Precision BioSciences, Inc. announced that its partner iECURE has received approval from the Australian Therapeutic Goods Administration for the initiation of a first-in-human Phase 1/2 trial evaluating ECUR-506, incorporating an ARCUS nuclease for the treatment of Ornithine Transcarbamylase (OTC) deficiency in pediatric (or neonatal) patients. OTC deficiency, the most common urea cycle disorder, is an inherited metabolic disorder caused by a genetic defect in a liver enzyme responsible for the detoxification of ammonia. Individuals with OTC deficiency can build up excessive levels of ammonia in their blood potentially resulting in devastating consequences, including irreversible neurological damage, coma and death.

The severe form of the condition emerges shortly after birth and is more common in boys than girls. The only corrective treatment for early onset severe OTC deficiency is a liver transplant. Currently available medical therapies do not correct the disease and do not eliminate the risk of life-threatening symptoms or crises.

In preclinical studies, administration of ECUR-506 resulted in a durable response in nonhuman primates, with up to 28.2% of liver cells demonstrating expression of the human OTC gene at the 1-year time point. A 5% threshold of enzymatic activity has the potential for clinical benefit as previously identified in Annals of Clinical and Translational Neurology. Separately, in a mouse model of OTC-deficiency, the injection of ECUR-506 in newborn mice efficiently inserted a healthy copy of the OTC gene.