Neurogene (NGNE) Study result summary

Unmet need and disease background

• Rett syndrome is a rare, progressive neurodevelopmental disorder caused by MECP2 gene variants, leading to severe developmental regression and lifelong care needs.

• No approved disease-modifying therapies exist; current treatments only manage symptoms.

• The patient population spans all age groups, with 15,000–20,000 affected in the US, EU, and UK, and a significant unmet need for transformative therapies.

Study background and design

• NGN-401 is a gene therapy targeting Rett syndrome, delivering functional MECP2 using proprietary EXACT transgene regulation technology.

• The phase I/II and EMBOLDEN trials are open-label, multicenter studies evaluating safety, tolerability, and efficacy at a 1E15 vector genome dose, with intracerebroventricular administration.

• The primary endpoint is a composite of improvement on CGI-I and at least one developmental milestone gain at 12 months, with milestones derived from natural history and caregiver input.

• Dosing is complete in both trials, totaling 35 participants, with follow-up ranging from 12 to 30 months.

• NGN-401 has received multiple regulatory designations, including Breakthrough Therapy, RMAT, Fast Track, Orphan Drug, and Rare Pediatric Disease from the FDA, and similar designations from European and UK agencies.

Efficacy and clinical outcomes

• 100% of phase I/II participants gained at least one developmental milestone and improved on CGI-I at 12 months, with 80% meeting the composite responder definition.

• Milestone gains averaged 4.7 per participant, occurring in a developmentally ordered, stepwise sequence across domains, with a median time to first response of two months.

• Gains were observed in fine motor, gross motor, and communication, with 21 of 28 possible milestones achieved and all seven hand function milestones reached.

• Quantitative assessments showed statistically significant improvements in gross motor and hand function compared to natural history, with a 5.2-point mean gain in gross motor function.

• Improvements were rapid, durable (no milestones lost up to 30 months), and deepened over time, with a 147% increase in milestone gains from 6 to ≥12 months.