Rett gains: Neurogene (NASDAQ: NGNE) shows durable NGN-401 milestone data
Filing Impact
Filing Sentiment
Form Type
8-K
Rhea-AI Filing Summary
Neurogene Inc. reported updated, positive Phase 1/2 results for NGN-401, its investigational gene therapy for females with Rett syndrome. Across 10 participants, 47 developmental milestones were gained, averaging 4.7 per participant, and 100% improved on the Clinical Global Impression-Improvement scale and gained at least one milestone.
Milestones accumulated in a progressive, developmentally ordered sequence with rapid onset, as median time to first clinical improvement was two months and gains deepened by 95% from 6 to 12 months and 147% from 6 to at least 12 months. No plateau or loss of milestones was seen through up to 30 months of follow-up, and NGN-401 at the 1E15 vg dose remained generally well-tolerated, with only mild or moderate treatment-related adverse events and no new treatment-related serious adverse events. Neurogene has completed dosing of 25 participants in the Embolden registrational trial, which uses a composite responder endpoint, and expects topline data in the second half of 2027.
Positive
- Robust efficacy signal: In the Phase 1/2 Rett study, 100% of 10 participants improved on CGI-I and gained ≥1 developmental milestone, with 47 total milestones (4.7 per participant) and deepening gains through 30 months.
- Durable, multidomain benefit versus natural history: Milestones accrued in a developmentally ordered sequence across motor, hand function and communication domains, contrasting with natural history data where post‑regression gains after age three are exceedingly rare.
- Encouraging safety profile: NGN-401 at the 1E15 vg dose remained generally well-tolerated, with all treatment-related adverse events Grade 1–2, no new treatment-related serious adverse events, and no dose-limiting toxicities reported.
- Registrational program fully enrolled: Dosing is complete in the 25-participant Embolden registrational trial, which uses a composite clinical responder endpoint and is expected to deliver topline data in the second half of 2027.
Negative
- None.
Insights
Early NGN-401 data show durable, multidomain Rett improvements with a clean safety profile.
Neurogene presented long-term Phase 1/2 results for NGN-401 in Rett syndrome. All 10 participants improved on CGI-I and gained at least one developmental milestone, totaling 47 milestones, with a median two-month onset and continued accumulation out to 30 months.
The multidomain gains in hand function, gross motor skills and communication, plus improvements on validated scales like RSGMS and RSHFS, compare favorably with natural history where milestone gains after age three are rare. Safety at the 1E15 vg dose appears manageable, with only Grade 1–2 treatment-related events and no new treatment-related serious events.
The Embolden registrational trial is fully dosed with 25 participants, targeting a 33% responder rate at 12 months; Phase 1/2 data show an 80% responder rate on a similar composite definition. Topline Embolden data are anticipated in 2H 2027, which will be pivotal for any future Biologics License Application and potential commercialization.
8-K Event Classification
3 items: 7.01, 8.01, 9.01
3 items
Item 7.01
Regulation FD Disclosure
Disclosure
Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.
Item 8.01
Other Events
Other
Voluntary disclosure of events the company deems important to shareholders but not covered by other items.
Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, and exhibit attachments filed with this report.
Key Figures
Participants in Phase 1/2: 10 participants
Total developmental milestones gained: 47 milestones
Average milestones per participant: 4.7 milestones
+5 more
8 metrics
Participants in Phase 1/2
10 participants
Females with Rett syndrome in NGN-401 Phase 1/2 trial
Total developmental milestones gained
47 milestones
Across 10 NGN-401-treated participants as of June 16, 2026
Average milestones per participant
4.7 milestones
NGN-401 Phase 1/2 Rett study
Responder rate on composite endpoint
80%
8 of 10 Phase 1/2 participants met Embolden-like responder definition at 12 months
Median time to first clinical improvement
2 months
Time to first response post NGN-401 treatment in Phase 1/2
Dose level
1E15 vg
NGN-401 vector genome dose in Phase 1/2 and Embolden
Embolden participants dosed
25 participants
Total dosed in registrational NGN-401 Embolden trial
Minimum success threshold in Embolden
33% response rate
Pre-specified 8 of 24 responder bar at 12 months
Key Terms
Clinical Global Impression-Improvement (CGI-I), Rett Syndrome Gross Motor Scale (RSGMS), Rett Syndrome Hand Function Scale (RSHFS), serious adverse event (SAE), +2 more
6 terms
Clinical Global Impression-Improvement (CGI-I) clinical
"100% of participants improved on the Clinical Global Impression-Improvement (CGI-I) scale"
A clinician global impression–improvement (CGI‑I) is a short, doctor-rated scale used in clinical trials to judge how much a patient’s overall condition has changed since starting treatment, usually scored from “much better” to “much worse.” Investors care because CGI‑I captures a physician’s broad, real-world judgment of benefit or harm beyond lab numbers, helping assess whether a drug produces noticeable clinical improvement that could drive regulatory approval and market uptake — think of it as a teacher’s quick overall grade of a student’s progress.
Rett Syndrome Gross Motor Scale (RSGMS) clinical
"Participants experienced clinically meaningful improvements across additional validated Rett syndrome scales, including the Rett Syndrome Gross Motor Scale (RSGMS)"
A standardized clinical scale that measures core movement abilities—like sitting, standing, walking and basic transfers—in people with Rett syndrome, producing a score that tracks changes over time. Investors care because the scale is often used as an objective endpoint in drug and device trials; meaningful score improvements can support regulatory approval, drive market value and influence whether a treatment is seen as effective, much like a report card showing progress.
