Challenges in intracellular NLRP3 inhibition: limitations of small molecule delivery to retinal and optic nerve targets using today’s technology 25 Intravitreally Small molecules are cleared quickly from the eye, limiting their efficacy Eye drops Poor patient compliance and insufficient drug concentration reaching target tissues, such as RGCs and the optic nerve What if we can create an intravitreally injected small molecule that does not clear the eye quickly? • There is a strong positive correlation between ocular half - life and molecular size for intravitreally injected biologics 1. Adapted from Crowell SR, et al. Trans Vis Sci Tech. 2019;8(6):1. Orally Poor ocular bioavailability and systemic side effects Limitations of small molecule delivery