Rat Laser CNV Efficacy Studies with the Novel Trispecific Protein RO-104

Abstract

Purpose : To investigate the in vivo efficacy of the trispecific Surrobody, RO-104 that targets Vascular Endothelial Growth Factor A and C (VEGF-A, VEGF-C), and Angiopoietin 2 (Ang-2). The benefits of bispecific inhibition of VEGF-A and Ang-2 have been established using faricimab. Recent clinical studies suggest VEGF-C is a third significant contributor to retinal neovascularization. We tested the in vivo efficacy of the trispecific RO-104 in a rat laser induced CNV (choroidal neovascularization) model. As a benchmark we included faricimab as a VEGF-A and Ang-2 bispecific treatment arm.

Methods : Our study used the common laser-induced choroidal neovascular model. On day 1 an 810nm diode laser was used to create four lesions of the Bruch’s membrane in each eye. These wounds cause progressive CNV that is readily quantifiable in one week by fluorescence angiography. After the laser on day 1, all rats received a 5μL intravitreal injection. The three study arms had 6 rats, group 1 received PBS vehicle treatment, group 2 received 0.1mg of faricimab, and group 3 received 0.1mg of RO-104. On day 8, fluorescence angiography images were taken and used to quantitate the resulting wound area of each lesion (Figure 1).

Results : Analysis of fluorescence angiography determined mean wound areas for all reliably observable lesions. For vehicle group 1 the average lesion area was 2369±1208(SD) area units(a.u.). For faricimab treated group 2 the mean area was 1889±1267(SD) a.u., an 18.6% reduction compared to vehicle, but lacks ANOVA significance (p=0.2201). In the RO-104 treated group 3 the mean area was 1223±97(SD) a.u., demonstrating a 46.6% mean reduction compared to vehicle and high ANOVA significance (p=0.0005).

Conclusions : Our data provides in vivo evidence of RO-104 and trispecific Surrobody inhibition providing beneficial effects against laser-induced CNV injury but reduction of wound neovascularization. The effects of RO-104 surpassed faricimab treatment. The trispecific observed benefit may be due to VEGF-C inhibition, more potent Ang-2 inhibition, and or other drug attributes. These results support further development of RO-104 for treatment potential in neovascular disease.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Comparison of the mean area of CNV lesions for each eye on day 8 after following described treatment.

 

Examples of fluorescence angiography from three eyes per group on day 8 following indicated treatment.