NGN-401 has been generally well-tolerated by first three patients dosed, with three to nine months of follow-up

No signs or symptoms of overexpression toxicity, including in one patient with a mild variant predicted to result in residual MeCP2 expression

Neurogene remains on track to provide interim efficacy data from the trial in 4Q:24

NEW YORK, NY, USA I May 07, 2024 I Neurogene Inc. (Nasdaq: NGNE), a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases, today announced initial safety and tolerability data from its ongoing Phase 1/2 gene therapy clinical trial for Rett syndrome, which showed that NGN-401 was generally well-tolerated by all three patients dosed, with follow-up of approximately nine, six and three months post-dosing. These data were presented during the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting.

“We designed NGN-401 to overcome the limitations of conventional gene therapy for Rett syndrome by incorporating our EXACTTM transgene regulation technology, which we believe provides tolerable and therapeutic levels of protein expression to the key areas of the brain and nervous system that drive disease,” said Rachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene. “The NGN-401 data presented at ASGCT demonstrate a favorable tolerability profile in the first three pediatric patients, including one with a mild variant predicted to result in residual MeCP2 expression, with no signs or symptoms of overexpression-related toxicity reported in any patient. We remain on track to share interim efficacy data from the first cohort of the trial in the fourth quarter of 2024.”

The Phase 1/2 open-label trial is evaluating the safety, tolerability, and preliminary efficacy of two dose levels of NGN-401 delivered via one-time intracerebroventricular (ICV) infusion. Enrollment of female patients ages 4-10 years old with classic Rett Syndrome and a Clinical Global Impression-Severity (CGI-S) score of 4-6 is ongoing in low-dose Cohort 1 and high-dose Cohort 2.

The baseline demographics of the first three patients who received NGN-401 in Cohort 1 (1E15 vector genomes) include:

Patient 1Patient 2Patient 3
Age at Dosing​7 years old4 years old​6 years old
MECP2 mutation​Mild​Severe​Severe​
Time post-NGN-401 administration​~9 months​~6 months​~3 months​

NGN-401 has been generally well-tolerated by all three patients. All adverse events (AEs) related to NGN-401 have been mild, or Grade 1, and transient or resolving. Most AEs are known potential risks of adeno-associated virus (AAV), including asymptomatic laboratory value changes.

There have been no signs or symptoms indicative of MeCP2 overexpression toxicity reported in any of the three patients, including the patient with a mild variant that is predicted to result in residual MeCP2 expression. There have been no treatment-emergent or ICV procedure-related serious AEs (SAEs).

“There is a high unmet need for new treatments that can address the incredible disease burden people with Rett syndrome and their families face on a daily basis,” stated Bernhard Suter, M.D., Medical Director of the Blue Bird Circle Rett Center at Texas Children’s Hospital, Associate Professor of Pediatrics at Baylor College of Medicine, and principal investigator in the NGN-401 clinical trial. “Gene therapy has the potential to address the underlying cause of Rett syndrome with a one-time treatment, and these interim safety data from the NGN-401 trial provide an important milestone on the path to realizing its potential for patients. I look forward to the continued work in conducting the trial as we evaluate NGN-401’s safety and efficacy.”

The presentation by Dr. Suter is available as an ePoster on the ASGCT Annual Meeting platform and The data cut-off date for this presentation was April 19, 2024.

Neurogene continues to expect to provide interim clinical data, including efficacy data, from Cohort 1 in the fourth quarter of 2024 and additional interim data, including from Cohort 2, in the second half of 2025.

About Neurogene

The mission of Neurogene is to treat devastating neurological diseases to improve the lives of patients and families impacted by these rare diseases. Neurogene is developing novel approaches and treatments to address the limitations of conventional gene therapy in central nervous system disorders. This includes selecting a delivery approach to maximize distribution to target tissues and designing products to maximize potency and purity for an optimized efficacy and safety profile. The Company’s novel and proprietary EXACT transgene regulation platform technology allows for the delivery of therapeutic levels while limiting transgene toxicity associated with conventional gene therapy. Neurogene has constructed a state-of-the-art gene therapy manufacturing facility in Houston, Texas. CGMP production of NGN-401 was conducted in this facility and will support pivotal clinical development activities. For more information, visit

SOURCE: Neurogene