Slide 1: Restarting Development in Rett Syndrome
Restarting Development in Rett Syndrome NGN-401 for Rett Syndrome Phase 1/2 Update June 29, 2026
Slide 2: Disclaimer
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: Today's Speakers
Today’s Speakers Rachel McMinn, Ph.D. Founder and Chief Executive Officer, Neurogene Bernhard Suter, M.D. Medical Director, Blue Bird Circle Rett Center, Texas Children’s Hospital Associate Professor of Pediatrics and Neurology, Baylor College of Medicine Julie Jordan, M.D. Chief Medical Officer, Ne
Slide 4: Introduction
Introduction Rachel McMinn, Ph.D. Founder and Chief Executive Officer, Neurogene
Slide 5: No Approved Disease-Modifying Therapies for Rett Syndrome
No Approved Disease-Modifying Therapies for Rett Syndrome NGN-401 Gene Therapy Targets Root Cause The Unmet Need The Market The Opportunity • Developmental regression begins at • The Rett syndrome community is 6–18 months 15,000–20,000 increasingly seeking therapies that patients — US, EU & UK can d
Slide 6: NGN-401 Phase 1/2 Trial Update: Clinically Meaningful, Durable Improvement
NGN-401 Phase 1/2 Trial Update: Clinically Meaningful, Durable Improvement Across Key Rett Syndrome Domains, Deepens Over Time 100% of Phase 1/2 participants (N=10) gained ≥1 47 total milestones gained 30 developmental milestone and improved on CGI-I months of continued improvement post-dose 80% met
Slide 7: Long-term Phase 1/2 Data Demonstrate Broad, Consistent Multidomain Developmental Gains
Long-term Phase 1/2 Data Demonstrate Broad, Consistent Multidomain Developmental Gains that Support Registration Regardless of Age, Disease Severity or Genotype 100% of Phase 1/2 participants (N=10) gained ≥1 developmental milestone and improved on CGI-I at ≥12 months Rapid onset of clinical respons
Slide 8: Phase 1/2 Data Update
ad YNevrocene Phase 1/2 Data Update ¢¢¢
Slide 9: NGN-401 Clinical Study Design for Treatment of Rett Syndrome
NGN-401 Clinical Study Design for Treatment of Rett Syndrome Phase 1/2 converted into a single registrational study Study Design • Baseline-controlled, open-label, multicenter, single- Embolden arm pivotal trial (13 US sites) Phase 1/2 Trial Registrational Trial • Evaluates efficacy, safety & tolera
Slide 10: Clearly Defined Developmental Milestones
28 Clearly Defined Developmental Milestones: Derived from Natural History Study & Key Component of Primary Endpoint Fine Motor/ Gross Motor/Ambulation Communication Hand Function Reached for toy Sat with support when placed Responded to familiar Taken a drink from a cup held Sat without support when
Slide 11: Rigorous Embolden Milestone Criteria Evaluation Applied to Phase 1/2 Data
Rigorous Embolden Milestone Criteria Evaluation Applied to Phase 1/2 Data Utilizing the same standardized assessment criteria enables the Phase 1/2 developmental milestone data to be comparable to the Embolden definition Baseline Assessment Post-Treatment Evidence Evaluation Methods Milestones confi
Slide 12: Evaluating the Impact of NGN-401 Across Full Spectrum of Disease Severity and Ages
Evaluating the Impact of NGN-401 Across Full Spectrum of Disease Severity and Ages Baseline Characteristics of the Phase 1/2 Participants Adult / Adolescent Pediatric Cohort (N=8) Cohort (N=2) Pt:1 Pt:2 Pt:3 Pt:4 Pt:5 Pt:6 Pt:7 Pt:8 Pt:9 Pt:10 Age at Dosing 7 4 6 7 6 4 6 8 18 14 (Years) Baseline 4 5
Slide 13: Phase 1/2 Data Update: Restarting Development in Long-Term NGN-401-Treated Participants
Phase 1/2 Data Update: Restarting Development in Long-Term NGN-401-Treated Participants Bernhard Suter, M.D. Medical Director of Blue Bird Circle Rett Center at Texas Children’s Hospital, Associate Professor of Pediatrics and Neurology, Baylor College of Medicine Principal Investigator in NGN-401 Cl
Slide 14: Rett Syndrome: Rare, Debilitating, Progressive, Neurodevelopmental Disorder
