First Patient Dosed in Phase 2 study evaluating THR-149 for treatment of DME

THR-149 is a plasma kallikrein (PKal) inhibitor for treatment of DME. Through the inhibition of the plasma kallikrein-kinin (PKaI-kinin) system, THR-149 prevents the induction of retinal vascular permeability, inflammation and angiogenesis. Literature data show that patients with DME have elevated levels of plasma kallikrein and that the vitreous level of plasma kallikrein varies less compared to VEGF, making it a potentially more effective target for treating DME. Oxurion has reported positive topline phase 1 results for the clinical study evaluating THR-149 for the treatment of DME.
- Pravin Dugel, MD - Read full presentation
Clinical study evaluating THR-149 (a PKal inhibitor) for treatment of diabetic macular edema (DME)
Completed
The Phase 1 trial is designed to evaluate the safety of a single intravitreal (IVT) injection of THR-149 a novel PKal inhibitor, of 3 ascending dose levels in subjects with visual impairment due to center-involved DME (CI-DME) (NCT03511898).
Topline data reported
THR-149 is well-tolerated and safe. No dose-limiting toxicities or drug-related serious adverse events reported.
Immediate onset of action - starting from Day 1 with increasing average improvement in Best Corrected Visual Acuity (BCVA) of up to 7.5 letters at Day 14 following a single injection of THR-149.
Prolonged durability of effect - average improvement in BCVA of 6.5 letters at Day 90 following a single injection of THR-149.
Phase 2 study with anti-VEGF poor responding DME patients in progress
Actively recruiting patients in Phase 2 study
NA
Preclinical studies on bicyclic peptide inhibitors of PKal, such as THR-149, including those published in The Journal of Medicinal Chemistry in March, have demonstrated nanomolar to picomolar potencies, and stability in biological matrices and reported prolonged retention in the eye together with in vivo efficacy in diabetic models of retinal vascular permeability. These outcomes support THR-149’s development as a possible treatment for DME and DR via a VEGF-independent mechanism of action.