Neurogene Secures FDA Alignment for Pivotal AAV Gene Therapy Trial (NGN-401) in Rett Syndrome

NEW YORK – June 30, 2025 – Neurogene Inc. (Nasdaq: NGNE), a clinical-stage company dedicated to developing genetic medicines for rare neurological diseases, today announced key details and U.S. Food and Drug Administration (FDA) written agreement for Embolden™, its registrational clinical trial evaluating NGN-401 gene therapy for females aged 3 years and older with Rett syndrome.

“We appreciate the partnership with the FDA as we aligned on the key elements of our NGN-401 registrational trial design, which will allow for rapid conversion of the current Phase 1/2 study to a pivotal trial,” said Rachel McMinn, Ph.D., Founder and CEO of Neurogene. “The robust endpoint design, informed by KOLs, caregiver input, and market research, will support NGN-401’s best-in-class potential and provide critical differentiating data.”

Embolden™ Registrational Trial Design (FDA Agreement)

Neurogene has obtained written FDA agreement on critical aspects of the Embolden™ trial, following discussions under the START program:

• Study Design: Open-label, single-arm, baseline-controlled (participants serve as their own control); proposed N=18.
• Patient Population: Females aged $\ge$ 3 years with Rett syndrome, aligning with natural history data showing rare developmental gains in this age group.
• Dose: 1E15 vector genomes (vg).
• Primary Endpoint: A responder-based composite endpoint evaluated at 12 months, assessing:

  • A Clinical Global Impression-Improvement (CGI-I) score of $\le$ 3 (“minimally improved”).
  • The gain of any one developmental milestone/skill from a pre-defined list of 28, captured via standardized video recordings and independently verified. These milestones were identified through caregiver surveys as clinically meaningful.

Dr. Elizabeth M. Berry-Kravis, Principal Investigator, highlighted the multi-domain approach and rigorous evaluation, noting, “Participants treated with NGN-401 have demonstrated increased independence, with both fine and gross motor function improvement, and gained the ability to better communicate wants, needs and choices.”

Supporting Data and Financial Position

Phase 1/2 Trial Data: Previously disclosed data from the Phase 1/2 study supports the registrational design. The first four participants collectively achieved 23 developmental milestones/skills across core domains (hand function/fine motor, communication/language, ambulation/gross motor) and each achieved a clinically meaningful “much improved” rating on the CGI-I. No evidence of HLH/hyperinflammatory syndrome has been observed at the 1E15 vg dose level across 10 participants. Updated clinical efficacy and safety data are expected in H2 2025.

Cash Runway Update: As of March 31, 2025, Neurogene reported $292.6 million in cash, cash equivalents, and investments. A strategic reallocation of capital to pivotal trial activities for NGN-401 is expected to fund operations into early 2028.

About NGN-401

NGN-401 is an investigational AAV9 gene therapy designed as a one-time treatment for Rett syndrome. It uniquely delivers the full-length human MECP2 gene under the control of Neurogene’s proprietary EXACT™ transgene regulation technology. This technology is critical for Rett syndrome, as it enables targeted MECP2 expression levels without the toxic effects associated with conventional gene therapy overexpression. NGN-401 has received multiple regulatory designations, including FDA’s START Pilot Program, RMAT, Orphan Drug, Fast Track, and Rare Pediatric Disease Designations, as well as EMA’s PRIME and Orphan designations, and UK MHRA’s ILAP designation.