Clinical Development - NGN-401 for Rett syndrome demonstrated promising interim clinical data, with the first participant dosed in Q4 2025 and enrollment expected to complete in 3-6 months[8] - The Embolden™ registrational trial for NGN-401 is a single-arm, open-label study with a sample size of 20 females, requiring a 35% response rate (7 out of 20 participants) for success[28] - The primary endpoint of the Embolden trial is a responder-based composite endpoint, with key secondary endpoints focusing on developmental milestones[28] - The trial design includes immunosuppression with corticosteroids for 91 days, followed by a taper, to enhance treatment efficacy[29] - 12 of 13 clinical trial sites for the Embolden trial have been initiated, with enrollment expected to complete in 3-6 months[44] - The first participant has been dosed in the Embolden trial, marking a significant milestone in the clinical development of NGN-401[44] - The trial design for ages over 3 is expected to enable the most efficient path to market for NGN-401[44] - Completion of Embolden registrational trial enrollment is anticipated within 3-6 months as of November 2025[90] Market Need - The U.S. prevalence of Rett syndrome is estimated to be between 6,000 and 9,000 patients, with a worldwide incidence of 1 in 10,000 females, indicating a significant unmet need for new treatment options[21] - Caregivers of Rett syndrome patients indicated that any skill gain or symptom improvement would provide significant respite and independence for their daughters[93] Efficacy and Safety - NGN-401 demonstrates significant skill gains, with 35 total skills acquired across participants, showing durability and no skills lost over time[46] - Early efficacy observed at 6 months post-treatment shows 3 of 3 participants with functional gains and a CGI-I of ≤ 3[54] - Participants have reported improvements in key domains, including communication, gross motor function, and fine motor skills, leading to enhanced quality of life[83] - NGN-401 remains generally well tolerated at the 1E15 vg dose level, with 9 out of 10 participants experiencing treatment-emergent adverse events[86] - All treatment emergent adverse events (TEAEs) related to NGN-401 have been Grade 1 (mild) or Grade 2 (moderate) in severity, with most participants experiencing mild liver enzyme elevations[87] - No evidence of hemophagocytic lymphohistiocytosis (HLH) in any participant, and seizures have remained well controlled following NGN-401 treatment[87] - NGN-401 demonstrated efficacy and safety in Mecp2 mouse models, showing targeted MeCP2 levels through ICV delivery[94] Technology and Manufacturing - The EXACT™ transgene regulation technology used in NGN-401 aims to deliver consistent and tightly controlled MeCP2 protein expression, addressing a key limitation in gene therapy[25] - The use of EXACT™ Technology in NGN-401 aims to limit expression and ensure safe delivery of therapy[46] - The EXACT platform delivers consistent levels of MECP2 expression on a cell-by-cell basis, indicating potential for precise therapeutic applications[97] - Neurogene's internal manufacturing capabilities are designed for commercial-grade products, with a facility of 42,000 sq ft in Houston, including 6,000 sq ft of cleanrooms[12] - Neurogene's manufacturing process allows for low-cost production and control over product quality and development timelines[16] Financial Outlook - Cash runway is expected to fund operations through Q1 2028, providing strategic flexibility for ongoing and future projects[8] - Cash runway is expected to fund operations through 1Q'28, ensuring financial stability for ongoing projects[90] - The company plans to provide a regulatory update in 1H:25 regarding the Embolden™ registrational trial and initiate trial activities[90] - The clinical trial footprint is expected to more than double in the U.S., with dosing in the Embolden registrational trial to be initiated soon[90] - The company aims to announce additional Phase 1/2 clinical data in 2H:25 and 2026, reflecting ongoing commitment to research and development[90] Pipeline Expansion - The company is evaluating opportunities for NGN-101 targeting CLN5 Batten Disease, expanding its pipeline of genetic medicines[9]
Aquinox(NLTX) - 2025 Q3 - Quarterly Results