The immunotherapy works through small molecule agonism of the tumor necrosis factor superfamily receptors. In the preclinical studies, published in the Journal for ImmunoTherapy of Cancer, the company showed that linking a costimulatory receptor (CD137) to the Bicycle TICAs to a tumor antigen (EphA2) activates the costimulatory receptor selectively in the presence of tumor cells expressing that antigen.

Treatment of C57/Bl6 mice (transgenic for the human CD137 extracellular domain, huCD137) bearing EphA2-expressing tumors resulted in increased infiltration of CD8+ T cells, the elimination of tumors, and generation of immunological memory, according to the company. Tumor target-dependent CD137 agonism using TICAs resulted in elimination of tumors in preclinical models using only intermittent dosing, suggesting the potential for a wide therapeutic index in humans.

Bicycle is planning on initiating a clinical trial for its lead TICA program, BT7480, in 2021.