iECURE Reports Durable Response With ECUR-506 in OTC-HOPE Trial and Reduced Hyperammonemic Events in Initial Cohort
iECURE has reported encouraging preliminary clinical data from the low-dose cohort of its ongoing OTC-HOPE trial evaluating ECUR-506, an investigational in vivo targeted gene insertion therapy for neonatal-onset ornithine transcarbamylase deficiency. The new findings, presented at the Society for Inherited Metabolic Disorders 2026 Annual Meeting, suggest that the therapy may provide meaningful clinical benefits for infants affected by one of the most severe inherited metabolic disorders.
The company announced that the first infant treated with ECUR-506 achieved a durable clinical response that included sustained discontinuation of standard-of-care therapies and the absence of hyperammonemic events through 18 months following treatment. Additionally, across the completed low-dose cohort, investigators observed statistically significant reductions in both hyperammonemic events and hyperammonemic crises after administration of the investigational therapy.
The results represent an important milestone for iECURE as it advances a gene insertion platform designed to address rare inherited neurometabolic disorders using variant-agnostic approaches. Unlike some genetic therapies that target only specific mutations, iECURE’s platform seeks to provide broader applicability across patients with disease-causing genetic variations.
Ornithine transcarbamylase deficiency, commonly known as OTC deficiency, is a rare but life-threatening inherited metabolic disorder caused by defects in the OTC enzyme, which normally helps eliminate ammonia from the body through the urea cycle. When the enzyme is deficient or absent, ammonia accumulates in the bloodstream to toxic levels, particularly affecting the brain and nervous system.
The neonatal-onset form of the disease is especially severe and often presents shortly after birth. Infants with this condition can rapidly develop hyperammonemic crises, or HACs, which involve dangerously elevated ammonia levels accompanied by neurological symptoms such as seizures, altered consciousness, coma, and rapid neurologic deterioration. These episodes are considered medical emergencies and can result in irreversible brain injury or death.
Current standard-of-care treatment options are limited and burdensome. Management typically involves strict dietary protein restriction, chronic administration of ammonia scavenger medications, intensive metabolic monitoring, and in some cases liver transplantation. Despite these interventions, many patients continue to experience recurrent hyperammonemic events that contribute to long-term neurological complications and poor survival outcomes.
ECUR-506 is being developed as a targeted gene insertion therapy intended to provide functional OTC enzyme activity within liver cells. The therapy uses in vivo genome editing technology designed to insert a healthy version of the OTC gene directly into hepatocytes, potentially restoring the body’s ability to process and eliminate ammonia more effectively.
According to iECURE Chief Medical Officer Gabriel Cohn, hyperammonemic crises remain one of the primary causes of mortality and morbidity in infants with neonatal-onset OTC deficiency. He noted that these events often trigger severe neurological complications, including seizures, coma, and rapid neurologic decline.
Cohn stated that the preliminary data presented at the SIMD meeting build upon earlier findings shared at the American Society of Gene & Cell Therapy Annual Meeting and provide additional evidence suggesting clinical activity at the low dose of ECUR-506. He emphasized that the observed durability of response and statistically significant reductions in hyperammonemic events are particularly encouraging given the vulnerability of the neonatal patient population enrolled in the study.
The preliminary analysis focused on the completed low-dose cohort of the OTC-HOPE clinical trial, which included three infants treated with ECUR-506 at a dose level of 1.3 x 10¹³ genome copies per kilogram. All participants completed the main study phase and continue in ongoing long-term follow-up.
Among the most notable findings was the durable response observed in the first treated infant. According to the company, the patient successfully discontinued ammonia scavenger therapy and remained free from hyperammonemic events through 18 months after treatment, including during periods of intercurrent illness that often trigger metabolic decompensation in OTC deficiency patients.
Investigators also progressively liberalized the child’s dietary protein intake to age-appropriate levels, an important achievement given the severe dietary restrictions normally required in neonatal-onset OTC deficiency management. The company noted that maintaining a sustained clinical response without standard-of-care therapy is highly unusual in this patient population.
