iECURE Presents Preliminary Clinical Data from Ongoing Clinical Trial of ECUR-506 in Ornithine Transcarbamylase Deficiency at the ASGCT Annual Meeting

• Preliminary data from participants enrolled in three dose cohorts (n=7) demonstrate that 71% of participants experienced no hyperammonemic crises (HACs) following ECUR-506 treatment, as of the April 20, 2026 data cutoff date.
  • HACs are defined as plasma ammonia levels above 100µmol/L with neurologic status change.
• Data from these cohorts also demonstrate approximately 52% reduction in the annualized rate of HACs following ECUR-506 administration.
  • HACs are the most clinically significant neurometabolic manifestation of ornithine transcarbamylase (OTC) deficiency. Reducing or preventing these crises is a key treatment goal, clinically meaningful measure of patient benefit, and an important efficacy endpoint in this highly vulnerable population.
• ECUR-506 was generally well tolerated across all dose cohorts to date, with no unexpected safety events.

PHILADELPHIA--(BUSINESS WIRE)--iECURE, Inc., a clinical-stage genome editing company developing variant-agnostic in vivo targeted gene insertion therapies for severe inherited neurometabolic disorders, today announced that data presented at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting from the ongoing OTC-HOPE clinical trial evaluating ECUR-506 in ornithine transcarbamylase (OTC) deficiency showed improved metabolic stability, with 71% of participants experiencing no hyperammonemic crises (HACs) post-treatment and a 52% reduction in the annualized rate of HACs across three dose cohorts of the trial, as of April 20, 2026.

“HACs, particularly those associated with neurologic symptoms, are the primary driver of morbidity and mortality in infants with neonatal-onset OTC deficiency,” said Margo Sheck Breilyn, MD, MS, Assistant Professor of Genetics and Genomic Sciences and Pediatrics at the Icahn School of Medicine at Mount Sinai. “Reductions in the frequency of these events can have a meaningful impact on clinical outcomes and long-term neurodevelopment. The reductions observed to date in the OTC-HOPE clinical trial are encouraging and support continued evaluation of this approach.”

OTC deficiency is a rare, serious genetic disorder caused by a defect in an enzyme responsible for removing ammonia from the bloodstream. HACs, the most clinically significant manifestation of the disease, are acute medical emergencies caused by toxic ammonia buildup, defined as plasma ammonia levels above 100µmol/L with neurologic status change. They often require hospitalization or intensive care and can lead to irreversible brain injury and potentially fatal complications. Treatment goals for neonatal-onset OTC deficiency include improving survival, supporting growth and neurodevelopment, and managing and preventing HACs. Current standard of care consists of administration of ammonia scavenging medications and adherence to a strict low-protein diet, which do not address the underlying cause of disease or fully prevent recurrent breakthrough HACs.

“Families managing infants affected with neonatal-onset OTC deficiency face an intense burden in adhering to current standard of care approaches,” said Gabriel Cohn, M.D., MBA, Chief Medical Officer of iECURE. “Despite this intensive management, affected infants remain at high risk of recurrent hyperammonemic crises, underscoring the need for new treatment approaches that reduce these events and offer hope to families for a different future.”

OTC-HOPE Trial Preliminary Clinical Outcomes Analysis Presented at ASGCT

• The preliminary 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
• Reduced HAC rates were observed following a single administration of ECUR-506 across all dose cohorts
  • 71% (5/7) of participants experienced no HACs post-treatment, with a 60% reduction in number of participants who experienced a HAC following administration of ECUR-506
  • Treatment with ECUR-506 was associated with an approximately 52% reduction in the annualized HAC rate (from ~3.12 to ~1.49 events per year)
  • Post-treatment observations reflect a combination of ECUR-506 and varying degrees of standard-of-care management
• ECUR-506 was generally well tolerated across all dose cohorts, with no unexpected safety events observed and a safety profile consistent with expectations for this modality
  • No infusion-related reactions or thrombotic microangiopathy (TMA) were observed, and no prophylactic immunosuppression was administered
  • Asymptomatic transaminitis (Grade 2–3) occurred in 5 of 7 participants, was effectively managed with reactive immunosuppression, and did not recur following taper
  • One death due to hypoxemic respiratory failure occurred; it was assessed as unrelated to ECUR-506 and attributable to underlying disease complications
• These findings provide early proof of concept and support an encouraging and manageable safety profile in this highly vulnerable neonatal population
• These data remain preliminary and are based on the initial participants dosed, with ongoing follow-up to further characterize durability and clinical outcomes

“Reducing life-threatening hyperammonemic crises and improving outcomes for infants with neonatal-onset OTC deficiency is incredibly meaningful for patients and families,” said Joseph Truitt, MBA, Chief Executive Officer of iECURE. “Preliminary data from infants with the most severe presentation of OTC deficiency show that ECUR-506 is associated with reductions in clinically severe HACs. This is encouraging progress that provides early evidence of clinical activity in this highly vulnerable patient population. We are in close contact with regulatory bodies and plan to complete treatment of the highest dose cohort as we work toward dose selection for our pivotal cohort.”

The full data presented at ASGCT is available in the Events & Presentations section of the iECURE website. Additional efficacy data and analyses from the completed low dose cohort will be presented at the Society for Inherited Metabolic Diseases (SIMD) 2026 Annual Meeting occurring May 17-20, 2026.

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), where it is 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.