Discovery Platform

Scientific Approach

Ensemble’s platform is an efficient and productive approach for developing synthetic macrocycles and other less conventional small molecules. While macrocycles are a class of compounds that have traditionally been obtained from natural sources, we are the first company to successfully and reliably engineer and exploit synthetic macrocycles possessing drug-like properties and features.

Using this approach, we have developed a pipeline of proprietary and partnered programs that focus on both extracellular proteins (e.g. IL-17) and challenging intracellular targets (e.g. IAPs, IDO and USP9x).


There is a growing appreciation of the drug potential of macrocycles — a unique class of compounds that offer small molecule properties with the potency and specificity of antibodies — ideally suited to address difficult disease targets, such as protein-protein interactions, irrespective of whether these are inside or outside the cell.

Macrocycles offer a number of unique attributes for drug discovery:

  • Nature’s way of targeting proteins — Macrocycles are found in nature from a range of fungal, bacterial, plant, and animal species. They have evolved to fulfill specific biochemical roles by interacting with high selectively with specific protein targets.
  •  Access to new and challenging drug targets — Macrocycles have the potential to unlock the door to many challenging disease targets unable to be accessed by antibodies or that present too large a surface area to drug using conventional small molecules.
  • Beneficial conformational flexibility – Macrocycles can flex to hide polar functionality, so they can cross cell membranes to access intracellular targets. The ring structure also provides metabolic stability such that the compounds can attain drug-like properties, including oral bioavailability, similar to conventional small molecules.
  • Allosteric binders – enzymes contain functional sites that catalyze chemical reactions. However, many of our macrocycles bind to alternative ‘allosteric’ sites on the protein target. Binding to allosteric sites still confers inhibitory activity but can also give significant target selectivity and avoid possible off target toxicity.