Neurogene (NasdaqGM:NGNE) Conference October 14, 2025 07:00 AM ET Speaker0Hello everyone, my name is Mitchell Kapoor, I'm a Senior Biotech Analyst at H.C. Wainwright. It's my pleasure to welcome you to the Genetic Medicines Conference. Today we have the pleasure of having Neurogene Inc. and from the company I have Rachel McMinn, the CEO. Rachel, thank you so much for joining us today.Speaker1Yeah, thanks Mitchell for the opportunity. Looking forward to it.Speaker0Absolutely. A lot of recent news in the spac ...

Core Insights - Neurogene (NASDAQ:NGNE) is actively participating in the H.C. Wainwright Genetic Medicines Virtual Conference, demonstrating its commitment to innovation in genetic medicine [1][2] - The stock rating for NGNE was upgraded to "Buy" by H.C. Wainwright on October 2, 2025, at a price of $20.97, which has led to a subsequent increase in stock price to $26.26, reflecting an approximate 11.89% rise [1][2] - NGNE's stock has shown significant volatility, with trading prices ranging from a low of $23.10 to a high of $27.56 today, indicating active trading and interest in the company [2] Market Performance - Over the past year, NGNE's stock has experienced a high of $74.49 and a low of $6.88, which has influenced investor decisions and market perception [2] - The company's current market capitalization is approximately $374.78 million, with a trading volume of 221,727 shares, suggesting strong investor interest in the genetic medicine sector on the NASDAQ exchange [2]

NEW YORK--(BUSINESS WIRE)--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 that the Compensation Committee of the Company's Board of Directors approved the grant of non- qualified stock options to purchase an aggregate of 9,390 shares of the Company's common stock to four new employees (the "Inducement Grants†) on October 1, 2025 (the "Grant Date†). The Induce. ...

[Company Overview](index=1&type=section&id=Company%20Overview) Neurogene's overview covers disclaimers, its focus on genetic medicines, clinical pipeline, and in-house AAV manufacturing capabilities [Disclaimer](index=2&type=section&id=Disclaimer) This section outlines the forward-looking nature of statements within the presentation, emphasizing that actual results may differ due to various risks and uncertainties - The communication contains forward-looking statements regarding Neurogene's therapeutic programs (NGN-401, NGN-101), clinical trial designs, expected results, market potential, safety, manufacturing capabilities, and financial runway, based on current beliefs and assumptions and involving risks and uncertainties detailed in SEC filings[3](index=3&type=chunk)[4](index=4&type=chunk) - Industry and market data are based on third-party sources and internal estimates, with Neurogene not independently verifying all information[5](index=5&type=chunk) - The presentation may contain trademarks, service marks, trade names, and copyrights belonging to their respective owners[6](index=6&type=chunk) [Neurogene at a Glance](index=3&type=section&id=Neurogene%3A%20Developing%20Life-Changing%20Genetic%20Medicines%20For%20Rare%20Neurological%20Diseases) Neurogene is focused on developing genetic medicines for rare neurological diseases, with its lead program NGN-401 for Rett syndrome showing promising interim clinical data - Neurogene's lead program, NGN-401 for Rett syndrome, has demonstrated **promising interim clinical data**, with registrational trial activities underway[8](index=8&type=chunk) - NGN-401 utilizes **EXACT™**, a proprietary transgene regulation technology addressing a key limitation in gene therapy[8](index=8&type=chunk) - The company has extended its **cash runway into early 2028**[8](index=8&type=chunk) [Clinical Stage Pipeline](index=4&type=section&id=Neurogene%20Clinical%20Stage%20Pipeline) Neurogene's clinical pipeline includes NGN-401 for Rett Syndrome, which is currently undergoing registrational trial activities with additional interim data expected in 2H:25 Neurogene Clinical Stage Pipeline | Product Candidate | Indication | Near-Term Expected Milestones | | :---------------- | :----------------- | :---------------------------------------------- | | NGN-401 | Rett Syndrome | Registrational Trial Activities Underway, Additional Interim Data 2H:25 | | NGN-101 | CLN5 Batten