Letter to our Rett Syndrome Community
Dear Rett Syndrome Community,
Today Neurogene announced key elements of the design of our registrational clinical trial, named Embolden™, for the investigational gene therapy, NGN-401, for Rett syndrome. A registrational clinical trial is designed to gather a comprehensive set of efficacy and safety data for review by regulatory agencies with the goal of obtaining regulatory approval to market the product for patients outside of a clinical trial. The purpose of this letter is to provide an overview of our plans and address questions you may have.
Which elements of the registrational clinical trial have been agreed upon with the FDA?
The age range will be females aged 3 years and older with a Clinical Global Impression-Severity (CGI-S) score of 4–6.
- The age range in the registrational clinical trial has expanded from what we had in the Phase 1/2 clinical trial and now includes females age 3 years and older.
The dose used will be 1E15 vector genomes (vg) total dose.
- This is the same, and only, dose that is currently being used in the Phase 1/2 clinical trial.
This is an open-label, single-arm, baseline-controlled trial, meaning:
- All participants will receive the investigational gene therapy; there is no placebo group.
- Each participant will serve as her own baseline (any changes in her status over the course of the trial will be compared to her status before receiving NGN-401).
The primary efficacy endpoint will have 2 components, 1) CGI-I, and 2) gain of developmental milestone/skill as determined based on analysis of video capture.
- The Clinical Global Impression-Improvement (CGI-I) scale with Rett syndrome anchors will be used by the study physician to determine improvement or worsening in the participant’s overall functioning compared to the participant’s status prior to receiving NGN-401.
- Video recordings will be used to capture whether or not a participant has gained any one developmental milestone/skill (from a list of 28) in the 12-month period after receiving the investigational gene therapy. The 28 developmental milestones/skills in the clinical trial assessment include gross motor/ambulation, fine motor/hand function, and communication skills.
- Neurogene’s analysis of the NIH-sponsored, International Rett Syndrome Foundation (IRSF) Rett syndrome natural history study shows patients ages 3 and above rarely learn new skills/reach developmental milestones or relearn skills once lost.
We want to extend our sincere gratitude to the families who shared their time and insights while participating in our research survey and interviews.
- The families confirmed that the gain of any one of these 28 gross motor, fine motor, and communication skills would be considered meaningful to them.
Which elements of the registrational clinical trial are not yet finalized?
- We are working with the FDA to determine the total number of participants and the potential to include an endpoint 6 months after dosing (in addition to the agreed upon 12-month endpoint).
- Neurogene proposed 18 participants for the trial, which is subject to feedback from the FDA.
- We are still finalizing the locations of the registrational clinical trial sites that will enroll new patients.
What happens next?
- We will continue our activities to prepare for the registrational trial.
- We will provide an update when the registrational trial is open for enrollment and post updated information on www.clinicaltrials.gov at that time.
- There is no mechanism for families to express their interest in registrational trial enrollment at this time, as this trial is not yet enrolling.
Sincerely,
Kimberly Trant, RN, MBA
Executive Director, Patient Advocacy and Engagement
Important Information
NGN-401 is not approved by any regulatory agency for use outside of the clinical trial.
Cautionary Note Regarding Forward-Looking Statements
Statements in this communication 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 safety, tolerability and efficacy of NGN-401; the effectiveness of the monitoring and treatment protocol for HLH in Neurogene’s Phase 1/2 clinical trial of NGN-401; the ability to reverse cases of AAV-related HLH when following this protocol, the timing of completion of dosing of our adolescent/adult protocol in the NGN-401 Phase 1/2 clinical trial, the timing of announcements of material information regarding our clinical trial results; and our ability to align with regulators on our clinical design plans. 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 March 31, 2025, filed with the SEC on May 9, 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.
