Neurogene Inc. · NASDAQ:NGNE
Neurogene — Investor Presentation (March 2024)
36 slides from Neurogene's investor presentation, Mar 4, 2024
Slide 1: Corporate Presentation March 2024
Exhibit 99.2 Corporate Presentation March 2024
Slide 2: Disclaimer: Forward Looking Statements
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 financ
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 Novel EXACT technology designed to overcome key limitations of conventional gene therapy $ Pipeline addresses attractive market opportunities, including Rett syndrome Internal manuf
Slide 4: Funding for Key Near Term Milestones Obtained in Reverse Merger and Concurrent Private Financing
Funding for Key Near Term Milestones Obtained in Reverse Merger and Concurrent Private Financing Completed in 2023 Reverse merger and concurrent financing secured funding to position Transaction Highlights Neurogene to deliver on anticipated near term milestones: • Merger closed on December 18, 2023
Slide 5: Neurogene Clinical Stage Pipeline
Neurogene Clinical Stage Pipeline Transgene Regulation CNS + Ocular Delivery Product Near-Term Indication IND* Enabling Phase I/2 Pivotal Candidate Expected Milestones Interim Data NGN-401 Rett Syndrome 4Q:24, Additional Data 2H:25 Interim Data 2H:24 NGN-101 CLN5 Batten Disease *IND = investigationa
Slide 6: Developed to Solve the Limitations of Conventional Gene Therapy
Developed to Solve the Limitations of Conventional Gene Therapy in Complex Neurological Disorders Today’s Gene Therapy Neurogene’s is Limited By: Solutions: Novel, modular EXACT gene regulation technology and other regulatory elements designed to optimize transgene Variable Gene Expression expressio
Slide 7: Wholly-Owned and Fully Integrated In-House AAV Manufacturing
Wholly-Owned and Fully Integrated In-House AAV Manufacturing GMP Manufacturing 42,000 sq ft facility in Houston, with 6,000 sq ft of cleanrooms Analytical Toxicology Batch Development Manufacturing Quality Process Control Development • Flexibility to manufacture AAV product at low cost • Own product
Slide 8: Experienced Leadership Team Backed by Top Tier Investors
Experienced Leadership Team Backed by Top Tier Investors Management Team Rachel McMinn, Ph.D. Christine Mikail, J.D. Stuart Cobb, Ph.D. Julie Jordan, M.D. Founder and CEO President and CFO CSO CMO Effie Albanis, M.D. Andrew Mulberg, M.D. Arvind Sreedharan Ricardo Jimenez SVP, Early Clinical and SVP,
Slide 9: NGN-401 for Rett Syndrome
NGN-401 for Rett Syndrome Leveraging EXACT gene regulation technology
Slide 10: Rett Syndrome – Devastating Disorder with High Unmet Need
Rett Syndrome – Devastating Disorder with High Unmet Need Genetics • X-Linked disorder causing mutations in the gene encoding for methyl-CpG binding protein 2 (MeCP2) • One of the most common genetic causes of developmental and intellectual impairment in females • Unknown incidence in boys, but typi
Slide 11: Rett Syndrome Treatment Requires Tight Gene Regulation
Rett Syndrome Treatment Requires Tight Gene Regulation MeCP2 Rett Syndrome* Duplication Disorder** Balanced Too little Too much treatment goal gene expression drives disease gene expression drives disease ~50% of cells express WT levels of MeCP2 ~100% cells express 2x MeCP2 levels ~50% are MeCP2 def
Slide 12: Acts As a Genetic Thermostat, Limiting Transgene Expression
Acts As a Genetic Thermostat, Limiting Transgene Expression 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 Protein Expressed disorders 12
Slide 13: Designed to Widen Therapeutic Window and Enable Gene Therapy for Rett Syndrome
Designed to Widen Therapeutic Window and Enable Gene Therapy for Rett Syndrome EXACT Dampens Variable AAV Wider Therapeutic Window Overexpression Transduction Endogenous Well tolerated in animal models Endogenous+NGN-401 Deficient Shows therapeutic effect in gold Deficient +NGN-401 standard model Fu
Slide 14: NGN-401 Demonstrates Efficacy and Safety in Mecp2 Mouse Models
NGN-401 Demonstrates Efficacy and Safety in Mecp2 Mouse Models ICV Delivery of NGN-401 Delivers Targeted MeCP2 Levels AAV9 capsid EXACT Full length EXACT Promoter recognition sites miRNA human MECP2 Survival in Male Knockout Survival in Female Het NGN-401 (regulated) 100 100 EXACT1 MECP2 75 75 23 37
Slide 15: ICV Administration Significantly Better Distribution Than IT-L
