iECURE Reports Sustained Clinical Response in the First Patient Dosed with ECUR-506 & Reductions in the Annualized Rates of Hyperammonemic Events and Crises in the First Completed Cohort of ECUR-506 in Ongoing OTC-HOPE Trial

iECURE, Inc., a clinical-stage genome editing company developing variant-agnostic in vivo targeted gene insertion therapies for severe inherited neurometabolic disorders, today announced positive results from a preliminary analysis of the completed low-dose cohort of ECUR-506 from the ongoing OTC-HOPE clinical trial in neonatal-onset ornithine transcarbamylase (OTC) deficiency. Data were presented at the Society for Inherited Metabolic Disorders (SIMD) 2026 Annual Meeting.

The first infant treated with ECUR-506 demonstrated a durable clinical response, with sustained discontinuation of standard-of-care therapies and no hyperammonemic events (HAEs) through 18 months post dose, as of February 11, 2026. In addition, participants (n=3) treated with the low dose (1.3 x 10¹³ gc/kg) of ECUR-506 experienced statistically significant reductions in the annualized rates of HAEs and hyperammonemic crises (HACs), with 57% (p=0.018) and 65% (p=0.011) reductions, respectively, in pre-dose to post-dose rates of events per person-year, as of April 20, 2026.

“In infants with neonatal-onset OTC deficiency, HACs, which are spikes in plasma ammonia >100 umol/L associated with neurological status change, are a primary driver of mortality and morbidity, sometimes resulting in seizures, coma, and rapid neurologic decline,” said Gabriel Cohn, M.D., Chief Medical Officer of iECURE. “The preliminary findings presented at SIMD build on data presented last week at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting and provide further evidence suggestive of clinical activity at the low dose, including durability of response and significant reductions in the annualized HAC and HAE rates in this highly vulnerable neonatal population.”

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 can accumulate to toxic levels, leading to recurrent HAEs, including more severe episodes known as HACs. HACs, the most clinically significant manifestation of the disease, are acute medical emergencies characterized by elevated ammonia levels with neurologic symptoms. These events often require hospitalization or intensive care and can lead to irreversible neurological injury or death.

Treatment goals for neonatal-onset OTC deficiency include improving survival, supporting growth and neurodevelopment, and managing and preventing hyperammonemic events. Despite intensive standard-of-care management with ammonia scavenger medications and strict dietary protein restriction, patients remain at high risk for breakthrough episodes, underscoring the need for treatment approaches that reduce these events and improve clinical outcomes.

“Families caring for infants with neonatal-onset OTC deficiency must navigate the daily challenges of managing this life-threatening condition,” said Joe Truitt, CEO of iECURE. “The emerging data, which now include statistically significant reductions in hyperammonemic events and evidence of durability in the first treated participant, are encouraging and highlight the potential to meaningfully reduce disease burden. We look forward to continuing to evaluate ECUR-506 as the study progresses.”

OTC-HOPE Trial Preliminary Clinical Outcomes Analysis Presented at SIMD

• The preliminary analysis includes the completed low-dose cohort (n=3) of infants with neonatal-onset OTC deficiency who have completed the OTC-HOPE main study, with ongoing long-term follow-up

• A durable clinical response was observed in the first treated infant
  • Sustained discontinuation of ammonia scavenger therapy was achieved

  • Dietary protein intake was progressively liberalized to age-appropriate levels

  • No HAEs were observed through 18 months post-dose, including during intercurrent illness

  • The described sustained clinical response in the absence of standard-of-care therapy in the first participant is not typically reported in patients with neonatal-onset OTC deficiency

• Statistically significant reductions in HAEs and HACs were observed following a single administration of low dose (1.3×10¹³ gc/kg) ECUR-506
  • Treatment with ECUR-506 was associated with a 57% reduction in annualized HAE rate and a 65% reduction in annualized HAC rate (p=0.018 and 0.011 respectively)

  • The majority of participants (2 of 3) experienced no HAEs or HACs post-treatment, with the remaining participant demonstrating meaningful reductions in event rates

  • Post-treatment outcomes reflect a combination of ECUR-506 and ongoing standard-of-care management

• Clinical outcomes reflected a range of participant experiences
  • One participant was removed from the liver transplant waiting list following treatment

  • One participant proceeded to liver transplantation during long-term follow-up, consistent with clinical management decisions in this population

• Across patients treated to date in all three dose cohorts (n=7), ECUR-506 was generally well tolerated, with a safety profile consistent with expectations for this modality
  • The preliminary safety analysis included 7 participants, composed of the complete low dose level (1.3 x 10¹³ GC/kg) (n=3) and intermediate dose level (2.4 x 10¹³ GC/kg) (n=3) cohorts, and the first participant in the high dose level (4.0 x 10¹³ GC/kg) cohort

  • No unexpected safety events related to ECUR-506 were observed

  • No infusion-related reactions or thrombotic microangiopathy (TMA) were reported

  • Asymptomatic transaminitis (Grade 2–3) was observed and managed with reactive immunosuppression, with no recurrence following taper

  • One death due to hypoxemic respiratory failure occurred; it was assessed as unrelated to ECUR-506 and attributable to underlying OTCD disease progression and resulting complications

• These findings remain preliminary and are based on the initial participants dosed, with ongoing follow-up intended to further characterize durability and clinical outcomes

• Evaluation of the intermediate and high-dose cohorts is ongoing, with additional data expected to inform dose selection and future development

• These preliminary findings provide further evidence suggestive of clinical activity, including durability of response, and an encouraging and manageable safety profile in this highly vulnerable neonatal population.

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.

[1] iECURE has licensed the ARCUS® nuclease from Precision BioSciences for four gene insertion programs including OTC, CTLN1 and PKU.

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