Rachel McMinn, Ph.D., is Chief Executive Officer of Neurogene and serves as Executive Chair of the company’s Board of Directors. She founded Neurogene in January 2018 with the mission of developing genetic medicines to improve the lives of neurologically-impaired people and their families. Prior to founding Neurogene, Dr. McMinn served as the Chief Business and Strategy Officer of Intercept Pharmaceuticals, a company dedicated to patients with serious liver disease. Prior to her industry experience, Dr. McMinn was an award-winning biotechnology analyst, with 13 years of experience at firms including Bank of America Merrill Lynch, Cowen, and Piper Jaffray. She graduated from Cornell University magna cum laude with a B.A. and earned her Ph.D. from The Scripps Research Institute and was awarded a Post-Doctoral Miller Fellowship at the University of California, Berkeley.
Christine Mikail, J.D., is President and Chief Financial Officer of Neurogene. In her role, Ms. Mikail leads Corporate Strategy and Business Development, Portfolio Management, Operations, and Finance. Ms. Mikail, who joined Neurogene in 2019, brings over two decades of experience supporting biotechnology and pharmaceutical companies in corporate strategy and business development, operations, legal and finance capacities. Prior to Neurogene, Ms. Mikail was Chief Administrative Officer and Head of External Business Development/Alliance Management and General Counsel at Axovant Sciences, Inc., where she was an integral member of the team that raised $362 million in the company’s IPO. Prior to joining Axovant, she held a variety of senior executive positions at NPS Pharmaceuticals, Inc., Dendreon Corporation, Eli Lilly and Company, and ImClone Systems. Ms. Mikail developed her life sciences focus as a corporate and securities lawyer at Reed Smith and WilmerHale. Ms. Mikail graduated cum laude with a B.A. from Rutgers University and earned her J.D. from Fordham University School of Law in 
Andrew Mulberg, M.D., serves as Senior Vice President, Regulatory Affairs, Quality Assurance, and Quality Control at Neurogene. Dr. Mulberg is a pediatric gastroenterologist with nearly 30 years of experience and has a strong passion for helping bring important new medicines to market for patients with devastating rare diseases. In his role at Neurogene, he provides strategic leadership and direction for regulatory and quality activities. Prior to joining Neurogene, Dr. Mulberg led global regulatory affairs for Amicus Therapeutics and held various roles of increasing responsibility within global drug development and medical affairs at Johnson & Johnson. In addition to Dr. Mulberg’s biotechnology and pharmaceutical experience, he spent six years as the Division Deputy Director in the Division of Gastroenterology and Inborn Errors Products at the U.S. FDA. He received his B.A. from Columbia University and his M.D. from Mount Sinai School of Medicine. Dr. Mulberg also previously served as Attending Physician and Fellowship Director of Gastroenterology and Hepatology at Children’s Hospital of Philadelphia. He is currently an adjunct Professor of Pediatrics at the University of Maryland Medical Center, and Chairman of the Medical Advisory Board Go4 the Goal foundation, a pediatric cancer advocacy 501(c)(3) organization.
Stuart Cobb, Ph.D., is Chief Scientific Officer at Neurogene. Dr. Cobb, who joined Neurogene in 2019, brings to the team more than 20 years of experience in translational neuroscience. He leads Neurogene’s scientific research, the development of scientific strategy to support the company’s existing and growing gene therapy portfolio, and efforts to identify novel technologies that complement Neurogene’s pipeline. In addition to his role at Neurogene, Dr. Cobb also leads a research team at the University of Edinburgh, where he is Professor of Translational Neuroscience at Simons Initiative in the Developing Brain and Centre for Discovery Brain Sciences. Prior to his work at Neurogene, Dr. Cobb was a Caledonian Research Fellow and led an academic research laboratory at the University of Glasgow. His research has focused on developing novel genetic treatments for brain disorders based on a deep understanding of the molecular and cellular pathology. Dr. Cobb’s work has been published in leading journals and includes seminal work on the inherent reversibility of neurological features in neurodevelopmental disease. Dr. Cobb has a B.Sc. from the University of Glasgow and a Ph.D. in Neuroscience from the University of Oxford.
