Neurogene FY Conference Summary Company Overview - **Company**: Neurogene (NasdaqGM:NGNE) - **Focus**: Development of gene therapies for neurological diseases, specifically targeting Rett syndrome Key Industry Insights - **Rett Syndrome**: A rare neurological disorder affecting primarily females, characterized by developmental delays and loss of previously acquired skills. Estimated prevalence is 15,000-20,000 patients in major markets with an incidence rate of 1 in 10,000 females worldwide [7][24]. - **Market Opportunity**: The gene therapy market for Rett syndrome is projected to be multi-billion dollars, with no current disease-modifying treatments available [5][7]. Core Company Insights - **Lead Program**: NGN401 for Rett syndrome, currently in the Embolden registrational trial aimed at FDA approval [4][5]. - **Clinical Progress**: - Dosing of patients commenced in Q4 2025, following alignment with the FDA on trial design [4]. - Interim data from phase 1/2 trial shows 100% of participants achieved functional improvements in key domains (hand function, gross motor function, communication) [9][10]. - 35 developmental milestones gained, with improvements durable for up to 24 months [9][10]. Clinical Trial Details - **Embolden Trial**: - Single-arm, baseline-controlled, open-label trial evaluating NGN401 in 20 females aged three years and older [15]. - Primary endpoint: Composite of Clinician Global Impression of Improvement (CGII) and developmental milestones, measured at 12 months [15]. - Anticipated completion of enrollment and dosing by Q2 2026 [5][29]. Financial and Commercial Readiness - **Financial Position**: Strong balance sheet expected to fund operations through Q1 2028, covering key milestones including BLA submission [19]. - **Commercial Strategy**: - Plans to convert clinical trial sites into commercial sites post-approval [18][32]. - Integrated manufacturing capabilities established for commercial product production [18][32]. - Strong reimbursement potential confirmed through payer research [18][26]. Future Outlook - **Upcoming Milestones**: - Completion of Embolden trial dosing in Q2 2026 [19][29]. - Presentation of new clinical data mid-2026, including 12 months of follow-up data for all participants [19][31]. - **Market Positioning**: Neurogene aims to establish itself as a leader in the Rett syndrome treatment landscape, with expectations of multiple gene therapy products entering the market [24][27]. Additional Insights - **Patient and Caregiver Impact**: Emphasis on improving daily living activities and reducing caregiver burden through meaningful functional changes [10][11][36]. - **Community Enthusiasm**: High levels of interest from physicians and caregivers regarding NGN401 and gene therapy options for Rett syndrome [29][30]. Conclusion - Neurogene is positioned for significant advancements in the treatment of Rett syndrome, with a clear regulatory path, strong clinical data, and a robust commercial strategy aimed at transforming the lives of affected families [20][36].

Core Insights - Marvel Biosciences Corp. has announced promising results from its preclinical study of MB-204, a treatment for Rett syndrome, which significantly outperformed Trofinetide, the only FDA-approved treatment for the condition [1][4]. Study Overview - The study compared MB-204 (10 mg/kg oral once daily) with Trofinetide (100 mg/kg injected once daily) in Mecp2 mice over approximately two weeks, assessing multiple endpoints [2]. Key Data Highlights - MB-204 demonstrated significant improvements in social behavioral deficiencies, with p-values less than 0.0001 compared to control, while Trofinetide showed no improvement [6]. - MB-204 also reversed impairments in following behavior (p<0.0001 vs control) and was significantly better than Trofinetide on this endpoint (p<0.001) [6]. - Both compounds reversed social preference behavior in the three-chamber test (p<0.0001 vs control), a common method for evaluating social behavior in autism models [6]. - MB-204 improved spatial working memory and repetitive behaviors as measured by the Y-maze test, with p-values less than 0.0001 compared to control, while Trofinetide showed no improvement [6]. Company Background - Marvel Biosciences Corp. is a Calgary-based preclinical stage pharmaceutical development biotechnology company focused on developing MB-204, a novel fluorinated derivative of Istradefylline, an approved anti-Parkinson's drug [5]. - The company is exploring the potential of MB-204 in treating various neurological diseases, including autism, depression, Alzheimer's Disease, and other neurodevelopmental disorders like Rett Syndrome and Fragile X Syndrome [5].