Surrozen, Inc. announced the publication of an article by Surrozen scientists in the journal Translational Vision Science and Technology The results observed with Surrozen's proprietary FZD4-specific agonist, SZN-413, highlight the potential for this novel mechanism of action to simultaneously address the retinal non-perfusion and vascular leakage observed in both oxygen-induced and VEGF-induced preclinical diabetic retinopathy (DR) models. Diabetic retinopathy is a microvascular complication of diabetes and a serious public health problem as it is a major cause of vision loss and disability in the middle-aged population. The pathogenesis of DR leads to vascular leakage, which causes diabetic macular edema, and capillary occlusion causing retinal ischemia.

These areas of retinal non- perfusion can lead to overproduction of multiple signaling molecules, such as VEGF, that contribute to vascular leakage and pathologic angiogenesis. There are currently multiple anti-VEGF therapies available, however these have not been shown to improve retinal ischemia -- leaving a high unmet medical need for new mechanisms of action that have the potential to achieve retinal reperfusion and can reduce the production of factors contributing to vascular leakage and pathologic neovascularization. SZN-413, a bi-specific antibody that targets FZD4 and LRP5, induced Wnt signaling and upregulated blood-retinal barrier gene expression in retinal endothelial cells (ECs).

FZD4-mediated Wnt signaling is known to play a critical role in retinal vascular development and vessel barrier function in humans and rodent models. The results presented in this paper confirmed that FZD4 and LRP5 are the most abundant and relatively specific receptors expressed in the retinal ECs and SZN-413 induced tight junction proteins in retinal vascular ECs. In a preclinical oxygen-induced retinopathy model, intravitreal injections of SZN-413 significantly reduced avascular area size compared to the positive control, aflibercept.

In addition, SZN-413 significantly reduced the pathologic neovascularization area size compared to vehicle and comparable to the positive control. In a VEGF-induced vascular leakage model, SZN-413 reduced retinal vascular leakage from baseline by approximately 80%.