Neurogene : NGN-401 Interim Clinical Data Presentation
NGNE
Interim Clinical Data from Phase 1/2 Trial Evaluating NGN-401 Gene Therapy for the Treatment of Rett Syndrome
November 11, 2024
CONFIDENTIAL
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Forward Looking Statements
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Agenda
Introduction and NGN-401 Program Overview
Rett Syndrome Overview and Natural History
NGN-401 Phase 1/2 Clinical Trial Design
Baseline Characteristics and Safety Data
Interim Low-Dose Cohort Efficacy Data
NGN-401 Next Steps
Q&A
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Compelling Interim Clinical Data in Low-Dose Cohort Shows Gains of Function Across Core Domains and Improvements in Autonomic Function
Durable improvements observed across multiple scales, incl. two-point improvement in CGI-I in all participants, with concordance of benefit across scales
Consistent gains observed across core clinical domains of hand function, gross motor and communication, despite heterogeneous presentation
Clinically meaningful gain of skills and developmental milestones
beyond those observed in natural history data
NGN-401
Objective improvements in autonomic domains of sleep and constipation
Rapid response post-treatment,with deepening of response over time
Favorable safety profile with low-dose NGN-401
As of data cut-off date of 17 October 2024
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Leveraging START and RMAT to Accelerate Program to Registration; New Adult Cohort Underway
Multiple Touch Points with FDA to Accelerate Registration
START Program participation provides clear channel of communication with FDA to accelerate registrational planning
RMAT designation provides eligibility for an Accelerated Approval pathway and rolling BLA and potential for Priority Review
FDA alignment on potency assay strategy to support future registrational trial and manufacturing scale-up plans at Neurogene Houston facility to support commercial launch plans
Initiated adolescent/adult cohort at high dose to support potential for a broad label to capture higher portion of prevalent population
Bold = New update
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Rett Syndrome Overview and Natural History
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Rett Syndrome is Defined By Regression Period in Early Development
Early
Normal Onset
Clinical function
Severely
Impaired
~6 mos. to
~18 mos.
Delayed early development
Developmental
Regression
~1 to 4 years
Phase 1/2 Study Age Range
"Relative Stability"
Disease Progression
~4 to 10 years
Adolescence to Adulthood
Pini G, et al. Orphanet Journal of Rare Diseases (2016) 11:132.
Neul J, et al. Journal of Neurodevelopmental Disorders (2014) 6:208 U.S. Natural History Study of Rett Syndrome (RNHS) Clinicaltrials.gov identifier: NCT02738281. Accessed 2022 from International Rett Syndrome Foundation (IRSF).
Simple Skills Are Generally Acquired but Majority Are Lost During Regression; More Complex Skills are Generally Not Acquired
Natural History of Rett Syndrome
Early Onset
Developmental Regression +
Hand Function
Fine motor more likely to be lost than gross motor
Gross Motor
Advanced skills less likely ever acquired
Communication
Expressive more
likely to be
lost/never learned
than receptive
Simple Skills
Generally Acquired
% Learned
Raking Grasp (~85%)
Transferred Objects (~80%)
Hold Bottle (~80%)
Pincer Grasp (70%)
Sitting (>~90%)
Walking (~60%)
Babbling (~90%)
Single Words (66%)
Loss
Loss
Simple Skills
Generally Lost*
% Lost
Raking grasp (~50%)
Transferred Objects (~60%)
Hold Bottle (~60%)
Pincer Grasp (~50%)
*If gross motor skills acquired,
not generally lost
Sitting - ~80% retain Walking - ~50% retain
Babbling (~45%)
Single Words (~60%)
Complex Skills
Not Generally Acquired
% Never Learned
Spoon/Fork Without Assist - (~80%)
Run (~75%)
Climb Up Stairs Without Help (82%)
Climb Down Stairs Without Help (86%)
Waved Bye (~50%)
Points When Wants (~80%)
Spoken Phrases (~80%)
U.S. Natural History Study of Rett Syndrome (RNHS) Clinicaltrials.gov identifier: NCT02738281. Accessed 2022 from International Rett Syndrome Foundation (IRSF).
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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
Neul J, et al. Journal of Neurodevelopmental Disorders (2014) 6:20
NGN-401 Phase 1/2 Trial Design and Interim Results
Disclaimer
Neurogene Inc. published this content on November 12, 2024, and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on November 12, 2024 at 04:09:08.924.