Dysregulation of the immune system causes a series of insults to the blood-ocular barrier, leading to breakdown of the barrier and release of inflammatory mediators Inflammatory insults (e.g., autoimmune disease) can trigger intraocular immune responses and disrupt the blood-retinal barrier Blood-retinal barrier breakdown allows immune cells and plasma into the retina, causing leakage and macular edema Yang et al. Int. J. Mol. Sci. 2023, 24: 4676. Metcalfe et al. Front. Immunol. 2020, 11: 1424. Shaik et al. Biomolecules. 2020, 10: 1673. Valle et al. Exp Eye Res. 2019, 178: 27. Mesquida et al. Trans Vis Sci Tech. 2019, 8: 32. IL-6 and VEGF are co-induced: VEGF promotes vascular leak and neovascularization, while IL-6 sustains inflammation and upregulates VEGF 1 2 3 42

Investor R&D Day Presentation - Page 41 Investor R&D Day Presentation Page 40 Page 42