SD-101 is a 30 nucleotide phosphorothioate (PS) oligodeoxynucleotide (ODN) containing juxtaposed CpG motifs with flanking nucleotides in a self-complimentary palindromic sequence. CpG motifs are found in bacterial DNA, which has long been recognized as having potent stimulatory effects on the immune system, including stimulating rejection of transplantable tumors in mice. The effects by the CpG motifs are mediated through recognition by Toll-like receptor 9 (TLR9), found in cells of the immune system.  This activity is mediated preferentially by specific DNA motifs containing a CpG dinucleotide and can be replicated by short synthetic ODNs. As agonists for TLR9, CpG-ODNs have been shown to stimulate IFN-α and interleukin (IL)-12 production as well as functional maturation in pDCs, and can induce proliferation and immunoglobulin (Ig) production in human B lymphocytes (B cells) . CpG-ODNs have no activity in mice with a homozygous deletion of the TLR9 gene.

SD-101 was specifically selected based upon its ability to stimulate very high levels on IFN-α as well as inducing maturation of pDCs to antigen presenting cells.  Consequently, SD-101 may have a significant antitumor effect by direct enhancement of innate immunity and indirect effect on T-cell immunity, stimulation of cytokines with direct or indirect antitumor activities (including IFN-α), and production of cytotoxic antibodies.

Intratumoral injection of SD-101 is expected to augment the response to humanized anti-PD-1 antibodies by inducing type I IFN and promoting T-cell infiltration and activation at the tumor sites