Delivering next-generation treatments for back of the eye disorders, with focus on diabetic eye disease

THR-149 (PKal Inhibitor)

Illustration THR-149

Mode of action

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 reached full enrollment for the Phase I clinical study evaluating THR-149 for the treatment of DME.

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Target indications

Diabetic macular edema

Topline data confirm that THR-149 is not only well-tolerated and safe, but also provides a rapid and sustained gain in BCVA. These findings demonstrate that THR-149 has the potential to become the best-in-class PKal inhibitor for the treatment of DME.

- Patrik De Haes, MD, CEO

 
Clinical trials
Phase I

Clinical study evaluating THR-149 (a PKal inhibitor) for treatment of diabetic macular edema (DME)

Status: 

Ongoing, fully enrolled

The THR-149-001 open-label, multicenter, dose escalation phase 1 clinical study (THR-149-001) assesses the safety of a single intravitreal injection of escalating dose levels of THR-149 in patients with DME. A total of 15 patient have been recruited.

Data: 

Oxurion NV reports positive topline phase 1 results.

Preclinical data

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.