Precision BioSciences Reports Full Clinical Response in Initial Infant Treated for OTC Deficiency in Phase 1/2 Trial

In a significant advancement in gene therapy, Precision BioSciences, Inc., a clinical-stage gene editing company, has revealed promising results from its collaborative Phase 1/2 OTC-HOPE study. The study involves a groundbreaking treatment for neonatal onset Ornithine Transcarbamylase (OTC) deficiency, executed through the administration of ECUR-506. This innovative therapy harnesses the potential of the ARCUS® platform, a proprietary tool developed by Precision BioSciences for precise in vivo gene editing. The ARCUS technology facilitates sophisticated gene modifications, including insertion, excision, and elimination.

The initial results reported by iECURE, a partner in the study, have shown that ECUR-506, an in vivo gene insertion therapy, has resulted in a complete clinical response in the first infant patient from three months post-treatment through the six-month follow-up period. This therapy utilizes a PCSK9-specific ARCUS nuclease to insert a functioning copy of the OTC gene. The trial has been a milestone in treating this severe genetic condition, characterized by a deficiency in a crucial liver enzyme that detoxifies ammonia. The deficiency leads to dangerous levels of ammonia in the blood, causing severe health issues, including potential neurological damage and, in extreme cases, death.

Michael Amoroso, CEO of Precision BioSciences, praised iECURE for the encouraging outcomes of their trial, highlighting the potential of ARCUS as a transformative in vivo gene editing method. He emphasized that these results affirm the therapeutic promise of ARCUS for further clinical applications by Precision and its partners.

In terms of safety, the administration of ECUR-506 was well received by the infant patient, showing no considerable clinical safety issues. The only noted side effect was asymptomatic transaminitis at the four-week mark, which was effectively managed with immunosuppressive therapy, resolving within another four weeks. Importantly, after a single dose of ECUR-506, the patient was able to discontinue ammonia scavenger medication after twelve weeks, and dietary protein was normalized without adverse effects. The patient’s ammonia levels stabilized within normal ranges and were lower than those before treatment, demonstrating the therapy’s efficacy.

The ongoing OTC-HOPE study is being conducted across several countries, including the United Kingdom, the United States, Australia, and Spain. iECURE plans to complete the enrollment phase by 2025 and aims to present comprehensive data from the study in the first half of 2026.

Precision BioSciences is also progressing with the ELIMINATE-B trial for PBGENE-HBV, targeting chronic hepatitis B, with trial sites in Moldova, Hong Kong, and New Zealand. The initial phase of this trial is expected to yield results in 2025.

An overview of Precision BioSciences reveals it as a clinical-stage gene editing enterprise committed to leveraging its ARCUS platform to address a wide range of genetic and infectious diseases. The company aims to offer enduring cures through its in vivo gene editing candidates, addressing diseases such as chronic hepatitis B, where current treatments fall short.

iECURE, on the other hand, focuses on developing therapies for liver disorders using in vivo gene insertion, independent of specific mutations. By adopting a strategy that enables the insertion of a functional gene copy, iECURE anticipates delivering long-term therapeutic benefits. Their team, experienced in global orphan drug and gene therapy trials, strives to identify optimal targets and modalities to address significant liver diseases efficiently.

The treatment of OTC deficiency remains critical, as this genetic disorder, which affects the liver enzyme responsible for ammonia detoxification, leads to severe consequences without effective intervention. Currently, a liver transplant is the only corrective measure for early-onset severe cases, emphasizing the urgent need for innovative solutions like those being explored in the OTC-HOPE study.