Entinostat is an oral small molecule inhibitor of Class 1 Histone Deacetylases (HDACs). Class 1 HDACs have been shown to impact the number and activity of the population of immuno-suppressive cells known as myeloid-derived suppressor cells, or MDSCs, and regulatory T cells, or Tregs.
By blocking the immuno-suppressive effects of MDSCs and Tregs, we believe entinostat could enhance the body’s immune response to tumors. In preclinical studies, entinostat demonstrated synergistic anti-tumor activity in combination with immune checkpoint inhibitors, suggesting a potential to further increase the ability of the patient’s T cells to attack the tumor.
Syndax has also demonstrated that the delivery of entinostat in combination with hormone therapy can result in improvements in overall survival in advanced hormone receptor positive, or HR+, breast cancer patients, which has led to Breakthrough Therapy Designation by the FDA for that indication.
Entinostat’s long half-life allows once-weekly dosing and continuous exposure to therapy which could lead to positive immuno-modulatory effects without corresponding cytotoxic effects. We believe entinostat’s well-characterized safety profile and mechanism of action allows it to be readily combined with, and thereby enhance the activity of, conventional and novel cancer therapies, such as immune checkpoint inhibitors, hormone therapies and chemotherapies.