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Orally Administered Connexin43 Hemichannel Inhibitor of the Inflammasome for the Treatment of GA And DR

Presenter:

Brian Levy, OD, MSc.

Authors:

Brian Levy, OD, MSc.

CEO Ocunexus Therapeutics

Affiliation:

Purpose: Physiologically connexin hemichannels are continuously forming in the cell membrane and remain closed until docked with a neighboring cell at which point they open to form a gap junction. The Ocunexus target is the Connexin43 (Cx43) hemichannel. Cx43 is overexpressed in chronic microvascular disease such as DR/DME and GA/AMD and coupled with premature opening of hemichannels results in pathological membrane pores which allow for ATP release into the extracellular space. This activates the innate immune system inflammasome (NLRP3) pathway of inflammation, inducing the release of multiple proinflammatory cytokines and creating a cycle of inflammation resulting in microvascular pathology including vessel leak, edema, ischemia and ultimately fibrosis.

Methods: Ocunexus compounds modulate Cx43 hemichannels, inhibiting the pathological release of ATP. This shuts down assembly of the NLRP3 inflammasome complex, preventing amplification and perpetuation of the cycle of inflammation and stopping continued release of multiple cytokines and their effect on the microvasculature. Scientific statistically relevant and repeated data will be presented validating the mechanism of action of its compounds in cellular assays and preclinical models of disease.

Results: Ocunexus compounds are acting far upstream of those currently in use or in development for the treatment of diseases of the posterior segment and the data presented will demonstrate that the drug target is present in the preclinical disease models of interest and also in fresh human cadaver eyes with the targeted disease state.

Conclusion: Data generated has scientifically and statistically demonstrated efficacy in acute and chronic phenotypical preclinical models with Ocunexus lead compound Xiflam, an orally administered Phase 2B ready small molecule for treating GA and DR.

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