Rett Syndrome: Rare, Debilitating, Progressive, Neurodevelopmental Disorder Cause: Variants in the MECP2 gene on the X chromosome lead to deficiency of functional MeCP2 protein MeCP2 is a DNA-binding protein essential for normal brain and nervous system function Onset: Developmental delay occurs at
Slide 15: Living with Rett Syndrome
Living with Rett Syndrome Kendall & Kati
Slide 16: Restarting Developmental Progression is the Goal for a One-time Gene Therapy
Restarting Developmental Progression is the Goal for a One-time Gene Therapy Restarted Developmental Typical Development Rett Syndrome Progression Organized, cumulative acquisition of Milestones lost in regression, NGN-401 has potential to restart the developmental milestones exceedingly rare to gai
Slide 17: Pt:1 Developmental Milestones Gained in Ordered, Developmental Progression
Pt:1 Developmental Milestones Gained in Ordered, Developmental Progression Baseline NGN-401 Restarted Developmental Progression Age: 7 Used a spoon/fork to eat Transferred an object from one Taken a drink from a cup held Used a pincer without assistance hand to the other without assistance grasp Fin
Slide 18: Pt:1 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones
Pt:1 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones At baseline Impaired hand use, Gross motor impairment, Severe communication impairment, (Age 7): Raking, no ability to hold objects ataxic, unable to climb stairs unable to follow commands Moves more Joins family Navi
Slide 19: Pt:2 Developmental Milestones Gained in Ordered, Developmental Progression
Pt:2 Developmental Milestones Gained in Ordered, Developmental Progression Baseline NGN-401 Restarted Developmental Progression Age: 4 Finger fed Used raking grasp to Reached for Taken a drink from a retrieve an object toy cup held without Fine motor assistance Severe impairment, unable to use hands
Slide 20: Pt:2 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones
Pt:2 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones At baseline Severe impairment, Gross motor impairment, Severe communication impairment, (Age 4): unable to use hands ataxic, needs help to stand unable to follow commands Less caregiver Moves more independently Connec
Slide 21: Pt:3 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones
Pt:3 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones At baseline Impaired hand use, Severe gross motor impairment, Severe communication impairment, (Age 6): raking grasp cannot sit/stand/walk independently unable to follow commands Uses both hands to follow Stands and m
Slide 22: Pt:4 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones
Pt:4 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones At baseline Impaired hand use, Severe gross motor impairment, Severe communication impairment, (Age 7): raking grasp cannot sit/stand/walk independently unable to follow commands Eats on her Sits up by Controls her Pl
Slide 23: Thank you to all participants and their families and caregivers!
Thank you to all participants and their families and caregivers!
Slide 24: Phase 1/2 Data Update
Phase 1/2 Data Update Julie Jordan, M.D. Chief Medical Officer
Slide 25: Rapid Response Observed Post NGN-401 that Deepened Over Time
Rapid Response Observed Post NGN-401 that Deepened Over Time Response Over Time in the Phase 1/2 Trial Pt:1 Pt:2 Pt:3 Pt:4 47 Total developmental milestones Pt:5 Pt:6 4.7 Average milestones per participant Pt:7 Pt:8 2 months Median time to first response Pt:9 Pt:10 0 3 6 9 12 15 18 24 30 36 Months p
Slide 26: NGN-401 Drove Durable Accumulation of Multidomain Milestones
NGN-401 Drove Durable Accumulation of Multidomain Milestones Across Core Domains That Matter Most to Caregivers Developmental Milestones Increased by Domain Over Time Post-NGN-401 Treatment Fine Motor/Hand Function Expressive & Receptive Communication Gross Motor/Ambulation 47 # of Developmental Mil
Slide 27: Milestones Gained from Embolden List Across Phase 1/2 Participants Treated with NGN-401