Disease | Evaluating Opportunities for Program | [Manufacturing Capabilities](index=5&type=section&id=Wholly%20Owned%20and%20Fully%20Integrated%20In-House%20AAV%20Manufacturing) Neurogene operates a wholly-owned, fully integrated in-house AAV manufacturing facility in Houston, spanning 42,000 sq ft with 6,000 sq ft of cleanrooms - Neurogene operates a **42,000 sq ft facility in Houston**, including **6,000 sq ft of cleanrooms**, for wholly-owned and fully integrated in-house AAV manufacturing[13](index=13&type=chunk) - Current research and clinical-grade manufacturing capabilities are designed for commercial-grade product to prevent future comparability issues[14](index=14&type=chunk) - In-house manufacturing provides **flexibility, low-cost production, control over product quality and timelines**, and expertise in HEK293 and Sf9/rBV platforms[16](index=16&type=chunk) [NGN-401 for Rett Syndrome](index=6&type=section&id=NGN-401%20for%20Rett%20Syndrome) This section details NGN-401, Neurogene's lead gene therapy for Rett Syndrome, covering its mechanism, clinical trial design, and interim Phase 1/2 data [Introduction to NGN-401](index=6&type=section&id=NGN-401%20for%20Rett%20Syndrome) NGN-401 is Neurogene's lead gene therapy program for Rett Syndrome, leveraging its proprietary EXACT™ transgene regulation technology to address the underlying genetic cause of the disease - NGN-401 is a gene therapy for Rett Syndrome utilizing the **EXACT™ transgene regulation technology**[17](index=17&type=chunk) [Rett Syndrome: Disease Overview and Unmet Need](index=7&type=section&id=Rett%20Syndrome%20-%20Devastating%20Disorder%20with%20High%20Unmet%20Need) Rett syndrome is a devastating, progressive X-linked neurological disorder caused by MECP2 gene mutations, primarily affecting females with a U.S. prevalence of ~6,000-9,000 patients - Rett syndrome is an X-linked disorder caused by **MeCP2 gene mutations**, with a U.S. prevalence of approximately **6,000-9,000 patients** and a worldwide incidence of **1:10,000 females**[21](index=21&type=chunk) - The disease is characterized by early onset developmental regression, loss of purposeful hand use, impaired motor skills, communication difficulties, and autonomic dysfunction, with **no approved treatments addressing the root cause**[22](index=22&type=chunk)[23](index=23&type=chunk) [NGN-401: Mechanism of Action and Delivery](index=9&type=section&id=NGN-401%3A%20Potential%20to%20be%20Best-in-Class%20Gene%20Therapy%20for%20Rett%20Syndrome) NGN-401 is designed as a potential best-in-class gene therapy for Rett Syndrome, utilizing EXACT™ technology to ensure consistent and tightly controlled MeCP2 protein expression - NGN-401 employs **EXACT™ transgene regulation technology** to deliver consistent and tightly controlled MeCP2 protein expression on a cell-by-cell basis[25](index=25&type=chunk) - The therapy utilizes the **full-length human MECP2 gene**, translating a fully functioning MeCP2 protein[25](index=25&type=chunk) - **Intracerebroventricular (ICV) delivery** provides broad targeting of brain and nervous system regions relevant to Rett syndrome pathophysiology, as shown in preclinical models[25](index=25&type=chunk) [Embolden™ Registrational Trial Design](index=10&type=section&id=NGN-401%20Embolden%E2%84%A2%20Registrational%20Trial) Neurogene has obtained FDA agreement on the design of the Embolden™ registrational trial for NGN-401, which is an open-label, single-arm, baseline-controlled study - FDA has provided written agreement on key elements of the **Embolden™ Registrational Trial design** for NGN-401[27](index=27&type=chunk) Embolden™ Registrational Trial Design | Design | Open-label, single arm, baseline control (patient acting as own control) | | :---------------- | :----------------------------------------------------------------------- | | Patient Population | Females ages ≥ 3 years with Rett syndrome | | Dose | 1E15 vg | | Primary Endpoint | Responder-based composite endpoint at 12 months: Gain of any one developmental milestone and CGI-I of < 3 skill captured through video recordings | - The Phase 1/2 trial is converting to a registrational trial, with a proposed **N=20** for the open-label, baseline-controlled arm, targeting females with Classic Rett syndrome in the post-regression