Neurogene (NGNE) investor relations material

NGN-401 clinical update

• Phase I/II treated 10 participants aged 4–18 at 1E15 vector genomes, spanning mild to severe disease; all improved on CGI-I and gained at least one developmental milestone.

• Milestones appeared as early as month 3 and continued to accumulate through months 6, 9, 12 and beyond; participants retained milestones once gained, verified using caregiver or clinician videos by an independent rater.

• Across Phase I/II, every participant gained hand-function milestones, most communication milestones were achieved, and about half of gross-motor milestones were achieved.

• Safety database totals 35 participants at 1E15, including 25 in Embolden and 10 in Phase I/II; as of Nov. 8, NGN-401 continued to be well tolerated, with no HLH observed at this dose.

Embolden design and success criteria

• Embolden is a baseline-controlled pivotal study; its 25 participants completed dosing, and the primary endpoint combines CGI-I improvement with gain of at least one of 28 prespecified developmental milestones.

• Baseline assessments set individualized challenge tasks; standardized videos go to two central raters blinded to patient, treatment, and assessment time, while CGI-I is clinician assessed.

• FDA agreed to include all 25 participants in the amended efficacy analysis; statistical success requires 9 of 25 responders, or 36%, against a lower null-hypothesis rate.

• Commercial potential depends on response breadth and the number of milestones gained, not only the responder proportion; even incremental gains such as self-feeding may matter to families.

Differentiation and data plans

• Head-to-head studies showed ICV delivery was 10–100x more effective at reaching the brain; preclinical transgene expression was detected by day 7, and the single-stranded vector accommodates the full-length gene.

• The program uses regulation technology to control overexpression toxicity; presentations addressed gene length, delivery, and claims about microRNA-based selectivity to inform clinical treatment decisions.

• No additional Phase I/II data are planned before Embolden results; long-term follow-up publication work continues, with 12–30 months of data already in the public domain ahead of the pivotal readout.