Oxurion Announces Preclinical Data on THR-687 for the Treatment of DME

Oxurion presented preclinical data from a study evaluating THR-687 for treatment of diabetic macular edema (DME) at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting.

Preclinical data shows THR-687's potent inhibition of vascular permeability, inflammation and reactive gliosis in diabetic rats supporting evidence of clinical utility of THR-687 in multiple retinal diseases.

THR-687 is a highly selective pan-RGD integrin antagonist that is initially being developed as a potential first line therapy for DME patients and may have the potential to deliver improved treatment outcomes for patients with wet age-related macular degeneration (AMD) and macular edema following retinal vein occlusion (ME-RVO). Targeting RGD-binding integrins is known to affect multiple disease hallmarks such as vascular leakage, inflammation, angiogenesis and fibrosis. The preclinical study investigated the therapeutic potential of THR-687, a potent pan-RGD integrin antagonist, in the streptozotocin (STZ)-induced diabetes rat model.

Following STZ-induced diabetes, different doses of THR-687 (6.7, 16.7 or 75 µg/eye) or its vehicle were administered via 3 consecutive intravitreal injections in both eyes (with 1-week interval, n=7 rats/group). Untreated, non-diabetic rats served as controls (n=5 rats). At 4 weeks after diabetes-induction, the effect of THR-687 was investigated by histological analysis for retinal vascular leakage (using the tracer FITC-BSA), for inflammatory cell activation (Iba1 immunoreactivity), and Müller cell gliosis (vimentin immunoreactivity). Statistical analysis was performed with a one-way analysis of variance using a Bonferroni multiple comparison test.

The updated data shows:

• THR-687 reduced diabetes-induced increases in retinal permeability versus vehicle in a dose-dependent manner. The highest dose (75 µg/eye) completely prevented vascular leakage (P<0.001) while the mid dose (16.7 µg/eye) significantly decreased this pathology by 34 ± 21% (P<0.05) and the low dose (6.7 µg/eye) had no effect.
• All doses of THR-687 also significantly reduced the number of inflammatory cells, as compared to vehicle. Indeed, a reduction of 57 ± 12% was seen after administration of the highest dose (P<0.01), a decrease of 43 ± 19% for the mid dose (P<0.05) and the low dose induced a reduction of 51 ± 13% (P<0.05).
• The highest dose of THR-687 also reduced the diabetes-induced increase in vimentin expression within the Müller cells back to baseline (P<0.05 versus vehicle), whereas no significant differences following injections of the mid or low dose were observed.

RGD-integrin antagonism using THR-687 potently inhibits vascular permeability, inflammation and gliosis induced by STZ in the diabetic rat retina. Given its broad mode of action, THR-687 is a promising drug candidate for the treatment of vision-threatening retinal pathologies and is currently in a Phase 2 clinical trial in DME patients (INTEGRAL - NCT05063734).

• A copy of the ARVO presentation is available under Conferences and Events within the Investors section of the company’s website. 

Oxurion is currently evaluating THR-687 in a two-part phase 2 clinical trial (INTEGRAL) in patients with DME. Part A dose optimization data from the INTEGRAL trial is anticipated this quarter. If successful, the efficacy and safety of THR-687 versus aflibercept (the current standard of care) will be evaluated in Part B of the INTEGRAL Phase 2 clinical trial in both treatment-naïve and treatment-experienced patients with DME with data expected in the second half of 2023.