Science

SERPINs

Physiological processes such as blood clotting, inflammation and immunity are essential for our wellbeing. While these process are very diverse in comparison to each other, they are actually all run by the same class of enzyme: Serine Proteases. Serine Proteases need to be controlled to prevent collateral damage due to excessive activity. Failure to do so can lead to a variety of inflammatory diseases, including Alzheimer’s disease, pulmonary emphysema, colitis, arthritis and sepsis, as well as complement-driven disorders. 

Serine protease inhibitors (SERPINs) are a superfamily of inhibitors, which act as molecular mousetraps. In physiology, SERPINs only interact with serine proteases after activation. This enables physiological protease activity, but limits it to prevent pathology. The inhibitory profile of SERPINs can be altered by changing their sequence in the reactive center loop (bait sequence), which has massive therapeutic potential.

By Thomas Shafee – Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=45596400

Our Technology

There is limited insight into how the bait sequence variation affects the SERPIN specificity. This hampers effective redesign of therapeutic SERPINs.

Our technology involves state-of-the art cloning strategies which make it possible to profile general SERPIN behavior and apply this information in a predictive manner. This enables SERPINx to developed a recombinant SERPIN library, in which the bait sequences are controllably modified. This functions as a universal platform to design therapeutic SERPINs.

Key Characteristics

  • Ability to select novel & multiple targets
  • Achieve stronger functionality
  • Ability to control selectivity

Our pipeline

 Our most advanced designed SERPIN, SPx-001 is an alpha1-antitrypsin mutant, which no longer targets chymotrypsin & elastase (wildtype), but is converted into a multi-target inhibitor of the kinin-kalikrein pathway to prevent bradykinin production (targeting FXIIa, plasma kallikrein, plasmin). SPx-001 is currently in development with preclinical proof-of-concept achieved in Heriditary Angioedema (Type I, II & III), Colitis and Thrombosis.