stage, aged >3 years, with pathogenic MECP2 mutation and CGI-S score of 4-6[28](index=28&type=chunk) [Trial Design and Endpoints](index=11&type=section&id=Trial%20Design%20and%20Endpoints) The Embolden™ registrational trial is an open-label, single-arm study with patients serving as their own controls, focusing on females aged ≥3 years with Rett syndrome - The trial will evaluate **28 developmental skills/milestones** across fine motor/hand function, gross motor/ambulation, and communication, selected for their meaningfulness to caregivers and rarity of acquisition after age 3 in natural history[29](index=29&type=chunk)[30](index=30&type=chunk)[31](index=31&type=chunk)[32](index=32&type=chunk) [Caregiver Feedback on Meaningfulness](index=14&type=section&id=Rett%20Syndrome%20Caregiver%20Research%20Demonstrated%20Clinical%20Meaningfulness%20of%20Developmental%20Milestone%2FSkill%20Acquisition) Research with Rett syndrome caregivers confirmed that all queried developmental skills across fine motor, gross motor, and communication domains are considered highly meaningful - Caregiver research (Nov-Dec 2024, Jan 2025) with **30-27 caregivers** of daughters aged 3-22 years confirmed that all queried developmental milestones/skills in fine motor, gross motor, and communication domains were considered **meaningful**[33](index=33&type=chunk)[34](index=34&type=chunk) - Caregivers emphasized that skill gains would provide **respite, increased independence, reduced physical strain, enhanced safety, and improved dignity** for patients and their families[34](index=34&type=chunk)[41](index=41&type=chunk) [Phase 1/2 Clinical Data](index=16&type=section&id=Phase%201%2F2%20Data%20Support%20Registrational%20Trial%20Design) Interim Phase 1/2 data for NGN-401 at the 1E15 vg dose level demonstrated durable and consistent improvements across multiple clinical scales and core domains - Phase 1/2 data demonstrated **durable improvements** across multiple scales, including a **two-point improvement in CGI-I** in all participants, with consistent gains in hand function, gross motor, and communication[42](index=42&type=chunk)[43](index=43&type=chunk) - **Clinically meaningful gains** of skills and developmental milestones were observed beyond natural history expectations, alongside objective improvements in autonomic domains such as sleep and constipation[43](index=43&type=chunk) - The **1E15 vg NGN-401 dose** was generally well-tolerated, with **no evidence of Hemophagocytic lymphohistiocytosis (HLH)** observed[43](index=43&type=chunk) [Efficacy and Patient Characteristics](index=16&type=section&id=Efficacy%20and%20Patient%20Characteristics) The initial four participants in the Phase 1/2 trial, ranging from moderate to severe disease, all achieved a CGI-I rating of 'Much Improved' (score ≤ 3) by 3-9 months post-treatment Baseline Characteristics of Dosed Participants (1E15 vg) | | Participant 1 (Pt:1) | Participant 2 (Pt:2) | Participant 3 (Pt:3) | Participant 4 (Pt:4) | Participant 5 (Pt:5) | | :----------------------- | :------------------- | :------------------- | :------------------- | :------------------- | :------------------- | | Age at Dosing in Years | 7 | 4 | ୧ | 7 | 6 | | MECP2 Mutation Severity | Mild | Severe | Severe | Severe | Severe | | Baseline Disease Severity (CGI-S) | 4 (moderately ill) | 5 (markedly ill) | 5 (markedly ill) | 5 (markedly ill) | 5 (markedly ill) | | Time Post Treatment (Months) | ~15 | ~12 | ~9 | < R | s | CGI-I Scores Post Treatment with NGN-401 (First Four Participants) | | 3 mos. | 6 mos. | 9 mos. | 12 mos. | 15 mos. | | :--- | :----------------- | :----------------- | :----------------- | :----------------- | :----------------- | | Pt:1 | 3 - Minimally Improved | 2 - Much Improved | 2 - Much Improved | 2 - Much Improved | 2 - Much Improved | | Pt:2 | 2 - Much Improved | 2 - Much Improved | 2 - Much Improved | 2 - Much Improved | | | Pt:3 | 3 - Minimally Improved | 3 - Minimally Improved | 2 - Much Improved | | | | Pt:4 | 2 - Much Improved | | | | | - Across the first four participants, an aggregate of **23 skills were acquired**, with consistent improvements observed across key Rett Syndrome scales (CGI-I, CGI-S, RSBQ) and functional improvements in core clinical domains (hand function, gross