ICV Administration Significantly Better Distribution Than IT-L To Key Areas of the Nervous System Underlying Rett Syndrome in NHPs Key areas of Rett syndrome pathology ICV M o to r C o rte x Speech F ro n ta l C o rte x Motor H ip p o c a m p u s C e re b e llu m B ra in s te m C e rv ic a l Autonom
Slide 16: NGN-401 Preclinical Data Enabled Pediatric Clinical Approach
NGN-401 Preclinical Data Enabled Pediatric Clinical Approach Delivery of full-length MECP2 Promising efficacy, favorable safety profile MAXIMIZES THERAPEUTIC POTENTIAL DEMONSTRATED CONTROLLED MeCP2 LEVELS No evidence of off-target or MeCP2 tox Robust MeCP2 levels to key brain areas PROVIDES TRANSLAT
Slide 17: Cardinal Clinical Features of Rett Syndrome
Cardinal Clinical Features of Rett Syndrome Inability to Impaired Fine and Autonomic Additional Disease Communicate Gross Motor Skills Dysfunction Manifestations • Severe apnea • Loss of purposeful • Loss of hand function • Seizures episodes • Gait abnormalities hand use & • Anxiety • Hyperventilati
Slide 18: Phase 1/2 Trial for NGN-401 Designed to Inform Future Pivotal Trial
Phase 1/2 Trial for NGN-401 Designed to Inform Future Pivotal Clinical Trial Enrollment • Cohort 1 dose of 1E15 vg (total), Cohort 2 dose of 3E15 vg (total) expected to Cohort 2 initiate 2Q24 • Cohorts to enroll concurrently N=8 • Both doses within GLP toxicology safety margin Currently Cohort 1 enr
Slide 19: NGN-401 Study Inclusion Criteria is Driven by Severity of Rett Syndrome
NGN-401 Study Inclusion Criteria is Driven by Severity of Rett Syndrome Domains Under CGI-S Modest Limited impairment Eligible for Phase 1/2 clinical trial impairment Clinical CGI-S=1 CGI-S=2 CGI-S=3 CGI-S=4 CGI-S=5 CGI-S=6 CGI-S=7 domains Language/ Normal May have unusual Phrases-sentences. May <5
Slide 20: NGN-401 Phase 1/2 Clinical Trial Status Update and Anticipated Milestones
NGN-401 Phase 1/2 Clinical Trial Status Update and Anticipated Milestones Phase 1/2 Clinical Trial Status q First patient dosed 3Q:23, second patient dosed 4Q:23, third patient dosed 1Q:24 q No treatment-emergent, procedure-related serious adverse events or overexpression toxicity observed to date 2
Slide 21: NGN-101 for CLN5 Batten Disease
NGN-101 for CLN5 Batten Disease Treating both CNS and vision through dual route of administration
Slide 22: CLN5 Batten Disease - Fatal, Neurodegenerative Disease With No Disease-Specific Treatment Options
CLN5 Batten Disease - Fatal, Neurodegenerative Disease With No Disease-Specific Treatment Options CLN5 Batten disease has no available treatment options Brineura, approved globally for a similar indication, CLN2, has transformed clinical outcomes in Batten disease Simonati A et al, Phenotype and nat
Slide 23: NGN-101 Dual Delivery Supported by Compelling Preclinical Data
NGN-101 Dual Delivery Supported by Compelling Preclinical Data Dual route of administration NGN-101 dosing (ICV+IVT) in CLN5 knockout sheep First clinical gene therapy study targeting both Combination dosing leads to halting of disease progression neurodegeneration and vision loss 30 20 +/- +/- CLN5
Slide 24: Clinical Study Design For NGN-101 Addresses Vision and CNS
Clinical Study Design For NGN-101 Addresses Vision and CNS Currently enrolling Fully enrolled High dose Fully enrolled Mid dose • Dose selection based on sheep studies Low dose Cohort 3 showing significant treatment effects Cohort 2 • Key assessments every 6 and 12 months Cohort 1 N=3 N=1 N=2 Effica
Slide 25: NGN-101 — Defining a Registration Path
NGN-101 — Defining a Registration Path FDA meeting focused on finalizing CMC plans Plan to request FDA meeting in 2H:24 to align on completed 4Q:23 clinical requirements for streamlined registration Potency Assay Complete enrollment of high dose FDA accepted proposed potency cohort in 2024 assay str
Slide 26: Key Anticipated Milestone Events
Key Anticipated Milestone Events
Slide 27: Key Upcoming Anticipated Milestones and Pipeline Developments
Key Upcoming Anticipated Milestones and Pipeline Developments Rett syndrome (NGN-401) ❑ Expand ongoing Phase 1/2 clinical trial in 1H:24 to enroll a larger cohort of patients ❑ Interim Phase 1/2 clinical data 4Q:24 ❑ Additional Phase 1/2 clinical data from expanded low dose and high dose cohorts in
Slide 28: Why Neurogene?
