FDA grants Breakthrough status to Neurogene (NGNE) Rett gene therapy

Rhea-AI Filing Summary

Neurogene Inc. announced that the U.S. FDA has granted Breakthrough Therapy designation to NGN-401, its investigational, one-time AAV9 gene therapy for Rett syndrome. The designation is based on interim Phase 1/2 data as of October 30, 2025, showing clinically meaningful, durable functional improvements across multiple Rett domains with continued skill acquisition over time.

NGN-401 uses Neurogene’s proprietary EXACT™ transgene regulation technology and is delivered via intracerebroventricular administration to broadly target the brain and nervous system. The therapy is being studied in the Embolden™ registrational trial, with dosing expected to complete in the second quarter of 2026 and additional interim Phase 1/2 data planned for mid-2026. NGN-401 also holds multiple other U.S., European and U.K. regulatory designations intended to support development for this serious rare disease.

Positive

• FDA Breakthrough Therapy designation for NGN-401 based on interim Phase 1/2 data demonstrating clinically meaningful, durable and multidomain functional improvements with continued skill acquisition in Rett syndrome.
• Advanced regulatory de-risking with multiple designations (Breakthrough Therapy, RMAT, Fast Track, Orphan, Rare Pediatric Disease, EMA ATMP/Orphan/PRIME and U.K. ILAP) and NGN-401 already in the Embolden™ registrational trial with dosing completion targeted for Q2 2026.

Negative

• None.

Insights

Biotech regulatory and clinical strategy analyst

FDA Breakthrough Therapy status for NGN-401 materially strengthens Neurogene’s Rett program.

The FDA granted Breakthrough Therapy designation to NGN-401 for Rett syndrome based on interim Phase 1/2 data showing clinically meaningful, durable, multidomain functional gains with continued skill acquisition. This recognizes both disease seriousness and the potential for substantial improvement over existing options.

Breakthrough status brings benefits such as eligibility for Priority Review, rolling Biologics License Application submission, and heightened FDA engagement to identify an efficient approval path. Combined with prior RMAT, Fast Track, Orphan, Rare Pediatric Disease and inclusion in the FDA’s START Pilot Program, it signals sustained regulatory attention to this program.

NGN-401 is already in the Embolden™ registrational trial, with dosing completion targeted for the second quarter of 2026 and additional interim Phase 1/2 data in mid-2026. Actual outcomes will depend on the robustness and durability of forthcoming data and ongoing safety observations.

0001404644FALSE00014046442024-03-182024-03-18

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): February 26, 2026

Neurogene Inc.

(Exact name of registrant as specified in its charter)

Delaware			001-36327			98-0542593
(State or other jurisdiction of incorporation or organization)			(Commission File Number)			(I.R.S. Employer Identification No.)

535 W 24th Street, 5th Floor

New York, NY 10011

(Address of principal executive offices, including zip code)

Registrant's telephone number, including area code: (877) 237-5020

N/A

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class

Trading Symbol(s)

Name of each exchange on which registered

Common Stock, $0.000001 par value

NGNE

The Nasdaq Global Market

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).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o

Item 7.01 Regulation FD Disclosure

On February 26, 2026, Neurogene Inc. (the “Company”) issued a press release announcing that NGN-401, the Company's investigational gene therapy in late-stage clinical development for the treatment of Rett syndrome, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration. A copy of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K.

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 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit Number						Description
99.1						Press Release dated February 26, 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: February 26, 2026			By:			/s/ Christine Mikail
						Name: Christine Mikail
						Title: President, Chief Financial Officer

Neurogene Announces FDA Breakthrough Therapy Designation for NGN-401 Gene Therapy for Rett Syndrome

Breakthrough Therapy designation granted based on interim NGN-401 Phase 1/2 data demonstrating clinically meaningful, durable and multidomain functional improvements

On track to complete dosing in Embolden™ registrational trial of NGN-401
in second quarter of 2026

Plans to present additional interim Phase 1/2 clinical data in mid-2026

NEW YORK – February 26, 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 that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to NGN-401, an investigational gene therapy in late-stage clinical development as a potential best-in-class treatment for Rett syndrome.

The Breakthrough Therapy designation was based on the FDA’s review of interim efficacy and safety data from the Phase 1/2 trial as of the data cutoff date of October 30, 2025, including patient-level data and supporting video documentation, demonstrating clinically meaningful and durable functional improvements across multiple Rett syndrome domains with continued skill acquisition over time.

NGN-401 is being evaluated as a one-time treatment for Rett syndrome and is designed to deliver the full-length human MECP2 gene under the control of Neurogene’s proprietary EXACT™ transgene regulation technology. It 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 currently being evaluated in the Embolden™ registrational clinical trial, with completion of dosing expected in the second quarter of 2026.

