OPT-302 is a soluble form of human vascular endothelial growth factor receptor-3 (VEGFR-3) comprising extracellular domains 1-3, expressed as an Fc-fusion protein.

OPT-302 functions by capturing (or ‘trapping’) and thus blocking the activity of VEGF-C and VEGF-D on the receptors VEGFR-2 and VEGFR-3. These receptors are mainly expressed on the endothelium of blood and lymphatic vessels.

Opthea has investigated OPT-302 in a Phase 1/2A study in wet AMD patients.  The results of this study indicated that OPT-302 is well tolerated when administered as a monotherapy and in combination with Lucentis® and suggested that combined administration of OPT-302 + Lucentis® may lead to improved clinical outcomes over Lucentis® alone. 

Furthermore, in a preclinical mouse model of wet AMD, we have demonstrated that OPT-302 can reduce the development of wet AMD lesions and inhibit leakage of associated vessels to a comparable extent as the marketed VEGF-A inhibitor Eylea®. When used together in the same model, an additive benefit is observed, with more effective inhibition of wet AMD lesions than using either agent alone (1,2).

Using this internationally recognised model of wet AMD in the mouse, our data has demonstrated that OPT-302 is able to inhibit the formation of wet AMD lesions when administered at the onset of the disease or when administered to mice with established lesions. Furthermore, OPT-302 can also reduce the expression of genes involved in blood vessel growth and inflammation, further implicating VEGF-C in wet AMD progression and the potential for OPT-302 as a therapeutic to improve vision in patients with the disease.

1 Lashkari et al., “Expression of VEGF-C, VEGF-D and their cognate receptors in experimental and clinical choroidal neovascularization.” ARVO, 9 May 2013

2 Lashkari et al., “VEGF-C and VEGF-D blockade by VGX-300 inhibits choroidal neovascularization and leakage in a mouse model of wet AMD.” ARVO, 6 May 2014