Neurogene Reports Positive Interim Efficacy Data from First Four Low-Dose Pediatric Participants in NGN-401 Gene Therapy Clinical Trial for Rett Syndrome

NGNE 11.11.2024

Full Press ReleaseSEC FilingsOur NGNE Tweets

About Gravity Analytica

Recent News

  • 11.19.2024 - Stifel 2024 Healthcare Conference
  • 11.18.2024 - Neurogene Reports Third Quarter 2024 Financial Results and Highlights Recent Updates
  • 11.18.2024 - Neurogene Provides Update on NGN-401 Gene Therapy Clinical Trial for Rett Syndrome

Recent Filings

  • 01.13.2025 - 8-K Current report
  • 01.13.2025 - EX-99.1 EX-99.1
  • 12.18.2024 - 424B3 Prospectus [Rule 424(b)(3)]

All participants experienced a 2-point improvement in the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale from baseline

All participants improved in the caregiver-completed Rett Syndrome Behavior Questionnaire (RSBQ), ranging from 28 to 52 percent improvement from baseline

All participants with disruptions in sleep, constipation, and dysphagia at baseline demonstrated objective improvements

Gains in skill and developmental milestones were consistent, durable, deepened over time and demonstrated improvements not expected based on natural history data

Low-doseNGN-401well-tolerated with favorable safety profile

Company plans to provide an update of registrational trial design in the first half of 2025

Company to host investor/analyst webcast today,November 11, 2024, at4:30 p.m. ET

NEW YORK--(BUSINESS WIRE)--Nov. 11, 2024--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 positive interim clinical data in the first four participants in the low-dose cohort of its ongoing Phase 1/2 open-label trial designed to evaluateNGN-401gene therapy for the treatment of female pediatric patients with Rett syndrome. Low-doseNGN-401has demonstrated a favorable safety profile.

“Today marks an important day for Neurogene and the Rett syndrome community as we share positive interim data forNGN-401from our low-dose cohort that shows the first four participants demonstrated meaningful gains of skills and developmental milestones in core clinical domains of Rett syndrome, which are not expected to occur when compared to and contextualized against the natural history of Rett syndrome. Data were also concordant across multiple scales and show consistency of effect across patients, despite their unique clinical presentations at baseline,” saidRachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene. “We are incredibly thankful to the participants, caregivers and Rett syndrome trial sites who are participating in our study.”

“Rett syndrome is a devastating neurodevelopmental disease that is incredibly challenging for patients and their caregivers given there are no treatment options available to address the underlying cause of the disease,” saidAleksandra Jacobs, M.D., Ph.D., Professor of Pediatric Neurology,Albert Einstein College of Medicineand Director of theCenter for Rett Syndromein the Children’s Hospital atMontefiore Medical Center. “The totality of the outcomes shared today withNGN-401gene therapy have never been seen before in the treatment of Rett syndrome. Notably, these initial participants acquired developmental skills post-treatment during the period in which the natural history of Rett syndrome indicates girls would not. I look forward to the continued progress in this program and additional data to come.”

Interim Clinical Data as of Data Cut-Off Date ofOctober 17, 2024

Interim Safety Data (N=7)*

Low-dose (1E15 vg) and high-dose (3E15 vg)NGN-401have been well-tolerated with a favorable safety profile in the first seven pediatric participants (N=5 low-dose; N=2 high-dose):

  • No treatment-related serious adverse events (SAEs)
  • No signs or symptoms indicative of MeCP2 overexpression toxicity
  • Most treatment-related adverse events (AEs) are known potential risks of adeno-associated virus (AAV), have been responsive to steroids, and are resolved or are resolving
  • No intracerebroventricular (ICV)-related AEs
  • No seizures for any participants followingNGN-401treatment

*Today, Neurogene became aware of an emerging treatment-related SAE consistent with known risks of AAV gene therapy in the third high-dose participant who was recently dosed.

