DTR8

DTR8 is a first-in-class, kidney-targeted therapeutic peptide and potent antagonist of heparin-binding epidermal growth factor-like growth factor (HB-EGF). Developed by DETERA Therapeutics, a spin-off from the French Alternative Energies and Atomic Energy Commission (CEA) and Inserm, DTR8 is engineered from the non-toxic receptor-binding domain of the diphtheria toxin, which naturally binds HB-EGF. It incorporates 12 mutations designed to enhance solubility, increase target affinity to picomolar levels (Kd < 4 pM), and reduce immunogenicity and antigenicity. DTR8 is being developed for the treatment of crescentic glomerulonephritis (CGN), also known as rapidly progressive glomerulonephritis (RPGN). By binding to HB-EGF, DTR8 prevents the activation of the epidermal growth factor receptor (EGFR) on podocytes and parietal epithelial cells, thereby blocking the abnormal cell proliferation and dedifferentiation that leads to glomerular destruction and rapid kidney failure.