Breakthrough Therapy Designation Request (Submitted 2014): This document provides the rationale for the Breakthrough Therapy Designation request for the treatment of nyctalopia in patients with Leber congenital amaurosis due to RPE65 mutations. It presented preliminary clinical evidence from the Phase 1 study indicating that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint. The designation was granted on September 24, 2014.