Applied Genetic Technologies Corporation reported positive three-month interim data from its ongoing Phase 2 Skyline trial of AGTC-501, a recombinant AAV viral vector-based gene therapy targeting mutations in the RPGR gene in patients with X-linked retinitis pigmentosa (XLRP). There were robust improvements in visual sensitivity, the trial's primary efficacy endpoint, in multiple patients three months after dosing, with a 62.5% response rate in dose group B and a 25% response rate in dose group A. This is well above the statistically significant 50% response rate the Vista Phase 2/3 trial for XLRP is powered to detect. The Company considers a responder to be a patient who has an improvement in visual sensitivity as assessed by microperimetry of at least 7 decibels (dB) in at least 5 loci.

Importantly, for responders in this trial, the number of loci that improved by at least 7 dB was between 9 and 17. It is also notable that the mean visual sensitivity of the entire macula increased and the area of the macula with visual sensitivity also increased in the patients who were responders. Although these results exceeded the current standard set by the United States Food and Drug Administration (FDA) that at least 5 loci increase by at least 7 dB, the improved loci were not pre-specified, as also required in the FDA standard.

There was a significant difference in visual sensitivity as assessed by MAIA microperimetry in the treated eyes compared with the untreated eyes of all Skyline responders at 3 months. In the Phase 1/2 trial, patients who were responders at 3 months remained responders at 12 months. Based on the durability of the Phase ½ improvements in visual sensitivity, believe the results observed at 3 months in the Skyline trial will be consistent at 12 months.

Consistent with the previously reported Phase 1/2 results, AGTC-501 was generally well-tolerated in this trial with no clinically relevant safety concerns attributed to the study agent. The majority of adverse events were non-serious and mild to moderate in severity. The Company believes that the favorable safety profile is largely the result of a strong focus on product design, extensive pre-clinical testing, enhanced inclusion and exclusion criteria, and surgical consistency.

Skyline is a 14 patient Phase 2 expansion of the Company's Phase 1/2 clinical trial, in which patients are randomized to either a high or low dose of AGTC-501 with the main objective to evaluate the efficacy, safety and tolerability of AGTC-501. The primary endpoint is the proportion of treated eyes that demonstrate improvement from baseline in visual sensitivity at 12 months with secondary endpoints (also at 12 months) that include improvements in best-corrected visual acuity (BCVA) and the patient's ability to navigate a mobility maze more successfully under varying light and challenge conditions. The interim analysis includes 13 male pediatric and adult patients that were treated over a 10-fold dose range in two groups.

The fourteenth patient had not yet reached the three-month time point at the cut-off date for the interim analysis. Patients in the Skyline trial were younger than the patients in the comparable dose groups from the Phase 1/2 clinical trial with better BCVA and better mean visual sensitivity at baseline than in the previously reported Phase 1/2 study. Given the higher baseline BCVA, improvements in BCVA at three months were less pronounced than in the Phase 1/2 clinical trial.

More than half of the patients, including four of the six responders in visual sensitivity, showed improvement in the mobility maze based on light levels passed, improved speed and/or reduced errors.