Neurogene Inc. · NASDAQ:NGNE
Neurogene — Investor Presentation (November 2025)
35 slides from Neurogene's investor presentation, Nov 13, 2025
Slide 1: Every Breakthrough Begins with Belief
Every Breakthrough BEGINS WITH BELIEF r r t r BE I S IT BELIEF Corporate Presentation November 2025
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 Embolden registrational trial ongoing with first participant dosed in 4Q:25; en
Slide 4: Neurogene Clinical Stage Pipeline
Product Candidate Indication IND* Enabling Phase I/2 Pivotal Near-Term Expected Milestones NGN-401 Rett Syndrome Embolden Registrational Trial Ongoing Additional Interim Phase 1/2 Data in 2026 NGN-101 CLN5 Batten Disease Evaluating Opportunities for Program Neurogene Clinical Stage Pipeline 4 *IND =
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 9 ICV = Intracerebroventricular IT-L = intrathecal lumbar 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
Slide 10: Embolden Registrational Trial Overview
Embolden Registrational Trial Overview
Slide 11: Key Elements of Embolden Registrational Clinical Trial
Key Elements of Embolden Registrational Clinical Trial of NGN-401 for Rett Syndrome 11 Design: Single-arm, open- label, baseline-controlled trial evaluating NGN-401 at 1E15 vg dose Sample Size: 20 females with Classic Rett syndrome 13 Clinical Sites Age Range: ≥ 3 years First Participant Dosed in Q4
Slide 12: Developmental Milestones/Skills Evaluated in Embolden Trial
28 Developmental Milestones/Skills from Rett Syndrome Natural History Study Being Evaluated in Embolden Trial 12*U.S. Natural History Study of Rett Syndrome (RNHS), sponsored by NIH, Clinicaltrials.gov identifier: NCT02738281. Accessed from International Rett Syndrome Foundation (IRSF); based on ana
Slide 13: Feedback on Meaningfulness of Developmental Milestones/Skills
Feedback on Meaningfulness of Developmental Milestones/Skills Showed Real-Life Examples of Potential Impact 13 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 14: NGN-401 Phase 1/2 Trial
NGN-401 Phase 1/2 Trial
Slide 15: NGN-401: Setting the Standard for Rett Syndrome Gene Therapy
NGN-401: Setting the Standard for Rett Syndrome Gene Therapy 15Entire presentation includes data cutoff date of October 30, 2025; N=8 for efficacy (ages 4-10 cohort) and N=10 for safety (ages 4-10 and ages > 11 cohorts) Multidomain improvements Progressive skill gains over time Durability of r
Slide 16: Best-in-Class Gene Therapy Requires Durable, Multidomain Gains
A Best-in-Class Gene Therapy for Rett Syndrome Requires Durable, Multidomain Gains that Grow Over Time 16As of data cutoff date of October 30, 2025 NGN-401 Phase 1/2 Pediatric Data Update 8 Participants included Multidomain Improvements 35 Skills Gained Overall Durable, No Skills Lost Results in Loc
Slide 17: Baseline Characteristics of Phase 1/2 Pediatric Participants
17 Time Post Dosing Pt:1 24 months Pt:2 18 months Pt:3 18 months Pt:4 15 months Pt:5 12 months Pt:6 6 months Pt:7 6 months Pt:8 6 months Age at Dosing 7 4 6 7 6 4 6 8 Baseline CGI-S Score 4 Moderately Ill 5 Markedly Ill 5 Markedly Ill 5 Markedly Ill 5 Markedly Ill 5 Markedly Ill 4 Moderately Ill 4 M
Slide 18: Responders Far Exceed Embolden Primary Endpoint at 12 Months
As of data cutoff date of October 30, 2025 Responders in Phase 1/2 Trial Far Exceed Bar of Embolden Primary Endpoint at 12 Months with Increased Skill Gains Over Time Pt:1 Pt:2 Pt:3 Pt:4 Pt:5 5 of 5 with functional gains 4 of 5 with CGI-I of ≤ 3, all durable - 4 of 5 with > 1 skills Gains in Hand Fu
Slide 19: Participants Dosed in 1H'25 Show Efficacy Prior to 12 Months
19As of data cutoff date of October 30, 2025 Participants Dosed in 1H’25 Show Efficacy Prior to 12-month Timepoint Pt:6 Pt:7 Pt:8 Gains in Hand Function, Communication, Gross Motor 3 of 3 with functional gains 3 of 3 with CGI-I of ≤ 3 2 of 3 acquired skills Early efficacy observed at 6 months is con
Slide 20: Early Multidomain Improvements with Skill Gains Increasing Over Time
Pt:7 6 months post-dose Pt:8 6 months post-dose Pt:4 15 months post-dose Pt:3 18 months post-dose Pt:2 18 months post-dose Pt:1 24 months post-dose Hand Function Gross Motor Function Communication 35 Total Skills Gained* 1 Skill 3 Skills 4 Skills 6 Skills 10 Skills 11 Skills Early Multidomain Improv
