Ariad Pharmaceuticals announced the initiation of a randomized, multi-center, phase-2 clinical trial to evaluate the safety and efficacy of oral deforolimus, its investigational mTOR inhibitor, in patients with advanced endometrial cancer. In collaboration with Merck & Co, deforolimus is currently being studied in multiple clinical trials, both alone and in combination with other therapies, in patients with several different types of cancer. Under terms of the agreement, Ariad will receive a $2.5 million milestone payment from Merck upon treating the first patient in this clinical study.

The clinical trial will compare single-agent oral deforolimus to progestin in patients with metastatic or recurrent endometrial cancer following first line chemotherapy. The primary endpoint for the study is progression-free survival. Overall survival and response rate will be evaluated as secondary endpoints. This is the second phase-2 clinical trial to begin this quarter examining the safety and efficacy of oral deforolimus in patients with different solid tumours.

"We have phase-2 data on the intravenous form of deforolimus in endometrial cancer and are pleased to now examine the potential of this drug candidate in its oral form in similar patients with this cancer," stated Pierre F Dodion, senior vice president and chief medical officer of Ariad. "There is significant unmet medical need for the effective treatment of patients with endometrial cancer, and this controlled clinical study is designed to help inform us of the potential impact of oral deforolimus on patients with this difficult-to-treat cancer."

The clinical trial will enrol 150 patients at approximately 50 sites including medical centers in North America, Europe, Asia and Australia. Patients will be randomized (1:1) to oral deforolimus or progestin, a commonly accepted treatment in patients with endometrial cancer. Enrolment in the trial is expected to be completed by the second half of 2009.

"With the start of this trial, we now have begun enrolment in two phase-2 clinical trials of oral deforolimus this quarter," said Harvey J Berger, MD, chairman and chief executive officer of Ariad. "The start of this study is another important milestone for deforolimus and for the joint development program with Merck. We are committed to completing these clinical trials as quickly as possible facilitating the potential development of deforolimus in multiple cancer indications."

Ariad announced the initiation last month of a phase-2 clinical trial of deforolimus in patients with advanced breast cancer.

Endometrial cancer, which develops from the inner lining of the uterus, is the most common cancer found in the female reproductive system. According to the American Cancer Society, about 40,100 new cases of endometrial cancer will be diagnosed in the United States and approximately 7,470 women will die from this disease in 2008. Prognosis for patients is primarily based on the time of diagnosis relative to the stage of the cancer. Initial treatment consists of surgery alone, or in combination with radiation, chemotherapy and/or hormonal therapy. For those women with disease progression, chemotherapy is the only currently available treatment option, and limited benefit has been seen in such cases, emphasizing the need for new therapies.

Ariad's lead product candidate, deforolimus, is a novel rapamycin analog that specifically and potently inhibits mTOR, a downstream activator of the PI3K/Akt and nutrient sensing pathways. The mTOR protein acts as a 'master switch' in cancer cells. Blocking mTOR creates a starvation-like effect in cancer cells by interfering with cell growth, division, metabolism, and angiogenesis.

Ariad is engaged in the discovery and development of breakthrough medicines to treat cancer by regulating cell signaling with small molecules. Ariad is developing a comprehensive approach to patients with cancer that addresses the greatest medical need - aggressive and advanced-stage cancers for which current treatments are inadequate.