Neurogene Inc. · NASDAQ:NGNE
Neurogene — Investor Presentation (June 2025)
35 slides from Neurogene's investor presentation, Jun 30, 2025
Slide 1: June 2025 Corporate Presentation
June 2025 Corporate Presentation
Slide 2: Disclaimer: Forward Looking Statements
2 Disclaimer Forward Looking Statements This communication 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 fina
Slide 3: Developing Life-Changing Genetic Medicines For Rare Neurological Diseases
Neurogene: Developing Life-Changing Genetic Medicines For Rare Neurological Diseases 3EXACT: Expression Attenuation via Construct Tuning Lead program NGN-401 for Rett syndrome demonstrated promising interim clinical data Registrational trial start up activities for NGN-401 underway Rett syndrome rep
Slide 4: Neurogene Clinical Stage Pipeline
Product Candidate Indication IND* Enabling Phase I/2 Pivotal Near-Term Expected Milestones NGN-401 Rett Syndrome Registrational Trial Activities Underway Additional Interim Data 2H:25 NGN-101 CLN5 Batten Disease Evaluating Opportunities for Program Neurogene Clinical Stage Pipeline 4 *IND = investig
Slide 5: Wholly Owned and Fully Integrated In-House AAV Manufacturing
Wholly Owned and Fully Integrated In-House AAV Manufacturing 5 GMP Manufacturing Toxicology Batch Manufacturing Process Development Quality Assurance Quality Control Analytical Development • Flexibility to manufacture AAV product at low cost • Own product quality and development timelines • Process
Slide 6: NGN-401 for Rett Syndrome
NGN-401 for Rett Syndrome Leveraging EXACT transgene regulation technology
Slide 7: Rett Syndrome – Devastating Disorder with High Unmet Need
Rett Syndrome – Devastating Disorder with High Unmet Need 7 Genetics • X-Linked disorder causing mutations in the gene encoding for methyl-CpG binding protein 2 (MeCP2) • Unknown incidence in boys, but typically lethal by ~3 years of age due to no healthy copy of MeCP2 U.S. prevalence estimate based
Slide 8: Rett Syndrome is a Debilitating, Progressive Neurological Disorder
Rett Syndrome is a Debilitating, Progressive Neurological Disorder, with No Approved Treatments Addressing Root Cause 8 • Loss of purposeful hand use & involuntary hand movements • Loss of spoken language • Loss of hand function • Gait abnormalities • Ambulation requiring assistance or non-ambulator
Slide 9: NGN-401: Potential to be Best-in-Class Gene Therapy for Rett Syndrome
NGN-401: Potential to be Best-in-Class Gene Therapy for Rett Syndrome 9ICV = Intracerebroventricular EXACT transgene regulation technology designed to deliver consistent and tightly controlled MeCP2 protein expression on a cell-by-cell basis. ICV route of delivery has been shown in preclinical model
Slide 10: NGN-401 Embolden Registrational Trial
NGN-401 Embolden Registrational Trial
Slide 11: Written Agreement from FDA on Key Elements of Embolden Trial Design
Obtained Written Agreement from FDA on Key Elements of Embolden Registrational Trial Design 11 Design Patient Population Dose Primary Endpoint Open-label, single arm, baseline control (i.e., patient acting as own control) Females ages ≥ 3 years with Rett syndrome, consistent with our natural history
Slide 12: FDA Accepts Conversion of Phase 1/2 to Registrational Trial
FDA Accepts Conversion of Phase 1/2 to Registrational Trial 12Three pediatric participants previously received 3E15 vg dose in Phase 1/2 portion Open-label, baseline-controlled trial evaluating single dose of NGN-401 (1E15 vg) Embolden Registrational Clinical Trial Ages > 3 years N = 18* Phase 1/2 P
Slide 13: Developmental Skills/Milestones to Be Evaluated in Embolden Trial
28 Developmental Skills/Milestones from the Natural History Study to Be Evaluated in Embolden Trial 13 Fine Motor/Hand Function • Reached for toy • Taken a drink from a cup held without assistance • Used raking grasp to retrieve an object • Used a pincer grasp (either refined or modified) • Finger f
