UI-102: a PNP-encapsulated TLR7/8 agonist for cancer treatment
UI-102 is a PNP formulation encapsulating a small molecule TLR7/8 agonist for systemic injection. UI-102 selectively accumulates in the tumor tissue where it is incorporated into DC-SIGN-expressing, immune suppressive M2-like TAMs. The TLR7/8 agonist then triggers re-polarization of these cells into immune stimulatory M1-like TAMs. M1-like TAMs then kill tumor cells by phagocytosis, present tumor antigens to anti-tumor T cells, and secret inflammatory cytokines and chemokines in the tumor microenvironment. This change transforms immune-/treatment-resistant “cold” tumor into immune-/treatment-sensitive hot tumor.
A series of our preclinical results using various mouse cold tumor models and in vitro cultured human macrophages support the above-mentioned therapeutic effects of UI-102 including synergy with immune checkpoint inhibitors and its mode-of-action. Reduction of TLR7/8 stimulation-associated side effects are observed with UI-102 in animal models. These pieces of preclinical evidence encourage clinical application of UI-102, and we intend to initiate the First-in-Human clinical study of UI-102 in mid-2025 as monotherapy and in combination with immune checkpoint inhibitors for the treatment of refractory solid tumors.