Across all three participants in the low-dose cohort, treatment with ECUR-506 was associated with statistically significant reductions in annualized rates of both hyperammonemic events and hyperammonemic crises. Specifically, investigators reported a 57% reduction in annualized hyperammonemic event rates and a 65% reduction in hyperammonemic crisis rates following treatment. The reported p-values of 0.018 and 0.011 respectively indicated statistical significance for both measures.
Two of the three participants experienced no hyperammonemic events or crises following treatment, while the third participant demonstrated meaningful reductions in event frequency compared with the pre-treatment period.
The company emphasized that post-treatment outcomes reflected a combination of ECUR-506 therapy and ongoing standard-of-care management, as clinical approaches varied between participants depending on individual disease severity and physician decision-making.
The preliminary analysis also highlighted differing long-term management outcomes among treated patients. One participant was removed from the liver transplant waiting list following treatment, suggesting meaningful stabilization of disease burden. Another participant ultimately proceeded to liver transplantation during long-term follow-up, a decision that investigators stated was consistent with routine clinical management considerations in this high-risk patient population.
Beyond efficacy observations, the company also presented updated preliminary safety findings from participants treated across all three dosing cohorts evaluated to date. The safety analysis included seven patients overall: three patients in the completed low-dose cohort, three patients in the intermediate-dose cohort, and the first participant treated in the high-dose cohort.
According to iECURE, ECUR-506 was generally well tolerated across the treated population, with a safety profile consistent with expectations for the underlying therapeutic modality.
Importantly, investigators reported no unexpected safety events related to ECUR-506 administration. No infusion-related reactions or cases of thrombotic microangiopathy, a potentially serious complication associated with some gene therapies, were observed.
Some participants experienced asymptomatic elevations in liver enzymes, classified as Grade 2 or Grade 3 transaminitis. These events were managed using reactive immunosuppression strategies, and investigators reported no recurrence following tapering of immunosuppressive therapy.
The company also disclosed one death due to hypoxemic respiratory failure. Investigators assessed the event as unrelated to ECUR-506 treatment and instead attributed it to progression of the underlying OTC deficiency disease and associated complications.
iECURE stressed that the reported findings remain preliminary and are based on a limited number of treated participants with ongoing follow-up still underway. Continued monitoring will be necessary to further evaluate long-term durability, safety, and clinical outcomes as more patients are enrolled and additional data mature.
Evaluation of both the intermediate-dose and high-dose cohorts is ongoing, and the company indicated that future data from these groups will help inform dose selection decisions and broader development strategy for ECUR-506.
Chief Executive Officer Joe Truitt said the new data underscore the substantial burden faced by families caring for infants with neonatal-onset OTC deficiency. He noted that daily disease management remains extraordinarily challenging despite currently available treatments.
Truitt stated that the emerging clinical findings, including statistically significant reductions in hyperammonemic events and evidence of sustained response in the first treated participant, are encouraging and suggest the potential for meaningful reduction in disease burden. He added that the company looks forward to continuing evaluation of ECUR-506 as the study progresses.
The broader gene editing field has increasingly focused on developing in vivo therapies capable of delivering durable correction for severe inherited disorders through a single administration. While ex vivo gene editing approaches require removal and reinfusion of patient cells, in vivo strategies seek to directly edit target tissues within the body, potentially simplifying treatment and expanding accessibility.
Rare metabolic diseases such as OTC deficiency are considered particularly attractive targets for these approaches because even partial restoration of missing enzyme activity may lead to clinically meaningful improvements.
However, neonatal genetic disorders also present unique development challenges, including fragile patient populations, rapidly progressive disease courses, and heightened sensitivity to treatment-related toxicities. As a result, early evidence of both clinical activity and manageable safety profiles is closely watched within the field.
