FDA Clears In-Vivo Gene Editing Therapy PBGENE-DMD for Duchenne Trial

Precision BioSciences (Precision), a clinical stage gene editing company headquartered in Durham, N.C., has received a Study May Proceed notification from FDA for PBGENE-DMD, a novel gene editing therapy, that enables the company to initiate institutional review board (IRB) activities and clinical site activation for a Phase I/II trial (FUNCTION-DMD) in ambulatory patients with Duchenne muscular dystrophy (DMD). The clearance of the company’s investigational new drug (IND) application allows it to begin activating specialized clinical trial sites in the United States, with IRB processes already underway at multiple centers, the company announced on Feb. 11, 2026 (1).

PBGENE-DMD, wholly owned by Precision, is an in-vivo gene editing investigational therapy designed to address the underlying genetic cause of DMD through a one-time gene excision strategy. The program leverages the company’s proprietary ARCUS platform to permanently edit the dystrophin gene in patients with mutations between exons 45 and 55, a mutation “hot spot” that represents approximately 60% of individuals with DMD, according to the company (1).

“Duchenne muscular dystrophy is a progressive disorder caused by mutations in the dystrophin gene that disrupt the production of the functional protein, resulting in continuous muscle degeneration,” said Aravindhan Veerapandiyan, MD, director, Comprehensive Neuromuscular Program, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, in a company press release (1). “PBGENE-DMD is designed to restore near full-length dystrophin, with the potential to provide significant functional benefits. This is an important milestone, and I look forward to participating in the [Phase I/II] FUNCTION-DMD clinical study to evaluate a gene excision approach in DMD patients with mutations involving exons 45-55.”

How does this therapy’s gene-excision strategy differ from microdystrophin and exon-skipping therapies?

DMD is a progressive neuromuscular disorder caused by mutations in the dystrophin gene that disrupt production of functional dystrophin protein, resulting in ongoing muscle degeneration affecting skeletal and cardiac muscle. Current therapeutic approaches, including micro-dystrophin gene therapies and exon-skipping agents, aim to restore partial dystrophin expression but are limited by truncated protein constructs or mutation specificity (2).

PBGENE-DMD is designed to restore production of a near full-length dystrophin protein while retaining approximately 80% of the full-length sequence. This result is substantially larger than micro-dystrophin constructs, which are approximately one-third the size of native dystrophin. The gene excision approach uses a single adeno-associated virus (AAV) vector encoding two ARCUS nucleases to permanently edit genomic DNA, which enables endogenous expression of the corrected dystrophin protein.

According to the company, preclinical data demonstrated restoration of near full-length dystrophin expression across multiple skeletal muscle groups and cardiac tissue in a humanized DMD mouse model. The program also showed editing of muscle satellite stem cells, a population believed to support durability of response through sustained regeneration and long-term protein expression (1).

What will the Phase I/II trial evaluate in ambulatory patients?

The FUNCTION-DMD Phase I/II study is designed to evaluate safety, tolerability, and preliminary efficacy in ambulatory patients with mutations in exons 45–55. The trial will incorporate immune modulation and safety monitoring strategies appropriate for systemic AAV-based gene editing. Early efficacy assessments will include measurement of near full-length dystrophin expression in muscle biopsy samples, along with functional outcome measures. Precision anticipates Initial data from multiple patients by the end of 2026. Following supportive data from at least 10 treated patients, the company plans to engage with FDA to discuss potential regulatory pathways.

PBGENE-DMD has also received FDA rare pediatric disease and orphan drug designations. The advancement of this program marks the company’s second wholly owned in-vivo gene editing candidate to enter clinical development. The company’s progress positions ARCUS-based editing as a potential modality for addressing high-prevalence genetic subsets within rare diseases.

References

1. Precision BioSciences. Precision BioSciences Receives U.S. FDA Clearance of Investigational New Drug Application for First-in-Class PBGENE-DMD for Treatment of Duchenne Muscular Dystrophy. Press Release. Feb. 11, 2026.
2. Happi Mbakam, C.; Lamothe, G.; Tremblay, J. P. Therapeutic Strategies for Dystrophin Replacement in Duchenne Muscular Dystrophy. Front Med (Lausanne) 2022, 9, 859930. DOI: 10.3389/fmed.2022.859930