Ophthalmic disease

In vitro, mouse and rat studies identified two bicyclic peptide inhibitors of KLKB1 that could help treat DME. Screening of a bicyclic peptide library in KLKB1 binding assays followed by optimization of hits and in vitro activity assays yielded two peptides that inhibited human KLKB1 with K_i values of 3 and 0.36 nM. In mouse and rat models of DME, intravitreal injection of the first or second compound, respectively, decreased vascular permeability in the retina compared with vehicle. Next steps by ThromboGenics N.V. could include testing the peptides in additional models of DME.

Bicycle Therapeutics Ltd. and ThromboGenics have THR-149, a KLKB1 inhibitor of undisclosed type, in preclinical testing for macular edema...