Neurogene Inc. · NASDAQ:NGNE
Neurogene — 2025 IRSF Rett Syndrome Scientific Meeting
16 slides from Neurogene's conference presentation, June 2025
Slide 1: NGN-401 Gene Therapy for Rett Syndrome Clinical Program
NGN-401 Gene Therapy for Rett Syndrome Clinical Program 2025 IRSF Rett Syndrome Scientific Meeting
Slide 2: Disclaimer
Disclaimer Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financi
Slide 3: NGN-401: Positioned to be Best-in-Class Gene Therapy for Rett Syndrome
NGN-401: Positioned to be Best-in-Class Gene Therapy for Rett Syndrome EXACT transgene regulation technology designed to deliver consistent and tightly controlled MeCP2 protein expression on a Complementary cell-by-cell basis. Recognition Sites NGN-401 includes the full-length human MECP2 gene, whic
Slide 4: NGN-401 Phase 1/2 Clinical Trial Design in Females with Rett Syndrome
NGN-401 Phase 1/2 Clinical Trial Design in Females with Rett Syndrome Trial Design Key Eligibility Criteria Trial evaluating 1E15 vg dose of NGN-401* • Females with Classic Rett syndrome in post regression stage of illness Ages > 11 • Clinical diagnosis and genetic confirmation of pathogenic MECP2 m
Slide 5: Improvements in Clinician and Caregiver Assessments with Skills Acquired Across 4 Participants
Improvements in Clinician and Caregiver Assessments with 23 Skills Acquired Across 4 Participants Gain of Skills, Developmental Milestones and CGI-I CGI-S Total Score RSBQ Symptom Improvement in RTT Clinical Domains How many How many How many Hand Communi- Attentive- Improved? Improved? Improved? po
Slide 6: Pt:1 Multi-Domain Improvements Deepened Over Time, and Not Expected Based on Natural History
Pt:1 Multi-Domain Improvements Deepened Over Time, and Not Expected Based on Rett Syndrome Natural History Select Pt:1 Months Post-NGN-401 Developmental Skills Post-NGN-401 3 6 9 12 15 Baseline – 7 Yrs Old Uses a pincer grasp Mild Disease Holds bottle or cup unpropped Raking, no ability to hold obje
Slide 7: Pt:2 Multi-Domain Improvements from Severe Impairments at Baseline Deepened Over Time
Pt:2 Multi-Domain Improvements from Severe Impairments at Baseline Deepened Over Time, and Not Expected Based on Rett Syndrome Natural History Months Post-NGN-401 Select Pt:2 Developmental Skills Post-NGN-401 3 6 9 12 Baseline - 4 Yrs Old Reaches for an object Severe impairment, unable Uses raking g
Slide 8: Pt:3 Multi-Domain Improvements Not Expected Based on Rett Syndrome Natural History
Pt:3 Multi-Domain Improvements Not Expected Based on Rett Syndrome Natural History Severe dysphagia Select Pt:3 Months Post-NGN-401 Developmental Baseline – 6 Yrs Old Skills 3 6 9 Uses a pincer grasp Raking grasp Fine Motor Able to self-feed Post Treatment Sits independently with NGN-401 Cannot sit,
Slide 9: Pt:4 Early Improvements in Hand Function Not Expected Based on Natural History
Pt:4 Early Improvements in Hand Function Not Expected Based on Rett Syndrome Natural History Months Post- Select Pt:4 NGN-401 Baseline – 7 Yrs Old Developmental Skills 3 Uses a pincer grasp Raking grasp, unable to hold objects Fine Motor Can use utensils to self-feed Post Treatment (without assistan
Slide 10: Hemophagocytic Lymphohistiocytosis (HLH)/Hyperinflammatory Syndrome Following High Dose AAV9 Therapy
Hemophagocytic Lymphohistiocytosis (HLH)/Hyperinflammatory Syndrome Following High Dose AAV9 Therapy Aimee Donald1, Simon Jones1, Barry J. Byrne2, Randy Q. Cron3, Effie Albanis4, Stuart Cobb4, Julie Jordan4 1. UK; 2. Department of Pediatrics, College of Medicine, University of Florida, Gainesville,
Slide 11: Hemophagocytic Lymphohistiocytosis (HLH)
Hemophagocytic Lymphohistiocytosis (HLH) • HLH is a rare, life-threatening hyperinflammatory syndrome characterized by immune dysregulation, cytokine storm, and multi-organ damage1-3 • Most cases are triggered by infections, malignancy, autoimmune disease, or CAR- T (3.5% incidence) • Over 90% of pa
Slide 12: HLH has been Rarely Reported Following High-dose AAV Gene Therapy
HLH has been Rarely Reported Following High-dose AAV Gene Therapy • Only one published case report1 and mention of similar cases2 reported HLH-like symptoms with high-dose systemic AAV treatment (1E14 vg/kg or higher) • Symptoms: Elevated ferritin within the first few days, fever, pancytopenia, rash
Slide 13: FAERS Database Shows HLH/HLH-Like Symptoms Following High-Dose Systemic AAV
FAERS Database Shows HLH/HLH-Like Symptoms Following High- Dose Systemic AAV (>1E14 vg/kg) While HLH is extremely rare, emerging post-marketing data suggests that HLH-like immune responses may occur in a small subset of patients treated with high-dose systemic AAV gene therapy1 • HLH-Related Finding
Slide 14: HLH Risk Mitigation Strategy Implemented in RTT-200 Clinical Trial
HLH Risk Mitigation Strategy Implemented in RTT-200 Clinical Trial • Dose level above 1E14 vg/kg not allowed • In the first week post-dosing: employ daily monitoring of ferritin, fever, and falling blood counts (cytopenia) • Exclude subjects with: • Any illness within 30 days of dosing, including EB
Slide 15: No Evidence of HLH at the 1E15 vg Dose Level
No Evidence of HLH at the 1E15 vg Dose Level • 5 additional participants dosed following new Ferritin Levels of Most Recently Dosed HLH monitoring protocol Participants – 1E15vg • 3 participants in the 4-10 years cohort • 2 participants in the 11 years and older cohort • No participants have present
Slide 16: Thank You, and Acknowledgments
Thank You, and Acknowledgments • Participants and caregivers/families in NGN-401 clinical trial • Clinical investigators • AAV and HLH specialists who consulted on the case 16
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