Neurogene Inc. · NASDAQ:NGNE
Neurogene — Investor Presentation (August 2024)
37 slides from Neurogene's investor presentation, Aug 9, 2024
Slide 1: August 2024 Corporate Presentation
August 2024 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 Interim Data 4Q:24, Additional Data 2H:25 NGN-101 CLN5 Batten Disease Interim Data and Regulatory Update 1Q:25 Neurogene Clinical Stage Pipeline 4 *IND = investigational new drug. Transge
Slide 5: Developed to Solve the Limitations of Conventional Gene Therapy
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 6: Wholly Owned and Fully Integrated In-House AAV Manufacturing
Wholly Owned and Fully Integrated In-House AAV Manufacturing 6 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 7: Experienced Leadership Team
Experienced Leadership Team 7 Rachel McMinn, Ph.D. Founder and CEO Christine Mikail, J.D. President and CFO Effie Albanis, M.D. SVP, Early Clinical and Translationall Research Andrew Mulberg, M.D. SVP, Regulatory Affairs Arvind Sreedharan SVP, Business Operations Stuart Cobb, Ph.D. CSO Management Te
Slide 8: NGN-401 for Rett Syndrome
NGN-401 for Rett Syndrome Leveraging EXACT transgene regulation technology
Slide 9: Rett Syndrome – Devastating Disorder with High Unmet Need
Rett Syndrome – Devastating Disorder with High Unmet Need 9 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 10: 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 10 ~100% cells express 2x
Slide 11: Acts As a Genetic Thermostat, Limiting Transgene Expression
Acts As a Genetic Thermostat, Limiting Transgene Expression 11 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
Slide 12: Designed to Widen Therapeutic Window and Enable Gene Therapy for Rett Syndrome
12 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 13: NGN-401 Demonstrated Efficacy and Safety in Mecp2 Mouse Models
NGN-401 Demonstrated Efficacy and Safety in Mecp2 Mouse Models 13 Survival in Male Knockout 0 5 10 15 20 25 30 35 40 45 50 0 25 50 75 100 S u rv iv a l (% ) 9 23 37wks Age (weeks) 0 5 10 15 20 25 0 25 50 75 100 Age (weeks) S u rv iv a l (% ) Survival in Female Het NGN-401 1e11 vg NGN-401 3e11 vg MEC
Slide 14: ICV Administration Resulted in Significantly Better Distribution Than IT-L
14ASGCT 2021 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 tonomic
Slide 15: NGN-401 Preclinical Data Enabled Pediatric Clinical Approach
NGN-401 Preclinical Data Enabled Pediatric Clinical Approach 15 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
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 assista
Slide 17: Phase 1/2 Trial for NGN-401 Designed to Inform Future Pivotal Clinical Trial
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 breat
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 18 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 conversation
Slide 19: Low-dose NGN-401 Has Continued to Show a Favorable Safety Profile
Low-dose NGN-401 Has Continued to Show a Favorable Safety Profile; High-dose NGN-401 Well-Tolerated 19 1Data cut-off date for first three low-dose participants: May 31, 2024 • All treatment-emergent adverse events (TEAEs) related to NGN-401 have been mild/Grade 1 and transient or resolving, and most
Slide 20: NGN-401 Chosen for FDA START Program and RMAT Designation
NGN-401 Chosen for FDA START Program and RMAT Designation, Synergistic Initiatives Intended to More Rapidly Advance Development 20 Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program • Selection criteria included potential for clinical benefit and clinical developme
Slide 21: NGN-401 Phase 1/2 Clinical Trial Status Update and Anticipated Milestones
❑ Expand ongoing Phase 1/2 clinical trial in 1H:24 to enroll a larger cohort of patients ❑ Selected for FDA START Pilot Program, which is designed to accelerate development ❑ Initiated dosing of Cohort 2 in 2Q:24 ❑ Received RMAT designation ❑ Complete dosing of Cohort 1 in 2H:24 ❑ Interim Phase 1/2
Slide 22: NGN-101 for CLN5 Batten Disease
NGN-101 for CLN5 Batten Disease Treating both CNS and vision through dual route of administration
Slide 23: CLN5 Batten Disease - Fatal, Neurodegenerative Disease With No Disease-Specific Treatment Options
CLN5 Batten Disease - Fatal, Neurodegenerative Disease With No Disease-Specific Treatment Options 23 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
Slide 24: NGN-101 Dual Delivery Supported by Compelling Preclinical Data
NGN-101 Dual Delivery Supported by Compelling Preclinical Data 24 Dual route of administration First clinical gene therapy study targeting both neurodegeneration and vision loss 0 5 10 15 20 25 0 10 20 30 Age (months) C li n ic a l s c o re ( /2 4 ) CLN5 +/- Control CLN5 -/- Untreated CLN5 -/- High
Slide 25: Clinical Study Design For NGN-101 Addresses Vision and CNS
Clinical Study Design For NGN-101 Addresses Vision and CNS 25 Cohort 1 Cohort 3 N=2 N=3 Fully enrolled Low dose Fully enrolled High dose • 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 C
Slide 26: NGN-101 — Defining a Registration Path
NGN-101 — Defining a Registration Path 26 Plan to request FDA meeting 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 impro
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 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 29: Why Neurogene?
29 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 S
Slide 30: Appendix
Appendix
Slide 31: 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 compa
Slide 32: Delivers Consistent Levels of MECP2 Expression on Cell-by-Cell Basis
Delivers Consistent Levels of MECP2 Expression on Cell- by-Cell Basis 32 Conventional NGN-MECP2 Achieves Narrow Expression of MECP2* 0 50 100 150 200 0 200 400 600 800 1000 Intensity (AU) N u m b e r o f c e ll s Unregulated Regulated EXACT GTx Conventional GTx *mouse cortex immunohistochemistry
Slide 33: 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 33 0 5 10 15 20 25 30 35 40 45 50 0 25 50 75 100 S u rv iv a l (% ) Survival 9 23 37wks Age (weeks) *RTT scored 0-5 for six domains: mobility, gait, clasping, breathing, tremor, body conditio
Slide 34: NGN-401 Via ICV Delivery Well Tolerated While Unregulated Gene Therapy is Toxic
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 34 NOTE: toxicity scoring developed to capture phenotypes associated with MeCP2 overexpression including gene
Slide 35: NGN-401 Distribution and Expression Levels in NHPs
NGN-401 Distribution and Expression Levels in NHPs Support Encouraging Profile for Human Testing 35 • 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 • Aggrega
Slide 36: GLP Toxicology in NHPs Support Favorable Safety Profile
GLP Toxicology in NHPs Support Favorable Safety Profile 36 • 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
Slide 37: Explanation of CGI-I and RSBQ
Explanation of CGI-I and RSBQ 37 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