The trial demonstrated an 85% median reduction in cerebrospinal fluid (CSF) levels of heparan sulfate D2S6, sustained for up to two years. How significant is this reduction in terms of addressing the neurocognitive and systemic aspects of Hunter syndrome?

At the pivotal dose level, 80% of patients discontinued intravenous enzyme replacement therapy or remained treatment-naïve. What implications does this have for long-term patient management, and how does RGX-121 potentially improve quality of life compared to continuous ERT?

Results from the dose-finding phase indicate that the majority of patients exceeded expectations in neurodevelopmental function compared to natural history data. How important are these findings, and what could they mean for early intervention in children with neuronopathic MPS II?

REGENXBIO is pursuing accelerated approval using cerebrospinal fluid GAG levels as a surrogate endpoint. How do surrogate endpoints like these help in fast-tracking treatments for rare diseases like Hunter syndrome, and what additional data might be needed to solidify clinical benefits?

With the trial showing sustained biomarker reductions for up to two years, what are your expectations regarding the long-term effectiveness of RGX-121? Could this potentially serve as a permanent or near-permanent solution for MPS II?

Given the success of RGX-121 in treating patients with neuronopathic MPS II, do you see any potential for expanding gene therapy applications to other forms of MPS or similar lysosomal storage disorders?

The trial has shown that RGX-121 is well tolerated in the 25 patients dosed across all phases. What are the key safety considerations for using gene therapy in children with MPS II, and how does this treatment compare to other emerging therapies in terms of risk?

With a Biologics License Application (BLA) filing expected in the near future, what are the key hurdles REGENXBIO must overcome to gain approval for RGX-121? How might this gene therapy change the treatment landscape for MPS II, particularly in terms of patient access and cost considerations?