Neurogene Inc. · NASDAQ:NGNE
Neurogene — Investor Presentation (March 2025)
49 slides from Neurogene's investor presentation, Mar 24, 2025
Slide 1: March 2025 Corporate Presentation
March 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: Neurogene is a Differentiated Clinical-Stage Company Utilizing EXACT Technology
Neurogene is a Differentiated Clinical-Stage Company Utilizing EXACT Technology to Treat Complex Neurological Diseases 3 Novel EXACT technology designed to overcome key limitations of conventional gene therapy Internal manufacturing provides financial and strategic pipeline flexibility Pipeline addr
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 Plans Update 1H:25 Additional Interim Data 2H:25 NGN-101 CLN5 Batten Disease Evaluating Opportunities for Program Neurogene Clinical Stage Pipeline 4 *IND = investiga
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 Treatment Requires Tight Transgene Regulation
• Rett syndrome (RTT) is a severe neurological disorder caused by mosaic mutations in X-linked MECP2 gene • Mice modeling RTT recapitulate many neurological phenotypes observed clinically; disease reversibility has been demonstrated in both immature and mature adult animals 8 ~100% cells express 2x
Slide 9: Acts As a Genetic Thermostat, Limiting Transgene Expression
Acts As a Genetic Thermostat, Limiting Transgene Expression 9 Protein Expressed EXACT miRNA controls transgene levels to targeted range Regulatory elements designed to avoid off- target effects EXACT is expected to enable gene therapy for Rett syndrome and other complex disorders Excess Transcript D
Slide 10: Designed to Widen Therapeutic Window and Enable Gene Therapy for Rett Syndrome
10 Designed to Widen Therapeutic Window and Enable Gene Therapy for Rett Syndrome ~50% of cells express WT levels of MeCP2 ~50% are MeCP2 deficient NGN-401 designed to provide therapeutic and tolerable levels of MeCP2 within this window Too low Rett Syndrome Too high MeCP2 Overexpression Toxicity Th
Slide 11: ICV Administration Resulted in Significantly Better Distribution Than IT-L in NHPs
11 ASGCT 2021 ICV = Intracerebroventricular ICV Administration Resulted in Significantly Better Distribution Than IT-L To Key Areas of the Nervous System Underlying Rett Syndrome in NHPs Key Areas of Rett Syndrome Pathophysiology Autonomic Motor Speech Speech Motor utonomic
Slide 12: Cardinal Clinical Features of Rett Syndrome
Cardinal Clinical Features of Rett Syndrome • Loss of purposeful hand use & involuntary hand movements • Loss of spoken language • Loss of hand function • Gait abnormalities • Ambulation requiring assistance or non-ambulatory • Severe apnea episodes • Hyperventilation • Constipation • Difficulty swa
Slide 13: 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 13Three pediatric participants previously received 3E15 vg dose; all future participants will receive 1E15 vg dose of NGN-401 Trial Design • Females with Classic Rett syndrome in post regression stage of illness • Clinical diagnos
Slide 14: Compelling Interim Clinical Data Show Gains of Function Across Core Domains
Compelling Interim Clinical Data Show Gains of Function Across Core Domains and Improvements in Autonomic Function 14 NGN-401 Durable improvements observed across multiple scales, incl. two-point improvement in CGI-I in all participants, with concordance of benefit across scales Consistent gains obs
Slide 15: Baseline Characteristics of Dosed Participants
15 Baseline Characteristics of Dosed Participants Range from Moderate to Severe Disease 1E15 vg Participant 1 (Pt:1) Participant 2 (Pt:2) Participant 3 (Pt:3) Participant 4 (Pt:4) Participant 5 (Pt:5) Age at Dosing in Years 7 4 6 7 6 MECP2 Mutation Severity Mild Severe Severe Severe Severe Baseline
Slide 16: Consistent Improvement Across Key Rett Syndrome Scales
Consistent Improvement Across Key Rett Syndrome Scales, Bolstered by Functional Improvements in Core Clinical Domains 16 As of data cut-off date of 17 October 2024 *Each participant achieved a 2-point improvement, or “much improved” from baseline CGI-I CGI-S Total Score RSBQ Improved? How many point
Slide 17: Understanding the CGI-I with Rett Syndrome-Specific Anchors
Understanding the CGI-I with Rett Syndrome-Specific Anchors 17 *Clinical Review Report: Brexpiprazole (Rexulti), 2017. Neul J, et al. J Child Neurol (2015) 30(13):1743–1748 • Clinician-rated scale assessing improvement from baseline • 1-point improvement considered clinically meaningful (score ≤ 3)*
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: Understanding the Rett Syndrome Behavior Questionnaire (RSBQ)