Rett Syndrome Hand Function Scale (RSHFS) clinical
"Participants experienced clinically meaningful improvements across additional validated Rett syndrome scales, including the Rett Syndrome Hand Function Scale (RSHFS)"
A Rett Syndrome Hand Function Scale (RSHFS) is a standardized clinical measurement that rates how well people with Rett syndrome can use their hands for everyday tasks, from grasping objects to releasing them. Investors pay attention because RSHFS scores are used in clinical trials to show whether a therapy improves motor ability; like a ruler for progress, better scores can support regulatory approval, market potential and reimbursement arguments.
serious adverse event (SAE) clinical
"Dosing complete in the Embolden registrational trial with no treatment-related SAEs or DLTs"
A serious adverse event (SAE) is a harmful medical outcome tied to a drug or treatment that causes death, is life‑threatening, requires or prolongs hospitalization, leads to lasting disability or birth defects, or otherwise needs urgent medical attention. For investors, SAEs act like emergency warning lights for a clinical program or product: they can pause trials, trigger regulatory scrutiny, delay approvals, and cause sharp stock moves because they affect a treatment’s safety profile and commercial prospects.
dose limiting toxicity (DLT) clinical
"no treatment-related SAEs or DLTs as of the data cutoff date of June 16, 2026"
Biologics License Application (BLA) regulatory
"support clear path to potential BLA"
A biologics license application (BLA) is a formal request to a government agency seeking approval to sell a biological medicine, such as vaccines or gene therapies, in the market. It is similar to a detailed report that proves the product is safe, effective, and manufactured properly. For investors, a BLA signifies a critical step toward commercial availability, often impacting a company's valuation and market prospects.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 OR 15(d) of The Securities Exchange Act of 1934
Date of Report (date of earliest event reported): June 29, 2026
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
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| Item 7.01 | Regulation FD Disclosure | ||||
On June 29, 2026, Neurogene Inc. (the “Company”) issued a press release announcing positive, updated clinical data from its Phase 1/2 trial evaluating NGN-401 gene therapy for the treatment of females with Rett syndrome. The Company will host a conference call and webcast today, Monday, June 29, 2026 at 8:00 a.m. Eastern Time, to discuss the data results A copy of the press release announcing such results is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
The information in this Item 7.01 and Exhibit 99.1 attached hereto are being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), or otherwise subject to the liabilities of that section, nor shall such information or Exhibit 99.1 be deemed incorporated by reference into any filing under the Exchange Act or the Securities Act of 1933, as amended, except as expressly set forth by specific reference to such filing.
| Item 8.01 | Other Events | ||||
On June 29, 2026, the Company also made publicly available a presentation announcing positive, updated clinical data from its Phase 1/2 trial evaluating NGN-401gene therapy for the treatment of females with Rett syndrome. A copy of the presentation is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
| Item 9.01 | Financial Statements and Exhibits. | ||||
(d) Exhibits
Exhibit Number | Description | |||||||
| 99.1 | Press Release dated June 29, 2026 | |||||||
| 99.2 | Corporate Presentation dated June 29, 2026 | |||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| NEUROGENE INC. | ||||||||
| Date: June 29, 2026 | By: | /s/ Christine Mikail | ||||||
| Name: Christine Mikail | ||||||||
| Title: President, Chief Financial Officer | ||||||||
Neurogene Reports Positive Long-term Clinical Data from Phase 1/2 Trial of NGN-401 Gene Therapy for Rett Syndrome
47 total developmental milestones gained across 10 participants, with durable treatment effect and no plateau or milestone loss through 30 months of follow-up
100% of participants improved in CGI-I score and gained ≥1 developmental milestone, with an average of 4.7 milestones per participant, and all gaining ≥1 developmental milestone in the past 12 months
Developmental milestones were gained in a progressive, stepwise sequence, suggesting a restart of development post-treatment
NGN-401 at the 1E15 vg dose remains generally well-tolerated (N=35) as of data cutoff date of June 16, 2026
Dosing complete in the Embolden™ registrational trial with no treatment-related SAEs or DLTs as of data cutoff date of June 16, 2026, with topline data anticipated in 2H 2027
Company to host investor/analyst webcast today at 8:00 a.m. ET
NEW YORK – June 29, 2026 – Neurogene Inc. (Nasdaq: NGNE), a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases, today announced updated, positive data from its Phase 1/2 clinical trial evaluating NGN-401 gene therapy for the treatment of females with Rett syndrome.
Across 10 participants, 47 total developmental milestones were gained (average of 4.7 per participant), with both pediatric and adolescent/adult participants demonstrating clinical response and continued, progressive improvements through 30 months of follow-up, with no plateau or loss of milestones observed.
“We are encouraged by the long-term Phase 1/2 data across a broad age range and wide spectrum of disease severity, which we believe demonstrate that NGN-401 is driving gain of durable and clinically meaningful developmental milestones, and continued improvements were observed through 30 months of follow-up,” said Rachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene. “Importantly, the gains of developmental milestones are not isolated events – they build over time with participants acquiring multiple milestones across the core Rett syndrome functional domains of hand function, gross motor function and communication. This multidomain progression is not observed in the natural history of Rett syndrome, and we believe supports NGN-401’s differentiated profile, driven by its purposeful design and targeted delivery.”
“In typical development, children gain milestones in an organized, cumulative sequence, with each milestone building on the last; in Rett syndrome, that process is stopped by regression,” said Bernhard Suter, M.D., Medical Director of the Blue Bird Circle Rett Center at Texas Children’s Hospital, Associate Professor of Pediatrics and Neurology at Baylor College of Medicine, and principal investigator in the NGN-401 Phase 1/2 clinical trial. “These results show that the participants treated with NGN-401 are now gaining developmental milestones in a manner that suggests restarting developmental progression, something not observed in the natural history of the disease. As a result, participants are gaining greater independence and are more engaged in day-to-day activities with their families.”
