Modern medicine's understanding of disease states continues to expand exponentially, including the identification of cellular pathways and targets that play key roles in disease. Unfortunately, there is a dramatic gap between our understanding of diseases and our ability to treat them because of the limitations inherent in existing drug platforms. At present, the entire pharmaceutical industry and available drug arsenal are based on technologies, primarily small molecules and therapeutic proteins, addressing only an estimated 10% to 20% of the identified therapeutic targets within the body. The majority of the universe of targets and diseases are presently "undruggable" by existing modalities.


Aileron's Stapled Peptide therapeutics provide the opportunity to greatly expand the number of "druggable" targets by targeting the thousands of intracellular and extracellular protein-protein interactions that cannot be functionally modulated by current therapeutics. Leveraging these unique attributes, Aileron is creating a new paradigm in drug discovery and development.

Peptides have proven to be valuable and effective drugs when targeting a limited number of extracellular receptors. The concept of using peptides to modulate intracellular processes has been investigated for decades, as peptides play a central role in every cell in the body. However, these strategies have historically failed because peptides lack the ability to enter cells, are inherently unstable within the body, are rapidly broken down into inactive fragments by circulating enzymes, known as proteases, and are filtered from the blood stream by the kidneys within minutes.


Aileron's breakthrough solution is based in the fact that proteases can only recognize and break down peptides when they are unraveled, so if they are locked into certain folded shapes, they are protected. Although there have been past efforts to stabilize peptides into shapes resistant to proteases, such chemically stabilized peptides often lose some if not all of their biological activity and have not gained the ability to penetrate cells while preserving their biologically functional structures.

Aileron's peptide stabilization technology involves ”stapling” peptides into an alpha-helical shape with an optimized cross-linking chemistry, mimicking the structure found at the interface of many protein-protein interactions. Click here to watch a video that demonstrates how our peptide stabilization technology works.

Aileron is developing a diverse toolkit of staples to optimize target binding and therapeutic product profiles, providing the potentially limitless possibilities for Stapled Peptide Therapeutics.


The resulting Stapled Peptide Therapeutics are endowed with unique and beneficial drug-like properties that solve critical problems previously plaguing the peptide class of drugs.   Like small molecules, Stapled Peptides are cell permeable and synthetically optimizable, but they are not as limited in the types of targets that they can bind. Stapled Peptides also retain the specificity and natural multitarget recognition capabilities of therapeutic proteins with very few limitations in their ability to address extracellular and intracellular targets.

Stapled Peptides Have Benefits Versus Other Important Drug Classes

Aileron's Stapled Peptide platform has been shown to work on a very broad range of peptides, and as such, it provides the first general scaffold for modulating intracellular protein-protein interactions and generating therapeutics that will exploit this very large and currently "undrugged" collection of targets in a broad range of diseases. As a result, Stapled Peptide Therapeutics represent an enormous R&D and commercial opportunity, due to their ability to address multiple target classes and disease categories.