Neurogene (NGNE) TD Cowen 46th Annual Health Care Conference summary

Program and platform overview

• Lead program NGN-401 targets Rett syndrome using the EXACT regulated gene therapy platform, designed to control MECP2 transgene expression and avoid toxicity from over- or under-expression.

• Rett syndrome affects 15,000–20,000 patients in the US and Europe, representing a multi-billion dollar market opportunity.

• The EXACT platform uses a microRNA-based safety valve to ensure cell-by-cell regulation of gene expression.

Clinical progress and data

• Enrollment for the phase III Embolden trial is expected to complete in Q2, with high demand and 13 clinical sites active.

• Breakthrough Therapy designation was granted based on October 30th phase I/II data, including video evidence of skill gains.

• Phase I/II data show consistent, time-dependent, multi-domain improvements in developmental milestones, with no plateau observed at 12 months.

• Patients have gained 23 to 35 developmental milestones, with deepening skill quality over time.

• The responder rate in early data is 80%, with gains seen across multiple domains such as hand function, motor skills, and communication.

Safety and risk management

• A prior HLH event at a higher dose led to dose adjustment and implementation of HLH monitoring and treatment protocols.

• No HLH cases have occurred at the current dose; nerve conduction studies are standard protocol due to AAV-related neuropathy risks.

• One transient case of abnormal nerve conduction was observed and resolved; such events are considered a class effect of AAV therapies.