Phase 1/2 Clinical Data as of Data Cutoff Date of June 16, 2026 (N=10, follow-up 12-30 months post-treatment)
Efficacy Data
•100% of participants improved on the Clinical Global Impression-Improvement (CGI-I) scale and gained ≥1 developmental milestone, consistent with the composite endpoint used to evaluate efficacy in the Embolden™ registrational trial
•47 total developmental milestones were gained across participants, averaging 4.7 milestones per participant
•All participants gained ≥1 developmental milestone in the past 12 months
•Participants gained milestones in a progressive, developmentally ordered stepwise sequence, suggesting a restart of developmental progression
•Rapid onset of treatment effect, with median time to first clinical improvement of 2 months post-treatment
•Milestone gains deepened over time, increasing by 95% from 6 to 12 months and 147% from 6 to ≥12 months
•7 of 10 participants gained ≥2 developmental milestones and demonstrated improvements across ≥2 core Rett syndrome domains; both of these improvements were observed in pediatric and adolescent/adult participants
•Continued improvement through 30 months post-dose, with no plateau observed and no milestones lost
•Participants experienced clinically meaningful improvements across additional validated Rett syndrome scales, including the Rett Syndrome Gross Motor Scale (RSGMS) and Rett Syndrome Hand Function Scale (RSHFS) (p<0.001)
Safety Data
•NGN-401 at the 1E15 vg dose remains generally well-tolerated
•All treatment-related adverse events have been mild (Grade 1) or moderate (Grade 2) in severity, and the majority are known potential risks of AAV and have resolved or are resolving
•No new treatment-related SAEs reported since last data cutoff date in October 2025
•NGN-401 continues to be generally well-tolerated in Embolden, with no treatment-related SAEs or DLTs as of the data cutoff date of June 16, 2026
Neurogene management and Dr. Suter will discuss these results during a live webcast today, June 29, 2026, at 8:00 a.m. ET. The live webcast presentation will be accessible from the Investor Relations section of the Company’s website under Events, where a replay of the event will also be available for a limited time.
These data, as well as a poster presentation on the Rett Syndrome Natural History Study analysis to assess treatment effect in the Embolden trial, will also be presented at the 2026 International Rett Syndrome Foundation (IRSF) Rett Syndrome Scientific Meeting taking place in Prior Lake, Minn., June 29 – July 1, 2026.
About Neurogene
Neurogene (NASDAQ: NGNE) is a clinical-stage biotechnology company focused on developing life-changing genetic medicines for people and their families impacted by devastating neurological diseases. The Company is using a biology-first approach paired with optimized delivery to develop purpose-built genetic medicines, including programs powered by its novel and proprietary EXACT™ transgene regulation technology. Neurogene is advancing its lead gene therapy program, NGN-401, as a potential best-in-class, one-time treatment for Rett syndrome. For more information, visit neurogene.com or follow on LinkedIn.
About NGN-401
NGN-401 is an investigational AAV9 gene therapy in late-stage clinical development as a potential best-in-class, one-time treatment for Rett syndrome. It is the only clinical candidate to deliver the full-length human MECP2 gene and includes Neurogene’s EXACT™ transgene regulation technology, which is designed to deliver consistent, tightly controlled MeCP2 protein expression on a cell-by-cell basis. NGN-401 is delivered through intracerebroventricular administration to achieve the broadest targeting directly to the brain and nervous system based on nonclinical biodistribution data. NGN-401 is being evaluated in the Embolden™ registrational clinical trial. Data from the Phase 1/2 trial (as of June 16, 2026) have shown that participants experienced multidomain, durable gains with continued developmental milestone acquisition observed over time, and NGN-401 at the 1E15 vg dose has been generally well-tolerated. NGN-401 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations and selection for the START Pilot Program from the U.S. Food and Drug Administration, Advanced Therapy Medicinal Product, Orphan and Priority Medicines designations from the European Medicines Agency and Innovative Licensing and Application Pathway designation from the United Kingdom Medicines and Healthcare products Regulatory Agency.
Cautionary Note Regarding Forward-Looking Statements
Statements in this press release are made as of the date of this press release. Neurogene does not undertake any obligation to make any updates to these statements to reflect events that occur or
circumstances that arise after the date of this press release, except as may be required under applicable U.S. securities law.
Statements in this press release which are not historical in nature are intended to be, and hereby are identified as, 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 financial condition, or otherwise, based on current expectations and beliefs of the management of Neurogene, as well as assumptions made by, and information currently available to, management of Neurogene, including, but not limited to, statements regarding: the therapeutic potential and utility, efficacy and clinical benefits of NGN-401; the safety and tolerability profile of NGN-401; the applicability of reported results from the NGN-401 Phase 1/2 clinical trial to participants in the Embolden registrational trial; the potential for NGN-401 to be a best-in-class gene therapy for Rett syndrome; trial designs and clinical development plans for the Company’s Embolden registrational clinical trial of NGN-401 for Rett syndrome; the response rate, expected durability and deepening of clinical data results from our NGN-401 clinical trial; expected timing and availability for release of topline data from our Embolden clinical trial of NGN-401 for Rett syndrome; the potential for success of the Embolden trial; the clinical benefit of delivering NGN-401 via intracerebroventricular administration; and expected future interactions with or positions of the FDA, including the timing and outcome of any such interactions and anticipated benefits of any regulatory designation for NGN-401, including the FDA’s Breakthrough Therapy designation, Rare Pediatric Disease designation, RMAT designation and participation in the FDA’s START program. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” “on track,” and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Forward-looking statements are based on current beliefs and assumptions that are subject to risks, uncertainties and assumptions that are difficult to predict with regard to timing, extent, likelihood, and degree of occurrence, which could cause actual results to differ materially from anticipated results and many of which are outside of Neurogene’s control. Such risks, uncertainties and assumptions include, among other things, the risks and uncertainties identified under the heading "Risk Factors" included in Neurogene’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, filed with the Securities and Exchange Commission (“SEC”) on May 12, 2026, and other filings that the Company has made and may make with the SEC in the future. Nothing in this communication should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that the contemplated results of any such forward-looking statements will be achieved. Forward-looking statements in this communication speak only as of the day they are made and are qualified in their entirety by reference to the cautionary statements herein. Except as required by applicable law, Neurogene undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.
