Developing next generation treatments to preserve vision for patients with diseases affecting the back of the eye

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 reported positive topline phase 1 results for the clinical study evaluating THR-149 for the treatment of DME.


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Target indications

Diabetic macular edema

"I am very encouraged to see signs of efficacy so early post-treatment, and to observe a clear durable benefit to the patient's vision as measured by BCVA."

- Pravin Dugel, MD -  Read full presentation

Clinical trials
Phase I

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



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 II

Phase 2 part B study with anti-VEGF poor responding DME patients in progress


First patient dosed in Part B of Phase 2 KALAHARI study Evaluating multiple administrations of THR-149 versus aflibercept for Treatment of Diabetic Macular Edema (DME)



Positive Phase 2 Part A THR-149 data

Patients in the highest dose group achieved an overall mean 6.1 letter improvement in Best Corrected Vision (BCVA) at Month 3, of which:

  • 63% showed at least a 5-letter gain
  • 38% achieved at least a 10-letter gain
  • 13% achieved at least a 15-letter gain
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.