Milestones Gained from Embolden List Across 10 Phase 1/2 Participants Treated with NGN-401 21 of 28 Total Milestones Gained from Embolden Milestone List 7/7 7/13 7/8 Fine Motor / Hand Function Gross Motor / Ambulation Communication Reached for toy Sat without support when placed Responded to familia
Slide 28: RSGMS Phase 1/2 Data Showed Meaningful Gains in Gross Motor Function
RSGMS Phase 1/2 Data Showed Meaningful Gains in Gross Motor Function Mean RSGMS Total-Score Gain Exceeded Natural History Overview of Rett Syndrome Gross Motor Scale (RSGMS) Normalized to One Year Rate Validated clinical tool that assesses 15 key gross motor abilities Post Treatment (N=10) 5.2-point
Slide 29: RSHFS Phase 1/2 Data Showed Meaningful Gains in Hand Function
RSHFS Phase 1/2 Data Showed Meaningful Gains in Hand Function Overview of Rett Syndrome Hand Function Scale (RSHFS) Mean RSHFS Total-Score Gains Exceed Natural History Validated clinical tool that assesses levels of hand function 100% improved Post Treatment (N=10; 1-2.5 years) specific to Rett synd
Slide 30: NGN-401 Remains Generally Well-Tolerated at the 1E15 vg Dose Level
NGN-401 Remains Generally Well-Tolerated at the 1E15 vg Dose Level in the Phase 1/2 Trial • All TEAEs related to NGN-401 have been Grade 1 (mild) or Phase 1/2 Trial 1E15 vg Dose Grade 2 (moderate) in severity; the majority are known Total N = 10 potential risks of AAV and have resolved or are resolv
Slide 31: Embolden Registrational Trial
Embolden Registrational Trial
Slide 32: Dosing Completed in Embolden Registrational Trial to Support Planned BLA Submission
Dosing Completed in Embolden Registrational Trial to Support Planned BLA Submission Primary Endpoint at 12 Months Responder-based composite endpoint defined as: • CGI-I of ≤ 3 and • Gain from baseline of any one developmental milestone 33% response rate, or 8 of 24 participants, needed for Single Ar
Slide 33: Natural History Study Shows Beyond Age 3, Milestone Gains Are Rare
Natural History Study Cumulative Incidence Model Shows Beyond Age 3, Milestone Gains Are Rare with Minimal Difference at Age 6 Likelihood of gaining a milestone at > 3 years of age is extremely low, based on RNHS analysis Fine Motor Gross Motor Communication Example Milestone: Taken a drink from a c
Slide 34: Compelling Clinical Data Strengthen Confidence in Potential Embolden Registrational Success
Compelling Clinical Data Strengthen Confidence in Potential Embolden Registrational Success 80% Response Rate (8 of 10) % Responders at 12 months Phase 1/2 response rate exceeds the success threshold defined for Embolden by 2.4x 33% NGN-401 has been generally well-tolerated in (8 of 24) Embolden Pre
Slide 35: Advancing NGN-401 Towards Commercialization
Advancing NGN-401 Towards Commercialization Rachel McMinn, Ph.D. Founder and Chief Executive Officer, Neurogene
Slide 36: Robust, Clinically Meaningful Responses Across Participants Support Potential Market Leading Therapy
Robust, Clinically Meaningful Responses Across Participants Support Potential Market Leading Therapy for Rett Syndrome NGN-401 Phase 1/2 Data (N=10) % of participants gained ≥1 developmental milestone at ≥12 months 100% Average milestones gained per participant 4.7 Total Participants achieving: - ≥2
Slide 37: NGN-401 is Poised to Transform Treatment for Rett Syndrome
NGN-401 is Poised to Transform Treatment for Rett Syndrome TODAY UPCOMING ANTICIPATED MILESTONES Compelling Clinical Data Start PPQ Campaign Mid-2026 Strong Cash Showed NGN-401 Balance (1Q’28) Restarts the Development Trajectory Expected to fund Topline Data from Embolden operations through in 2H 20
Slide 38: Thank you to all participants, caregivers, families, investigators
Thank you to all participants, caregivers, families, investigators, clinical site coordinators, study coordinators, site staff and the Rett syndrome community for your trust, partnership and ongoing support of the development of NGN-401!