Data on the clinical and preclinical development of ENMD-2076, published in the December 3, 2010 on-line issue of the American Association for Cancer Research (AACR) journal, Clinical Cancer Research, is expected appear in an upcoming edition of the publication.

ENMD-2076, which is being developed by EntreMed Inc. , a clinical-stage pharmaceutical company, is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. Preclinical studies with ENMD-2076 demonstrated significant antitumor activity, including tumor regression, in multiple solid and hematological malignancies. 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. While ENMD-2076 is currently in a Phase II trial in ovarian cancer, preclinical and clinical activities are ongoing in assessing the compound’s applicability in other forms of cancer.

Trial Results
Results from the Phase I dose-escalation study in 67 heavily pre-treated patients with refractory advanced solid tumors demonstrated that among the fifty-eight patients evaluable for tumor response, two patients (3%) had partial responses as determined by RECIST, 49 patients (85%) had stable disease, and seven patients (12%) had progressive disease when ENMD-2076 was given orally daily. Both partial responses were observed in platinum resistant ovarian cancer patients. 18 of the 20 ovarian cancer patients had some reduction in the tumor marker, CA-125. Antitumor activity was demonstrated in other patients with a variety of cancers through reductions in tumor markers, reductions in tumor volume, and improvement in cancer-related symptoms. Prolonged clinical benefit (>6 months without progression or significant side effects) was achieved in patients with ovarian, liver, colorectal, renal cell, breast cancer and melanoma. In addition, encouraging clinical efficacy was seen in advanced and refractory ovarian cancer patients with both radiographic and CA-125 responses. ENMD-2076 is currently in a multi-center Phase II study in ovarian cancer patients, as well as in Phase I studies in multiple myeloma and leukemia.

In addition, preclinical results for ENMD-2076 were published in the AACR journal, Molecular Cancer Therapeutics, Vol. 10 (1), January 2011. Results included data generated from the initial discovery of the compound through its testing in preclinical models. ENMD-2076 was shown to have selective activity against multiple kinases including the mitotic kinase Aurora A, as well as kinases involved in angiogenesis including VEGFRs and FGFRs. Orally-administered ENMD-2076 induced regression or complete inhibition of tumor growth, in vivo, at well-tolerated doses in tumor xenograft models derived from breast, colon, melanoma, leukemia, and multiple myeloma cell lines.

“We continue to be encouraged by the activity ENMD-2076 has demonstrated in patients with refractory cancers. ENMD-2076 is active in patients who have received prior therapies directed towards the VEGF pathway and with traditional chemotherapy. Although ovarian cancer was chosen for the initial Phase II study, these results demonstrate that ENMD-2076 is active in patients with other solid tumors and are consistent with the preclinical results,” commented Dr. Carolyn F. Sidor, EntreMed’s Vice President and Chief Medical Officer. “These data will be instrumental in evaluating and selecting additional indications for further Phase II studies.”

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Gratifying Results
Dr. Mark Bray, Vice President Research at EntreMed, commented on the publications, “It is extremely gratifying to have the early preclinical data for ENMD-2076 in print concurrently with the exciting results from the Phase I clinical trials that have been presented and published. The Molecular Cancer Therapeutics manuscript is the culmination of several intensive years of work by a dedicated team, who were able to show through a series of rigorous experiments that ENMD-2076 is a highly active, well-tolerated compound with a novel mechanism of action involving both antiangiogenic and antiproliferative components. Information obtained through the course of this research has been invaluable in designing and interpreting correlative studies within our ongoing clinical trials.”

EntreMed initiated a multi-center Phase II study for ENMD-2076 in ovarian cancer patients in 2010. Ovarian cancer was selected as the initial Phase II indication based on results from the Phase I study in patients with solid tumors in which the clinical benefit of ENMD-2076 was observed in this patient population. Recently, the Company completed enrollment for the Phase II study in ovarian cancer patients and, once the data have been analyzed, intends to present results of the study at an upcoming scientific meeting.

As previously announced, data from the Phase I studies in multiple myeloma and leukemia were presented during the American Society of Hematology meeting in December 2010. Of nine evaluable patients who participated in the Phase I study with ENMD-2076 in multiple myeloma, three patients had stable disease and one patient achieved a partial response. The study continues to enroll patients. In the Phase I study in patients with relapsed or refractory leukemia, results for 20 evaluable patients showed that ENMD-2076 was associated with anti-leukemia activity. One patient achieved a durable CRi (complete remission with incomplete hematological recovery) and three patients achieved a morphologic leukemia-free state (MLFS). An additional 4 patients had reductions in bone marrow blast counts of 11%, 14%, 23%, and 65%.

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