Circle is advancing a new paradigm in macrocycle drug discovery to develop intrinsically cell permeable macrocycles against important therapeutic targets. Our technology allows us to address therapeutic targets that are considered “undruggable” with small molecules or biologicals, in particular intracellular protein-protein interactions. This target class covers a wide range of therapeutic indications and includes many high value targets that have been biologically validated but, as yet, not successfully drugged.
We selected several intracellular protein-protein interactions (“PPIs”) that play key roles in oncology as Circle’s first target group for our internal development pipeline. The clinical and commercial potential of this target class is well recognized but it has proven largely intractable to small molecule drugs since these are too small to disrupt the dispersed molecular interactions typical of PPIs. And, while macrocyclic peptides are large enough to disrupt those interactions, permeability challenges have so far limited progress in this promising drug class. Circle’s ability to design intrinsically cell permeable macrocycles gives us a unique opportunity to develop first-in-class drugs against these high value drug targets.
Circle assembled a panel of renowned oncology experts to assist in reviewing and selecting particular PPIs from this target class, considering criteria including biological validation of the target’s role as a driver of cancer, unmet clinical need and availability of structural information on the PPIs involved. This first target group includes a balance of well established targets such as PPIs in the Wnt/beta-catenin pathway, and emerging targets such as PPIs involved in epigenetic regulation.
Beyond cancer, our technology platform is applicable to a wide range of other disease conditions, including those driven by fibrosis, inflammation or infection, covering indications such as cardiovascular, metabolism and neurology / pain.