iECURE Announces Presentation of Full Data for the First Infant Dosed with ECUR-506 in OTC-HOPE Phase 1/2 Clinical Trial at the 2025 ACMG Annual Clinical Genetics Meeting
First participant dosed achieved complete clinical response per study protocol and data suggests partial restoration of functional OTC enzyme activity in the liver
iECURE, Inc., a gene editing company focused on the development of mutation-agnostic in vivo gene insertion therapies for the treatment of liver disorders with significant unmet need, today announced that data presented at the 2025 ACMG Annual Clinical Genetics Meeting from the ongoing OTC-HOPE Phase 1/2 study of ECUR-506 suggest partial restoration of functional ornithine transcarbamylase (OTC) enzyme activity in the first patient dosed.
"Long-term restoration of ornithine transcarbamylase activity has the potential to allow infants afflicted with neonatal onset OTC deficiency to live healthier lives unburdened by hyperammonemic crises and ongoing medical management," said Gabriel Cohn, M.D., MBA, Chief Medical Officer of iECURE. "The data generated for the first six months post treatment with ECUR-506 continue to be encouraging for us. We are eager to continue enrolling patients into the OTC-HOPE study and are hopeful that we will continue to see similar results."
The data presented build upon previously announced preliminary findings from the first infant dosed in the OTC-HOPE study, which detailed the complete clinical response for that infant as per study protocol. Notably, the first patient received a single infusion of the lowest dose (1.3 x 1013 GC/kg) of ECUR-506 at 6.5 months of age. At 12 weeks post-ECUR-506 dosing, ammonia scavenger medication was discontinued based on reduced serum glutamine levels, and protein allowance was increased to the age-appropriate level for infants without OTC deficiency. Treatment with ECUR-506 was generally well tolerated, however, asymptomatic Grade 3 transaminitis was noted at four weeks post ECUR-506 exposure which resolved by eight weeks post ECUR-506 exposure following immunosuppressive therapy management.
Additional data presented included the observation that the mean blood urea nitrogen (BUN) level post ECUR-506 treatment was markedly higher in comparison to the pre-treatment mean, which was close to the lower limit of normal. The increased BUN level may suggest increased functional activity as BUN is usually low in patients who lack the OTC gene due to impaired urea production.
"The observation at the end of the 6-month follow-up period that plasma ammonia levels remained within normal limits following the removal of ammonia scavenger medicines and restoration of a diet with typical protein levels as well as increased blood urea nitrogen levels suggest some OTC enzyme activity may have been restored following treatment with ECUR-506," said Julien Baruteau, M.D., Ph.D., MRC Clinical Scientist Fellow and Group Leader at University College London Great Ormond Street Institute of Child Health and Consultant in Metabolic Medicine at Great Ormond Street Hospital for Children in London, and principal investigator in the study. "For families who have struggled to manage their babies' health while waiting for liver transplant, currently the only long-term solution for those afflicted with the most severe forms of OTC deficiency, a solution that could restore OTC activity would be an incredibly exciting option."
About OTC Deficiency
OTC deficiency is a serious rare genetic disease wherein ammonia, a waste product that is generated when the body breaks down proteins, builds up in the blood (hyperammonemia). Ammonia is toxic to the brain when it accumulates at high levels. Newborns with neonatal onset OTC deficiency experience symptoms of hyperammonemia shortly after birth, including lethargy, poor suck and vomiting, that if left untreated can quickly escalate to seizures, brain damage, coma and eventual death.
About ECUR-506
iECURE's approach to gene editing for its initial programs, including OTC deficiency, relies on the delivery of two adeno-associated virus (AAV) vectors comprised of the same capsid, but each carrying different payloads. ECUR-506 comprises two vectors, an ARCUS® nuclease vector targeting gene editing in the well-characterized PCSK9 gene locus and a donor vector that inserts the desired functional OTC gene. iECURE has licensed the ARCUS® nuclease for ECUR-506 from Precision BioSciences (NASDAQ:DTIL).1 The cut in the PCSK9 site designed to serve as a safe harbor, insertion site for the OTC gene, providing a potential path to permanent expression of a functional gene.
About the OTC-HOPE Study
The OTC-HOPE study is a Phase 1/2 first-in-human clinical trial of ECUR-506 in baby boys with genetically confirmed neonatal onset OTC deficiency and has been cleared to evaluate ascending dose levels of ECUR-506, if necessary. The study is enrolling newborn males up to seven months of age at screening who are diagnosed with severe neonatal onset OTC deficiency and meet certain other criteria. The primary objective is to assess the safety and tolerability of intravenous administration of a single dose of ECUR-506. It will also assess the pharmacokinetics and efficacy of ECUR-506 administration and the potential effects of ECUR-506 on disease-specific biologic markers, developmental milestones and quality of life. The main study will occur in a series of stages over a 10-month period, including screening, stabilization, dosing eligibility, study drug administration, and six-month follow-up. Upon completion of the OTC-HOPE study, participants transition to the 14.5 year long term follow up study (ECUR-LTFU). For more information, visit https://OTC-HOPE.com.
About iECURE
iECURE is a clinical-stage gene editing company focused on developing therapies that utilize mutation-agnostic in vivo gene insertion for the treatment of liver disorders with significant unmet need. We believe our approach has the potential to restore the function of a dysfunctional gene, regardless of mutation, by knocking-in a functional copy of that gene to offer durable gene expression and long-term, potentially curative, therapeutic benefit. Our management team has extensive experience in executing global orphan drug and gene therapy clinical trials and successfully commercializing multiple products. We intend to leverage our team's core strength in research and development strategy to identify what we believe to be the most suitable target and modality for our product candidates to address particular liver diseases. 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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