Media Contact:
Mike Devine
Executive Director, Corporate Communications
michael.devine@neurogene.com
Mike Devine
Executive Director, Corporate Communications
michael.devine@neurogene.com
Investor Contact:
Lina Li
Lina Li
Executive Director, Investor Relations
lina.li@neurogene.com
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Restarting Development in Rett Syndrome NGN-401 for Rett Syndrome Phase 1/2 Update June 29, 2026
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 financial condition, or otherwise, based on current expectations and beliefs of the management of Neurogene, as well as assumptions made by, and information currently available to, management of Neurogene, including, but not limited to, statements regarding: the therapeutic potential and utility, efficacy and clinical benefits of its programs, including NGN-401; the potential for commercial approval of NGN-401 and the speed with which any such approval might be obtained; market opportunities for Neurogene's product candidates, including the estimated prevalence of Rett syndrome and expected levels of demand for NGN-401; the safety and tolerability profile of NGN-401; the applicability of reported results from the NGN-401 Phase 1/2 clinical trial to participants in the EmboldenTM registrational clinical trial of NGN-401; the likelihood of gaining approval of NGN-401 from the U.S. Food and Drug Administration (FDA) or any other regulator; trial designs and clinical development plans for the Embolden trial; the response rate, expected durability and deepening of clinical data results from the NGN-401 clinical trials; expected timing and availability of topline results from the Embolden registrational trial; the timing of a potential submission of a Biologics License Application (BLA) to the FDA based on the results of the Embolden trial and the ability of the Embolden registrational trial to support planned BLA submissions; the potential for NGN-401 to be a best-in-class or first-in-class gene therapy for Rett syndrome; the potential for success of the Embolden registrational clinical trial of NGN-401 for Rett Syndrome; the potential real-world impact of NGN-401; and Neurogene's cash runway, including the time period over which existing cash resources may be sufficient to fund the Company’s operations. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation, the risk factors included in the Company’s most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission, as well as risk factors associated with companies, such as Neurogene, that operate in the biopharma industry. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Neurogene’s control) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. Nothing in this communication should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that the contemplated results of any such forward-looking statements will be achieved. Forward-looking statements in this communication speak only as of the day they are made and are qualified in their entirety by reference to the cautionary statements herein. Except as required by applicable law, Neurogene undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. Industry and Market Data Certain information contained in this Presentation relates to or is based on studies, publications, surveys and Neurogene’s own internal estimates and research. In this Presentation, Neurogene relies on, and refers to, publicly available information and statistics regarding market participants in the sector in which Neurogene competes and other industry data. Any comparison of Neurogene to any other entity assumes the reliability of the information available to Neurogene. Neurogene obtained this information and statistics from third-party sources, including reports by market research firms and company filings. In addition, all of the market data included in this Presentation involve a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while Neurogene believes its internal research is reliable, such research has not been verified by any independent source and Neurogene has not independently verified the information. Trademarks This Presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this Presentation may be listed without the TM, SM © or ® symbols, but Neurogene will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights. Disclaimer 2
Today’s Speakers Rachel McMinn, Ph.D. Founder and Chief Executive Officer, Neurogene Julie Jordan, M.D. Chief Medical 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 3
Introduction Rachel McMinn, Ph.D. Founder and Chief Executive Officer, Neurogene
5 No Approved Disease-Modifying Therapies for Rett Syndrome NGN-401 Gene Therapy Targets Root Cause The Unmet Need • Developmental regression begins at 6–18 months • Previously acquired milestones are lost • Development plateaus at age ~3 • Milestone acquisition is rare post- regression • Patients require lifelong, 24/7 care • No approved therapies to address underlying cause, current options limited to symptom management The Market 15,000–20,000 patients — US, EU & UK 1 in 10,000 female births | ~175–180 new cases/yr (U.S.) U.S. Real-World Data – ~6,000 Diagnosed 52% Pediatric 48% Adult All living with profound unmet need The Opportunity • The Rett syndrome community is increasingly seeking therapies that can deliver meaningful and durable functional improvements • Patient population across all age groups creates the potential for broad adoption of transformative therapies Rett syndrome is a lifelong disease. The opportunity spans every age group and remains entirely unaddressed at the genetic level NGN-401 is designed to deliver functional MECP2 — targeting the root cause with the potential to restart typical developmental progression Major market prevalence based on internal estimates; U.S. prevalence estimate based on published incidence rates; Laurvick CL, et al. J Pediatr 2006;148(3):347–352. WW incidence estimate based on published incidence rates; Pini G, et al. Orphanet Journal of Rare Diseases (2016) 11:132. Cheng et al., BMC Neurology, 2023 (IQVIA Claims, N=5,940)