Slide 21: Pt:1 Gained Skills Across All Core Domains, Durable to 24 Months
Pt:1 Gained 11 Developmental Milestones/Skills Across All Core Domains with Durability out to 24 Months 21 As of data cutoff date of October 30, 2025 *Not included in Embolden developmental milestones/skills list; previously reported skill from other validated scale Images are representative of skil
Slide 22: Pt:2 Gained Skills Across All Core Domains, Durable to 18 Months
Pt:2 Gained 10 Developmental Milestones/Skills Across All Core Domains with Durability out to 18 Months 22 As of data cutoff date of October 30, 2025 *Not included in Embolden developmental milestones/skills list; previously reported skills from other validated scales Images are representative of sk
Slide 23: Pt:3 Gained Skills Across All Core Domains, Durable to 18 Months
Fine Motor Gross Motor Pt:3 Gained 6 Developmental Milestones/Skills Across All Core Domains with Durability out to 18 Months 23 As of data cutoff date of October 30, 2025 Images are representative of skills Pt:3 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 9 12 15 18 Used a
Slide 24: Pt:4 Gained Skills Across Core Domains, Durable to 15 Months
Pt:4 Gained 4 Developmental Milestones/Skills Across 2 Core Domains with Durability out to 15 Months 24 Fine Motor Baseline: 7 Yrs Old Raking grasp, unable to hold objects Pt:4 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 9 12 15 Used a pincer grasp (either refined or modifie
Slide 25: Pt:7 Gained Developmental Milestone/Skill at Early Timepoint
Pt:7 Gained 1 Developmental Milestone/Skill at Early Timepoint 25As of data cutoff date of October 30, 2025 Images are representative of skills Pt:7 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 Used a spoon/fork to eat without assistance Baseline: 6 Yrs Old Fine Motor Post Tr
Slide 26: Pt:8 Gained Skills Across Core Domains at Early Timepoint
Pt:8 Gained 3 Developmental Milestones/Skills Across 2 Core Domains at Early Timepoint 26 As of data cutoff date of October 30, 2025 *Not included in Embolden developmental milestones/skills list; previously reported skill from other validated scale Images are representative of skills Pt:7 Developme
Slide 27: Communication, Autonomic, Gross Motor and Fine Motor Improvements
Communication Can communicate needs & wants, and foster greater social connections Says words with meaning Follows daily routines, e.g., getting ready for school Communicates needs and wants; can ID colors Engages with friends and family; shows affection Starting/ improved communication with use of
Slide 28: Caregiver Quotes on Participant Improvements
“Sleep improved significantly as she is able to sleep all through the night without any issue.” “Her understanding has improved, especially with me when I ask her to do small tasks, then she will do it immediately almost every time…” “The other day she...ran a couple steps while out…” “She uses both
Slide 29: NGN-401 Remains Generally Well Tolerated at the 1E15 vg Dose Level
• All TEAEs related to NGN-401 have been Grade 1 (mild) or Grade 2 (moderate) in severity; the majority are known potential risks of AAV and have resolved or are resolving • Most participants experienced mild liver enzyme elevations • SAEs (Grade 2) related to abnormal nerve conduction findings occu
Slide 30: Key Anticipated Milestone Events
Key Anticipated Milestone Events
Slide 31: Key Upcoming Anticipated Milestones
Key Upcoming Anticipated Milestones 31 Provide regulatory update in 1H:25 regarding Embolden registrational trial Initiate Embolden registrational trial activities Expand clinical trial footprint, more than doubling presence in U.S. Initiate dosing in Embolden registrational trial Announce additiona
Slide 32: Appendix
Appendix
Slide 33: Caregiver Research on Meaningfulness of Developmental Skill Gains
• 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 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: Delivers 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