16 February 2021 - - UK-based clinical-stage gene therapy company Gyroscope Therapeutics Ltd has released positive interim safety, protein expression and biomarker data from the ongoing open-label Phase I/II FOCUS clinical trial of its investigational gene therapy, GT005, in patients with geographic atrophy secondary to age-related macular degeneration, the company said.

Interim results showed GT005 was well tolerated and resulted in sustained increases in vitreous Complement Factor I levels in the majority of patients, as well as decreases in the downstream complement proteins associated with over-activation of the complement system.

These results were observed both in GA patients who had rare variants in their CFI gene as well as those who did not.

The data were presented TODAY at the Angiogenesis, Exudation, and Degeneration 2021 virtual meeting by Nadia Waheed, M.D., MPH, Chief Medical officer, Gyroscope Therapeutics.

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).

Interim results were reported TODAY from patients in Cohorts 1 to 4. The three doses of GT005 evaluated were well tolerated and there were no signs of GT005-induced inflammation.

There were no dose-related trends in the frequency or type of adverse events and no GT005-related serious adverse events.

There was one possible GT005-related adverse event, which was a suspected choroidal neovascularization of moderate intensity at the patient's six-month follow up. This was successfully treated with anti-vascular endothelial growth factor therapy.

There were 12 adverse events considered to be related to the surgical procedure; the majority of these were mild (mild n=9; moderate n=3).

Interim results showed sustained increases in vitreous CFI levels in the majority of patients, as well as decreases in the vitreous levels of key proteins associated with complement over-activation (Ba and C3 breakdown proteins: C3b, iC3b and C3c).

Nine out of 10 patients treated with GT005 had increases in CFI levels, with an average increase of 146% compared to baseline (p=0.02).

Of the nine patients with increased CFI levels, eight showed sustained increases at week 24 and beyond, with one showing a sustained increase at 84 weeks. The most recent measurement for the ninth patient with increased CFI levels was week 12.

Increases in CFI levels were observed in patients with rare variants in the CFI gene as well as those who did not have rare variants.

There was an average decrease of 41% in levels of the Ba protein compared to baseline at weeks 24 to 56 (n=6; p=0.03), and an average decrease of 42% in the C3 breakdown proteins compared to baseline at weeks 24 to 56 (n=9; p=0.03). These decreases were observed in patients with and without CFI rare variants.

There was a significant correlation between increased CFI levels and decreases in Ba levels (p=0.03).