Announcement • Jun 09
Neurogene Completes Dosing in Embolden Registrational Trial of Ngn-401 for Rett Syndrome Neurogene Inc. has completed dosing in the Embolden registrational trial of NGN-401, an investigational gene therapy designed to be a potential best-in-class, one-time treatment for Rett syndrome. The initial enrollment target was 20 participants, and the statistical analysis plan pre-specified an intent-to-treat (ITT) population of up to 24 participants. Due to strong demand from the Rett syndrome community and to ensure timely completion of dosing, the company elected to overenroll the trial and dose all eligible participants already in screening for a total of 25. NGN-401 has been generally well-tolerated, with no cases of hemophagocytic lymphohistiocytosis (HLH) at the 1E15 vg dose. Additional interim Phase 1/2 data is expected mid-2026. Topline data from Embolden is anticipated in the second half of 2027. Embolden is a multi-center, single-arm, open-label, baseline-controlled registrational trial designed to evaluate the efficacy, safety and tolerability of a one-time dose of NGN-401 (1E15 vg) in females with Rett syndrome ages three and older. The primary endpoint is a composite of a Clinical Global Impression-Improvement (CGI-I) score of = 3 and a gain from baseline of any one developmental milestone from a pre-specified list. The primary analysis to support the planned Biologics License Application (BLA) submission is expected to occur after the first 24 participants (pre-specified ITT) have completed 12 months of follow-up, with topline data expected in the second half of 2027. The threshold for success required for the registrational trial is a 33% (or 8 of 24 participants) minimum response rate. Data from the additional participant is expected to supplement the overall safety and durability dataset. As of June 7, 2026, NGN-401 at the 1E15 vg dose (n=35) continues to be generally well-tolerated. There were no cases of hemophagocytic lymphohistiocytosis (HLH) at this dose level in the Phase 1/2 trial or the Embolden trial. The Embolden trial builds on positive interim data from the Phase 1/2 trial of NGN-401, which demonstrated multidomain, durable gains with continued developmental milestone acquisitions as of the most recently disclosed safety and efficacy data, with a cutoff date of October 30, 2025. Neurogene plans to present updated interim safety and efficacy data from the Phase 1/2 trial, including at least 12 months of follow-up for all 10 participants, in mid-2026. NGN-401 is an investigational AAV9 gene therapy in late-stage clinical development as a potential best-in-class, one-time treatment for Rett syndrome. It is the only clinical candidate to deliver the full-length human MECP2 gene and includes Neurogene’s EXACT transgene regulation technology, which is designed to deliver consistent, tightly controlled MeCP2 protein expression on a cell-by-cell basis. NGN-401 is delivered through intracerebroventricular administration to achieve the broadest targeting directly to the brain and nervous system based on nonclinical biodistribution data. NGN-401 is being evaluated in the Embolden registrational clinical trial. Interim data from the Phase 1/2 trial (as of October 30, 2025) have shown that participants experienced multidomain, durable gains with continued skill acquisition observed over time, and NGN-401 at the 1E15 vg dose has been generally well-tolerated. NGN-401 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations and selection for the START Pilot Program from the U.S. Food and Drug Administration, Advanced Therapy Medicinal Product, Orphan and Priority Medicines designations from the European Medicines Agency and Innovative Licensing and Application Pathway designation from the United Kingdom Medicines and Healthcare products Regulatory Agency. Board Change • May 21
High number of new directors There are 5 new directors who have joined the board in the last 3 years. President, CFO & Director Christine Cvijic was the last director to join the board, commencing their role in 2026. The company’s lack of board continuity is considered a risk according to the Simply Wall St Risk Model. Announcement • May 12
Neurogene Inc Highlights Data Supporting Therapeutic Rationale For ICV Delivery Method In CNS-Targeted Gene Therapy Neurogene Inc. highlighted data at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting supporting the intracerebroventricular (ICV) route of administration as a routine approach for delivering medicines, including gene therapies, to treat central nervous system (CNS) disorders. The presentation further highlights that the ICV procedure is routine, and administration takes approximately 10 minutes; therefore, the clinical safety and monitoring in gene therapy programs is driven primarily by factors related to transgene expression, dose and total viral load rather than the delivery procedure itself. The poster, “Gene Therapy Targeting CNS Diseases: ICV Administration as a Growing Standard for Delivery,” provides an overview of ICV delivery of NGN-401 gene therapy for Rett syndrome with findings from a preclinical study as well as an ongoing Phase 1/2 trial in participants with Rett syndrome, which has completed dosing. The ICV procedure is utilized by pediatric and adult neurosurgeons tens of thousands of times annually, and the administration of NGN-401 gene therapy takes approximately 10 minutes. Compared to intrathecal lumbar (IT-L) delivery of NGN-401, ICV delivery showed greater biodistribution to the key areas of the brain, including the motor cortex, frontal cortex and cerebellum, and CNS that underlie Rett syndrome in preclinical models. In the Phase 1/2 trial of NGN-401, all participants who received the 1E15 vg dose in the pediatric cohort (ages 4-10; n=8) showed functional improvements, with a total of 35 developmental milestones gained with no plateau up to 24 months, and NGN-401 and the ICV procedure were generally well-tolerated as of the data cutoff date of October 30, 2025 (n=10). NGN-401 is also being administered through ICV in the Embolden registrational clinical trial, and investigators have the option to discharge participants one day after the procedure and implement an outpatient gene therapy monitoring protocol. Clinical safety in CNS gene therapy is driven primarily by vector biology, dose and transgene expression rather than the route of administration itself. NGN-401 is an investigational AAV9 gene therapy in late-stage clinical development as a potential best-in-class, one-time treatment for Rett syndrome. It is the only clinical candidate to deliver the full-length human MECP2 gene and includes Neurogene’s EXACT transgene regulation technology, which is designed to deliver consistent, tightly controlled MeCP2 protein expression on a cell-by-cell basis. NGN-401 is delivered through intracerebroventricular administration to achieve the broadest targeting directly to the brain and nervous system based on nonclinical biodistribution data. NGN-401 is being evaluated in the Embolden registrational clinical trial. Interim data from the Phase 1/2 trial (as of October 30, 2025) have shown that participants experienced multidomain, durable gains with continued skill acquisition observed over time, and NGN-401 at the 1E15 vg dose has been generally well-tolerated. NGN-401 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations and selection for the START Pilot Program from the U.S. Food and Drug Administration, Advanced Therapy Medicinal Product, Orphan and Priority Medicines designations from the European Medicines Agency and Innovative Licensing and Application Pathway designation from the United Kingdom Medicines and Healthcare products Regulatory Agency. 
