Neurogene (NASDAQ:NGNE) is advancing a genetic medicines pipeline focused on rare neurologic diseases, with its lead program NGN-401 aimed at treating Rett syndrome, President and CFO Christine Mikail said at Guggenheim’s 2026 Emerging Outlook Biotech Summit.
Mikail described Rett syndrome as a “devastating neurologic disease” that primarily affects girls. She said children often show developmental delays before losing previously acquired milestones around 18 months to 2–3 years of age, followed by a period of relative stability marked by profound impairments in hand use, communication, and gross motor function. Neurogene’s development focus, she said, is to drive meaningful change in those core domains.
NGN-401 pivotal study timeline and 2026 catalysts
She also outlined a data update planned for “the middle of 2026,” when Neurogene expects to present updated Phase I/II results across 10 dosed patients with at least 12 months of follow-up.
As context for the program’s clinical profile, Mikail referenced Phase I/II data presented last year in eight participants, which she said showed 35 milestones gained across the group—about four skills per patient on average. She characterized the improvements as multi-domain, durable, and continuing to deepen over time, which she said reduces risk heading into the pivotal study.
Design choices and differentiation in Rett gene therapy
Asked about differentiation versus other AAV gene therapies in the clinic, Mikail said Neurogene pursued a “biology-first” approach intended to support a best-in-class profile in Rett syndrome. She highlighted three design priorities:
- Delivering the therapy to the key areas of the brain implicated in Rett syndrome.
- Using a construct that encodes the full-length human MECP2 gene, which she said is intended to ensure translation of functional protein.
- Constraining and regulating transgene expression because MECP2 has a “very narrow therapeutic window” and is “highly toxic” when overexpressed.
Mikail attributed the expression-regulation technology to work by Stuart Cobb and his team at Edinburgh, describing it as proprietary to Neurogene and designed to help avoid overexpression toxicity.
She also addressed the company’s intracerebroventricular (ICV) route of administration. Based on Neurogene’s market research, Mikail said caregivers generally understand the disease’s origin in the brain and have not viewed ICV delivery as a barrier. She added that key opinion leaders have agreed, at least theoretically, that delivering drug into the brain is necessary, and payers have told the company they are largely “route agnostic” and focused instead on objective, disease-modifying efficacy. Mikail said payers responded positively to milestone gains as an endpoint because it is straightforward to see differences in patients.
Safety discussion: HLH and nerve conduction finding
Mikail addressed a prior safety event at a higher dose level, noting that the company had seen hemophagocytic lymphohistiocytosis (HLH) at a 3E15 dose and is now operating at a 1E15 dose in the pivotal study. She said Neurogene is “pretty confident” the 1E15 dose will be clean, citing dose dependence and the fact that 1E15 is three times lower than the dose where HLH occurred.
She said Neurogene added ferritin to its standard immune monitoring labs and is tracking key criteria including hyperferritinemia, cytopenia, and fever. Mikail said HLH can be “fully reversible” if detected early, typically managed with steroids as first-line treatment and anakinra (an IL-1 agent) as a potential second-line option. She added that the company has not seen signs or symptoms of HLH in patients dosed at the 1E15 level and said the company has dosed more than 10 patients without needing to intervene.
On whether anything was unique about the HLH patient, Mikail said Neurogene was not able to conduct an autopsy or determine whether there was a genetic predisposition, noting that some patients can have an underlying disposition to HLH. She said HLH concerns are concentrated early—within the first few days—and that if ferritin elevation and fever are not seen by around day five, the company becomes less concerned for HLH, though gene therapy monitoring generally remains intense over the first two weeks.
Mikail also discussed an abnormal nerve conduction finding reported in one patient. She said the finding was transient and the patient later returned to a normal nerve conduction range. Mikail characterized neuropathy as a potential “class effect” risk with AAV gene therapies, pointing to neuropathy observations across other programs and routes of administration, and said the mechanism may relate to dorsal root ganglion pathology rather than being specific to ICV delivery.
Regulatory engagement and CMC preparedness
Mikail described the regulatory environment as volatile for cell and gene therapy and said Neurogene has tried to reduce risk through frequent engagement with FDA under its START designation. She said the company has quarterly meetings with FDA that include clinical and CMC discussions, and that Neurogene receives and follows written FDA feedback.
As an example, Mikail said Neurogene does not have a six-month interim analysis for registration purposes because FDA advised in writing that six months is not sufficient. She added that Neurogene revisited key trial design questions again in September, seeking updated feedback and making adjustments based on FDA counsel.
On manufacturing, Mikail said Neurogene has its own manufacturing process and a facility in Houston, which she said gives the company control over quality. She said the product’s full-to-empty capsid ratio is highly pure and consistent, and “better than” what she has seen others advertise. Mikail added that Neurogene is manufacturing for commercial at the same scale used in Phase I/II to mitigate comparability risk, and said the company is preparing for process performance qualification (PPQ) as it readies for commercialization.
Commercial outlook and market dynamics
Discussing market dynamics for a one-time gene therapy, Mikail said she does not view Rett syndrome as a “winner-takes-all” market and suggested multiple players could be supported, comparing the situation to Duchenne muscular dystrophy and DM1. She said caregivers are thoughtful consumers because once treated with a gene replacement therapy, patients generally cannot be redosed, and she expects adoption to take time rather than forming a rapid “hockey stick” for any single entrant. She also pointed to infrastructure needs for administering gene therapy as another factor likely to moderate early uptake.
Mikail said success clinically would mean replicating prior Phase I/II findings, including multi-domain and durable improvements in hand function, gross motor function, and communication that accumulate over time. She also said the FDA threshold for success in the pivotal trial is seven out of 20 patients (35%), while adding that Neurogene’s current experience suggests an approximately 80% response rate. She said the study is powered at 99% based on the sample size and assumptions that include a non-intervention response rate, though she said that rate has not been disclosed.
On commercialization preparations, Mikail said Rett syndrome is a centers-of-excellence market and therefore more “finite and containable” to commercialize. She noted the pivotal study uses 13 sites, representing about 60% of U.S. Rett centers of excellence, which she said could convert into top-tier commercial sites. She added that the company is planning for reimbursement support through a patient hub and described a “T-minus 30” plan underway for U.S. launch readiness.
In Europe, Mikail said Neurogene believes there is an opportunity but characterized European regulators as more complicated, particularly around single-arm trial designs. She said the company’s near-term focus is building a strong U.S. file for a biologics license application (BLA) while engaging European regulators in the background to determine how to advance the program there.
About Neurogene (NASDAQ:NGNE)
Neurogene, Inc is a clinical‐stage biotechnology company specializing in the development of gene therapies for rare neurological diseases. The company’s lead platform employs adeno‐associated virus (AAV) vectors designed to deliver functional copies of disease-causing genes directly to the central nervous system. Neurogene’s pipeline focuses on inherited lysosomal storage disorders, including investigational programs for GM1 and GM2 gangliosidoses, with additional preclinical efforts targeting other monogenic neurodegenerative conditions.
Neurogene’s proprietary AAV9‐based delivery system has been engineered to cross the blood-brain barrier, aiming to provide durable gene expression in affected tissues.
