Neurogene Inc. · NASDAQ:NGNE
Neurogene — Investor Presentation (January 2024)
35 slides from Neurogene's investor presentation, Jan 5, 2024
Slide 1: January 2024 Corporate Presentation
January 2024 Corporate Presentation Exhibit 99.2
Slide 2: Disclaimer: Forward Looking Statements
Disclaimer Forward Looking Statements This communication contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. These statements may discuss goals, intentions and
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 Internal manufacturing provides financial and strategic pipeline flexibility Pipeline addres
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 *After the closing of merger, private placement, and 1-for-4 reverse stock split. This number includes 4,063,364 Neurogene Pre-Funded Warrants. Transaction Highlights Merger closed on D
Slide 5: Neurogene Clinical Stage Pipeline
Product Candidate Indication IND* Enabling Phase I/2 Pivotal Near-Term Expected Milestones NGN-401 Rett Syndrome Interim Data 4Q:24, Additional Data 2H:25 NGN-101 CLN5 Batten Disease Interim Data 2H:24 Neurogene Clinical Stage Pipeline *IND = investigational new drug. Transgene Regulation CNS + Ocul
Slide 6: Developed to Solve the Limitations of Conventional Gene Therapy in Complex Neurological Disorders
Variable Gene Expression Inefficient Gene Delivery Developed to Solve the Limitations of Conventional Gene Therapy in Complex Neurological Disorders Select ICV delivery approach to maximize AAV9 distribution to target CNS tissues Novel, modular EXACT gene regulation technology and other regulatory e
Slide 7: Wholly-Owned and Fully Integrated In-House AAV Manufacturing
Wholly-Owned and Fully Integrated In-House AAV Manufacturing 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 developm
Slide 8: Experienced Leadership Team Backed by Top Tier Investors
Experienced Leadership Team Backed by Top Tier Investors Rachel McMinn, Ph.D. Founder and CEO Christine Mikail, J.D. President and CFO Albena Patroneva, M.D. SVP, Clinical Development Effie Albanis, M.D. SVP, Early Clinical and Translationall Research Andrew Mulberg, M.D. SVP, Regulatory Affairs Ric
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 typically
Slide 11: Rett Syndrome Treatment Requires Tight Gene 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 ~100% cells express 2x MeCP2
Slide 12: Acts As a Genetic Thermostat, Limiting Transgene Expression
Acts As a Genetic Thermostat, Limiting Transgene Expression 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
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 Deficient Deficient +NGN-401 Endogenous Endogenous+NGN-401 Functional MeCP2 protein levels ~50% of cells express WT levels of MeCP2 ~50% are MeCP2 deficient Variable AAV Transduction EXACT Dampens Overexpression Wider The
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 Promoter EXACT miRNA Full length human MECP2 EXACT recognition sites AAV9 capsid Survival in Male Knockout 9 23 37wks Age (weeks) Survival in Female Het NGN-401 1e11 vg NGN-401 3e11
Slide 15: NGN-401 Preclinical Data Enabled Pediatric Clinical Approach
NGN-401 Preclinical Data Enabled Pediatric Clinical Approach Promising efficacy, favorable safety profile DEMONSTRATED CONTROLLED MeCP2 LEVELS Robust MeCP2 levels to key brain areas PROVIDES TRANSLATIONAL FOUNDATION FOR HUMANS No evidence of off-target or MeCP2 tox GENERATED COMPREHENSIVE SAFETY PAC
Slide 16: Cardinal Clinical Features of Rett Syndrome
“Relative” stability Risk of scoliosis increases Risk of seizures developing Hand function loss 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
Slide 17: Clinical Study For NGN-401 Designed to Evaluate Pediatric Population
Key Eligibility Criteria Female, age ≥4 to ≤10 years with Classic Rett syndrome Clinical diagnosis & genetic confirmation of pathogenic MeCP2 mutation Clinical Global Impression-Severity (CGI-S) score of 4-6 Efficacy Assessments of Interest Autonomic Function Objective device to monitor breathing Ha
