Oxurion NV delivered a preclinical presentation evaluating the pharmacokinetic properties of THR-149 at KININ2022, held in Annecy, France, June 5-8, 2022. Overview: THR-149, a bicyclic peptide identified by a combination of phage-based selections and directed medicinal chemistry, is a potent and specific inhibitor of plasma kallikrein. In preclinical studies, THR-149 effectively blocked the release of bradykinin in the vitreous and reduced the level of edema and retinal vascular leakage in rodent models.

Results: IVT-PK and IV-PK data were analyzed based on a mono-compartmental pharmacokinetic model, leading to ocular and systemic half-lives of 36 h and 1.1 h, respectively. The model indicates IVT administration of THR-149 reduces the four DME disease hallmarks: retinal vascular leakage, retinal edema, retinal inflammation and reactive gliosis. THR-149 is being developed as a potential new standard of care for the up to 50% of diabetic macular edema (DME) patients showing suboptimal response to anti-VEGF therapy.

Oxurion is currently evaluating THR-149 for the treatment of DME in Part B, the second part of its two-part Phase 2 KALAHARI trial.