Randomized/Controlled Proof of Concept Studies in Diabetic Retinopathy and the Dry Form of AMD (Retinal Degeneration)

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 (XiflamTM). Both the Inflammasome and the pro-inflammatory cytokines went back to physiological baseline.

·       In a critically important 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/XiflamTM)  treated animals. Treated eyes demonstrated 86% less leakage than the placebo treated controls. This is a critical experiment since ischemia/perfusion is integral to the diseases InflammX is treating in the clinic.

·       Additionally studies have been undertaken in a phenotypical retinal degeneration  model of dry AMD (GA) and a rat model of Diabetic Retinopathy. The rat model was unique in that the rats were born with diabetes and exhibited signs of diabetic retinopathy (micro and macro aneurysms) at 4 weeks. In a randomized study where the rats with diabetic retinopathy received either Xiflam or Placebo orally administered. Both regression of aneurysms and improved ERG was measured in the treated rats. The placebo treated continued to deteriorate in both structure and function.

·       In a diabetic challenge model in human ex-vivo retina, and in human retinal pigment epithelium and endothelial cell models, 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.

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

·       Radiolabeled whole body studies after a single dose of orally administered XiflamTM    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 still and still measurable at 24-36 hours. Remarkably similar values were seen in the kidney.InflammX