Neurogene AAV Gene Therapy NGN-401 Shows Multidomain Skill Gains in Rett Syndrome Trial

NEW YORK — November 12, 2025 — Neurogene Inc. (Nasdaq: NGNE) today announced positive, updated interim clinical data from the pediatric cohort (ages 4-10) of its ongoing Phase 1/2 trial evaluating NGN-401, an investigational AAV gene therapy, for the treatment of females with Rett syndrome. The data reveals that all eight participants demonstrated functional gains, with durable skill acquisition continuing over time, regardless of their initial disease severity.

The total cumulative gains observed across the pediatric cohort included the acquisition of 35 developmental milestones/skills across core domains of Rett syndrome, including hand function, communication, and gross motor skills. Management will discuss these results during the Stifel 2025 Healthcare Conference webcast today at 4:40 p.m. ET.

Durable Efficacy with AAV and EXACT Technology

The interim results underscore the potential for NGN-401 to be a best-in-class, one-time treatment for this devastating neurodevelopmental disorder.

Rachel McMinn, Ph.D., Founder and CEO of Neurogene, emphasized the clinical significance: “Updated interim data from our Phase 1/2 trial of NGN-401 show that all pediatric participants… have gained developmental milestones/skills or experienced functional gains, with durability and continued skill acquisition over time.”

The therapeutic benefits observed are attributed to the unique design of this AAV gene therapy. NGN-401 is an investigational AAV9 gene therapy that delivers the full-length human MECP2 gene, but critically, the AAV vector is regulated by Neurogene’s proprietary EXACT™ transgene regulation technology. This technology is essential for Rett syndrome because it ensures targeted therapeutic levels while mitigating the risk of overexpression-related toxic effects associated with conventional AAV gene therapy approaches.

Dr. Bernhard Suter, a principal investigator in the trial, highlighted the patient impact: “The interim NGN-401 results are particularly encouraging, showing continued skill acquisition across these areas with durable gains observed up to 24 months post treatment… These gains also translate into meaningful improvements in daily function, reduced caregiver burden and greater ability to express needs and wants.”

Favorable Safety Profile Supports Next Steps

Safety data, current as of the October 30, 2025 cutoff date, shows that NGN-401 at the registrational dose (1E15 vg) continues to be generally well-tolerated across both the pediatric and adolescent/adult cohorts (N=10).

All treatment-related adverse events have been mild (Grade 1) or moderate (Grade 2) and are consistent with known potential risks of AAV gene therapy, having either resolved or currently resolving. Crucially, no evidence of hemophagocytic lymphohistiocytosis (HLH)—a potentially fatal immune complication—has been observed in any participant.

The demonstrated efficacy and favorable safety profile at the registrational dose far exceed the bar set for the planned Embolden™ registrational trial. Neurogene is now focused on advancing the NGN-401 AAV gene therapy through its pivotal development pathway.