Study ID: AAV2-RPE65-NHP-PK-003
Study Title: Biodistribution and Shedding of Voretigene Neparvovec Following Subretinal Administration in Non-Human Primates.

Study Report Body:
Objective: To determine the distribution and potential for shedding of voretigene neparvovec vector DNA following subretinal injection in normal non-human primates (NHPs).
Methods: Cynomolgus monkeys received a single unilateral subretinal injection of voretigene neparvovec at a dose level equivalent to the proposed human dose. A comprehensive set of tissues, including ocular tissues, brain regions, major organs, gonads, and bodily fluids (blood, urine, tears), were collected at multiple time points up to 3 months post-administration. Vector DNA levels were quantified using a validated qPCR assay.
Results: The highest levels of vector DNA were found in the injected eye, specifically in the retina/RPE/choroid complex. Low levels of vector DNA were detected in the ipsilateral optic nerve, consistent with local diffusion. Vector DNA was not consistently detected in the brain or any other non-ocular tissues, including the gonads, at any time point. Vector DNA was detected transiently at very low levels in tear and blood samples within the first 72 hours post-injection, and was undetectable thereafter.
Conclusion: Following subretinal administration, voretigene neparvovec remains largely confined to the injected eye, with minimal and transient systemic exposure. These data support the safety of the local administrative route.