6 NGN-401 Phase 1/2 Trial Update: Clinically Meaningful, Durable Improvement Across Key Rett Syndrome Domains, Deepens Over Time 30 months of continued improvement post-dose no plateau observed – no milestones lost Restarted Development Milestones acquired in a developmentally ordered stepwise sequence — suggesting a restart of developmental trajectory Real-World Impact ↑ Gains across daily living ↑ Increased independence ↓ Reduced caregiver burden Embolden Registrational Trial: All 25 participants successfully dosed – overenrolled based on demand from the Rett syndrome community Topline Results Expected 2H 2027 As of data cutoff date of June 16, 2026 CGI-I = Clinician Global Impression-Improvement; DLT = Dose limiting toxicity; SAE = Serious adverse event 100% of Phase 1/2 participants (N=10) gained ≥1 developmental milestone and improved on CGI-I 80% met Embolden composite responder definition at 12 months (8 of 10) 47 total milestones gained 4.7 average milestones per participant Safety: 1E15 vg dose generally well-tolerated No Treatment-Related SAEs or DLTs in Embolden
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 response, with median first improvement observed at 2 months post-treatment, followed by early emergence of developmental milestones Durable, deepening treatment effect — developmental milestones continued to accumulate over time – Developmental milestone gains increased by 95% from 6 to 12 months and 147% from 6 to ≥12 months – Durable treatment effect, with no plateau and no loss of milestones in any participant through 30 months of follow-up Broad, multidomain functional impact demonstrated consistently across core disease domains, regardless of age, disease severity or genotype – 7 of 10 participants gained ≥2 developmental milestones – 7 of 10 participants gained milestones in ≥2 core Rett syndrome domains – Durable, multidomain gains drive increased independence in activities of daily living, reduced caregiver burden and enhanced social engagement Robust, clinically meaningful responses at 6 months, 12 months and beyond support clear path to potential BLA – Average milestones per participant showed robust response: 1.9 at 6 months, 3.7 at 12 months, deepening to 4.7 at ≥12 months – Embolden overenrolled by 25% (N=25), across broad age range, strengthening statistical power and potential for broader label – Phase 1/2 data exceeds Embolden’s minimum success threshold by 2.4x No new treatment-related SAEs and no DLTs observed in any participants, with all participants ≥12 months of follow-up 7As of data cutoff date of June 16, 2026
Phase 1/2 Data Update
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- arm pivotal trial (13 US sites) • Evaluates efficacy, safety & tolerability of one-time ICV-delivered NGN-401 Population Eligibility Criteria • Females with genetically confirmed classic Rett syndrome • Post-regression (≥6 months since last skill loss); CGI-S 4–6 at screening Key Clinical Assessments • CGI-I and CGI-S with Rett-specific anchors • Developmental milestones • RSGMS and RSHFS Phase 1/2 Trial 1E15 vg Dosing complete (N=10) Ages 4-10, >11 years old Embolden Registrational Trial 1E15 vg Dosing complete (N=25) Primary efficacy population (N=24) Ages >3 years old 35 CGI-I ≤3 + EMBOLDEN PRIMARY ENDPOINT · RESPONDER REQUIRES BOTH AT 12 MONTHS Gain from baseline of ≥1 developmental milestone participants dosed at the 1E15 vg dose Total NGN-401 safety database — Phase 1/2 + Embolden CGI-S = Clinical Global Impression–Severity; ICV = intracerebroventricular; RSGMS = Rett Syndrome Gross Motor Scale; RSHFS = Rett Syndrome Hand Function Scale; vg = vector genomes 9
28 Clearly Defined Developmental Milestones: Derived from Natural History Study & Key Component of Primary Endpoint Fine Motor/ Hand Function Gross Motor/Ambulation Communication 1.2% - 3% 0.3 – 6.6% 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 (i.e., walk with support) 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) 10
Rigorous Embolden Milestone Criteria Evaluation Applied to Phase 1/2 Data Baseline Assessment Post-Treatment Evidence Milestones documented in caregiver and CGI videos Evaluation Methods Gain from baseline scored by independent central rating using prespecified Embolden criteria Utilizing the same standardized assessment criteria enables the Phase 1/2 developmental milestone data to be comparable to the Embolden definition 11 Milestones confirmed absent at baseline — from medical history, caregiver report and video
12 Evaluating the Impact of NGN-401 Across Full Spectrum of Disease Severity and Ages As of data cutoff date of June 16, 2026 Pt = Participant Pediatric Cohort (N=8) Adult / Adolescent 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 (Years) 7 4 6 7 6 4 6 8 18 14 Baseline CGI-S Score 4 Moderately Ill 5 Markedly Ill 5 Markedly Ill 5 Markedly Ill 6 Severely Ill 5 Markedly Ill 4 Moderately Ill 4 Moderately Ill 4 Moderately Ill 5 Markedly Ill Genetic Variant Severity Mild Severe Severe Severe Severe Moderate Mild-Moderate Mild-Moderate Severe Severe Follow-up Period (Months) 30 24 24 24 18 12 12 12 15 12 Baseline Characteristics of the Phase 1/2 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 Clinical Trial
14 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 6-18 months, followed by loss of previously acquired milestones during regression and subsequent developmental plateau at ~3 years Hallmark features: Loss of expressive and receptive communication Loss of purposeful hand function with repetitive movements Gait abnormalities and mobility challenges Seizures, breathing irregularities, severe constipation Rett Syndrome: Rare, Debilitating, Progressive, Neurodevelopmental Disorder