Donna M. Cochener, J.D., LL.M., is Senior Vice President and General Counsel of Neurogene. She is a seasoned legal and executive professional with over two decades of experience in corporate law, governance, and executive leadership across the biotechnology and financial services sectors. Prior to joining Neurogene, Ms. Cochener held the roles of Interim Chief Executive Officer and General Counsel at Neoleukin Therapeutics, where she led the company through its merger with Neurogene in December 2023. Her earlier career includes serving as Senior Vice President and Deputy General Counsel at HomeStreet, Inc., the parent company of HomeStreet Bank, where she was primarily responsible for securities reporting and compliance, corporate governance, and led various transactions including mergers and acquisitions. Ms. Cochener was previously a partner at Davis Wright Tremaine LLP in Seattle, and also held associate positions at Heller Ehrman LLP, Riddell Williams P.S., and Perkins Coie LLP.
Julie Jordan, M.D., is Chief Medical Officer at Neurogene. Dr. Jordan brings over 20 years of industry and clinical expertise involving the design and execution of global clinical trials across multiple development areas, including gene therapy and central nervous system disorders. Before joining Neurogene, she was Chief Medical Officer at Homology Medicines, where she was responsible for leading clinical development and operations, leading regulatory interactions and supporting translational research programs for the company’s pipeline of gene therapy and gene editing candidates for rare diseases. She previously held global leadership roles of increasing responsibility at Cerevel Therapeutics, Avanir Pharmaceuticals and Teva Pharmaceutical Industries. Prior to her industry experience, Dr. Jordan was a practicing physician for 10 years and previously served as Clinical Instructor of Medicine at Harvard Medical School and in the Department of Medicine at Massachusetts General Hospital (MGH). She holds an A.B. in Biology from Harvard College and an M.D. from Harvard Medical School and completed her residency in Internal Medicine at MGH, Harvard Medical School.
Arvind Sreedharan serves as Senior Vice President, Business Operations at Neurogene. Mr. Sreedharan, who leads business operations at Neurogene, has over three decades of commercial experience in the pharmaceutical and biotechnology industry, including significant experience in CNS disorders and multiple orphan diseases. Prior to Neurogene, he served as Vice President, U.S. Commercial Operations for AveXis, the gene therapy company that developed Zolgensma®, an FDA-approved treatment for spinal muscular atrophy (SMA), which was acquired by Novartis for $8.7 billion. Earlier, Mr. Sreedharan served as Vice President of Marketing at Auspex Pharmaceuticals, a biopharmaceutical company focused on hyperkinetic movement disorders and rare diseases, acquired by Teva Pharmaceutical for $3.5 billion. Before Auspex, he served as Director, Movement Disorders at Lundbeck, where he played an integral commercial role in the successful product launch and management of Xenazine®, the first FDA-approved drug for the treatment of chorea associated with Huntington’s disease. Mr. Sreedharan has supported and partnered with numerous rare disease advocacy groups throughout his career. He previously served on the Huntington’s Disease Society of America Board of Trustees and is currently a member of the Board of Directors for The Huntington Study Group (HSG), the first Huntington’s Disease cooperative therapeutic research organization and a world leader in facilitating high-quality clinical research trials and studies in Huntington’s Disease. Mr. Sreedharan holds a B.A. in both Biology and History from the University of North Carolina.
Ricardo Jimenez serves as Senior Vice President, Technical Operations at Neurogene. Mr. Jimenez has nearly three decades of experience in the pharmaceutical and biotechnology industry, the majority of which has been focused in the gene therapy field. He joined Neurogene in 2018 and during his tenure has led the company’s internal build out of process and analytical development, the CGMP manufacturing facility including its design, manufacturing operations, quality assurance, and quality control supporting viral vector manufacturing from research grade to clinical scale. Prior to his work at Neurogene, Mr. Jimenez was the site head of the Lonza Houston manufacturing facility and played a leading role in establishing Lonza as a leading contract cell and gene therapy manufacturer, including designing and overseeing the construction of the cell and gene therapy facility in Texas. He began his career in gene therapy in 2005 at Introgen Therapeutics, where he was responsible for the validation activities for adenoviral-based products, and subsequently served as Head of Quality at Vivante GMP Solutions, a gene therapy contract manufacturing organization acquired by Lonza in 2010. Mr. Jimenez holds a B.S. in Biomedical Science from Texas A&M University.