iECURE Presents Updated Clinical Data from OTC-HOPE Trial of ECUR-506 in Neonatal-Onset Ornithine Transcarbamylase Deficiency at SSIEM 2026

• Phase 1/2 dosing completed across all dose cohorts; participant evaluations ongoing
• Preliminary safety observations show ECUR-506 was generally well tolerated, with no unexpected treatment-related safety events observed
• Updated low-dose cohort data demonstrate a 74% reduction in annualized hyperammonemic crises (HACs), the most serious and life-threatening manifestation of the condition, following ECUR-506 administration
• Low-dose cohort data provide evidence of targeted hepatic editing and improved metabolic control

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 encouraging updated clinical data from the ongoing OTC-HOPE clinical trial evaluating ECUR-506 for neonatal-onset ornithine transcarbamylase (OTC) deficiency. The data are being presented today in an oral platform presentation at the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) in Helsinki, Finland.

Updated data from the low-dose cohort demonstrated a 57% reduction in the annualized rate of hyperammonemic events (HAEs; p=0.02) and a 74% reduction in the annualized rate of hyperammonemic crises (HACs; p=0.01) following ECUR-506 administration. HAEs are episodes of elevated ammonia, with more severe episodes known as HACs. HACs are acute medical emergencies characterized by elevated ammonia levels with neurologic symptoms and can lead to hospitalization, irreversible neurological injury, or death.

“The clinical activity observed in the low-dose cohort is encouraging, particularly given that OTC-HOPE is evaluating some of the youngest and most severely affected patients with OTC deficiency,” said Julien Baruteau, M.D., Ph.D., University College London Great Ormond Street Institute of Child Health and an investigator in the OTC-HOPE study. “The safety, editing and clinical data generated to date are helping us better understand the relationship between underlying disease severity and the level of enzyme restoration that may be needed to achieve metabolic correction. These findings support the continued evaluation of higher ECUR-506 dose levels.”

The presentation also includes preliminary safety observations from all nine participants treated across the low-, intermediate- and high-dose cohorts, as well as analyses of editing efficiency and metabolic control from the low-dose cohort.

“Completing Phase 1/2 dosing across all three dose cohorts represents an important milestone for the OTC-HOPE program and provides us with a growing body of clinical experience with ECUR-506,” said Gabe Cohn, M.D., Chief Medical Officer of iECURE. “With nine participants now treated, we are encouraged by the safety profile observed to date and the clinical and editing data emerging from the study. We look forward to continuing to build on these findings as we advance the clinical development of ECUR-506.”

Updated OTC-HOPE Data Presented at SSIEM

Safety

• Nine participants have received ECUR-506 across three dose cohorts, with three participants each receiving the low dose (1.3 x 10¹³ GC/kg), intermediate dose (2.4 x 10¹³ GC/kg) or high dose (4.0 x 10¹³ GC/kg).
• As of July 28, 2026, ECUR-506 was generally well tolerated across all three dose cohorts, with no unexpected treatment-related safety events reported.
• There were no cases of thrombotic microangiopathy or infusion reactions.
• Asymptomatic, non-dose-dependent, transient Grade 2–3 transaminitis resolved with reactive immunosuppression in seven of eight participants; one participant received prophylactic corticosteroids following ECUR-506 administration per protocol.
• One participant experienced hypoxemic respiratory failure resulting in death, which was determined to be unrelated to ECUR-506 and attributable to underlying OTC deficiency disease progression and resulting complications.

Targeted Hepatic Editing

• Twenty-four-week liver biopsies were performed in two of the three participants in the low-dose cohort; the family of the third participant did not consent to the biopsy.
• Analyses demonstrated evidence of targeted hepatic editing following ECUR-506 administration.
• Reductions in serum PCSK9 levels were observed across the low-dose cohort, providing additional evidence consistent with editing at the targeted PCSK9 locus.
• Liver biopsy analyses from the intermediate- and high-dose cohorts are pending.

Clinical Response

• In the low-dose cohort, annualized rates of HAE and HAC (the more severe subset of HAEs) were reduced by 57% (p=0.02) and 74% (p=0.01), respectively, compared with pre-treatment rates following ECUR-506 administration. The updated 74% HAC reduction, compared with the previously reported 65% reduction, reflects the identification of an additional pre-treatment HAC since the prior data cutoff, included following updated review of the pre-treatment medical history.
• The three participants demonstrated heterogeneous clinical responses despite receiving the same dose. One participant, whose peak ammonia level at initial presentation was 840 µmol/L, achieved a complete clinical response and discontinued ammonia scavenger therapy and protein restriction. The other two participants had peak ammonia levels of 1,600 µmol/L or greater at presentation and demonstrated improvements in clinical measures consistent with reduced disease burden, with one participant successfully weaned from one of two ammonia scavenger medications.
• These observations, together with published natural history data demonstrating a relationship between OTC enzyme activity, initial ammonia levels and disease severity, support the hypothesis that baseline disease severity may influence treatment response. Patients with more profound underlying OTC deficiency may require greater restoration of OTC enzyme activity to achieve metabolic stability.

“We are pleased with the progress of the OTC-HOPE program and what we have learned through the completion of Phase 1/2 dosing,” said Joe Truitt, Chief Executive Officer of iECURE. “This milestone reflects the tremendous commitment of participating families, investigators and clinical teams, and brings us another step forward in our goal of developing a meaningful new treatment option for infants with neonatal-onset OTC deficiency.”

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.