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Restarting Developmental Progression is the Goal for a One-time Gene Therapy Frankenburg et al., Denver II Technical Manual May D, et al. J Neurodev Disord. 2024;16(1):42 Graphs for illustrative purposes only Typical Development Rett Syndrome Restarted Developmental Progression Birth Birth Birth Regression (age ~1-3 years) NGN-401 Organized, cumulative acquisition of developmental milestones Milestones lost in regression, exceedingly rare to gain milestones post-regression NGN-401 has potential to restart the typical developmental progression Developmental milestones build over time across domains in a coordinated and integrated manner Simple developmental milestones are gained and then lost during regression, leading to 24/7, lifelong care Restart of developmental trajectory across multiple domains can lead to increased independence and reduced caregiver burden Years Years Years 16
Pt:1 Developmental Milestones Gained in Ordered, Developmental Progression Baseline NGN-401 Restarted Developmental Progression 12 300 Taken a drink from a cup held without assistance Used a pincer grasp Used a spoon/fork to eat without assistance Transferred an object from one hand to the other Climbed up stairs without help Climbed down stairs without help Heel-to-toe walking Come to sitting Followed a command without a gesture Pointed for something they want Waved bye bye Fine motor Raking, no ability to hold objects Gross motor Walking, ataxic gait, no ability to climb stairs Communication Severe impairment, unable to follow commands or indicate wishes Age: 7 Months Post NGN-401 InitiationAs of data cutoff date of June 16, 2026 17
Pt:1 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones As of data cutoff date of June 16, 2026 Moves more independently at home Gets in/out of bathtub, on/off furniture & up/down stairs, without help Shops with Mom, carrying the basket with both hands Joins family outings Navigates the world independently Climbs in & out of the car & shuts the door herself Follows multi- step directions Carries her backpack, takes the stairs, & closes the door – following directions in 2 languages Follows instructions to pick the right colors Uses hands to select correct colors when asked Greets family in context Waves hello to greet people on video calls Enhanced Independence and Reduced Caregiver Burden Post-NGN-401 18 Impaired hand use, Raking, no ability to hold objects At baseline (Age 7): Gross motor impairment, ataxic, unable to climb stairs Severe communication impairment, unable to follow commands
Pt:2 Developmental Milestones Gained in Ordered, Developmental Progression Months Post NGN-401 InitiationAs of data cutoff date of June 16, 2026 12 240 Baseline NGN-401 Restarted Developmental Progression Fine motor Severe impairment, unable to use hands Gross motor Impaired, ataxic, help to stand Communication Severe impairment, unable to follow commands, non- verbal Age: 4 Reached for toy Taken a drink from a cup held without assistance Finger fed Used raking grasp to retrieve an object Pulled to standing Stepped off curb with help Bent down, touched floor, and recovered Come to sitting Followed a command without a gesture Responded to familiar names/words Climbed up stairs with help Used words with meaning “Mama” 19
Pt:2 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones As of data cutoff date of June 16, 2026 Self-feeds and holds own drinks Bends down to pick up toys & blankets without help Turns when called, says words with meaning & follows instructions Less caregiver assistance at mealtime Moves more independently with less supervision Connects with family Enhanced Independence and Reduced Caregiver Burden Post-NGN-401 20 Gross motor impairment, ataxic, needs help to stand Severe impairment, unable to use hands At baseline (Age 4): Severe communication impairment, unable to follow commands
Pt:3 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones As of data cutoff date of June 16, 2026 Requires less physical support to stand and move Follows directions in two languages and chooses the correct puzzle piece Self-feeds using a pincer grasp Uses both hands to follow instructions Stands and moves with less help Feeds herself Enhanced Independence and Reduced Caregiver Burden Post-NGN-401 21 Impaired hand use, raking grasp Severe gross motor impairment, cannot sit/stand/walk independently Severe communication impairment, unable to follow commands At baseline (Age 6):
Pt:4 Multidomain Improvements Led to New Abilities Beyond Developmental Milestones As of data cutoff date of June 16, 2026 Turns the lights on and off herself, taking charge of her surroundings Feeds herself with a regular spoon — easier, more independent mealtimes Eats on her own Pushes herself up from lying down, moving through her day with more freedom Sits up by herself Controls her space Catches a ball with both hands and plays back- and-forth with others Plays with Mom with both hands Plays with balloons at a family celebration, demonstrating her new hand use Joins in family play Tells her caregiver what she wants more reliably using her communication device Makes her own needs known Shares more moments with family, including giving “high fives” Connects with family Enhanced Independence and Reduced Caregiver Burden Post-NGN-401 22 Severe gross motor impairment, cannot sit/stand/walk independently Impaired hand use, raking grasp Severe communication impairment, unable to follow commands At baseline (Age 7):
Thank you to all participants and their families and caregivers!
Phase 1/2 Data Update Julie Jordan, M.D. Chief Medical Officer
Rapid Response Observed Post NGN-401 that Deepened Over Time 25 0 3 6 9 12 15 18 24 30 36 Months post-NGN-401 Pt:1 Pt:2 Pt:3 Pt:4 Pt:5 Pt:6 Pt:7 Pt:8 Pt:9 Pt:10 Response Over Time in the Phase 1/2 Trial Total developmental milestones 47 4.7 Average milestones per participant CGI-I ≤ 3 + ≥ 1 Developmental Milestone from Embolden List CGI-I response First developmental milestone 2 months Median time to first response As of data cutoff date of June 16, 2026 Four previously disclosed developmental milestones included are derived from other validated scales and are not included in the Embolden list: Pt. 1 - Heel to toe walking – 9 mos.; Pt. 2 – Bent down, touched floor and recovered – 9 mos.; Stepped off curb with help – 12 mos.; Pt. 8 – Bent down, touched floor and recovered – 3 mos.