Slide 14: Caregiver Perspective on Meaningfulness of Developmental Milestones
• Rett syndrome caregivers provided perspective on meaningfulness of gains of developmental milestones/skills in the core domains of Rett syndrome: fine motor, gross motor and communication • All skills queried, across all categories, were considered meaningful by majority of respondents • Caregiver
Slide 15: Feedback on Meaningfulness of Milestones Showed Real-Life Impact
Feedback on Meaningfulness of Developmental Milestones/Skills Showed Real-Life Examples of Potential Impact 15 Even a small improvement would definitely be meaningful because even if she could stand with support or bear her own weight, even for 30 seconds or less, that would allow us to be able to p
Slide 16: Phase 1/2 Data Support Registrational Trial Design
Phase 1/2 Data Support Registrational Trial Design 16 As of data cut-off date of 17 October 2024 *As of 2 June 2025; HLH monitoring and treatment protocol added to Phase 1/2 protocol in January 2025 HLH = Hemophagocytic lymphohistiocytosis NGN-401 Durable improvements observed across multiple scales
Slide 17: Baseline Characteristics of Dosed Participants
Baseline Characteristics of Dosed Participants Range from Moderate to Severe Disease 17 As of data cut-off date of 17 October 2024 As of 11 November 2024, Neurogene discontinued use of 3E15 vg dose and updated Phase 1/2 protocol to use 1E15 vg dose for all future participants 1E15 vg Participant 1 (
Slide 18: Participants Achieved CGI-I Rating of Much Improved
Participants* Achieved CGI-I Rating of “Much Improved” CGI-I Score ≤ 3 = Clinically Meaningful Improvement Pt:1 3 – Minimally Improved 2 – Much Improved 2 – Much Improved 2 – Much Improved 2 – Much Improved Pt:2 2 – Much Improved 2 – Much Improved 2 – Much Improved 2 – Much Improved Pt:3 3 – Minimal
Slide 19: Improvements in Clinician and Caregiver Assessments
Improvements in Clinician and Caregiver Assessments with Aggregate 23 Skills Acquired Across 4 Participants 19*Each participant achieved a 2-point improvement, or “much improved” from baseline CGI-I CGI-S Total Score RSBQ Improved? How many points?* Improved? How many points? Improved? How many poin
Slide 20: Pt:1 Multi-Domain Improvements Deepened Over Time
Pt:1 Multi-Domain Improvements Deepened Over Time, and Not Expected Based on Rett Syndrome Natural History 20 *Skill learned is “Wave hello;” however, RNHS tracked “Waves Bye Bye” As of data cut-off date of 17 October 2024 Images are representative of skills and are not photos of participants in the
Slide 21: Pt:2 Multi-Domain Improvements from Severe Impairments
Pt:2 Multi-Domain Improvements from Severe Impairments at Baseline Deepened Over Time, and Not Expected 21 As of data cut-off date of 17 October 2024 Images are representative of skills and are not photos of participants in the NGN-401 clinical trial Select Pt:2 Developmental Skills Post-NGN-401 Mon
Slide 22: Pt:3 Multi-Domain Improvements
Fine Motor Gross Motor Pt:3 Multi-Domain Improvements Not Expected Based on Rett Syndrome Natural History 22 As of data cut-off date of 17 October 2024 Images are representative of skills and are not photos of participants in the NGN-401 clinical trial Select Pt:3 Developmental Skills Months Post-NG
Slide 23: Pt:4 Early Improvements in Hand Function
Pt:4 Early Improvements in Hand Function Not Expected Based on Rett Syndrome Natural History 23 Fine Motor Baseline: 7 Yrs Old Raking grasp, unable to hold objects Select Pt:4 Developmental Skills Months Post-NGN-401 3 Uses a pincer grasp Can use utensils to self-feed (without assistance) Post Treat
