PRO-XTEN^® protease-releasable masking platform

Masking “shields” a TCE, reducing its ability to bind to its target outside of its intended site of action. This keeps TCEs inactive until they reach the tumor microenvironment, enabling us to improve their safety profile and therapeutic index.

With PRO-XTEN^®, our product candidates are “masked” while in circulation, remaining inactive and minimizing unwanted effects in healthy tissues. Once the masked drug reaches a tumor, the heightened protease activity in the tumor microenvironment specifically cleaves a linker, which leads to the mask “falling off” and the drug becoming active precisely where it’s needed. This selective activation dramatically reduces off-tumor toxicity, allowing us to target previously inaccessible oncology targets with potentially greater safety and efficacy. There are two key components that enable this targeted activation:

PRO-XTEN^® mask
The mask has two main functions. The first one is that it acts as a spatial shield around the functional parts of a drug, keeping it inactive while in circulation. In addition, it extends the drug’s half-life, helping ensure it remains in the bloodstream long enough to reach the tumor. Unlike other masking strategies that require specific tailoring to each drug, the PRO-XTEN^® mask is universally applicable, and can be used to mask different TCE drugs without the need for individual optimization. 

Protease-cleavable linker
The PRO-XTEN^® mask is fused to the TCE with a linker, engineered to be preferentially cleaved by the proteases present in tumor environments, while remaining stable in healthy tissues and in the bloodstream. This ensures the drug is “unmasked” and activated mainly at the tumor site, driving efficacy where it’s needed while providing safety throughout the rest of the body. Additionally, unmasked TCEs are rapidly cleared from the body, which limits them from triggering unwanted effects if they leak out of the tumor and enter in contact with healthy cells.

By combining these advanced components, PRO-XTEN^® opens up the possibility to advance TCEs for targets that were previously too risky to approach due to toxicity, potentially enabling a new generation of safer, more effective cancer therapies.

The PRO-XTEN^® masking platform is extremely versatile and has potential applications beyond masking TCEs. It can be applied to other molecules such as cytokines, as well as other therapeutic areas such as infectious diseases. 

To learn more about the areas in which we are using the PRO-XTEN^® masking platform, click here.

Vir Biotechnology has exclusive rights to the PRO-XTEN^® masking platform for oncology and infectious disease. PRO-XTEN^® is a trademark of Amunix Pharmaceuticals, Inc., a Sanofi company.