Circle is developing a new paradigm for macrocycle drug discovery deploying structure-based rational design and synthetic chemistry. Circle’s technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by multiple routes, including oral administration. Circle’s macrocycle drug discovery & development platform is applicable across a wide range of serious diseases; the company is initially focusing its development efforts on intracellular protein-protein interactions that are key drivers in cancer. Its lead programs target cyclin proteins, which are part of the regulatory machinery that controls progression of cells through the growth and division cycle. Inhibition of cyclin A is synthetically lethal to cancer cells that carry mutations causing dysregulation of the Rb pathway – such mutations are frequently found in small cell lung cancer. Cyclin E upregulation is found in many tumor types including uterine and ovarian cancer, and is often associated with resistance to widely used cancer therapies, including trastuzumab and cdk4/6 inhibitors.