THE CHALLENGE
A major commercial hurdle in developing guanidine-based therapeutics lies in their poor oral bioavailability, which limits their effectiveness despite strong therapeutic potential. These compounds, while highly potent due to their ability to engage key molecular targets, struggle to reach the bloodstream when taken by mouth because of their high basicity (pKa ~13.6), leading to poor absorption and rapid breakdown in the gut and liver. Existing delivery solutions—like chemical masking, using permeation enhancers, or leveraging biological transporters—have shown limited and inconsistent success, often introducing safety risks, manufacturing complexity, or unpredictable drug activation. This challenge presents a significant barrier not just scientifically but also commercially, as oral pills remain the most scalable, cost-effective, and patient-friendly delivery method, especially in chronic diseases where adherence and production costs are key business concerns. A breakthrough in solving this bioavailability issue could unlock the market potential of a valuable class of small-molecule drugs currently stalled by delivery limitations.
OUR SOLUTION
We offer a breakthrough in making powerful guanidine-based drugs suitable for oral dosing, a key requirement for commercial success in chronic disease markets. By attaching specially designed β-alkoxy acetamide groups to the drug’s guanidine head, we create prodrugs that temporarily mask the compound’s high charge, improving its absorption in the gut and enabling it to survive the body's natural metabolic filters. These prodrugs are modular, meaning they can be fine-tuned for optimal performance, and are made using straightforward chemical reactions from a shared intermediate, streamlining development and manufacturing. In preclinical studies, our approach showed up to 25-fold improvements in active drug levels in the blood compared to the original molecule—offering a scalable, patentable, and broadly applicable solution for transforming previously undeliverable guanidine-based molecules into viable oral therapies.
Advantages:
Potential Application: