iECURE reported that pipeline candidate ECUR-506 produced statistically significant reductions in hyperammonemic events in the OTC-HOPE trial, with the completed low-dose cohort showing a 57% reduction in annualized hyperammonemic event rates and a 65% reduction in hyperammonemic crises. The findings, if sustained at higher doses, could challenge the chronic management paradigm that has defined ornithine transcarbamylase (OTC) deficiency treatment for decades.
The OTC-HOPE study is a first-in-human, open-label, dose-escalation trial evaluating ECUR-506 in male infants up to seven months of age with genetically confirmed neonatal-onset OTC deficiency. The trial has dosed seven participants across three cohorts — low dose (1.3 × 10¹³ gc/kg, n=3), intermediate dose (2.4 × 10¹³ gc/kg, n=3), and high dose (4.0 × 10¹³ gc/kg, n=1) — with the primary objective of assessing safety, tolerability, and efficacy of a single intravenous administration.
ECUR-506 is an investigational in vivo gene insertion therapy that uses two adeno-associated virus vectors carrying distinct payloads: one delivers an ARCUS nuclease, licensed from Precision BioSciences (Nasdaq: DTIL), designed to create an insertion site within the PCSK9 locus in liver cells, and the second delivers a functional copy of the OTC gene for targeted insertion. The approach is designed to restore OTC enzyme activity and reduce toxic ammonia accumulation — the central pathological mechanism in OTC deficiency — through a single administration rather than the lifelong daily dosing required by current standard-of-care nitrogen scavengers.
Key results from the low-dose cohort
Data presented at the Society for Inherited Metabolic Disorders 2026 Annual Meeting covered the completed low-dose cohort (n=3), with a data cutoff of April 20, 2026, for the cohort-level analysis and February 11, 2026, for the first-treated patient.
The primary efficacy signal came from pre-dose to post-dose comparisons of annualized event rates per person-year. The low-dose cohort demonstrated a 57% reduction in annualized hyperammonemic events (p=0.018) and a 65% reduction in annualized hyperammonemic crises — defined as plasma ammonia exceeding 100 µmol/L with associated neurological status change (p=0.011). Two of three participants experienced no hyperammonemic events or crises following treatment; the third demonstrated meaningful reductions in event rates. One participant was removed from the liver transplant waiting list following treatment, while one proceeded to liver transplantation during long-term follow-up, consistent with clinical management decisions in this population.
The most detailed data came from the first infant treated, who showed zero hyperammonemic events through 18 months post-dose, achieved sustained discontinuation of ammonia scavenger therapy, and had dietary protein intake progressively liberalized to age-appropriate levels. The company noted that sustained clinical response in the absence of standard-of-care therapy is not typically reported in patients with neonatal-onset OTC deficiency.
Post-treatment outcomes in the cohort reflect a combination of ECUR-506 and ongoing standard-of-care management, a qualification that limits interpretation of the magnitude of the gene therapy's independent contribution.