Arno Therapeutics, Inc. announced that it has advanced its Phase I clinical trial evaluating its lead compound onapristone in women with progesterone receptor expressing tumors to the expansion stage and has now begun enrolling patients at the recommended Phase II dose of 50mg extended release tablets twice daily. This dose has been determined by an independent safety review committee to be safe and is the single agent dose which will be used in future clinical studies. The expansion stage of the Phase I study will include approximately 24 patients and is expected to primarily enroll patients with gynecologic tumors (including endometrial, ovarian and other uterine tumors) who have received fewer prior chemotherapy regimens than the patients enrolled in the dose escalation stage of the study.

Onapristone is an oral, anti-progestin hormone blocker that has been shown in previous Phase II clinical trials (not sponsored by Arno) to exhibit anti-tumor activity in patients with breast cancer. In pre-clinical testing, onapristone has been shown to block the activation of the progesterone receptor (PR), which is believed to be a mechanism that inhibits the growth of activated progesterone receptor (APR) driven breast, endometrial and other, primarily gynecological tumors. APR has the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic currently under development.

Arno Therapeutics has improved the manufacturing process for onapristone and developed a proprietary, sustained release formulation to avoid the high peak concentrations associated with previously investigated immediate release type formulations and to allow the continuous suppression of the APR. The ongoing, open-label Phase I study is currently enrolling patients and is designed to evaluate the safety of onapristone in the selected patient population, determine the recommended Phase II dose, and assess any antitumor activity. This multi-site trial is taking place in France and is expected to enroll a total of approximately 70 patients.

Arno is working with Biotrial S.A.S., a drug evaluation and pharmacology research company, as its contract research organization for this trial. To date, the Phase I clinical trial has enrolled 48 patients with PR positive tumors in the dose escalation stage, including 28 patients with gynecologic malignancies and 19 patients with breast cancer. Prior to entering this study, these heavily pre-treated patients had, on average, previously received three chemotherapy treatment regimens and one hormone therapy regimen.

In general, onapristone was well tolerated without substantial dose limiting toxicities. A total of three patients experienced Grade 3 liver function test abnormalities associated with progression of liver metastases and discontinued onapristone treatment. None of these adverse events were deemed to be drug-related by an independent safety review committee.

Currently, 15 patients from the dose escalation stage are still receiving onapristone therapy in the study. Five of the 48 patients enrolled in the dose escalation stage have been on study for less than eight weeks and are awaiting their first disease assessment evaluation. Of the 43 evaluable patients, one patient with serous ovarian cancer receiving 10mg twice daily of the extended release formulation has had a durable partial response (ongoing at 24 weeks).

In addition, 5 of 26 patients with gynecologic tumors and 2 of 16 patients with breast tumors have stable disease for greater than 16 weeks.