Slide 18: 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 Clinical domains CGI-S=1 CGI-S=2 CGI-S=3 CGI-S=4 CGI-S=5 CGI-S=6 CGI-S=7 Language/ Communication Normal May have unusual features (eg echolalia, reading disability) Phrases-sentences. May have conversations o
Slide 19: NGN-401 Phase 1/2 Clinical Trial Status Update and Anticipated Near Term Milestones
NGN-401 Phase 1/2 Clinical Trial Status Update and Anticipated Near Term Milestones Phase 1/2 Clinical Trial Status First patient dosed 3Q:23, second patient dosed 4Q:23 DSMB meeting completed in January 2024 to enable third patient dosing in early 1Q:24 No treatment-emergent, procedure-related or o
Slide 20: NGN-101 for CLN5 Batten Disease
NGN-101 for CLN5 Batten Disease Treating both CNS and vision through dual route of administration
Slide 21: 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 22: NGN-101 Dual Delivery Supported by Compelling Preclinical Data
NGN-101 Dual Delivery Supported by Compelling Preclinical Data Dual route of administration First clinical gene therapy study targeting both neurodegeneration and vision loss NGN-101 dosing (ICV+IVT) in CLN5 knockout sheep Combination dosing leads to halting of disease progression CLN5+/- Control CL
Slide 23: Clinical Study Design For NGN-101 Addresses Vision and CNS
Clinical Study Design For NGN-101 Addresses Vision and CNS Cohort 1 Cohort 3 N=2 N=3 Fully enrolled Low dose Currently enrolling Dose selection based on sheep studies showing significant treatment effects Key assessments every 6 and 12 months Age ≥3 to ≤9 years Genetic diagnosis of CLN5 Onset of dis
Slide 24: NGN-101 — Defining a Registration Path
NGN-101 — Defining a Registration Path Plan to request FDA meeting in 2H:24 to align on clinical requirements for streamlined registration FDA meeting focused on finalizing CMC plans completed 4Q:23 FDA alignment on proposed comparability strategy for using Neurogene-made material with substantially
Slide 25: Key Milestone Events
Key Milestone Events
Slide 26: 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 expansion and higher dose cohorts in 2H:25 CLN5 B
Slide 27: 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 28: Appendix
Appendix
Slide 29: 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 Limiting expression of MeCP2 to only the brain/spinal cord results in a near normal mouse NHP biodistribution study shows 10-100x greater distribution for ICV/ICM compared
Slide 30: Delivers Consistent Levels of MECP2 Expression on Cell-by-Cell Basis
Delivers Consistent Levels of MECP2 Expression on Cell-by-Cell Basis Conventional NGN-MECP2 Achieves Narrow Expression of MECP2* EXACT GTx Conventional GTx *mouse cortex immunohistochemistry Neurogene Confidential Information
Slide 31: 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 Promoter EXACT miRNA Full length human MECP2 EXACT recognition sites ICV Delivery of NGN-401 Delivers Targeted MECP2 Levels Survival 9 23 37wks Age (weeks) *RTT scored 0-5 for six domains: mo
Slide 32: NGN-401 Via ICV Delivery Well Tolerated in Multiple Studies
NGN-401 low dose NGN-401 high dose AAV9-RTT251 low dose AAV9-RTT251 high dose NGN-401 Via ICV Delivery Well Tolerated in Multiple Studies While Conventional Unregulated Gene Therapy is Toxic NOTE: toxicity scoring developed to capture phenotypes associated with MeCP2 overexpression including general
Slide 33: NGN-401 Distribution and Expression Levels in NHPs Support Encouraging Profile for Human Testing
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 transg
Slide 34: 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 consistent
Slide 35: Explanation of CGI-I and RSBQ
Explanation of CGI-I and RSBQ CGI-I (Clinician Global Impression of Improvement) 1=Very much Improved 2=Much Improved 3=Minimally Improved 7=Very much Worsened 6=Much Worse 5=Minimally Worse RSBQ (Rett Syndrome Behavior Questionnaire) 4=No Change Domain Total Possible Points (90) General mood 16 Bre