“The FDA’s decision to grant Breakthrough Therapy designation validates the clinically meaningful, durable and multidomain functional improvements observed with NGN-401, including continued skill acquisition observed over time, and underscores the significant unmet medical need of those living with Rett syndrome,” stated Rachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene. “We appreciate the Agency’s continued engagement, including through our participation in the START Pilot Program and now our Breakthrough Therapy designation, to support the rapid advancement of NGN-401.”

Breakthrough Therapy designation is intended to expedite the development and review of medicines for the treatment of serious conditions which have shown preliminary clinical evidence indicating the potential for substantial improvement over available therapies on a clinically significant endpoint. The benefits of Breakthrough Therapy designation include

eligibility for Priority Review, rolling submission of sections of the Biologics License Application and FDA’s organizational commitment to help determine an efficient route to approval.

This designation for NGN-401 is the latest of several regulatory designations granted by FDA, including Regenerative Medicine Advanced Therapy (RMAT) and Rare Pediatric Disease designations, and selection for FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program.

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 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. Interim data from the Phase 1/2 trial (as of October 30, 2025) have shown that participants experienced multidomain, durable gains with continued skill 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 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 interim results from the NGN-401 Phase 1/2 clinical trial to other participants or potential participants, including adolescent or adult participants; 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 EmboldenTM registrational clinical trial of NGN-401 for Rett Syndrome, including timing of anticipated dosing and completion of participant dosing in our clinical trial; the response rate, expected durability and deepening of clinical data results from our NGN-401 clinical trials; expected timing for release of additional data from our Phase 1/2 clinical trial of NGN-401; the potential for success of the Embolden registrational clinical trial of NGN-401 for Rett Syndrome; 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 interaction 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 Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission (SEC) on March 24, 2025, Neurogene’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, filed with the SEC on  November 13, 2025, 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.

# # #

Company Contact:
Mike Devine

Executive Director, Corporate Communications
michael.devine@neurogene.com

Investor Contact:
Argot Partners
Neurogene@argotpartners.com

FAQ

What did Neurogene (NGNE) announce about NGN-401 and the FDA?

Neurogene announced that the FDA granted Breakthrough Therapy designation to NGN-401 for Rett syndrome. The decision was based on interim Phase 1/2 data showing clinically meaningful, durable functional improvements across multiple disease domains with continued skill acquisition over time in treated participants.

Why is FDA Breakthrough Therapy designation important for Neurogene (NGNE)?

Breakthrough Therapy designation is intended to expedite development and review of promising treatments for serious conditions. For NGN-401, it provides eligibility for Priority Review, rolling BLA submission, and enhanced FDA guidance to help define an efficient route to potential approval for Rett syndrome.

What clinical results support NGN-401’s Breakthrough Therapy designation?

The designation is based on interim Phase 1/2 data as of October 30, 2025. These data, including patient-level information and video documentation, showed clinically meaningful, durable functional improvements across multiple Rett syndrome domains and continued skill acquisition over time at the 1E15 vg dose.

What is NGN-401 and how is it administered for Rett syndrome?

NGN-401 is an investigational AAV9 gene therapy delivering the full-length human MECP2 gene using Neurogene’s EXACT™ transgene regulation technology. It is given as a one-time treatment via intracerebroventricular administration to broadly target the brain and nervous system based on nonclinical biodistribution data.

What is the status of the Embolden registrational trial of NGN-401?

NGN-401 is being evaluated in the Embolden registrational clinical trial for Rett syndrome. Neurogene expects to complete participant dosing in the second quarter of 2026 and plans to present additional interim Phase 1/2 clinical data for NGN-401 in mid-2026, subject to ongoing trial progress.

What other regulatory designations has NGN-401 received besides Breakthrough Therapy?

NGN-401 has multiple designations, including RMAT, Fast Track, Orphan Drug and Rare Pediatric Disease in the United States, inclusion in the FDA’s START Pilot Program, Advanced Therapy Medicinal Product, Orphan and PRIME designations from the European Medicines Agency, and ILAP designation from the U.K. MHRA.

Filing Exhibits & Attachments

4 documents

Press Releases

• EX-99.1 EX-99.1 16.7 KB

Other Documents

• EX-101 XBRL TAXONOMY EXTENSION SCHEMA DOCUMENT 1.7 KB
• EX-101 XBRL TAXONOMY EXTENSION LABEL LINKBASE DOCUMENT 22.0 KB
• EX-101 XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE DOCUMENT 12.7 KB