Depleting Circulating Galectin-3 with Therapeutic Apheresis: A NovelTreatment for Sepsis/AKI

Project Summary-Abstract Sepsis and consequent acute kidney injury (AKI) are major public health concerns, with high mortality and morbidity and increasing incidence. Despite efforts to develop new interventions, current therapeutic options are limited in scope and effectiveness. Eliaz Therapeutics Inc. (ETI), based on substantial literature, successful initial proof of concept in a porcine cutaneous inflammatory injury model, and recent extraordinary survival data in sepsis-AKI in a rat model, in accordance to recent guidance from the FDA, is progressing toward safety and human clinical trials to depletion of the endogenous galectin-3 (Gal-3) protein from septic patients’ blood using a novel high-affinity immunoadsorption apheresis column. Gal-3 is a known vital driver of organ inflammation and fibrosis in numerous acute and chronic disorders, with substantial amelioration shown in experimental inhibition and Gal-3 -/- (genetic knockout) and Gal-3 inhibitors models. Gal-3, while essential for initial immune pathogen recognition and immune activation in infections, becomes a driver of excessive and dysregulated cytokine responses in sepsis development and subsequent organ damage. Previous preclinical models showed reduced pathology and improved survival by removing or inhibiting Gal-3. We hypothesize that selectively depleting Gal-3 by apheresis will exert synergistic therapeutic effects on both sepsis and sepsis-related AKI. Our medical device filter intervention, which attaches to presently used apheresis machines, has the potential to address the urgent need for mortality and morbidity reduction, advance sepsis/AKI treatment options, and expand applications in apheresis medicine. ETI is now ready to test the scale up to the commercial “XGal-3” prototype and its safety in use in a swine pilot and treatment study and get on the road to human clinical studies and commercialization. Aim 1: Fabricate and evaluate the prototype Gal-3 selective apheresis columns with safety testing toward a commercialization pathway. Aim 2: Perform a porcine safety study to assess the potential for an unacceptable adverse biological response resulting from contact of the extracorporeal apheresis column’s component materials with blood. Aim 3: Develop the clinical and regulatory road map and clinical trial design to prepare for a human GMP/GPL safety study.