Syndax’s lead product entinostat has been studied in more than 600 cancer patients where objective tumor responses have been observed in both solid and hematologic malignancies. Entinostat’s established safety profile as both a single agent and in combination with a number of commercially available targeted therapies differentiates it from other histone deacetylase (HDAC) inhibitors. Having shown potential in breast and lung cancer, entinostat is moving toward pivotal clinical testing. It is a novel inhibitor of class I histone deacetylases, key enzymes that alter the structure of chromatin to control gene expression. This aberrant gene expression can result in reversible, epigenetically-based drug tolerance5,6
. Designed to selectively target the HDAC isoforms most relevant to the biology of tumors, entinostat can normalize dysregulated gene expression in cancer cells7
To maintain or increase sensitivity to targeted therapies with an HDAC inhibitor in combination, the drug must not significantly increase the toxicity profile for the combination. This will in part be determined by the effective dose and schedule of the HDAC inhibitor required to reverse the epigenetic resistance to the targeted therapies. Entinostat’s unique profile maximizes the opportunity to enhance and extend the benefit of proven cancer therapies. It is differentiated from competitor molecules because of its structure, isoform selectivity, convenient oral dosing schedule, prolonged 80-100 hour half-life, lack of both p450 inhibition and QTc prolongation.