ngn-4012h25update

Every Breakthrough BEGINS WITH BELIEF r r t r BE I S IT BELIEF NGN-401 Phase 1/2 Interim Data Update November 2025

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NGN-401: Setting the Standard for Rett Syndrome Gene Therapy 3Entire presentation includes data cutoff date of October 30, 2025; N=8 for efficacy (ages 4-10 cohort) and N=10 for safety (ages 4-10 and ages > 11 cohorts) ✓ Multidomain improvements ✓ Progressive skill gains over time ✓ Durability of response ✓ Reproducibility across patients ✓ Improvements across full spectrum of disease severity ✓ 1E15 vg dose remains generally well-tolerated Best-in-Class Potential First-in-Class Potential ✓ First participant dosed in Embolden trial ✓ 12 of 13 clinical trial sites initiated ✓ Enrollment expected to complete in 3-6 months ✓ Single trial design in ages > 3 expected to enable most efficient path to market

A Best-in-Class Gene Therapy for Rett Syndrome Requires Durable, Multidomain Gains that Grow Over Time 4As of data cutoff date of October 30, 2025 NGN-401 Phase 1/2 Pediatric Data Update 8 Participants included Multidomain Improvements 35 Skills Gained Overall Durable, No Skills Lost Results in Local Delivery into the Brain is a Demonstrated Strategy that Drives Efficacy Delivering Fully Functional Protein is the Optimal Strategy to Lead to Efficacy Controlling for Overexpression is Required to Deliver Therapy Safely NGN-401 uses ICV Delivery NGN-401 uses Full-length MECP2 NGN-401 uses EXACT Technology to Limit Expression

NGN-401 Phase 1/2 Interim Data Summary 5

6 Time Post Dosing Pt:1 24 months Pt:2 18 months Pt:3 18 months Pt:4 15 months Pt:5 12 months Pt:6 6 months Pt:7 6 months Pt:8 6 months Age at Dosing 7 4 6 7 6 4 6 8 Baseline CGI-S Score 4 Moderately Ill 5 Markedly Ill 5 Markedly Ill 5 Markedly Ill 5 Markedly Ill 5 Markedly Ill 4 Moderately Ill 4 Moderately Ill Genetic Variant Severity Mild Severe Severe Severe Severe Moderate Mild- Moderate Mild- Moderate Baseline Characteristics of Phase 1/2 Trial Pediatric Participants Evaluating the Impact of NGN-401 Across Entire Spectrum of Disease Severity

As of data cutoff date of October 30, 2025 Responders in Phase 1/2 Trial Far Exceed Bar of Embolden Primary Endpoint at 12 Months with Increased Skill Gains Over Time Pt:1 Pt:2 Pt:3 Pt:4 Pt:5 5 of 5 with functional gains 4 of 5 with CGI-I of ≤ 3, all durable - 4 of 5 with > 1 skills Gains in Hand Function & Communication Embolden registrational trial primary endpoint: • CGI-I of ≤ 3 • Gain of any 1 developmental milestone/skill at 12 months 12 Months Post NGN-401 Treatment 14 Skills 21 Skills 27 Skills 31 Skills 6 9 12 >12 Participants (N=5) >12 months Post NGN-401 Treatment Significant Skill Gains that Increase Over Time Minimum Threshold for Success is 7 of 20 Participants (35%) 6 months 9 months 12 months >12 months

8As of data cutoff date of October 30, 2025 Participants Dosed in 1H’25 Show Efficacy Prior to 12-month Timepoint Pt:6 Pt:7 Pt:8 Gains in Hand Function, Communication, Gross Motor 3 of 3 with functional gains 3 of 3 with CGI-I of ≤ 3 2 of 3 acquired skills Early efficacy observed at 6 months is consistent with previously dosed participants 6 Months Post NGN-401 Treatment Embolden registrational trial primary endpoint: • CGI-I of ≤ 3 • Gain of any 1 developmental milestone/skill at 12 months Minimum Threshold for Success is 7 of 20 Participants (35%)

Pt:7 6 months post-dose Pt:8 6 months post-dose Pt:4 15 months post-dose Pt:3 18 months post-dose Pt:2 18 months post-dose Pt:1 24 months post-dose Hand Function Gross Motor Function Communication 35 Total Skills Gained* 1 Skill 3 Skills 4 Skills 6 Skills 10 Skills 11 Skills Early Multidomain Improvements with Skill Gains Increasing Over Time that Remain Durable # o f S k il ls G a in e d P e r D o m a in 4 4 4 4331 1 2 3212 1 As of data cutoff date of October 30, 2025 *31 total skills acquired match Embolden developmental milestones/skills list; 35 total skills include previously reported skills from other validated scales * **

