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The first clinical trial of Prolanta to treat ovarian cancer is anticipated to begin in Q3 2011. The preclinical testing required prior to the first-in-human clinical trial was completed in Q4 2010. The Phase I trial will be an open-label safety and pharmacokinetic study in women aged 18 and over (non-pregnant, women of childbearing age either on birth control or who have undergone an oophorectomy) with advanced ovarian cancer. The trial will test three escalating doses in cohorts of three to six patients recieving daily subcutaneous administration. The primary objective of this study will be to evaluate the tolerability and determine the optimal dose of Prolanta. The safety evaluation will be determined by assessing adverse events, physical examination, electrocardiogram, changes in clinical laboratory results including clinical chemistry, hematology and urinalysis. Vital signs including blood pressure, pulse and respiratory rate will be included in the clinical evaluation. The optimal dose of Prolanta will be determined by evaluating both the safety profile and blood levels of Prolanta.

The Phase IIA trial is planned in ovarian cancer. The trials will be open label, randomized, controlled trials evaluating the optimal dose of Prolanta added to standard of care chemotherapy, in patients who have relapsed at least 6 months following treatment cessation of first-line platinum-containing therapy. Approximately 30 patients will be enrolled in each trial, with a 2:1 randomization of Prolanta plus chemotherapy to chemotherapy only. Patients in the treatment groups will receive daily subcutaneous injections of Prolanta at the optimal dose along with chemotherapy. The primary objective of these trials will be to determine the effect of Prolanta on progression-free survival. Tumor response will be determined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Safety and the pharmacokinetics of Prolanta in combination with the chemotherapy will also be studied. Various tumor proteins will be analyzed from tumor biopsies obtained before and after the treatment period to evaluate the pharmacodynamics of Prolanta and to identify a potential biomarker to recognize patients that may respond to treatment with Prolanta for future trials. Tumor markers to be analyzed may include Ki67 and PCNA (both markers of cell proliferation), PRL, PRLR, Bcl-2, and phosphorylated MAPK, STAT3 and STAT5 proteins. The serum protein CA-125 will be evaluated in the ovarian cancer patients.

The Phase IIB will be designed similarly with a sample size that will have 80% power to detect the difference at a 2-sided alpha level of 0.05 using a log-rank test for equality of survival curves.The sample size is anticipated to fall between 120 and 150 patients. Treatment of the patients will continue until signs of disease progression occur, or side effects of the chemotherapy necessitate cessation. The primary outcome measure will be progression-free survival.

Secondary outcome measures will include overall survival, safety and tolerability, and objective tumor response, as evaluated by RECIST criteria. Tumor markers will be analyzed from tumor biopsies obtained before and after the treatment period, as described above.