A Novel Oncology Drug Candidate
Syndax is developing entinostat as a combination therapy in multiple cancer indications, with our initial focus on tumors that have shown sensitivity to immunotherapy, including lung cancer, melanoma, ovarian cancer and triple-negative breast cancer. Entinostat is an oral, small molecule histone deacetylase, or HDAC, inhibitor that has direct effects on both cancer cells and immune regulatory cells, potentially enhancing the body’s immune response to tumors.
Entinostat has demonstrated synergistic anti-tumor activity in combination with immune checkpoint inhibitors in preclinical studies. 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.
HDACs are enzymes that are subdivided into four classes and are known to play a role in controlling cell survival, proliferation, angiogenesis and immunity. While most HDAC inhibitors broadly inhibit multiple classes of HDACs, preclinical studies have shown that entinostat’s inhibitory activity is selective to Class 1 HDACs, which 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. Through blocking the immuno-suppressive effects of MDSCs and Tregs, we believe entinostat has the potential to be used synergistically with therapies such as immune checkpoint inhibitors, resulting in the increased ability of the T cells to attack the tumor.
The long half-life of entinostat allows for continuous exposure to therapy potentially resulting in positive immuno-modulatory effects without corresponding cytotoxic effects. Another benefit of entinostat’s long half-life is the potential to minimize the frequency of dosing and reduce the severity and frequency of adverse events. 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.