motor, communication, autonomic, attentiveness)[49](index=49&type=chunk) [Safety Profile (HLH)](index=25&type=section&id=No%20Evidence%20of%20HLH%2FHyperinflammatory%20Syndrome%20at%20the%201E15%20vg%20Dose%20Level) Neurogene has implemented comprehensive HLH risk mitigation protocols for the Phase 1/2 and registrational trials, including dose level restrictions and daily monitoring - HLH risk mitigation protocols include **dose level restrictions (not at/above 1E14 vg/kg)**, daily monitoring of ferritin, fever, and falling blood counts in the first week post-dosing, and requiring sites to have anakinra available[68](index=68&type=chunk) - **No participants at the 1E15 vg dose level** have presented with clinical symptoms of HLH/hyperinflammatory syndrome[71](index=71&type=chunk) - **Transient ferritin elevations** were observed in **4 of 5 recently dosed subjects**, peaking at Study Day 5-6 and recovering to Baseline by Day 10-12 without intervention[71](index=71&type=chunk) [Key Anticipated Milestones](index=27&type=section&id=Key%20Anticipated%20Milestone%20Events) This section outlines Neurogene's upcoming regulatory and clinical milestones for NGN-401 and NGN-101, along with its projected cash runway [Key Upcoming Anticipated Milestones and Pipeline Developments](index=28&type=section&id=Key%20Upcoming%20Anticipated%20Milestones%20and%20Pipeline%20Developments) Neurogene anticipates providing a regulatory update and initiating registrational trial activities for NGN-401 in 1H:25, with additional Phase 1/2 clinical data expected in 2H:25 - For Rett Syndrome (NGN-401), Neurogene plans a regulatory update and initiation of registrational trial activities in **1H:25**, with additional Phase 1/2 clinical data expected in **2H:25**[73](index=73&type=chunk)[74](index=74&type=chunk) - For CLN5 Batten Disease (NGN-101), the company is evaluating program opportunities[74](index=74&type=chunk) - Cash runway is projected to fund operations into **early 2028**[75](index=75&type=chunk) [Appendix](index=29&type=section&id=Appendix) The appendix provides supplementary detailed data on autonomic function improvements and preclinical efficacy and safety of NGN-401 in mouse models [Detailed Autonomic Function Data](index=30&type=section&id=Detailed%20Autonomic%20Function%20Data) The appendix provides detailed objective data on autonomic function improvements observed in Phase 1/2 participants - Pt:1 and Pt:2, with baseline sleep deficits, experienced improvements in sleep parameters (e.g., sleep efficiency increased from **83% to 90% for Pt:1**, and **90% to >95% for Pt:2**) and constipation, measured by wearable devices and caregiver-reported Bristol Stool Form Scale[66](index=66&type=chunk)[77](index=77&type=chunk)[79](index=79&type=chunk)[80](index=80&type=chunk)[82](index=82&type=chunk) - Pt:3, with severe dysphagia at baseline, gained the ability to swallow liquids and chew/swallow soft foods by **3 months post-NGN-401**, and could self-feed by **9 months**[67](index=67&type=chunk)[83](index=83&type=chunk) - Pt:4 experienced improvements in constipation by **Month 4 post-treatment**[66](index=66&type=chunk)[85](index=85&type=chunk)[86](index=86&type=chunk) [Preclinical Data (Mouse Models)](index=34&type=section&id=NGN-401%20Demonstrated%20Efficacy%20and%20Safety%20in%20Mecp2%20Mouse%20Models) Preclinical studies in Mecp2 mouse models demonstrated NGN-401's efficacy and safety, showing that ICV delivery achieved targeted MeCP2 levels and improved survival - **ICV delivery of NGN-401** in Mecp2 mouse models achieved targeted MeCP2 levels and improved survival in both male knockout and female heterozygous mice[90](index=90&type=chunk)[91](index=91&type=chunk) - **EXACT™ technology** ensures consistent and narrow expression of MeCP2 on a cell-by-cell basis, preventing potential issues from unregulated gene expression[93](index=93&type=chunk)[94](index=94&type=chunk)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION For the quarterly period ended June 30, 2025 Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 (State or other jurisdiction of incorporation or organization) (I.R.S. Employer Identification No.) 535 W 24th St. 5th Floor New York, NY 10011 (Address of principal executive offices) (Zip Code) (855) 508-3568 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES ...

