Syndax Pharmaceuticals, a clinical-stage epigenetics oncology company, announced allowance by the European Patent Office for the patent application titled “N-(2-AMINOPHENYL)-4[N-(PYRIDINE-3-YL) - METHOXYCARBONYL—AMINOMETHYL]-BENZAMINE (MS-
275) POLYMORPH B.” This allowance follows the recent US issuance which was granted in June adding to the extensive patent estate for the Company’s lead product, entinostat.

The patent covers the novel polymorph form B of the oral histone deacetylase inhibitor, entinostat, which is the specific polymorph being developed by Syndax for combination therapy with aromatase inhibitors for metastatic breast cancer and epidermal growth factor receptor tyrosine kinase inhibitors for advanced non-small cell lung cancer.

“This European allowance combined with the recent US issuance provides a strong patent position for entinostat, our lead product candidate, as we move forward into phase III testing for women with metastatic breast cancer,” said Joanna Horobin, MD, president and chief executive officer of Syndax. “We look forward to presenting the results from our randomized phase II placebo-controlled study in metastatic breast cancer at the ASCO 2011 Breast Cancer Symposium in September. We believe entinostat may help address the significant need to improve outcomes for the thousands of women in the United States living with metastatic breast cancer by extending the benefit of hormone therapy and delaying initiation of chemotherapy.”

Syndax’s lead product entinostat is a novel, oral small molecule inhibitor of class I histone deacetylases, key enzymes that alter the structure of chromatin to control gene expression. Entinostat is differentiated from other members of the class through its unique selectivity profile, pharmacokinetic properties and safety profile.

Entinostat has been studied in more than 600 cancer patients where objective tumour responses have been observed in both solid and haematologic malignancies. Breast cancer animal models demonstrated that resistance to aromatase inhibitors occurs through upregulation of growth factor signaling pathways and down-regulation of estrogen receptor-alpha (ER).

Entinostat effectively down-regulates growth factor signalling in breast cancer cells where these pathways are active. Entinostat also up-regulates the expression of ER in breast cancer cells which have negligible or undetectable levels of ER. In pre-clinical testing entinostat induced tumour regression when combined with an aromatase inhibitor after the development of hormone resistance.

The ability to target multiple mechanisms of resistance establishes entinostat as a promising candidate for preventing and overcoming aromatase inhibitor resistance through epigenetic modulation. Additional phase II studies with entinostat have demonstrated promising results in combination with the EGFR-TKI erlotinb (ENCORE-401) in non-small cell lung cancer and as a single agent in Hodgkin’s lymphoma (ENGAGE-501). Results from the ENCORE clinical programme have provided the basis for moving entinostat in pivotal, phase III testing across a platform of breast and lung cancer indications.