Neurogene Doses First Participant in Registrational Embolden Trial of AAV Gene Therapy NGN-401 for Rett Syndrome

NEW YORK — Nov. 6, 2025 — Neurogene Inc., a clinical-stage company developing precision genetic medicines, today announced a major step forward for the Rett syndrome community: the first participant has been dosed in the Embolden™ registrational clinical trial of NGN-401, an investigational AAV gene therapy.

NGN-401 has the potential to be a best-in-class and first-in-class gene therapy for Rett syndrome, a devastating neurodevelopmental disorder with significant unmet medical need. This pivotal, single trial is expected to support a future Biologics License Application (BLA) submission for patients aged three years and older.

Rachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene, commented on the rapid execution: “Dosing the first participant in the Embolden registrational trial of NGN-401 marks a major milestone in advancing a gene therapy for Rett syndrome. We prioritized operational excellence this year, doubling our U.S. site footprint and initiating 12 of 13 clinical sites to meet patient demand, positioning us to complete enrollment within the next three to six months.”

AAV Delivery and EXACT Regulation

NGN-401 is an investigational AAV9 gene therapy being developed as a one-time treatment. It utilizes the AAV delivery system to administer the full-length human MECP2 gene. Crucially, the AAV vector is controlled by Neurogene’s proprietary EXACT transgene regulation technology.

The AAV approach is administered via a single intracerebroventricular (ICV) injection, allowing the AAV to distribute the therapy throughout the central nervous system. The EXACT technology is vital because it enables targeted levels of MECP2 transgene expression, thus limiting the potential overexpression-related toxic effects associated with conventional AAV gene therapy approaches. Preclinical studies demonstrated that NGN-401, delivered via AAV, showed greater expression of the therapeutic mRNA in key brain regions compared to other administration methods.

Embolden Trial Overview and Regulatory Momentum

The Embolden trial is a single-arm, open-label, baseline-controlled study evaluating the 1E15 vector genome (vg) dose of NGN-401 in 20 females aged three years and older with Rett syndrome. The trial is currently enrolling in the U.S.

The NGN-401 AAV gene therapy has accumulated significant regulatory designations, underscoring its potential:

• Selected by the FDA for its START Pilot Program.
• Granted Regenerative Medicine Advance Therapy (RMAT), Orphan Drug, Fast Track, and Rare Pediatric Designations from the FDA.
• Received Priority Medicines (PRIME) designation, Orphan Designation, and Advanced Therapy Medicinal Product designation from the European Medicines Agency (EMA).
• Received the Innovative Licensing and Application Pathway (ILAP) designation from the UK Medicines and Healthcare products Regulatory Agency (MHRA).