ECUR-506A

ECUR-506A is an investigational *in vivo* gene editing therapy developed by iECURE for the treatment of neonatal-onset ornithine transcarbamylase (OTC) deficiency. The therapy utilizes a dual-vector adeno-associated virus serotype 8 (AAV8) system to deliver two components to the liver: an ARCUS meganuclease and a functional human OTC gene donor template. The ARCUS meganuclease, licensed from Precision BioSciences, is engineered to create a site-specific double-strand break at a "safe harbor" locus within the *PCSK9* gene. This targeted break facilitates the stable integration of the functional OTC gene into the hepatocyte genome via homology-directed repair or targeted insertion. By achieving permanent integration, ECUR-506A aims to provide durable expression of the OTC enzyme as the liver grows, potentially offering a curative approach for infants with this life-threatening urea cycle disorder. The program has received Orphan Drug and Rare Pediatric Disease designations from the FDA and is currently being evaluated in the Phase 1/2 OTC-HOPE clinical trial.