Pt:1 Gained 11 Developmental Milestones/Skills Across All Core Domains with Durability out to 24 Months 10 As of data cutoff date of October 30, 2025 *Not included in Embolden developmental milestones/skills list; previously reported skill from other validated scale Images are representative of skills Pt:1 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 9 12 15 18 24 Used a pincer grasp (either refined or modified) Taken a drink from a cup held without assistance Used a spoon/fork to eat without assistance Transferred an object from one hand to the other Heel-to-toe walking* Climbed up stairs without help Climbed down stairs without help Come to sitting New skill acquired since last update Followed a command without gesture Waves bye bye Pointed for something they want Fine Motor Gross Motor Communication Baseline: 7 Yrs Old Walking, ataxic gait, no ability to climb stairs Raking, no ability to hold objects Severe impairment, unable to follow commands, indicate wishes Post Treatment with NGN-401

Pt:2 Gained 10 Developmental Milestones/Skills Across All Core Domains with Durability out to 18 Months 11 As of data cutoff date of October 30, 2025 *Not included in Embolden developmental milestones/skills list; previously reported skills from other validated scales Images are representative of skills Pt:2 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 9 12 15 18 Reached for toy Used raking grasp to retrieve an object Finger fed Taken a drink from a cup held without assistance New skill acquired since last update Pulled to standing Bent down, touched floor, and recovered* Stepped off curb with help* Climbed up stairs with help New skill acquired since last update Followed a command without a gesture Used words with meaning Fine Motor Gross Motor Communication Baseline: 4 Yrs Old Impaired, ataxic, help to stand Severe impairment, unable to use hands Severe impairment, unable to follow commands, non-verbal Post Treatment with NGN-401

Fine Motor Gross Motor Pt:3 Gained 6 Developmental Milestones/Skills Across All Core Domains with Durability out to 18 Months 12 As of data cutoff date of October 30, 2025 Images are representative of skills Pt:3 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 9 12 15 18 Used a pincer grasp (either refined or modified) Finger fed Transferred an object from one hand to the other New skill acquired since last update Sat without support when placed Followed command without gesture New skill acquired since last update Followed command with gesture New skill acquired since last update Baseline: 6 Yrs Old Cannot sit, stand or walk independently Raking grasp Post Treatment with NGN-401 Severe Dysphagia Communication Cannot follow commands

Pt:4 Gained 4 Developmental Milestones/Skills Across 2 Core Domains with Durability out to 15 Months 13 Fine Motor Baseline: 7 Yrs Old Raking grasp, unable to hold objects Pt:4 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 9 12 15 Used a pincer grasp (either refined or modified) Used a spoon/fork to eat without assistance Taken a drink from a cup held without assistance New skill acquired since last update Followed a command without a gesture New skill acquired since last update Post Treatment with NGN-401 As of data cutoff date of October 30, 2025 Images are representative of skills Communication Unable to follow commands

Pt:7 Gained 1 Developmental Milestone/Skill at Early Timepoint 14 As of data cutoff date of October 30, 2025 Images are representative of skills Pt:7 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 Used a spoon/fork to eat without assistance Baseline: 6 Yrs Old Fine Motor Post Treatment with NGN-401 Could not use utensils

Pt:8 Gained 3 Developmental Milestones/Skills Across 2 Core Domains at Early Timepoint 15 As of data cutoff date of October 30, 2025 *Not included in Embolden developmental milestones/skills list; previously reported skill from other validated scale Images are representative of skills Pt:7 Developmental Milestones/Skills Post-NGN-401 Months Post-NGN-401 3 6 Bent down, touched floor, and recovered* Followed a command with a gesture Used words with meaning Baseline: 8 Yrs Old Gross Motor Communication Unable to follow commands, cannot use words with meaning Unable to bend at waist Post Treatment with NGN-401 Hi! How are you? Hey!.. Good!

Communication Can communicate needs & wants, and foster greater social connections Says words with meaning Follows daily routines, e.g., getting ready for school Communicates needs and wants; can ID colors Engages with friends and family; shows affection Starting/ improved communication with use of assisted device Autonomic Enhanced comfort and reduced distress Improvements in constipation Drinks clear liquids, eats solids for first time Absent aspiration pneumonia events Sleeps through the night Gross Motor/Ambulation Reduced physical burden for caregivers for activities of daily living Sits without support Walks up and down stairs unassisted Bends at waist and stands back up Bears more weight for ease of transfer Can get on/off furniture, out of bathtub, into car unassisted Fine Motor/Hand Function Less dependence on caregivers for basic needs Uses hands to self-feed, drink, play with toys, self-soothe Decreased to no stereotypies Uses utensils to self-feed 16 As of data cutoff date of October 30, 2025 NGN-401: Delivering What Matters to Families New Functional Abilities and Improvements Post-Treatment with NGN-401 Improvements in Key Domains Lead to: Multidomain improvements Participation in activities of daily living Improvements in health-related quality of life

