Neurogene (NGNE) Leerink Global Healthcare Conference 2025 summary

Program overview and disease context

• Lead program NGN-401 targets Rett Syndrome, a rare neurodevelopmental disorder affecting about 1 in 10,000 females globally, with no approved treatments addressing the root cause.

• Rett Syndrome presents with severe impairments in hand function, communication, motor skills, seizures, GI issues, and breathing abnormalities.

• NGN-401 uses a regulated gene therapy approach to control transgene expression, balancing efficacy and safety.

• Initial clinical data from four patients showed encouraging efficacy, with ongoing discussions with the FDA about the registrational path.

• NGN-401 is part of the FDA's START pilot program, designed to accelerate promising rare disease therapies.

Regulatory and trial design considerations

• The START program enables more flexible, frequent FDA interactions, expediting key trial design decisions.

• Placebo control is not feasible due to the invasive ICV procedure and required immunosuppression, making blinding impossible and unethical.

• Control arm options include single-arm studies with natural history comparison or delayed-start designs.

• Pediatric cohort focuses on post-regression girls aged 4-10 to avoid confounding from ongoing regression.

• Natural history data is used to contextualize efficacy, distinguishing between skills lost and regained versus skills never acquired.

Efficacy and endpoint strategy

• Early data showed all four treated girls improved on the Clinician Global Impression of Improvement (CGI-I), with 25-50% reductions in RSBQ scores.

• No similar improvements have been seen in prior open-label or blinded trials for Rett.

• Endpoints are being selected based on input from clinicians, patients, and caregivers to ensure clinical meaningfulness.

• Study powering and effect size will be based on the highest level of spontaneous improvement seen in natural history cohorts.