NGN-401 for Rett Syndrome - NGN-401, a gene therapy leveraging EXACT transgene regulation technology, is being developed for Rett syndrome [15] - Rett syndrome affects an estimated 6,000-9,000 patients in the U S [20] - The worldwide incidence of Rett syndrome is estimated at 1 in 10,000 females [20] - Phase 1/2 data showed durable improvements, including a two-point improvement in CGI-I in all participants [38] - All four participants in the Phase 1/2 trial achieved a CGI-I rating of "Much Improved" [41] - The company expects to announce additional Phase 1/2 clinical data in the second half of 2025 [64] Clinical Trial and Regulatory Updates - The FDA has accepted the conversion of the Phase 1/2 trial to a registrational trial for NGN-401 [28] - The Embolden registrational trial is designed as an open-label, single-arm, baseline-controlled study [27] - The proposed number of participants in the Embolden trial is 18, subject to FDA feedback [28] - The company anticipates providing a regulatory update regarding the registrational trial in the first half of 2025 [64] Manufacturing and Financials - Neurogene has a 42,000 sq ft in-house AAV manufacturing facility in Houston, with 6,000 sq ft of cleanrooms [11] - The company's cash runway is expected to fund operations into early 2028 [6, 64]

Financial Results - Neurogene Inc. reported financial results for Q1 2025, with a focus on operational performance and financial condition[5] - The financial results include key metrics that will be elaborated in the attached press release[5] - The report does not include specific financial figures or performance metrics in the provided content[6] Press Release - The press release detailing these results was issued on May 9, 2025, and is attached as Exhibit 99.1[5] - The report was signed by Christine Mikail, President and Chief Financial Officer, on the date of the press release[11] Company Information - The company is listed on The Nasdaq Global Market under the trading symbol NGNE[3] - Neurogene Inc. is not classified as an emerging growth company under the Securities Act of 1933[4] - The company’s principal executive office is located in New York, NY[2] Compliance and Filing - The filing is intended to comply with the requirements of the Securities Exchange Act of 1934[9] - The report includes an Interactive Data File as part of its exhibits[7]

Financial Performance - Neurogene reported a net loss of $22.6 million for the three months ended March 31, 2025, compared to a net loss of $16.9 million for the same period in 2024[102]. - The net loss for the three months ended March 31, 2025, was $22.65 million, compared to a net loss of $16.92 million for the same period in 2024, representing an increase of $5.73 million[120]. - The company has not generated any commercial revenue from product sales and does not have any products approved for commercial sale[104]. - As of March 31, 2025, Neurogene had an accumulated deficit of $284.9 million and cash, cash equivalents, and short-term investments totaling $292.6 million[102]. - Interest income for the three months ended March 31, 2025, was $3.21 million, an increase of $0.89 million compared to $2.32 million for the same period in 2024[120]. - General and administrative expenses increased to $8.2 million for the three months ended March 31, 2025, from $5.2 million in the same period of 2024, representing a 56% increase[125]. - The company expects general and administrative expenses to increase in the future to support heightened research and development activities[126]. - Net cash used in operating activities was $20.8 million for the three months ended March 31, 2025, compared to $21.7 million for the same period in 2024, indicating a 4% improvement[136][137]. - The company anticipates needing substantial additional capital to complete the development of product candidates and build necessary infrastructure for commercialization[131]. Research and Development - The Phase 1/2 clinical trial of NGN-401 for Rett syndrome has shown consistent improvements in clinical assessments, with participants achieving meaningful gains in skills and developmental milestones[92]. - The trial for NGN-401 