We are focused on developing two categories of Bicycles against our oncology targets:
Our Bicycle conjugates, including both toxin conjugates and targeted innate immune activators, are designed to rapidly deliver drugs systemically. The toxin conjugates deliver toxin payloads into solid tumors, while the targeted innate immune activators are designed to precisely target local immune activation within tumors without activating the immune system in bystander normal tissues, avoiding the need for direct tumor injection. These conjugates have favorable pharmacokinetic characteristics that provide extensive tissue penetration and a pronounced pharmacodynamic effect with a short duration of systemic exposure. Bicycles are excreted by the kidney (rather than the liver) and have shown no signs of immunogenicity to date. Together, these attributes support a favorable toxicological profile to minimize damage to normal tissue.
Strategies that activate cytotoxic T-cells, a type of cell involved in the immune response, have been observed to improve outcomes in cancer. We believe that Bicycles represent a differentiated approach to target these T-cells that may confer several advantages over existing modalities due to the multivalency and pharmacokinetic characteristics of Bicycles. Our Bicycle T-cell modulators are designed to circumvent the limitations of antibody and biologic therapies, such as liver toxicity and limited efficacy, to better enable combination therapy. The modular nature of Bicycles allows us to optimize therapeutic molecules for specific targets.
We have identified potent Bicycle activators of multiple tumor necrosis factor (or TNFR family) receptors, including CD137 – a receptor that activates T-cells, in an effort to better enable combination therapy. In preclinical studies, we have linked these TNFR binding Bicycles to a range of tumor antigen targeting Bicycles to construct bi-specific molecules and observed that these bi-specific molecules agonize the CD137 receptor only in the presence of cells that express the appropriate tumor antigen, effectively converting the tumor cell into the equivalent of an antigen presenting cell.