Additional information about EntreMed is available on the Company's website at www.entremed.com and in various filings with the Securities and Exchange Commission (the SEC).

About ENMD-2076

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in Phase 1 clinical trials in solid tumor cancers, leukemia, and multiple myeloma. ENMD-2076 is currently completing a Phase 2 trial for ovarian cancer.  EntreMed, Inc. recently initiated a Phase 2 study of ENMD-2076 in triple-negative breast cancer.

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: the risk that we may be unable to continue as a going concern as a result of our inability to raise sufficient capital for our operational needs; the possibility that we may be delisted from trading on the Nasdaq Capital Market; the volatility of our common stock; the difficulty of executing our business strategy in China; our inability to enter into strategic partnerships for the development, commercialization, manufacturing and distribution of our proposed product candidate; risks relating to the need for additional capital and the uncertainty of securing additional funding on favorable terms; declines in actual sales of Thalomid^® resulting in reduced royalty payments; risks associated with our product candidates; any early-stage products under development; results in preclinical models are not necessarily indicative of clinical results; uncertainties relating to preclinical and clinical trials, including delays to the commencement of such trials; the lack of success in the clinical development of any of our products; dependence on third parties; and risks relating to the commercialization, if any, of our proposed products (such as marketing, safety, regulatory, patent, product liability, supply, competition and other risks). Such factors, among others, could have a material adverse effect upon our business, results of operations and financial condition. We caution readers not to place undue reliance on any forward-looking statements, which only speak as of the date made. Additional information about the factors and risks that could affect our business, financial condition and results of operations, are contained in our filings with the U.S. Securities and Exchange Commission ("SEC"), which are available at www.sec.gov.

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Investor Relations
EntreMed, Inc.
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