has received FDA clearance for the Investigational New Drug (IND) application, and participants have been dosed in the UK, Australia, and the US[91]. - Neurogene's NGN-401 program is part of the FDA's START Pilot Program, which aims to accelerate the development of therapies for rare diseases[97]. - The RMAT designation for NGN-401 allows for early and frequent communications with the FDA, facilitating a streamlined development process[97]. - The company expects to continue to incur significant research and development expenses as it advances its programs and product candidates through clinical development[124]. - Research and development expenses increased to $17.76 million for the three months ended March 31, 2025, compared to $13.54 million for the same period in 2024, reflecting a change of $4.22 million[120]. - The Rett syndrome program saw an increase in expenses primarily due to a $1.2 million rise in preclinical costs and a $0.6 million increase in clinical trial costs[122]. - The company is currently evaluating options for the NGN-101 program after the RMAT application for CLN5 Batten disease was denied, indicating challenges in advancing this program[99]. - The company’s RMAT application for the NGN-101 CLN5 Batten disease gene therapy program was denied, leading to a reevaluation of the program[104]. Collaborations and Agreements - The collaboration agreement with the University of Edinburgh was amended and extended through December 2026 to support pipeline development and scientific innovation[104]. - The company entered into a collaboration with the University of Edinburgh, extending the initial 40-month term by an additional 33 months, with obligations for semi-annual payments related to project funding[150]. - Under the March 2022 Edinburgh License Agreement, the company obtained an exclusive worldwide license for certain patents, with low single-digit percentage royalties on future commercial net sales of licensed products, and potential milestone payments up to $30.3 million[151]. - The company has a Non-Exclusive License Agreement with Virovek, Inc., which includes development milestone payments of up to $0.2 million and low single-digit percentage royalties on future commercial net sales[152]. - A Non-Exclusive License Agreement with Sigma-Aldrich Co. requires the company to pay up to $2.5 million in development-related milestones and a small annual fee once the first product candidate enters the clinic[153]. - The company entered into a Nonexclusive License Agreement with Stanford University, obligating it to pay up to $0.5 million in licensing fees over a 10-year term[154]. Financial Position and Capital Needs - The company raised approximately $521.9 million from private placements since its inception, primarily funding its operations through outside capital[102]. - Cash, cash equivalents, and short-term investments totaled $292.6 million as of March 31, 2025, with net proceeds from private placements amounting to approximately $521.9 million since inception[130]. - The company may require substantial additional capital to support its operations and product development efforts, which could include income from collaborations or partnerships[104]. - As of December 31, 2024, the company had federal and state net operating loss carryforwards of $319.8 million and $39.6 million, respectively[119]. Regulatory and Compliance - Neurogene discontinued the 3E15 vg dose level in the NGN-401 trial due to safety concerns following a participant's death from a hyperinflammatory syndrome[95]. - Financial statements are prepared in accordance with U.S. GAAP, requiring management to make estimates and judgments that may affect reported amounts[156]. - As a smaller reporting company, the company is not required to provide quantitative and qualitative disclosures about market risk[158]. - The total contingent value rights liability as of March 31, 2025, was $1.1 million, slightly up from $1.09 million as of December 31, 2024[148]. - Other expenses decreased by $0.5 million for the three months ended March 31, 2025, primarily due to the accrual of contingent consideration liabilities related to licensing agreements[128].

