About Circle Pharma
A New Paradigm For Macrocycle Drug Development
Circle Pharma operates an indication-agnostic discovery engine for the development of cell permeable macrocyclic peptide therapeutics. Our discovery engine combines computational structure-based design with automated, fully synthetic chemistry. In our computational design workflow, we generate and screen large virtual libraries of diverse macrocycles for intrinsic cell permeability and target affinity, enabling us to tackle important intracellular targets, including protein-protein interactions, as well as to achieve oral bioavailability. Our automated chemistry synthesis capability enables us to assess, in parallel, multiple design hypotheses for a given target, and to rapidly explore structure activity relationships (SAR) for hit to lead progression.
We are working on important therapeutic targets that are challenging to address with conventional small molecules or biologics, but which are well suited for macrocycles. Our initial focus is on intracellular protein-protein interactions that are key drivers in oncology pathways.
An example of our work, undertaken in a collaboration with Pfizer, entitled
“Discovery of potent and orally bioavailable macrocyclic peptide-peptoid hybrid CXCR7 modulators” has been published in the Journal of Medicinal Chemistry.
Developing potent, specific and intrinsically cell permeable macrocycles against important and challenging therapeutic targets
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.
With input from an advisory panel of noted oncology experts, we have selected several intracellular protein-protein interactions (“PPIs”) that play key roles in cancer as the first group of targets for our internal development pipeline. The clinical and commercial potential of this target class is well recognized, but these targets have proven largely intractable to small molecule drugs because of the dispersed molecular interactions involved in PPIs. Macrocyclic peptides are significantly larger in size than small molecules and can form multiple interactions with a target, which in theory means they have an increased likelihood of successfully disrupting these targets. However, permeability challenges have so far limited progress against intracellular PPIs, and they have been referred to as the “Holy Grail” for macrocycle drug development. 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’s first group of pipeline targets includes beta-catenin, MCL1, cyclinA/cdk2 and p53.
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.