The preliminary OTC-HOPE findings position ECUR-506 as a potentially important investigational therapy within the evolving landscape of genome editing for rare pediatric metabolic disorders. If future studies continue to demonstrate durable efficacy and acceptable safety, the therapy could represent a meaningful advance for patients and families affected by neonatal-onset OTC deficiency, a condition that currently carries substantial risks of neurological injury, lifelong disability, and early mortality.
About OTC Deficiency
Ornithine transcarbamylase (OTC) deficiency is a rare, serious genetic disorder caused by a defect in a liver enzyme responsible for removing ammonia from the bloodstream. As a result, ammonia, a waste product generated when the body breaks down protein, accumulates in the blood (hyperammonemia) to levels that are toxic to the brain.
The disease is characterized by recurrent and often unpredictable hyperammonemic crises (HACs), which can lead to hospitalization, irreversible neurological injury, and death. Newborns with neonatal-onset OTC deficiency typically present shortly after birth with symptoms such as lethargy, poor feeding, and vomiting, which can rapidly progress to seizures, coma, and life-threatening complications if not promptly treated.
Current management includes a strict protein-restricted diet and ammonia scavenger medications, which must be taken multiple times daily and often throughout a patient’s life. While these approaches may help manage ammonia levels, they do not eliminate the risk of metabolic crises or ongoing disease burden, and patients remain vulnerable to acute decompensation and long-term complications.
About the OTC-HOPE Study
The OTC-HOPE study is a first-in-human clinical trial evaluating ECUR-506 in male infants with genetically confirmed neonatal-onset OTC deficiency. The trial is enrolling eligible male infants up to seven months of age at screening who are diagnosed with severe neonatal-onset OTC deficiency and meet study entry criteria. The primary objective is to assess the safety, tolerability and efficacy of intravenous administration of a single dose of ECUR-506.
The study will also assess the pharmacokinetics of ECUR-506 administration and the potential effects of ECUR-506 on clinical outcome measures, disease-specific biologic markers, developmental milestones and quality of life. The main study includes screening, stabilization, dosing eligibility, study drug administration, and six-month follow-up, after which participants transition to a 14.5 year long term follow-up study (ECUR-LTFU). For more information, visit https://OTC-HOPE.com.
About ECUR-506
ECUR-506 is an investigational in vivo targeted gene insertion therapy designed to restore OTC enzyme activity by inserting a functional copy of the OTC gene into the well-characterized PCSK9 gene locus in liver cells. The therapy utilizes two adeno-associated virus (AAV) vectors using the same capsid, each carrying a distinct payload. One vector contains an ARCUS® nuclease designed to create an insertion site within the PCSK9 locus, while the second vector delivers a functional OTC gene for targeted insertion. iECURE has licensed the ARCUS® nuclease for ECUR-506 from Precision BioSciences (Nasdaq: DTIL).1
About iECURE
iECURE is a clinical-stage genome editing company focused on developing therapies that utilize variant-agnostic in vivo targeted gene insertion to address severe genetic diseases with significant unmet need. The company’s approach is designed to restore the function of a missing or dysfunctional gene by inserting a functional copy into a patient’s genome, enabling durable gene expression and the potential for long-term therapeutic benefit.
iECURE is advancing a pipeline of investigational therapies targeting inherited neurometabolic disorders, a group of rare genetic diseases that can lead to severe metabolic and neurological complications, including ornithine transcarbamylase (OTC) deficiency, citrullinemia type 1 (CTLN1), and phenylketonuria (PKU). For more information, visit https://iecure.com and follow on LinkedIn.
About Precision BioSciences & ARCUS®
Precision BioSciences, Inc. is a clinical stage gene editing company dedicated to improving life (Nasdaq: DTIL) with its novel and proprietary ARCUS® genome editing platform that is designed to differ from other technologies in the way it cuts, its smaller size, and its simpler structure. Key capabilities and differentiating characteristics may enable ARCUS nucleases to drive more intended, defined therapeutic outcomes.
Using ARCUS, Precision’s pipeline is comprised of in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases, such as chronic hepatitis B where no adequate treatments exist. For more information about Precision BioSciences, visit www.precisionbiosciences.com.
