Severe oxalate-related conditions such as primary hyperoxaluria (PH), secondary hyperoxaluria (SH) (as a result of short bowel syndrome, chronic inflammatory bowel disease, cystic fibrosis, post bariatric, and other malabsorption syndromes), Zellweger spectrum disorders (ZSD) and chronic and end-stage renal failure continues to be a healthcare problem, without an effective treatment. These diseases occur when dietary oxalate is hyper-absorbed or liver overproduction generates excessive oxalate. Oxalate absorption and secretion occur throughout the entire gastrointestinal (GI) tract, but normal net flow reflects absorption. High concentrations of oxalate and deposition of calcium oxalate (CaOx) crystals in the kidneys can evoke an inflammatory response and induce tubulo-interstitial damage leading to fibrosis, loss of nephrons, and eventually to chronic and end-stage renal failure. CaOx supersaturation in blood can result in CaOx crystal deposition in multiple organs, which can cause dysfunction or graft failure. There is currently no effective treatment for these complications. Therefore, the approach underlying this application is to reduce urinary and plasma oxalate by shifting net flow from the blood to the GI tract and by intercepting dietary sources of oxalate. By using a novel purified/formulated oxalate-degrading enzyme, soluble metabolically derived oxalate could be continuously removed at the site of secretion, and thus, utilize this alternate route of excretion to reduce life-threatening systemic oxalate levels. Confidential Information
Severe oxalate-related disease conditions, such as primary hyperoxaluria (PH), secondary hyperoxaluria (SH) (as a result of short bowel syndrome, chronic inflammatory bowel disease, cystic fibrosis, post bariatric, and other malabsorption syndromes), Zellweger spectrum disorders (ZSD), and chronic or end-stage renal failure, which are the result of increased dietary absorption and/or metabolic synthesis of oxalate continues to be a healthcare problem, without an effective treatment. Captozyme is proposing to use its novel enzyme formulation strategy to develop an oxalate-degrading enzyme therapeutic that can effectively remove metabolically generated oxalate as well as dietary oxalate, throughout the entire length of the GI tract. Confidential Information