Why Neurogene? Unlocking multi-billion dollar neurological disease markets Proprietary capabilities and technology enable addressing complex diseases Strategy focused on efficiency and maximizing probability of success Leadership team with deep operational, technological and clinical experience Lead
Slide 29: Appendix
Appendix
Slide 30: Rett Syndrome Primarily Results from Loss of MECP2 Function in the Brain
Rett Syndrome Primarily Results from Loss of MECP2 Function in the Brain, Making the Brain the Key Target Area for Gene Therapy Mecp2 Knockout • Limiting expression of MeCP2 Peripheral Mecp2 Knock Out Mouse to only the brain/spinal cord results in a near normal mouse Peripheral knockout WT • NHP bio
Slide 31: Delivers Consistent Levels of MECP2 Expression on Cell-by-Cell Basis
Delivers Consistent Levels of MECP2 Expression on Cell- by-Cell Basis NGN-MECP2 Achieves Narrow Expression of MECP2* 1000 EXACT GTx 800 Conventional GTx 600 Unregulated Regulated 400 Conventional 200 0 0 50 100 150 200 *mouse cortex Intensity (AU) immunohistochemistry 31 Number of cells
Slide 32: NGN-401 Demonstrates Tight MECP2 Regulation in a Knockout Mouse Model
NGN-401 Demonstrates Tight MECP2 Regulation That Translates to Compelling Outcomes in a Knockout Mouse Model ICV Delivery of NGN-401 Delivers Targeted MECP2 Levels AAV9 capsid EXACT Full length EXACT Promoter recognition sites miRNA human MECP2 Clinical Score* Survival 100 30 25 75 NGN-401 1e11 vg K
Slide 33: NGN-401 Via ICV Delivery Well Tolerated in Multiple Studies
NGN-401 Via ICV Delivery Well Tolerated in Multiple Studies While Conventional Unregulated Gene Therapy is Toxic NGN-401 Well Tolerated in NHP studies, NGN-401 Well Tolerated in Female Tight mRNA Levels in NHPs for Mouse Model, Unregulated While Unregulated MeCP2 NGN-401, While Unregulated Has Demon
Slide 34: NGN-401 Distribution and Expression Levels in NHPs Support Encouraging Profile
NGN-401 Distribution and Expression Levels in NHPs Support Encouraging Profile for Human Testing • NGN-401 distributes to key regions underlying RTT pathophysiology in WT non-human primates • Degree of mRNA expression tracks vector genome biodistribution of AAV9 across key brain regions • Aggregate
Slide 35: GLP Toxicology in NHPs Support Favorable Safety Profile
GLP Toxicology in NHPs Support Favorable Safety Profile • NGN-401 evaluated in GLP NHP toxicology study with 90-day and 180-day cohorts • No signs or symptoms of MeCP2 overexpression observed • >4x safety margin relative to NGN-401 clinical starting dose in Phase 1/2 • Overall toxicology profile con
Slide 36: Explanation of CGI-I and RSBQ
Explanation of CGI-I and RSBQ 5=Minimally 1=Very much Worse Improved CGI-I (Clinician Global Impression of Improvement) 6=Much Worse 2=Much Improved 4=No Change 7=Very much 3=Minimally Worsened Improved Domain Total Possible Points (90) RSBQ General mood 16 (Rett Syndrome Behavior Questionnaire) Bre