July 1, 2026 —
Neurogene reported updated positive data from its Phase 1/2 clinical trial evaluating NGN-401, an investigational AAV9 gene therapy for Rett syndrome. The company also announced the launch of a proposed public offering to support continued development and pre-commercial activities for the program.
Across 10 participants with 12 to 30 months of follow-up, patients gained a total of 47 developmental milestones, with an average of 4.7 milestones per participant. All participants improved on the Clinical Global Impression-Improvement scale and gained at least one developmental milestone. Neurogene also reported that every participant gained at least one new developmental milestone in the past 12 months, with no plateau or milestone loss observed through 30 months of follow-up.
Rett syndrome is a rare neurodevelopmental disorder most commonly associated with pathogenic variants in the MECP2 gene. The disease can lead to developmental regression, loss of hand function, impaired communication, motor dysfunction, seizures, breathing abnormalities, and other severe neurological symptoms.
NGN-401 is designed as a one-time gene therapy to deliver the full-length human MECP2 gene. The therapy uses an AAV9 vector and incorporates Neurogene’s proprietary EXACT™ transgene regulation technology, which is designed to provide tightly controlled MeCP2 protein expression on a cell-by-cell basis. NGN-401 is delivered by intracerebroventricular administration to support broad targeting of the brain and nervous system.
The updated Phase 1/2 data showed that developmental gains occurred in a progressive, stepwise sequence, which investigators said may suggest a restart of developmental progression after treatment. Improvements were observed across core Rett syndrome functional domains, including hand function, gross motor function, and communication.
The onset of clinical improvement was rapid, with a median time to first clinical improvement of two months after treatment. Milestone gains also deepened over time, increasing by 95% from six to 12 months and by 147% from six months to at least 12 months. Seven of 10 participants gained at least two developmental milestones and demonstrated improvements across at least two core Rett syndrome domains.
Neurogene also reported clinically meaningful improvements across additional validated Rett syndrome measures, including the Rett Syndrome Gross Motor Scale and Rett Syndrome Hand Function Scale.
From a safety perspective, NGN-401 at the 1E15 vg dose remained generally well tolerated. All treatment-related adverse events were mild or moderate in severity, and most were known potential risks of AAV that had resolved or were resolving. No new treatment-related serious adverse events were reported since the prior data cutoff in October 2025.
Neurogene has completed dosing in the Embolden™ registrational trial, with no treatment-related serious adverse events or dose-limiting toxicities reported as of the June 16, 2026 cutoff. Topline data from Embolden are anticipated in the second half of 2027.
In parallel with the clinical update, Neurogene announced that it has commenced a proposed public offering of shares of common stock or, for certain investors, pre-funded warrants to purchase common stock. The company also expects to grant underwriters a 30-day option to purchase additional shares at the public offering price, less underwriting discounts and commissions. Neurogene said all securities in the offering are being offered by the company, and the offering remains subject to market and other conditions.
Neurogene intends to use the net proceeds from the offering, together with existing cash, cash equivalents, and marketable securities, to fund the ongoing clinical development of NGN-401, pre-commercial activities for NGN-401, working capital, and other general corporate purposes. Leerink Partners, Stifel, Guggenheim Securities, LifeSci Capital, and William Blair are acting as joint bookrunning managers for the proposed offering.
NGN-401 has received multiple regulatory designations, including Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA, as well as selection for the FDA START Pilot Program. The therapy has also received Advanced Therapy Medicinal Product, Orphan, and PRIME designations from the EMA, and an Innovative Licensing and Application Pathway designation from the U.K. MHRA.
If the registrational trial confirms the Phase 1/2 findings, NGN-401 could represent an important one-time genetic medicine approach for Rett syndrome, with the potential to address the underlying loss of functional MECP2 rather than only managing symptoms. The proposed financing further underscores Neurogene’s focus on advancing NGN-401 through late-stage development and preparing for potential commercialization.