Developmental Milestones Increased by Domain Over Time Post-NGN-401 Treatment 26 NGN-401 Drove Durable Accumulation of Multidomain Milestones Across Core Domains That Matter Most to Caregivers 3 4 6 10 14 2 6 7 13 15 4 9 14 14 18 3 Mos. 6 Mos. 9 Mos. 12 Mos. ≥12 Mos.* 19 9 27 37 # o f D ev el o p m en ta l M ile st o n es A ch ie ve d Fine Motor/Hand Function Expressive & Receptive Communication Gross Motor/Ambulation 47 As of data cutoff date of June 16, 2026 Four previously disclosed developmental milestones included are derived from other validated scales and are not included in the Embolden list: Pt. 1 – Heel to toe walking – 9 mos.; Pt. 2 – Bent down, touched floor and recovered – 9 mos.; Stepped off curb with help – 12 mos.; Pt. 8 – Bent down, touched floor and recovered – 3 mos. *N=6 participants with data > 12 mos. post-NGN-401 and N=4 participants with 12-month data N = 10 N = 10 N = 10 N = 10 N = 10 0.9 average milestones / participant 1.9 average milestones / participant 2.7 average milestones / participant 3.7 average milestones / participant 4.7 average milestones / participant • Milestones increased by 95% from 6 to 12 months and 147% from 6 to ≥12 months post-NGN-401 • 7 of 10 participants gained: • ≥2 milestones • Milestones in ≥2 core domains
Connecting with the people around them — understanding others, and making their wants and feelings known Communication Spoken in phrases Used words with meaning Pointed for something they want Waved bye-bye Responded to familiar names/words Participating in self care and increasing independence — playing games with family, feeding themselves, drinking from a cup Fine Motor / Hand Function Used a spoon/fork without assistance Taken a drink from a cup held without assistance Finger fed Used a pincer grasp (either refined or modified) Used raking grasp to retrieve an object Reached for toy Transferred an object from one hand to the other Moving more independently — sitting up, standing, and walking — easing everyday care for families Gross Motor / Ambulation Climbed up stairs without help Climbed down stairs without help Climbed up stairs with help Cruised / walk with support Pulled to standing Come to sitting Sat without support when placed 27 Milestones Gained from Embolden List Across 10 Phase 1/2 Participants Treated with NGN-401 As of data cutoff date of June 16, 2026 7/7 Followed a command with a gesture Followed a command without a gesture 21 of 28 Total Milestones Gained from Embolden Milestone List 7/13 7/8
Overview of Rett Syndrome Gross Motor Scale (RSGMS) Mean RSGMS Total-Score Gain Exceeded Natural History Normalized to One Year Rate RSGMS Phase 1/2 Data Showed Meaningful Gains in Gross Motor Function Real World Impact of RSGMS Gains: Examples of Reduced Caregiver Burden SIT TO STAND Reduces physical burden on caregiver, enhances independence 7 unable to perform independently at baseline 5/7 improved STAND UP FROM FLOOR Complex motor planning allowing for greater autonomy and reduced caregiver physical burden 6 ambulatory unable to perform independently at baseline 5/6 improved Validated clinical tool that assesses 15 key gross motor abilities specifically in individuals with Rett syndrome Increase in 3+ points is considered a meaningful gain in motor ability Post Treatment (N=10) 5.2-point increase (95% CI: 1.3,9.0) Natural History* (N=33) 0.8-point decrease * Bisgaard AM et al. Front Neurol 2026; 16: 1702703 As of data cutoff date of June 16, 2026 IRSF Scientific Meeting 2026 P<0.001; One sample Wilcoxon test 28
RSHFS Phase 1/2 Data Showed Meaningful Gains in Hand Function Validated clinical tool that assesses levels of hand function specific to Rett syndrome Increase in 1+ points is considered a meaningful gain in hand function Overview of Rett Syndrome Hand Function Scale (RSHFS) Mean RSHFS Total-Score Gains Exceed Natural History 29 100% improved in hand function P<0.001; Exact binomial test Post Treatment (N=10; 1-2.5 years) Natural History (N=158; over 3-6 years*) 15% improved Real World Impact: More ability to play, less reliance on caregiver at mealtime, participation in family routines GRASPING, PICKING UP, HOLDING LARGE OR SMALL OBJECTS Enhances ability to self-feed, increases independence 10/10 improved 7/9 bilateral improvement N=9 at baseline had significant hand function impairment MORE COMPLEX ACTIVITIES Enables using utensils, more coordination to play, interact, and be independent N=8/10 improved in total score, N=1 improved grasp, N=1 acquired new hand function developmental milestone *Downs J et al. J Pediatr 2021; 237: 244–249; PMID: 34214590 As of data cutoff date of June 16, 2026 IRSF Scientific Meeting 2026 1.8 point gain per hand
Phase 1/2 Trial 1E15 vg Dose Total N = 10 N Events TEAEs related to NGN-401 9 68 Serious TEAEs Unrelated to NGN-401 3 6 Serious TEAEs Related to NGN-401 1 2 • 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 common related TEAEs: mild ALT/AST elevation • No new treatment-related SAEs reported since last data cutoff date (October 2025) • Two previously disclosed Grade 2 SAEs in Pt:5 resolved • No cases of hemophagocytic lymphohistiocytosis (HLH) • No intracerebroventricular (ICV) procedure-related AEs • No signs or symptoms of MeCP2 overexpression • Seizures have remained well controlled following NGN-401 As of data cutoff date of June 16, 2026 TEAE = Treatment emergent adverse event NGN-401 Remains Generally Well-Tolerated at the 1E15 vg Dose Level in the Phase 1/2 Trial 30
Embolden Registrational Trial
32 Dosing Completed in Embolden Registrational Trial to Support Planned BLA Submission Developmental Milestones • CGI-I score of ≤ 2 • Gain from baseline of at least 2 developmental milestones Single Arm, Baseline-Controlled, Open-Label Trial of NGN-401 in Females with Rett Syndrome 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 success Primary Endpoint at 12 Months Key Secondary Endpoints • Pre-specified from a list of 28 • Captured through standardized video recordings and rated by independent, central, blinded raters Screening Period (Up to 45 days) NGN-401 One-time 1E15 vg dose Patients ≥ 3 years Total participants dosed: N=25 Primary efficacy population: N=24 Primary Observation (12 Months) Immunosuppression: Steroid prophylaxis during first 90 days, followed by taper BLA = Biologics license application
