Philadelphia – August 27, 2026
iECURE, Inc. presented updated clinical data from the ongoing OTC-HOPE Phase 1/2 trial of ECUR-506 in infants with neonatal-onset ornithine transcarbamylase (OTC) deficiency at the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) in Helsinki, Finland. The company reported that Phase 1/2 dosing has been completed across all three dose cohorts, with nine participants treated and ongoing evaluations. For cGxP.wire, the key development is the progression of ECUR-506 through dose escalation and clinical evaluation, providing additional evidence on the investigational gene-editing therapy’s safety, targeted liver editing and potential metabolic effects. The low-dose cohort showed a 74% reduction in annualized hyperammonemic crises (HACs) following treatment, while annualized hyperammonemic events declined by 57%. The updated findings add clinical experience to the program as iECURE continues evaluating higher dose levels.
iECURE Completes ECUR-506 Phase 1/2 Dosing
The completion of dosing across the low-, intermediate- and high-dose cohorts marks an important milestone for iECURE’s ECUR-506 development program. Three participants received each dose level, with doses ranging from 1.3 × 10¹³ GC/kg to 4.0 × 10¹³ GC/kg. As of July 28, 2026, the company reported that ECUR-506 was generally well tolerated across the nine treated participants, with no unexpected treatment-related safety events reported. No cases of thrombotic microangiopathy or infusion reactions were observed. Transient Grade 2–3 transaminitis occurred in eight participants and resolved following reactive immunosuppression in seven cases, while one participant received prophylactic corticosteroids under the study protocol. One participant died following hypoxemic respiratory failure; iECURE reported that the event was determined to be unrelated to ECUR-506 and attributed to progression and complications of the underlying OTC deficiency. The safety findings remain preliminary as participant follow-up continues.
ECUR-506 Shows Targeted Hepatic Editing
The clinical update also provides evidence relevant to the gene-editing mechanism of ECUR-506. Twenty-four-week liver biopsies were conducted in two participants from the low-dose cohort, with analyses demonstrating evidence of targeted hepatic editing after administration of ECUR-506. The company also reported reductions in serum PCSK9 levels across the low-dose cohort, providing additional evidence consistent with editing at the targeted PCSK9 locus. Biopsy analyses from participants in the intermediate- and high-dose cohorts remain pending. ECUR-506 is designed as an in vivo targeted gene-insertion therapy, using two AAV vectors to deliver an ARCUS nuclease and a functional copy of the OTC gene. The nuclease is intended to create an insertion site within the PCSK9 gene locus in liver cells, allowing the therapeutic OTC gene to be inserted and potentially restore production of the deficient enzyme. The ongoing analyses are therefore important for establishing the relationship between targeted editing and subsequent clinical or metabolic outcomes.
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iECURE Reports 74% Reduction in Hyperammonemic Crises
The most notable clinical finding from the updated low-dose cohort was a 74% reduction in annualized hyperammonemic crises, compared with pretreatment rates, alongside a 57% reduction in annualized hyperammonemic events. iECURE reported statistical significance for both measures, with p=0.01 for HACs and p=0.02 for HAEs. The company noted that the updated HAC reduction increased from the previously reported 65% after an additional pretreatment crisis was identified during medical-history review. Responses varied among the three participants despite receiving the same dose, with one participant achieving a complete clinical response and discontinuing ammonia scavenger therapy and protein restriction. The other participants showed improvements in clinical measures, although their more severe underlying disease may have required greater restoration of OTC enzyme activity. These findings remain preliminary and are based on the low-dose cohort, while evaluations from the intermediate- and high-dose groups continue. iECURE plans to use the accumulating safety, editing and metabolic data to guide continued development of ECUR-506 for neonatal-onset OTC deficiency.
Source:iECURE,press relese
