Neurogene Announces Positive Regulatory Update for NGN-401 AAV Gene Therapy in Rett Syndrome

NEW YORK – October 9, 2025 – Neurogene Inc. ($\text{Nasdaq}$: $\text{NGNE}$) announced today that it has finalized the registrational protocol with the $\text{U.S. Food and Drug Administration}$ ($\text{FDA}$) for its EmboldenTM trial for the $\text{Rett}$ $\text{syndrome}$ gene therapy candidate, $\text{NGN-401}$, while new preclinical data presented at $\text{ESGCT}$ confirmed $\text{ICV}$ delivery provides superior expression in key brain regions over $\text{IT-L}$ delivery.

Clinical and Preclinical Highlights

• Dosing for the EmboldenTM registrational trial is scheduled to begin in the fourth quarter of $2025$ and will be conducted across 13 clinical sites to expedite patient enrollment.
• Preclinical data from nonhuman primates demonstrated that $\text{ICV}$ (intracerebroventricular) administration of $\text{NGN-401}$ leads to greater expression of the therapeutic $\text{MECP2}$ gene in key brain regions compared to $\text{IT-L}$ (intrathecal lumbar) delivery at equivalent doses.
• The company noted that this finding provides a rationale for the significant improvement and $23$ developmental milestones/skills reported in the first four $\text{NGN-401}$ $\text{Phase}$ 1/2 trial participants.
• Crucially, the preclinical study also found comparable peripheral exposure (including to the liver) between $\text{ICV}$ and $\text{IT-L}$ delivery, confirming $\text{IT-L}$ offers no liver-sparing advantage.
• $\text{Neurogene}$ $\text{CEO}$ $\text{Rachel}$ $\text{McMinn}$, $\text{Ph.D}$., highlighted the benefit of having $\text{FDA}$ $\text{START}$ pilot program and $\text{RMAT}$ designations, positioning the company for early $\text{FDA}$ engagement and a goal of expedited $\text{BLA}$ submission for $\text{NGN-401}$.