33 Natural History Study Cumulative Incidence Model Shows Beyond Age 3, Milestone Gains Are Rare with Minimal Difference at Age 6 % ever gained/regained: 69% | At ≥3 years: 2.5% | At ≥6 years: 0.4% Communication Example Milestone: Used words with meaning Age (years) % ever gained/regained: 46% | At ≥3 years: 4.2% | At ≥6 years: 1.3% Fine Motor Example Milestone: Taken a drink from a cup held without assistance Age (years) % ever gained/regained: 72% | At ≥3 years: 1.5% | At ≥6 years: 0.3% Gross Motor Example Milestone: Cruised around furniture or holding on to someone (i.e., walk with support) Age (years) Phase 1/2 trial participants were evaluated using the Embolden Developmental Milestone List, and in every age group, NGN-401-treated participants gained multiple milestones Ex: Participant Age 4 10 milestones gained Age-matched RNHS analysis cumulative incidence rate: 0.3-7.9% Ex: Participant Age 7 10 milestones gained Age-matched RNHS analysis cumulative incidence rate: 0.0-2.0% Ex: Participant Age 14 2 milestones gained Age-matched RNHS analysis cumulative incidence rate: 0.0% Likelihood of gaining a milestone at > 3 years of age is extremely low, based on RNHS analysis As of data cutoff date of June 16, 2026 IRSF Scientific Meeting 2026 C um ul at iv e In ci de nc e C um ul at iv e In ci de nc e C um ul at iv e In ci de nc e
34 Compelling Clinical Data Strengthen Confidence in Potential Embolden Registrational Success 33% (8 of 24) Pre-Specified Minimum Response Rate for Success 80% Response Rate (8 of 10) % R es p o n d er s at 1 2 m o n th s Phase 1/2 Phase 1/2 response rate exceeds the success threshold defined for Embolden by 2.4x NGN-401 has been generally well-tolerated in Embolden No treatment-related SAEs or DLTs in Embolden trial As of data cutoff date of June 16, 2026
Advancing NGN-401 Towards Commercialization Rachel McMinn, Ph.D. Founder and Chief Executive Officer, Neurogene
NGN-401 Phase 1/2 Data (N=10) Developmental Milestones % of participants gained ≥1 developmental milestone at ≥12 months 100% Average milestones gained per participant 4.7 Total Participants achieving: - ≥2 milestones - Response on ≥2 domains 7 out of 10 Average # milestones at: % increase from: # of milestones lost in any participant 0 Embolden Composite % meeting rigorous composite responder definition (CGI-I ≤3 + ≥1 milestone) 80% Rapid Response Median time to first response observed post treatment 2 months RSGMS RSHFS Independent, quantitative validated scales of function in Rett syndrome compared to natural history data • 5.2-point increase vs. 0.8-point decrease (p<0.001) • 100% vs. 15% improved in hand function (p<0.001) No new treatment-related SAEs and no DLTs observed in any participants, with all participants ≥12 months of follow-up Robust, Clinically Meaningful Responses Across Participants Support Potential Market Leading Therapy for Rett Syndrome Phase 1/2 shows robust response across key Embolden endpoints having the potential to drive a differentiated label Embolden fully dosed, topline data expected 2H 2027 36 - 6 months 1.9 - 12 months 3.7 - ≥12 months 4.7 - 6 to 12 months 95% - 6 to ≥12 months 147% As of data cutoff date of June 16, 2026
Compelling Clinical Data Showed NGN-401 Restarts the Development Trajectory NGN-401 is Poised to Transform Treatment for Rett Syndrome 37 Completed Dosing in Embolden Registrational Trial Early Commercial- Readiness Underway • Chief Commercial Officer Added to Senior Leadership Team Expected to fund operations through Embolden data readout, BLA submission and key pre-launch activities TODAY UPCOMING ANTICIPATED MILESTONES Start PPQ Campaign Mid-2026 Topline Data from Embolden in 2H 2027 BLA Submission for NGN-401 Continue Additional Commercial-Readiness Activities Strong Cash Balance (1Q’28)
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!
FAQ
What did Neurogene (NGNE) report about its NGN-401 Phase 1/2 Rett syndrome trial?
Neurogene reported positive long-term Phase 1/2 data for NGN-401 in females with Rett syndrome. All 10 participants improved on CGI-I and gained at least one developmental milestone, totaling 47 milestones, with sustained, progressive gains through up to 30 months of follow-up.
How strong were the developmental milestone gains in Neurogene’s NGN-401 Phase 1/2 trial?
Across 10 participants, 47 developmental milestones were gained, an average of 4.7 per participant. Milestone gains increased by 95% from 6 to 12 months and 147% from 6 to at least 12 months, with no plateau or milestone loss observed over 30 months.
What safety profile did NGN-401 show in Neurogene’s Rett syndrome study?
NGN-401 at the 1E15 vg dose remained generally well-tolerated. All treatment-related adverse events were mild or moderate, most were known AAV-related risks that resolved or were resolving, and no new treatment-related serious adverse events or dose-limiting toxicities were reported as of June 16, 2026.
What is the Embolden registrational trial and how does it relate to the Phase 1/2 NGN-401 data?
Embolden is a baseline-controlled, open-label, single-arm registrational trial of NGN-401 in females with classic Rett syndrome. It uses a composite endpoint based on CGI-I and developmental milestones; dosing is complete in 25 participants, and Phase 1/2 results already meet this definition in 80% of participants.
When does Neurogene expect topline data from the Embolden NGN-401 Rett syndrome trial?
Neurogene anticipates topline data from the Embolden registrational trial in the second half of 2027. The company has completed dosing 25 participants at the 1E15 vg dose and plans to use these results to support a potential Biologics License Application submission.
How do NGN-401 results compare with Rett syndrome natural history data discussed by Neurogene?
Neurogene highlighted that post-regression milestone gains are extremely rare in natural history data, especially after age three. In contrast, NGN-401-treated participants across pediatric and adolescent/adult cohorts gained multiple milestones in a progressive, developmentally ordered sequence across key domains.