Low-Dose Interim Efficacy Data (N=4)

The first four participants (age range 4-7 years old, efficacy assessments at 15, 12, 9, and 3 months post-dosing) in low-dose Cohort 1 showed consistent, concordant and durable improvements across key Rett syndrome assessments:

  • All participants achieved a rating of “much improved,” or a score of 2, on the clinician-rated Clinical Global Impression Scale of Improvement (CGI-I) from baseline; a score of<3 is considered clinically meaningful
  • All participants improved in the caregiver-completed Rett Syndrome Behavior Questionnaire (RSBQ), ranging from 28 to 52 percent improvement from baseline
  • All participants acquired skills and/or developmental milestones in one or more core clinical domains of Rett syndrome - hand function/fine motor, language/communication and ambulation/gross motor
    • These improvements include complex skills that are rarely learned in this population and skills that are rarely relearned after developmental regression when compared to theNIH-sponsored Rett syndrome natural history
    • New skills and milestones have increased and deepened over time

Initiation of Adolescent/Adult Cohort inNGN-401Clinical Trial

Neurogene announced today that it has initiated an adolescent/adult Cohort 3 to gain initial data on the potential ofNGN-401to treat a broader patient population. This cohort is designed to enroll three participants ages 16 and above at the high dose.

FDA Alignment on CMC Requirements to Initiate Future Registrational Trial and Support Potential Product Launch

Neurogene also announced today that it has gained alignment with the FDA on its potency assay strategy forNGN-401, which is necessary to have in place prior to initiating a registrational trial. In addition, the FDA is aligned with Neurogene’s manufacturing scale-up plans forNGN-401, which is important to support a future commercial product launch.

Completed and Upcoming Milestones for theNGN-401Program

  • Expect to complete enrollment in the low-dose pediatric Cohort 1 (N=8) in the fourth quarter of 2024
  • Plans to provide an update of registrational trial design in the first half of 2025
  • Plans to announce additional interim Phase 1/2 clinical data in the second half of 2025

CLN5 Batten Disease Program Update

Neurogene announced today that the Company does not expect to move forward with theNGN-101CLN5 Batten disease gene therapy program at this time. Given the rarity of the disease, continued investment in the program was predicated on alignment on a streamlined registrational pathway with FDA. To support a streamlined pathway, Neurogene submitted a Regenerative Medicine Advance Therapy (RMAT) application to the FDA. Despite the Company’s belief that the application met the standard of preliminary clinical evidence required to obtain an RMAT designation, the RMAT application was denied. Neurogene is currently evaluating options for the program.

Investor/Analyst Webcast Details

Management will host a live webcast and conference call today,November 11, 2024, at4:30 p.m. ETto review the interim data from theNGN-401clinical trial. Access information is available in the Investor Relations section of Neurogene’s website under Events, where the webcast replay will also be available for a limited time.

AboutNGN-401

NGN-401is an investigational AAV9 gene therapy being developed as a one-time treatment for Rett syndrome. It is the first clinical candidate to deliver the full-length humanMECP2gene under the control of Neurogene’s EXACTTM transgene regulation technology. EXACT technology is an important advancement in gene therapy for Rett syndrome, specifically because the disorder requires a treatment approach that enables targeted levels ofMECP2transgene expression without causing overexpression-related toxic effects associated with conventional gene therapy.

NGN-401was selected by theU.S. Food and Drug Administration(FDA) for its START Pilot Program and has also received Regenerative Medicine Advance Therapy (RMAT) designation, orphan drug designation, Fast Track designation and rare pediatric designation from the FDA. Neurogene was previously granted an INTERACT meeting with the FDA regarding the EXACT technology.NGN-401also received orphan designation and advanced therapy medicinal product designation from theEuropean Medicines Agency(EMA) and theInnovative Licensingand Application Pathway (ILAP) designation from theUnited Kingdom(UK) Medicines and Healthcare products Regulatory Agency (MHRA).