Understanding the Rett Syndrome Behavior Questionnaire (RSBQ) • Caregiver-completed scale consisting of 45 items measuring behavior in females with RTT • Developed as a diagnostic tool to differentiate females with Rett syndrome from those with severe intellectual disability • Scale is limited due t
Slide 20: Participants Have Experienced Improvement in RSBQ Score
Participants* Have Experienced Improvement in RSBQ Score 20 Participant Baseline CGI-S Score Baseline RSBQ Score Change from Baseline % Change Pt:1 4 39 -10 -28% Pt:2 5 62 -32 -52% Pt:3 5 17 -5 -29% Pt:4 5 29 -8 -28% *As of data cut-off date of 17 October 2024 C ha ng e fro m B as el in e in To ta l
Slide 21: Participants Experienced Improvements in Autonomic Function
Participants* Experienced Improvements in Autonomic Function, as Measured by Objective Assessments 21Detailed data provided in Appendix • Pt:1 and Pt:2, who had sleep deficits at Baseline, experienced improvements in sleep parameters, as measured by a wearable device • Pt:1 sleep efficiency increase
Slide 22: Participant Vignettes
Participant Vignettes
Slide 23: Rett Syndrome is Defined By Regression Period in Early Development
Rett Syndrome is Defined By Regression Period in Early Development 23 Pini G, et al. Orphanet Journal of Rare Diseases (2016) 11:132. C lin ic al fu nc tio n ~6 mos. to ~18 mos. ~1 to 4 years ~4 to 10 years Normal Adolescence to Adulthood Developmental Regression Early Onset Disease Progression“Rela
Slide 24: Simple Skills Generally Acquired but Majority Lost During Regression
Simple Skills Are Generally Acquired but Majority Are Lost During Regression; More Complex Skills are Generally Not Acquired 24 Data from the RNHS; N=200 female subjects with classic RTT, age 4-10 years, CGI-S score of 4 to 6 at baseline, confirmed genetic mutation Raking Grasp (~85%) Transferred Ob
Slide 25: Pt:1 From Pre-Treatment to 15 Months Post NGN-401
Hand Function / Fine Motor • Had a raking grasp, briefly held objects, dropping items quickly, with limited ability to self-feed Ambulation / Gross Motor • Walked independently, but would stay on her tip-toes, freeze often and required a parent to help her go up/down stairs or get on/off a bed Langu
Slide 26: 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 26 Select Pt:1 Developmental Skills Post-NGN-401 Months Post-NGN-401 3 6 9 12 15 Uses a pincer grasp Holds bottle or cup unpropped Uses spoon/fork to self-feed Transfers objects between hands H
Slide 27: Pt:2 Pre-Treatment to Post NGN-401
Hand Function / Fine Motor • Had no functional hand use, clenched hands, could not grab, reach, hold objects Ambulation / Gross Motor • Walked independently, but fell frequently, couldn’t stand up from seated position without being pulled up, couldn’t bend over Language / Communication • No babbling
Slide 28: Pt:2 Multi-Domain Improvements from Severe Impairments
Pt:2 Multi-Domain Improvements from Severe Impairments at Baseline Deepened Over Time, and Not Expected Based on Rett Syndrome Natural History 28 Data from the RNHS; N=200 female subjects with classic RTT, age 4-10 years, CGI-S score of 4 to 6 at baseline, confirmed genetic mutation As of data cut-o
Slide 29: Pt:3 From Pre-Treatment to 9 Months Post NGN-401
Hand Function / Fine Motor • Raking grasp, required caregiver to spoon feed all meals due to inability to swallow anything safely other than pureed food Ambulation / Gross Motor • Could not sit, stand, or walk independently due to poor core strength and lower extremity weakness Language / Communicat
Slide 30: Pt:3 Multi-Domain Improvements Not Expected Based on Natural History
Pt:3 Multi-Domain Improvements Not Expected Based on Rett Syndrome Natural History 30 Select Pt:3 Developmental Skills Months Post-NGN-401 3 6 9 Uses a pincer grasp Able to self-feed Sits independently Data from the RNHS; N=200 female subjects with classic RTT, age 4-10 years, CGI-S score of 4 to 6
Slide 31: Pt:4 From Pre-Treatment to 3 Months Post NGN-401
Hand Function / Fine Motor • Raking grasp, able to use adaptive utensils to self-feed, unable to hold or use regular utensils Ambulation / Gross Motor • Could not stand or walk independently Language / Communication • No babbling, unable to follow commands, laughed out of context 31Images are repres
Slide 32: Pt:4 Early Improvements in Hand Function
Pt:4 Early Improvements in Hand Function Not Expected Based on Rett Syndrome Natural History 32 Select Pt:4 Developmental Skills Months Post- NGN-401 3 Uses a pincer grasp Can use utensils to self-feed (without assistance) Data from the RNHS; N=200 female subjects with classic RTT, age 4-10 years, C
