Gyroscope Therapeutics Holdings plc announced positive interim data from the ongoing open-label Phase I/II FOCUS clinical trial of its investigational one-time gene therapy, GT005, in people with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were presented in an oral session at the Retina Society’s 54th Annual Scientific Meeting. Safety data from 28 patients showed GT005 continues to be well tolerated with no treatment-related serious adverse events. There was no evidence of clinically significant GT005-induced inflammation. Biomarker data from 13 patients, ranging from approximately seven months post treatment to nearly two years, continued to demonstrate sustained increases in vitreous complement factor I (CFI) levels compared to baseline in the majority of patients, as well as sustained decreases in downstream proteins associated with complement system activation. A new analysis showed no increases in systemic CFI levels circulating in the blood, suggesting GT005’s effects remain localised to the eye as intended. These data are being presented by Szilárd Kiss, M.D., Associate Professor in Ophthalmology and Director of Clinical Research in the Department of Ophthalmology, Weill Cornell Medical College. GA is a leading cause of permanent vision loss for people aged 55 and older, and there are no approved treatments. An overactive complement system is believed to be a key driver of AMD, and CFI is a natural regulator of complement system overactivity. Updated Interim Data from Phase I/II FOCUS Trial: FOCUS [NCT03846193] is an open-label Phase I/II clinical trial evaluating the safety and dose response of three doses of GT005 given as a single subretinal injection to patients with GA secondary to AMD. The trial is divided into several cohorts, including dose escalation (Cohorts 1, 2, 3, 5 and 6) and dose expansion (Cohorts 4 and 7). GT005 is delivered to patients in Cohorts 1 to 4 using the standard transvitreal procedure and in Cohorts 5 to 7 using Gyroscope’s proprietary OrbitTM subretinal delivery system. Data were reported from patients in Cohorts 1 to 4. Safety data from 28 patients showed: There were no dose-related trends in the frequency or type of adverse events and no GT005-related serious adverse events. As previously reported, there was one possible GT005-related adverse event, which was a suspected choroidal neovascularization of moderate severity at one patient’s six-month follow-up. This was successfully treated with anti-vascular endothelial growth factor (VEGF) therapy. There were 16 adverse events considered to be related to the surgical procedure; the majority of these were mild (mild n=12; moderate n=4). Biomarker data were reported from 13 patients who had received GT005 at least 29 weeks before analysis: Eleven out of 13 patients treated with GT005 had increases in CFI levels, with an average increase of 122% compared to baseline (p=0.002). Of the 11 patients with increased CFI levels, all showed sustained increases compared to baseline at their most recent point of analysis (week 29 or beyond), with two of these patients showing sustained increases at nearly two years (one at 84 weeks and one at 100 weeks). There were sustained decreases in the vitreous levels of key proteins associated with complement activation (Ba and C3 breakdown proteins: C3b and iC3b). An average decrease of 46% was observed in levels of the Ba protein compared to baseline (n=11; p=0.001); and, an average decrease of 46% was also observed in the C3 breakdown proteins compared to baseline (n=13; p=0.001). Increases in CFI levels and decreases in Ba and the C3 breakdown proteins were observed in patients with rare variants in the CFI gene as well as those in the broader GA population.