SD-101 is a proprietary investigational TLR9 agonist designed to elicit a potent and focused immune response to cancer. By targeting TLR9 in both the early and late endosomes of plasmacytoid dendritic cells, SD-101 is intended to stimulate multiple mechanisms of tumor killing.
SD-101 was designed for highly efficient activation of the two principal TLR9 signaling pathways. One pathway leads to rapid Interferon-α production which in turn, stimulates a number of critical activities including activating natural killer cells, blocking immune suppression, and promoting Th1 and CD8+ T cell homing into the tumor. The second pathway leads to efficient generation and activation of tumor-specific cytotoxic CD8+ T cells.
By delivering SD-101 directly into the tumor, we can potentially focus cancer killing activities associated with TLR9 stimulation to the tumor and take advantage of high concentrations of tumor antigens from dying cells. Exposure to the tumor antigens can generate memory T cells that maintain long-lasting therapeutic effects. By stimulating the natural immune response SD-101 has the potential to be broadly effective in multiple tumor types.
Preclinical data support the use of TLR9 agonists in patients with solid tumors and hematologic malignancies. SD-101 has shown anti-tumor activities in multiple mouse models alone and in combination with immune checkpoint inhibitors. These experiments suggest there could be synergies created between anti-PD-1 and SD-101. Based on data to date, SD-101 may increase CD8+ T cell infiltration into tumors compared to anti-PD-1 alone.