Group 1 - The NASDAQ Biotechnology Index increased by 1.56%, closing at 4,260.4, with a gain of 65.2 points [1][3] - Sutro Biopharma saw a significant rise of 20.04%, while Mersana Therapeutics and Neurogene also experienced notable increases of 17.19% and 15.12% respectively [1][3] - Other companies that performed well include Kyverna Therapeutics (+13.24%), Sana Biotechnology (+11.11%), and Larimar Therapeutics (+10.88%) [3] Group 2 - Tempus AI had a decline of 4.83%, ranking fourth from the bottom, followed by Prothena Plc. (-5.06%), Grail (-6.28%), and OmniAb (-8.11%) [2][4] - The overall performance of the biotechnology sector showed mixed results, with several companies experiencing significant losses alongside those that gained [2][4]

Financial Stability and Operations - Neurogene's cash runway extends into the second half of 2027, allowing operations beyond key clinical inflection points[8] - Cash runway is expected to fund operations into the second half of 2027, ensuring continued development and operational stability[71] Clinical Development and Trials - The company is advancing its NGN-401 program for Rett syndrome, with a pivotal trial design evaluating a 1E15 vg dose in female participants aged 4-10 years[32] - The company has discontinued the use of the 3E15 vg dose in favor of the 1E15 vg dose for future participants in the NGN-401 trial, reflecting an adaptive approach to clinical development[37] - The company anticipates providing a regulatory update in the first half of 2025 regarding pivotal trials for NGN-401[71] - The company plans to announce additional Phase 1/2 clinical data in the second half of 2025, indicating ongoing research and development efforts[71] - The company is leveraging the START and RMAT programs to accelerate registration and approval processes with the FDA, enhancing the potential for quicker market access[68] Patient Outcomes and Improvements - Interim clinical data for NGN-401 shows consistent improvements across multiple scales, with all participants achieving a 2-point improvement in the Clinician Global Impression-Improvement (CGI-I) scale[34] - Clinical trial data indicates that participants experienced objective improvements in autonomic function and developmental milestones, surpassing natural history data expectations[35] - Participants experienced significant improvements in various developmental skills post-treatment with NGN-401, including fine motor skills where participant 1 developed a pincer grasp and began self-feeding[55] - Sleep efficiency for participant 1 increased from 83% to 90% and for participant 2 from 90% to over 95% at 6 months post-treatment[47] - Participant 2 showed improvements in communication, now able to say "mama," "dada," and "nana" clearly and in context[58] - Participant 3 improved from requiring spoon-feeding to being able to self-feed solid foods and swallow liquids independently[63] - Participant 4 demonstrated early improvements in hand function, now able to use utensils to self-feed without assistance[67] - Participants demonstrated improvements in self-feeding skills, with some able to take multiple bites and use utensils effectively[78] - Significant gains in gross motor function were observed, with one participant experiencing a 75% reduction in falls[80] - Communication abilities improved, with one participant making food choices 100% of the time, while others showed varying degrees of choice-making capabilities[82] - Breathing dysrhythmias were reduced significantly, with one participant experiencing them less than 5% of the time[87] - Total sleep time increased from 6.6 to 7 hours per night, indicating improved sleep efficiency[89] - Constipation improved over time, as measured by stool consistency, with a transition towards more normal stool types[91] - Participants showed meaningful improvements in hand function, with many achieving higher-level grasping skills[77] - Patient 3 showed significant improvement in swallowing abilities, transitioning from a pureed diet to self-feeding soft foods within 9 months post-NGN-401 treatment[94] - Patient 4 experienced a 100% improvement in constipation by Month 4, as measured by stool consistency and frequency[96] - Sleep quality for both patients was maintained post-treatment, with no baseline deficits reported in the autonomic category of sleep[94][96] Technology and Manufacturing - Neurogene's EXACT technology aims to deliver therapeutic levels of MeCP2 to deficient cells while maintaining non-toxic levels in unaffected cells, addressing the complexities of gene therapy for Rett syndrome[20] - The company operates a 42,000 sq ft GMP manufacturing facility in Houston, which provides flexibility and cost efficiency in producing AAV products[13] - Neurogene's in-house manufacturing capabilities enhance its strategic flexibility and control over product quality and development timelines[12] - NGN-401 program leverages a unique transgene regulation mechanism to optimize gene expression, potentially widening the therapeutic window for treatment[25] - ICV delivery of NGN-401 achieved targeted MeCP2 levels, showing survival rates of 23% in male knockout and 37% in female heterozygous models[98] - EXACT technology delivered consistent levels of MECP2 expression on a cell-by-cell basis, indicating precision in gene therapy[99] - NGN-MECP2 achieved narrow expression of MECP2, suggesting potential for reduced side effects in treatment[100] Disease Context and Market Need - The U.S. prevalence of Rett syndrome is estimated at approximately 6,000-9,000 patients, indicating a significant unmet medical need for effective treatments[17] - The majority of patients with Classic Rett Syndrome have a CGI-S score of 4-6, indicating moderate to severe illness[75] - The data cut-off date for the reported improvements was October 17, 2024, indicating ongoing monitoring of patient progress[79]