Positive results from Phase 2, open-label ENCORE 303 trial to be presented at ASCO 2010

Syndax Pharmaceuticals, Inc., a clinical-stage epigenetics oncology company, reported final results from the Phase 2, open-label ENCORE 303 trial in post-menopausal women with advanced, estrogen receptor (ER) positive breast cancer who were progressing on aromatase inhibitor (AI) therapy. Safety and efficacy results from the trial will be presented in a poster at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL tomorrow, Saturday, June 5, 2010.

"These findings are significant given that the patients enrolled were heavily hormonally pre-treated and relatively hormone resistant," said Joanna Horobin, president and chief executive officer of Syndax. "Resistance to AI therapy is multi-factorial and involves up-regulation of growth factor signaling pathways and down-regulation of estrogen receptor expression which may result from epigenetic modifications to the DNA and associated proteins. The disease stabilization achieved with the addition of entinostat supports our hypothesis that entinostat has the ability to normalize gene expression, thereby restoring sensitivity to targeted agents. We are optimistic that our ongoing ENCORE 301 study, a double-blind, randomized, placebo-controlled phase 2 study of entinostat in combination with the aromatase inhibitor exemestane, will provide further evidence supporting the clinical benefit and tolerability of entinostat in combination with aromatase inhibitors."

The primary endpoint of the study was Clinical Benefit Rate (CBR), defined as the proportion of patients who experience a complete or partial response or stable disease (SD) during the first six cycles of study treatment. Of the 26 evaluable patients in the ENCORE 303 study, one achieved a partial response (PR) and three achieved SD of greater than six months. The CBR of 15.4% exceeded the pre-specified rate of 5% defined in the study design with a p-value of 0.039. An additional six patients experienced SD between four and six months.

Secondary endpoints were objective response (OR) and progression-free survival (PFS), which were 3.9% and a median of 4.8 months, respectively. Overall survival, pharmacokinetics and correlation of selected biomarkers with clinical outcome were also measured. The most common adverse events considered to be related to entinostat were fatigue, nausea and diarrhea. No unexpected side effects were observed.

Syndax is also presenting two posters during the Society's new "Trials in Progress" session. These include abstract TPS128, which reviews ENCORE 301, a double-blind, randomized, placebo-controlled phase 2 study of entinostat in combination with exemestane, an aromatase inhibitor, in 114 post-menopausal women with ER positive metastatic breast cancer; and abstract TPS298, which reviews ENGAGE 501, an open-label, multicenter Phase 2 study in patients with Hodgkin's lymphoma. Data are anticipated from ENCORE 301 and ENGAGE 501 within 12 months.