May 18, 2026 —
iECURE announced positive preliminary results from the completed low-dose cohort of ECUR-506, its investigational in vivo targeted gene insertion therapy for neonatal-onset ornithine transcarbamylase deficiency, also known as OTC deficiency. The data were presented at the Society for Inherited Metabolic Disorders 2026 Annual Meeting and build on findings shared at ASGCT, suggesting early clinical activity in a highly vulnerable infant population.
OTC deficiency is a rare, life-threatening urea cycle disorder caused by deficiency of the liver enzyme ornithine transcarbamylase, which is required to remove ammonia from the bloodstream. In neonatal-onset disease, ammonia can rapidly accumulate to toxic levels, causing hyperammonemic events and hyperammonemic crises that may lead to seizures, coma, irreversible neurologic injury, or death. Despite intensive standard-of-care management with ammonia scavenger medications and strict protein restriction, infants remain at risk for breakthrough metabolic crises.
ECUR-506 is designed to restore OTC enzyme activity by inserting a functional copy of the OTC gene into the well-characterized PCSK9 locus in liver cells. The therapy uses two AAV vectors with the same capsid: one carrying an ARCUS® nuclease to create the insertion site, and the other delivering the functional OTC gene for targeted insertion. This approach is intended to provide durable gene correction while addressing a broad range of disease-causing variants.
In the completed low-dose cohort of the ongoing OTC-HOPE trial, three infants received ECUR-506 at 1.3 × 10¹³ gc/kg. The first treated infant demonstrated a durable clinical response, including sustained discontinuation of standard-of-care ammonia scavenger therapy, progressive liberalization of dietary protein intake to age-appropriate levels, and no hyperammonemic events through 18 months post-dose, including during intercurrent illness.
Across the low-dose cohort, ECUR-506 was associated with statistically significant reductions in annualized hyperammonemic events and hyperammonemic crises. The annualized HAE rate was reduced by 57%, while the annualized HAC rate was reduced by 65% from pre-dose to post-dose rates of events per person-year. Two of three participants experienced no HAEs or HACs after treatment, while the remaining participant showed meaningful reductions in event rates.
The preliminary safety analysis included seven participants treated across the low, intermediate, and first high-dose cohorts. ECUR-506 was generally well tolerated, with no unexpected safety events related to treatment, no infusion-related reactions, and no thrombotic microangiopathy reported. Asymptomatic Grade 2–3 transaminitis was observed and managed with reactive immunosuppression, with no recurrence after taper. One death due to hypoxemic respiratory failure occurred and was assessed as unrelated to ECUR-506.
The findings remain preliminary, and longer follow-up will be needed to further characterize durability, dose response, safety, and long-term clinical outcomes. However, the early data provide encouraging evidence that targeted in vivo gene insertion may reduce disease burden in neonatal-onset OTC deficiency, a condition where treatment options remain limited and where preventing hyperammonemic crises is central to improving survival and neurodevelopmental outcomes.
