EntreMed Commences Study In Ovarian/Endometrial Cancers

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Ovarian/Endometrial Cancers

EntreMed commenced Phase 2 study with its novel cell cycle inhibitor, MKC-1, in recurrent or resistant epithelial ovarian cancer and advanced endometrial cancer patients. The study will be conducted at multiple sites in Canada with Dr. Amit Oza, Senior Staff Physician and Associate Professor of Medicine, Princess Margaret Hospital, University of Toronto, serving as the principal investigator.

The primary objective of this Phase 2 study will be to determine the antitumor activity of MKC-1 administered orally as a single agent in platinum or taxane refractory ovarian and endometrial cancer patients. In addition, safety, response duration in patients with an objective response, and progression free survival (PFS) will also be assessed. The study will be a two arm parallel group design with each group having two stages.

MKC-1 is a novel, orally-active cell cycle inhibitor with in vitro and in vivo efficacy against a broad range of human solid tumor cell lines, including multi-drug resistant cell lines. Data from previous studies with MKC-1 demonstrate broad-acting antitumor effects, showing tumor growth inhibition or regression in multiple preclinical models, including paclitaxel-resistant models.

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MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M-phase (mitosis) of the cell cycle, and induce apoptosis. Furthermore, MKC-1 inhibits the Akt-mTOR signaling pathways, which may occur through inhibition of the mTOR/rictor pathway. The Akt-mTOR pathway is the most frequently mutated pathway in human tumors and mutations have been shown to promote tumor progression and decrease survival in cancer patients."

Commencement of this Phase 2 multi-center study represents the continuation of our focus on the development of MKC-1 in diseases where, based on its mechanism of action, we would expect activity," commented Carolyn F. Sidor, M.D., M.B.A., EntreMed's Vice President and Chief Medical Officer. "We now have five clinical trials underway to test the safety and efficacy of MKC- 1 in solid and hematological cancers, including two clinical development programs in Canada. We expect to invest in further clinical trials during 2008 to test the extent of MKC-1's clinical utility in multiple tumor types."

About Ovarian and Endometrial Cancers

Ovarian cancer accounts for 4% of all cancers among women in the United States, and ranks fifth as the cause of cancer deaths. The American Cancer Society estimates that there will be approximately 22,000 newly diagnosed cases of ovarian cancer in the U.S. in 2007 resulting in approximately 15,000 deaths. About half of all ovarian cancers occur in post-menopausal women. Ovarian cancer is frequently asymptomatic in the early stages. As a result, ovarian cancer is often not diagnosed until stage III or IV, where 5-year survival rates decline to 10-20%. Current drug therapy involves paclitaxel and carboplatin/cisplatin regimens. Many patients develop resistance to these drugs, so there is substantial need for innovative therapies that can overcome resistance, either as a single agent or in combination with approved chemotherapeutic agents.

Endometrial cancer, the most common cancer found in women's reproductive organs, starts in the inner lining of the uterus (endometrium). The American Cancer Society estimates that there will be approximately 39,000 new cases of cancer of the uterine body diagnosed in the U.S. in 2007, resulting in approximately 7,400 deaths. There are currently four basic types of treatment for endometrial cancer including surgery, radiation, hormone therapy, and chemotherapy, of which surgery is the most common treatment.

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