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

Rhea-AI Summary

iECURE presented encouraging data from its OTC-HOPE Phase 1/2 clinical trial of ECUR-506 for ornithine transcarbamylase (OTC) deficiency at the 2025 ACMG Annual Clinical Genetics Meeting. The first infant patient, dosed at 6.5 months old with 1.3 x 1013 GC/kg of ECUR-506, showed promising results after six months of treatment.

Key findings include:

• Complete clinical response achieved per study protocol
• Successful discontinuation of ammonia scavenger medication at 12 weeks post-treatment
• Increased protein allowance to age-appropriate levels
• Higher blood urea nitrogen (BUN) levels post-treatment, suggesting improved OTC enzyme function
• Normal plasma ammonia levels maintained after medication removal

While treatment was generally well-tolerated, a temporary Grade 3 transaminitis was observed at four weeks post-exposure, which resolved by week eight with immunosuppressive therapy.

Positive

• Complete clinical response achieved in first treated patient
• Successful discontinuation of ammonia scavenger medication
• Increased protein allowance to normal levels
• Evidence of restored OTC enzyme activity through increased BUN levels
• Normal plasma ammonia levels maintained after medication removal

Negative

• Grade 3 transaminitis adverse event requiring immunosuppressive therapy
• Only one patient data available so far
• 6-month follow-up period

Insights

Biotechnology Analyst

The data presented by iECURE for their ECUR-506 gene therapy in OTC deficiency represents a meaningful clinical milestone with potential relevance to Precision BioSciences (DTIL). While not explicitly mentioned in the release, DTIL has a partnership with iECURE that licenses DTIL's ARCUS gene editing platform for programs including OTC deficiency.

The clinical data from the first patient is particularly encouraging on several fronts: complete clinical response, suggested partial restoration of functional OTC enzyme activity, and the ability to discontinue ammonia scavenger medication while increasing protein intake to normal levels. The observed increase in blood urea nitrogen (BUN) levels provides biochemical evidence supporting functional enzyme restoration.

For context, OTC deficiency is a serious urea cycle disorder where patients cannot properly eliminate ammonia, potentially leading to hyperammonemic crises that can cause brain damage or death. Current standard of care involves severe protein restriction, medications, and often liver transplantation for severe cases.

While these results are from a single patient at the lowest dose level (1.3 x 10¹³ GC/kg), they represent an important proof-of-concept for this approach. The treatment appears generally well-tolerated with manageable safety signals - the Grade 3 transaminitis resolved with immunosuppressive management.

For DTIL, successful application of their technology platform in a clinical setting potentially validates their approach to gene editing and could enhance the value of their broader pipeline and partnership strategy.

Medical Genetics Specialist

The clinical data presented for iECURE's ECUR-506 in OTC deficiency demonstrates meaningful therapeutic potential for this severe genetic disorder. The observed partial restoration of OTC enzyme activity addresses the fundamental pathophysiology of the disease by targeting the underlying genetic mutation rather than just managing symptoms.

Several biomarkers support actual enzymatic function restoration: sustained normal ammonia levels despite discontinuing scavenger medications, tolerance of age-appropriate protein intake, and importantly, the increase in blood urea nitrogen (BUN) levels. In OTC deficiency, BUN is typically low because the urea cycle - which converts ammonia to urea for excretion - is dysfunctional. The normalized BUN suggests the treatment may be enabling proper ammonia processing.

The transient Grade 3 transaminitis (liver enzyme elevation) is a common challenge with liver-directed gene therapies and appears manageable with immunosuppressive therapy. This safety profile is relatively favorable for a first-in-human gene therapy trial, especially considering the severity of untreated OTC deficiency.

For affected families, the clinical implications are profound. Current management of severe OTC deficiency requires strict dietary protein restriction, multiple medications, frequent monitoring, emergency protocols for hyperammonemic crises, and often culminates in liver transplantation - which brings its own significant complications. A one-time treatment that could provide durable enzyme activity would represent a transformative advance for these patients.

While encouraging, these results from a single patient will need confirmation in additional patients to establish consistency and durability of effect.

First participant dosed achieved complete clinical response per study protocol and data suggests partial restoration of functional OTC enzyme activity in the liver

PHILADELPHIA--(BUSINESS WIRE)-- 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20250321586569/en/

Investors:

David Garrett

dgarrett@iecure.com

Media:

Janine Bogris

Inizio Evoke Comms

janine.bogris@inizioevoke.com

Source: iECURE, Inc.

FAQ

What are the key results from iECURE's ECUR-506 Phase 1/2 trial in OTC deficiency?

The first infant showed complete clinical response, maintained normal ammonia levels, discontinued scavenger medication at 12 weeks, and demonstrated increased BUN levels suggesting restored OTC enzyme activity.

What safety concerns were observed in the ECUR-506 OTC-HOPE trial?

A temporary Grade 3 transaminitis occurred at 4 weeks post-treatment, which resolved by week 8 with immunosuppressive therapy.

What is the dosing protocol used in the ECUR-506 OTC-HOPE trial?

The first infant received a single infusion of 1.3 x 1013 GC/kg of ECUR-506 at 6.5 months of age.

How long after ECUR-506 treatment were patients able to discontinue ammonia scavenger medication?

The first patient was able to discontinue ammonia scavenger medication 12 weeks after ECUR-506 treatment.