“Sleep improved significantly as she is able to sleep all through the night without any issue.” “Her understanding has improved, especially with me when I ask her to do small tasks, then she will do it immediately almost every time…” “The other day she...ran a couple steps while out…” “She uses both hands to grab her blanket...She holds a banana and takes bites.” “She is paying attention, and even at school with decision- making…she knows what we are asking of her.” “She reacts to…[the] puppy. We have never seen that…nothing going on before, nothing was worth her attention. Now she is enjoying day-to- day.” “She is happier.” “I am grateful [NGN-401] has seemed to benefit [her] health and life…” “She is so happy all the time and calm.” “Before, she was really stuck a lot. Her gait has improved a lot.” “Walking and standing are so much better. Before she would fall all the time and now she doesn’t. She is so much stronger and rarely falls.” “She holds onto things longer…she is eating pieces of fruit using a fork, a new skill.” “She kissed me for the first time ever.” 17As of data cutoff date of October 30, 2025 Phase 1/2 Caregiver Testimonials Following Treatment with NGN-401 Highlight Improvements Important to Families

• All TEAEs related to NGN-401 have been Grade 1 (mild) or Grade 2 (moderate) in severity; the majority are known potential risks of AAV and have resolved or are resolving • Most participants experienced mild liver enzyme elevations • SAEs (Grade 2) related to abnormal nerve conduction findings occurred in Pt:5: - Areflexia and related elective inpatient diagnostic testing - Nerve conduction findings have returned to normal range - Unrelated to NGN-401, Pt:5 also experienced a leg fracture confounding her Month 12 gross motor assessment • No evidence of hemophagocytic lymphohistiocytosis (HLH) in any participant • Seizures have remained well controlled following NGN-401 • No intracerebroventricular (ICV) procedure-related AEs • No signs or symptoms indicative of MeCP2 overexpression 18 NGN-401 Remains Generally Well Tolerated at the1E15 vg Dose Level 1E15 vg Dose Total N=10 N Events TEAEs related to NGN-401 9 59 Serious TEAEs Unrelated to NGN-401 3 4 Serious TEAEs Related to NGN-401 1 2 As of data cutoff date of October 30, 2025 TEAE = Treatment emergent adverse event

Key Upcoming Anticipated Milestones 19 Provide regulatory update in 1H:25 regarding Embolden registrational trial Initiate Embolden registrational trial activities Expand clinical trial footprint, more than doubling presence in U.S. Initiate dosing in Embolden registrational trial Announce additional Phase 1/2 clinical data in 2H:25 Complete Embolden registrational trial enrollment in 3-6 months Announce additional Phase 1/2 clinical data in 2026 Cash Runway Expected to Fund Operations Through 1Q’28 Rett Syndrome (NGN-401)

Embolden Registrational Trial Overview 20

Key Elements of Embolden Registrational Clinical Trial of NGN-401 for Rett Syndrome 21 Design: Single-arm, open- label, baseline-controlled trial evaluating NGN-401 at 1E15 vg dose Sample Size: 20 females with Classic Rett syndrome 13 Clinical Sites Age Range: ≥ 3 years First Participant Dosed in Q4’25; Expect to Complete Enrollment in 3-6 months Key Secondary Endpoints: • CGI-I score of ≤ 2 • Gain of at least 2 developmental milestones/skills from Embolden list of 28 skills captured through standardized video recordings and rated by independent, blinded central raters Immunosuppression: Corticosteroids for 91 days, followed by taper Primary Endpoint: Responder- based composite endpoint • Responder defined as attaining: - CGI-I of ≤ 3 and - Gain of any one developmental milestone/skill from Embolden list of 28 skills captured through standardized video recordings and rated by independent, blinded central raters • 35% response rate, or 7 of 20 participants, needed for success • Primary analysis at 12 months

28 Developmental Milestones/Skills from Rett Syndrome Natural History Study Being Evaluated in Embolden Trial 22 *U.S. Natural History Study of Rett Syndrome (RNHS), sponsored by NIH, Clinicaltrials.gov identifier: NCT02738281. Accessed from International Rett Syndrome Foundation (IRSF); based on analysis of >400 subjects. Fine Motor/Hand Function • Reached for toy • Taken a drink from a cup held without assistance • Used raking grasp to retrieve an object • Used a pincer grasp (either refined or modified) • Finger fed • Transferred an object from one hand to the other • Used a spoon/fork to eat without assistance • Sat with support when placed • Sat without support when placed • Come to sitting • Pulled to standing • Stood while holding on • Stood independently • Cruised around furniture or holding on to someone • Walked independently • Climbed up stairs with help • Climbed up stairs without help • Climbed down stairs with help • Climbed down stairs without help • Ran 10 feet without falling • Responded to familiar names/words • Followed a command with a gesture • Followed a command without a gesture • Pointed for something they want • Waved bye-bye • Babbled • Used words with meaning • Spoken in phrases (2 words or more with meaning) Skills Chosen Based on Meaningfulness to Caregivers and Rarely Learned/Relearned > 3 Years* Gross Motor/Ambulation Communication