Zedira’s drug discovery approach targets dysregulated transglutaminase activity in disease states.  

In the human body, eight transglutaminase isoenzymes (TG1-TG7 and coagulation factor XIII) fulfill a broad variety of physiological functions. However, transglutaminases are also involved in the pathophysiology of various disorders.  

In celiac disease, Zedira’s drug candidate ZED1227¹, an irreversible direct-acting and specific inhibitor of human tissue transglutaminase (TG2), showed proof of concept in a phase 2a study. The groundbreaking results have been published in the New England Journal of Medicine. An overview is given in our press release.    

This proof of concept is of utmost importance not only for celiac disease but beyond. For the first time, a transglutaminase was validated as a druggable target. Moreover, our transglutaminase inhibitor ZED1227 was proven to be safe and well tolerated.   

This remarkable success has a favorable effect on several other transglutaminase-related disorders. In particular, fibrotic disorders affecting the lung, liver, or kidney may be addressed with our compounds. Our newest class of reversible direct-acting and specific inhibitors of tissue transglutaminase (TG2) are orally bioavailable proprietary compounds. An overview is given in our press release.  

Transglutaminase blocker drug candidates are also available to target coagulation factor XIII (F13, plasma transglutaminase). This novel and unique approach dissociates the antithrombotic effect from the increased bleeding tendency in anticoagulation. Results obtained in an in vivo study of the direct-acting factor XIIIa inhibitor ZED3197 have been published in the Journal of Thrombosis and Haemostasis. For detailed information, please refer to the respective open-access scientific publication.  

 
 
¹ Büchold C, Hils M, Gerlach U, Weber J, Pelzer C, Heil A, Aeschlimann D, Pasternack R. Features of ZED1227: The First-In-Class Tissue Transglutaminase Inhibitor Undergoing Clinical Evaluation for the Treatment of Celiac Disease. Cells. 2022; 11(10):1667. https://doi.org/10.3390/cells11101667