Slide 24: Improvements in Autonomic Function Across Participants
All Participants* Experienced Improvements in Autonomic Function, as Measured by Objective Assessments 24Detailed data provided in Appendix Pt:1 and Pt:2 Pt:1, Pt:2 and Pt:4 Pt:3 Had sleep deficits at Baseline, and experienced improvements in sleep parameters, as measured by a wearable device • LD:1
Slide 25: Phase 1/2 Trial Update: HLH Risk Mitigation
• In 2025, dosed 3 participants in the 4–10 years cohort and 2 participants in the > 11 years cohort - No evidence of HLH • HLH risk mitigation included in Phase 1/2 and registrational trial design - Dose level at/above 1E14 vg/kg not allowed - In the first week post dosing: employ daily monitoring
Slide 26: No Evidence of HLH/Hyperinflammatory Syndrome at 1E15 vg Dose
• No participants have presented with the “three Fs” – Fever, elevated Ferritin, and Falling blood counts (cytopenia) • Transient ferritin elevations observed in 4 of 5 subjects recently dosed, peaking at Study Day 5-6 with recovery to Baseline by Day 10–12 with no intervention • No clinical symptom
Slide 27: Key Anticipated Milestone Events
Key Anticipated Milestone Events
Slide 28: Key Upcoming Anticipated Milestones and Pipeline Developments
Key Upcoming Anticipated Milestones and Pipeline Developments 28 Provide regulatory update in 1H:25 regarding registrational trial Initiate registrational trial activities Announce additional Phase 1/2 clinical data in 2H:25 Cash Runway Expected to Fund Operations Into Early 2028 Rett Syndrome (NGN-
Slide 29: Appendix
Appendix
Slide 30: Pt:1 Autonomic Function: Sleep and Constipation Improvements
Pt:1 Autonomic Function: Objective Improvements Observed in Sleep Parameters and Constipation 30 Total sleep time increased from 6.6 to 7 hrs./night Number of position changes decreased from 37 to 18 per night Sleep efficiency* increased from 83% to ~90% (95% is ideal) Improvements in All Sleep Para
Slide 31: Pt:2 Autonomic Function: Sleep and Constipation Improvements
0% 20% 40% 60% 80% 100% Month 0 Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 None Type 1 - Separate hard lumps, like nuts Type 2 - Sausage-like, but lumpy Type 3 - Like a sausage or snake, smooth and soft Type 4 - Fluffy pieces with ragged edges, a mushy stool Type 5 - Watery, no solid pieces Pt:
Slide 32: Pt:3 Autonomic Function: Improvement in Swallowing
Beginning 3 months post-NGN-401, Pt:3 could swallow liquids, such as clear soup and water from a sippy cup, and chew and swallow soft items, such as meatballs and cooked carrots, without choking At 9 months post-NGN-401, she is now able to grasp food such as apple slices and self-feed At Baseline, P
Slide 33: Pt:4 Autonomic Function: Improvement in Constipation
Pt:4 did not have Baseline deficits in autonomic category of sleep Sleep quality maintained post-treatment Pt:4 Autonomic Function: Objective Improvement Observed in Constipation 33 Constipation Improved in Month 4, as Measured by Stool Consistency and Frequency* *As measured by Caregiver on modifie
Slide 34: NGN-401 Demonstrated Efficacy and Safety in Mecp2 Mouse Models
NGN-401 Demonstrated Efficacy and Safety in Mecp2 Mouse Models 34 Survival in Male Knockout 0 5 10 15 20 25 30 35 40 45 50 0 25 50 75 100 Su rv iv al (% ) 9 23 37wks Age (weeks) 0 5 10 15 20 25 0 25 50 75 100 Age (weeks) Su rv iv al (% ) Survival in Female Het NGN-401 1E11 vg NGN-401 3E11 vg MECP2EX
Slide 35: Consistent Levels of MECP2 Expression on Cell-by-Cell Basis
Delivers Consistent Levels of MECP2 Expression on Cell- by-Cell Basis 35 Conventional NGN-MECP2 Achieves Narrow Expression of MECP2* 0 50 100 150 200 0 200 400 600 800 1000 Intensity (AU) Nu m be r o f c el ls Unregulated Regulated EXACT GTx Conventional GTx *mouse cortex immunohistochemistry