Neurogene (NasdaqGM:NGNE) 2026 Conference Summary Company Overview - **Company**: Neurogene - **Focus**: Genetic medicines for devastating neurological diseases, particularly Rett syndrome - **Lead Program**: NGN-401 for the treatment of Rett syndrome, a severe disorder primarily affecting girls [3][4] Industry Context - **Market Opportunity**: Approximately 15,000-20,000 patients in the U.S. and major European markets, representing a multi-billion dollar market with limited current penetration [4] - **Gene Therapy Pricing**: Premium pricing expected for gene therapies, which may limit initial market penetration [4] Clinical Development - **Trial Status**: The Embolden registrational trial is ongoing, with multiple patients dosed before the end of the previous year. Enrollment and dosing are expected to complete in Q2 of the current year [5][19] - **Data Updates**: Phase 1/2 data from an 8-patient pediatric cohort announced in November, with a more comprehensive update expected mid-year [5] Efficacy and Outcomes - **Functional Gains**: The primary endpoint focuses on developmental milestones, with families and payers looking for functional gains rather than just single milestones. Multiple skill gains have been observed in patients, with no plateau in function noted so far [10][11] - **Durability of Benefits**: The therapy shows potential for durable gains over time, consistent with the biology of the disease [16] Delivery Method - **ICV Administration**: Intracerebroventricular (ICV) administration is a routine neurosurgical procedure, not seen as a barrier to adoption. It is performed by trained neurosurgeons and takes about one hour [18][20] - **Monitoring**: Post-procedure monitoring for potential toxicities is standard practice, similar to other gene therapies [21][22] Regulatory Considerations - **FDA Requirements**: The FDA requires at least 12 months of data for gene therapy approvals, which Neurogene is adhering to, avoiding the risk of a 6-month endpoint [27][28] - **Global Regulatory Path**: Currently focused on the U.S. market, with PRIME designation in Europe. Future updates on European regulatory engagement will be provided [33][34] Commercial Strategy - **Manufacturing Capacity**: Neurogene has in-house manufacturing capabilities in Houston, Texas, which will support the commercial launch without significant capital expenditures [30][31] - **Market Positioning**: The U.S. is the primary target market, with considerations for pricing strategies to ensure value is maintained without significant discounts in other regions [34][35] Patient Population and Eligibility - **Eligibility Criteria**: Patients with prior experience on other treatments like DAYBUE can qualify for gene therapy, provided they meet specific immunosuppression criteria [46][49] - **Market Demand**: There is a significant demand for treatment among families, with a focus on the urgency of access to gene therapy [51][54] Conclusion - Neurogene is advancing its lead program for Rett syndrome with a strong focus on clinical efficacy, regulatory compliance, and strategic market positioning. The company is well-prepared for the upcoming pivotal data and potential commercialization, addressing a significant unmet need in the patient population.

Financial Data and Key Metrics Changes - Research and development expenses increased to $20.1 million for Q2 2025 from $15.1 million in Q2 2024, driven by BLA enabling processes and clinical trial activities [53] - General and administrative expenses rose to $8.6 million for Q2 2025 compared to $7.3 million in Q2 2024, primarily due to higher legal and professional fees [53] - Net loss for Q2 2025 was $26.9 million or $0.09 per share, compared to a net loss of $20.9 million or $0.09 per share for Q2 2024 [54] - As of June 30, 2025, the company had $312.8 million in cash and cash equivalents, reflecting gross proceeds of $230 million from a follow-on financing [54][55] Business Line Data and Key Metrics Changes - The REVEAL pivotal trial for TATIA-102 has commenced site activation, with patient enrollment expected to begin in Q4 2025 [11][12] - In the Part A data of the REVEAL trials, all 10 patients treated with TATIA-102 gained or regained one or more developmental milestones, indicating a 100% response rate [15][32] Market Data and Key Metrics Changes - Rett syndrome affects an estimated 15,000 to 20,000 patients across the U.S., Europe, and the UK, highlighting the market potential for TATIA-102 [12][13] Company Strategy and Development Direction - The company aims to redefine the treatment landscape for Rett syndrome with TATIA-102, a gene therapy targeting the genetic root cause of the disease [13][14] - The pivotal trial design focuses on the developmental plateau population, where the likelihood of achieving developmental milestones is approximately zero percent after age six [15][27] - The company has established a two-study approach to generate safety and efficacy data across the broad Rett syndrome population [19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress made towards the potential registration of TATIA-102, with a clear path forward following alignment with the FDA [11][57] - The company anticipates reporting new supplemental clinical data from Part A of the REVEAL trials in Q4 2025, supporting the therapeutic impacts of TATIA-102 [57] Other Important Information - The company completed a public follow-on offering that extended its cash runway into 2028 [16] - The pivotal trial will evaluate the percentage of patients in the developmental plateau population who gain or regain developmental milestones, with each patient serving as their own control [20][22] Q&A Session Summary Question: Is the 100% response rate for the pivotal trial primary endpoint in Part A the bar for Part B? - Management noted that while the results in Part A are compelling, maintaining a 100% standard is difficult. The statistical plan for Part B will use a null hypothesis of 6.7% for milestone gains, which is significantly lower than the observed results in Part A [59][60] Question: Are there specific time points for milestone occurrences? - Management indicated that improvements are seen over time, with gains typically occurring at most follow-up visits. Some critical gains may not be captured in the milestone assessment but still represent significant improvements in daily functioning [63][66] Question: How does the gene therapy differentiate from competitors? - The company emphasized its unique approach in defining clinical efficacy through meaningful functional gains, supported by a comprehensive natural history dataset. This sets it apart from competitors and aligns with regulatory expectations [69][72] Question: Will there be pushback on using interim readouts for BLA filing? - Management confirmed that the interim analysis approach was discussed with the FDA and is based on robust data from Part A, which supports the primary endpoint at both six and twelve months [79][82] Question: What to expect from the new supplemental REVEAL Part A data in Q4? - Management anticipates sharing additional data points, including video documented milestones and their impact on daily living, at both a medical conference and a company update [84][85]