OPT-302 for treatment of wet AMD

OPT-302 is designed to treat Wet age-related macular degeneration (wet AMD), a disease that affects the individual of
age 50 or above. In wet AMD, the uncontrolled growth of blood vessels below the retina leads to leakage of fluid and
protein from the vessels results in the loss of functionality of the central area of the visual field. OPT-302 blocks the
activity of the two proteins called VEGF-C and VEGF-D that cause uncontrolled growth of blood vessels.
VEGF family is the secreted glycoprotein and includes VEGF-A, VEGF-C and VEGF-D proteins which are important
for the lymphatic vessel growth and blood vessel development (Tamella 2005). The endothelial cell of the blood and/
or lymphatic vessels mainly expresses the receptors (VEGFR-1, VEGFR-2 and VEGFR-3) of these proteins that are
structurally similar tyrosine kinases (Tammela.2005.). VEGF-A can bind to VEGFR-1 and VEGFR-2 present on the
surface of the endothelial cells which leads to the angiogenesis (Tamella 2005). Binding of VEGFR-2 and VEGFR-3
to VEGF-C and VEGF-D induces the angiogenesis whereas lymph-angiogenesis is stimulated by the binding of
VEGFR-3 alone (Joukov 1997). Several studies have shown that binding of VEGFR-2 to VEGF-C, activates the
VEGF-C which amplify the vascular permeability. The edema formation and vascular leakage are associated with the
increased vascular permeability (Joukov 1998). Vascular permeability, lymph-angiogenesis and angiogenesis are
linked with various eye diseases such as wet AMD, retinal vein occlusion, diabetic macular edema, dry eye disease
etc and hence main target for ophthalmic treatments (Goyal). At back of the eye, a layer of cells underneath the retina
called retinal pigment epithelial cells expresses VEGF-C, the level of VEGF-C are up-regulated by the VEGF-A
(Zhao). The pathology analysis in the wet AMD has revealed that VEGF-A and VEGF-C both are vascular
permeability.
Manufacturing Process:
OPT-302 will be produced in the CHO-M cell-line and associated technology by Selexis SA, Geneva, Switzerland.
Selexis SA is a life science company, mainly concentrated on drug discovery, cell line development and Scale up of
mammalian bio-products. Opthea Pty. Ltd has made contract with Selexis SA for production of modified VEGFR-3.