IMO-2125

Drug Overview

IMO-2125 is a synthetic phosphorothioate oligonucleotide-based agonist of toll-like receptor 9 (TLR9) designed to mimic the bacterial DNA that normally activates TLR9. The phosphorothioate bond, which substitutes a sulfur atom for a non-binding oxygen in the phosphate backbone of the oligonucleotide, confers nuclease resistance, vastly improving its half-life in the body. Stimulation of TLR9 initiates a cascade of innate and adaptive immune responses, which may promote an antitumor response.

Idera is positioning IMO-2125 in combination with Yervoy (ipilimumab; Bristol-Myers Squibb/Ono Pharmaceutical) for patients refractory to the widely used anti-programmed death-1 (PD-1) therapies. Yervoy is already commonly used in this patient population as a monotherapy, as its cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) target differentiates it from anti-PD-1 therapy. In the context of patients with BRAF mutations, a common next step after failure of treatment with a PD-1 antibody is treatment with mitogen-activated protein kinase (MAPK) inhibitors; therefore, these drugs represent notable competition in this space. Nevertheless, if IMO-2125 can add benefit to Yervoy in this setting, the combination will likely be widely adopted in the approximately 40–75% of patients who do not have a response to PD-1 inhibitors such as Opdivo (nivolumab; Bristol-Myers Squibb/Ono Pharmaceutical) and Keytruda (pembrolizumab; Merck & Co).