Slide 33: Leveraging START and RMAT to Accelerate Program to Registration
Leveraging START and RMAT to Accelerate Program to Registration 33 START Program participation provides clear channel of communication with FDA intended to accelerate registrational planning RMAT designation provides eligibility for an Accelerated Approval pathway and rolling BLA and potential for P
Slide 34: Key Anticipated Milestone Events
Key Anticipated Milestone Events
Slide 35: Key Upcoming Anticipated Milestones and Pipeline Developments
Key Upcoming Anticipated Milestones and Pipeline Developments Rett syndrome (NGN-401) CLN5 Batten disease (NGN-101) Evaluate opportunities for the program 35 Cash runway expected to fund operations into 2H:27 Provide regulatory update in 1H:25 regarding pivotal trial Announce additional Phase
Slide 36: Appendix
Appendix
Slide 37: Understanding the CGI-S with Rett Syndrome-Specific Anchors
Score CGI-S 1 Normal, not at all ill 2 Borderline ill 3 Mildly ill 4 Moderately ill 5 Markedly ill 6 Severely ill 7 Extremely ill Understanding the CGI-S with Rett Syndrome-Specific Anchors 37 • Clinician-rated scale of disease severity across 7 clinical domains • Communication, ambulation, and hand
Slide 38: CGI-S Clinical Domains Provide Insights Into Core Functional Areas
CGI-S Clinical Domains Provide Insights Into Core Functional Areas; Scale Was Not Designed as Clinical Outcome Measure 38Neul J, et al. J Child Neurol (2015) 30(13):1743–1748 Clinical Domains CGI-S 3 CGI-S 4 CGI-S 5 CGI-S 6 Language/ Communication Phrases-sentences. May have conversations or echolal
Slide 39: Hand Function: Participants Gained Meaningful Improvements
Hand Function: Participants* Gained Meaningful Improvements and Gained Skills that Deepened Over Time 39 Pt:1 7 yrs. at dosing CGI-S Domain Score 4 4 4 4 4 4 Raking grasp; Limited self-feeding • More consistent self- feeding, able to take multiple bites of foods without dropping • Modified pincer gr
Slide 40: Ambulation: Participants Gained Improvements in Gait and Mobility
40 Pt:1 7 yrs. at dosing CGI-S Domain Score 4 4 3 3 4 3 Impaired, ataxic, unstable gait; Freezes often and walks on tip-toes; Unable to ascend or descend stairs independently • More fluid gait, more heel-to toe • Able to ascend stairs independently • Can get on and off bed independently • Ascends st
Slide 41: Communication: Improvement in Ability to Convey Choices (Slide 1 of 2)
Communication: Participants* Demonstrated Improvement in Ability to Convey Choices (Slide 1 of 2) 41 Pt:1 7 yrs. at dosing CGI-S Domain Score 6 6 5 5 4 4 Makes choices 50% of time; Unable to follow commands • Some choice-making • Makes choices most of time; food 80–90% of time • Intermittently follo
Slide 42: Communication: Improvements in Ability to Express Themselves (Slide 2 of 2)
Communication: Participants* Experiencing Improvements in Ability to Express Themselves (Slide 2 of 2) 42 Pt:1 7 yrs. at dosing CGI-S Domain Score 6 6 5 5 4 4 Vocalizations • Vocalizations • Vocalizations • Vocalizations • Babbles • Consistently waves “hello” on command • Shouts or yells to express
Slide 43: Autonomic Function: Breathing Dysrhythmias Are Variable
Autonomic Function: Breathing Dysrhythmias Are Variable, Difficult to Assess Clinically Meaningful Improvements at Clinic Visits 43 Pt:1 7 yrs. at dosing CGI-S Domain Score 5 5 3 4 4 5 Breathing dysrhythmias 50% of the time • Breathing dysrhythmias 50% of the time • No or minimal breathing abnormali
Slide 44: Pt:1 Autonomic Function: Improvements in Sleep Parameters and Constipation
Pt:1 Autonomic Function: Objective Improvements Observed in Sleep Parameters and Constipation 44 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 45: Pt:2 Autonomic Function: Improvements in Sleep Parameters and Constipation
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 46: Pt:3 Autonomic Function: Improvement in Swallowing and Self-feeding
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 47: Pt:4 Autonomic Function: Improvement Observed 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 47 Constipation Improved in Month 4, as Measured by Stool Consistency and Frequency* *As measured by Caregiver on modifie
Slide 48: NGN-401 Demonstrated Efficacy and Safety in Mecp2 Mouse Models
NGN-401 Demonstrated Efficacy and Safety in Mecp2 Mouse Models 48 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 49: Delivers Consistent Levels of MECP2 Expression on Cell-by-Cell Basis
Delivers Consistent Levels of MECP2 Expression on Cell- by-Cell Basis 49 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