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Exploring the potential for Bicycles to activate the body’s immune response in ways not possible with existing treatments, and improve patient outcomes in cancer.

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 Bicycles, as synthetic small molecules, potentially 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 agonists by coupling them 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 and 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, 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. We have observed these Bicycle TICA™ molecules agonize the CD137 receptor only in the vicinity of cells that express the associated tumor antigen, effectively converting the tumor cell into the equivalent of an antigen presenting cell.

Bicycle is advancing two novel candidates: BT7480, a Nectin-4/CD137 Bicycle TICA; and BT7455, an EphA2/CD137 Bicycle TICA. BT7480 entered the clinic in November 2021 and BT7455 is progressing through preclinical development. Bicycle also has a strategic collaboration with Genentech to potentially discover, develop and commercialize novel Bicycle-based immuno-oncology treatments.

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