Powered by the invention of our revolutionary new class of medicines, we are developing innovative treatments for cancers with high unmet medical needs.
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 control damage to normal tissue.
Strategies that activate T and NK (“natural killer”) cells, which form part of the body’s normal immune response, have been observed to improve patient outcomes in cancer. We believe that Bicycles, as synthetic small molecules, represent a paradigm shift in targeting these cell types as they may confer several advantages over existing modalities, namely their small size, modularity for conjugation and favorable pharmacokinetics. The modular nature of Bicycles allows us to rapidly generate agonists of immune cell receptors, for example CD137, and to direct these by coupling to tumor cell antigen targeting Bicycles. These Bicycle® immune cell agonists are designed to better enable combination therapy and may circumvent many of the limitations of existing antibody and biologic therapies, such as liver or gastrointestinal toxicities.
We have identified potent Bicycle® agonists of multiple tumor necrosis factor (or TNFR family) receptors, including CD137 – a receptor that activates T cells, and other immune cell types, 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 Bicycle® tumor-targeted immune cell agonizing molecules (Bicycle TICAs). We have observed that these TICA molecules agonize the CD137 receptor only in the vicinity of cells that express the cognate tumor antigen, effectively converting the tumor cell into the equivalent of an antigen presenting cell.
Bicycle is advancing two novel candidates, BT7480, a novel Nectin-4/CD137 Bicycle TICA™, and BT7455, an EphA2/CD137 Bicycle TICA. BT7480 entered the clinic in 4Q21 and BT7455 is progressing through preclinical development. Bicycle also has a strategic collaboration with Genentech to discover, develop and commercialize novel Bicycle®-based immuno-oncology treatments.