About NeurogeneThe mission of Neurogene is to treat devastating neurological diseases to improve the lives of patients and families impacted by these rare diseases. Neurogene is developing novel approaches and treatments to address the limitations of conventional gene therapy in central nervous system disorders. This includes selecting a delivery approach to maximize distribution to target tissues and designing products to maximize potency and purity for an optimized efficacy and safety profile. The Company’s novel and proprietary EXACT transgene regulation platform technology allows for the delivery of therapeutic levels while limiting transgene toxicity associated with conventional gene therapy. Neurogene has constructed a state-of-the-art gene therapy manufacturing facility inHouston, Texas. CGMP production ofNGN-401was conducted in this facility and will support pivotal clinical development activities. For more information, visitwww.neurogene.com.

Cautionary Note Regarding Forward-Looking StatementsStatements 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 ofNGN-401; the safety and tolerability profile and efficacy results ofNGN-401; anticipated future improvements for participants in theNGN-401Phase 1/2 trial for the treatment of Rett syndrome trial designs, clinical development plans and timing forNGN-401, including anticipated timing of enrollment in and clinical trial results from the Company’sNGN-401Phase 1/2 trial for Rett syndrome and expansion of that clinical trial to a third cohort for adolescent/adult patients; expected benefits of RMAT designation and participation in the FDA’s START pilot program forNGN-401, including future interactions with the FDA; the timing and success of Neurogene’s plans for scale-up of commercial production ofNGN-401; any potential alternatives for the future development ofNGN-101; and our expected cash resources and liquidity. 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: risks related to the timing and success of enrolling patients in the expanded cohort of our Phase 1/2 clinical trial ofNGN-401for the treatment of Rett syndrome; the expected timing and results of dosing of patients in our clinical trials, includingNGN-401; the potential for negative impacts to patients resulting from using a higher dose ofNGN-401in Cohort 2 of the Phase 1/2 clinical trial for the treatment of Rett syndrome; the potential for unexpected results or negative impacts to adolescent or adult patients in Cohort 3 of the Phase 1/2 clinical trial forNGN-401; the risk that we may not be able to report additional data on the predicted timeline; risks related to our ability to obtain regulatory approval for, and ultimately commercialize, our product candidates, includingNGN-401; and other risks and uncertainties identified under the heading "Risk Factors" included in our Annual Report on Form 10-K for the year endedDecember 31, 2023, filed with theSecurities and Exchange Commission(“SEC”) onMarch 18, 2024, or our Quarterly Report on Form 10-Q for the quarter endedJune 30, 2024, and other filings that the Company has made and may make with theSECin 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.

This communication contains hyperlinks to information that is not deemed to be incorporated by reference into this communication.

View source version onbusinesswire.com:https://www.businesswire.com/news/home/20241111403774/en/

Company Contact:Cara MayfieldVice President, Corporate Affairscara.mayfield@neurogene.comInvestor Contact:Melissa ForstArgot PartnersNeurogene@argotpartners.com

Source:Neurogene Inc.

Please be aware that the following content has been generated by an AI system and may contain errors, inconsistencies, or outdated information. It is provided as-is without any warranties or guarantees of accuracy. We strongly recommend using this content as a starting point for further research and consultation with relevant experts or authorities. We disclaim any liability for damages or losses resulting from the use or reliance on this content.Please note that this is a beta version of the Gravity Analytica LLC’s AI Service which isstill undergoing final testing before its official release. Theplatform, its software and all content found on it are provided on an“as is” and “as available” basis. Gravity Analytica LLC does not give any warranties,whether express or implied, as to the suitability or usability of thisservice, webpage, or its software or any of its content.Should you encounter any bugs, glitches, lack of functionality orother problems on the website, please let us know immediately so wecan rectify these accordingly. Your help in this regard is greatlyappreciated! You can write to us at this addressteam@gravityanalytica.com