iECURE, in partnership with Precision BioSciences, has announced positive clinical efficacy and safety data from the Phase 1/2 OTC-HOPE study of ECUR-506, an in vivo gene insertion therapy for neonatal-onset Ornithine Transcarbamylase (OTC) deficiency. The study demonstrated a complete clinical response in the first infant dosed, showcasing the potential of ARCUS gene editing technology.
Clinical Efficacy and Safety
ECUR-506, which utilizes Precision BioSciences' ARCUS nuclease to insert a functional copy of the OTC gene, was generally well-tolerated in the infant. The only notable adverse event was asymptomatic transaminitis at four weeks, which was successfully managed with immunosuppressive therapy and resolved within four weeks. Twelve weeks after a single dose of ECUR-506, ammonia scavenger medication was discontinued, and the infant's mean daily protein intake was increased to age-appropriate levels. The mean ammonia level remained within normal limits and was reduced compared to the pre-treatment level. This response was maintained through six months, indicating a complete clinical response.
Impact on OTC Deficiency
OTC deficiency, the most common urea cycle disorder, results from a genetic defect that impairs the detoxification of ammonia. This can lead to severe neurological damage, coma, and death. Currently, the only corrective treatment for severe early-onset OTC deficiency is a liver transplant. ECUR-506 offers a potential alternative by inserting a functional OTC gene, addressing the root cause of the disease.
The ARCUS Platform
Michael Amoroso, CEO of Precision BioSciences, stated, "These results showcase that a complete clinical response can be achieved through in vivo gene editing for children born with this devastating genetic disease." The ARCUS platform's ability to perform precise gene insertion, excision, and elimination is seen as a significant advancement in gene editing therapies.
Ongoing Studies and Future Expectations
The OTC-HOPE study is ongoing in the United Kingdom, the United States, Australia, and Spain, with iECURE expecting to complete enrollment in 2025 and provide complete data in the first half of 2026. Precision BioSciences is also conducting the ELIMINATE-B trial for PBGENE-HBV in chronic hepatitis B, with Phase 1 data expected in 2025.
Analyst Perspective
BMO Capital Markets upgraded Precision BioSciences, acknowledging the promising nature of the iECURE data. Analyst Kostas Biliouris noted that the early ECUR-506 efficacy provides initial clinical derisking of the in vivo ARCUS editing platform. Biliouris estimates a roughly 65% probability for DTIL's in vivo HBV program to show acceptable safety and strong efficacy, which could drive the stock up by 100-200%.
