Randomized/Controlled Proof of Concept Studies in Retinal Vascular Disease and the Dry Form of AMD

InflammX has carried out significant in vitro and pre-clinical models of disease studies, demonstrating the mechanism of action and the effect of Xiflam™ in modifying the pathology mediated by the NLRP3 Inflammasome.

·       These studies include challenging RPE cells to signal the Inflammasome which in turn activated multiple pro-inflammatory cytokines. The measurement of overexpressed Cx43 hemichannels, release of ATP extra-cellularly and Inflammasome activation under challenged conditions of the RPE were accurately measured. Similarly pro-inflammatory cytokines were measured as a result of the inflammasome activation and assembly.  

Subsequent deactivation of the inflammasome was measured following addition of the pathological Cx43 Hemichannel blocker (Xiflam™). Xiflam stops ATP release, preventing inflammasome complex assembly and significantly reducing the release of multiple inflammatory cytokines including Il-1b, Il-18, IL-6, IL-8, ICAM-1 and VEGF. Both the Inflammasome and the pro-inflammatory cytokines went back to physiological baseline.

·       In a critically important retinal model of ischemia/reperfusion where the IOP in a rat eye is raised to 120mm/Hg for 60 minutes and then allowed to reperfuse by acute dropping of the IOP, leakage in retinal blood vessels was measured in both the placebo and drug (Cx43 blocker/Xiflam™)  treated animals. Treated eyes demonstrated 86% less leakage than the placebo treated controls. This is a critical experiment since ischemia/vessel leak is integral to the diseases InflammX is treating in the clinic.

·       In a Phototoxic model of Retinal Degeneration (Dry AMD) animals were randomized to treatment with Xiflam™ vs Placebo.  The Xiflam™ Retina’s maintained both structure (OCT) and function (ERG) 3 months post light exposure while Placebo treated Retina had massive retinal atrophy/thinning (OCT) and ERG was extinguished at 3 months post light exposure.

·       Radiolabeled whole body studies after a single dose of orally administered Xiflam™ show high bioavailability peaking at 6 hours with trace drug still evident at day 3. Importantly the bioavailability in the retina and choroid demonstrated high drug levels peaking at 6 hours and was still measurable at 24-36 hours.