Gyroscope Therapeutics Announces Positive Interim Phase I / II Data for Experimental Gene Therapy GT005 at Retina Society Annual Scientific Meeting


LONDON–(COMMERCIAL THREAD) – Gyroscope Therapeutics Holdings plc (“Gyroscope”), a clinical-stage gene therapy company focused on eye disease, announced positive interim data from the ongoing FOCUS Phase I / II open-label clinical trial of its unique gene therapy experimental trial, GT005, in people with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were presented today in an oral session at the 54th Retina Society Annual Scientific Meeting.

Safety data from 28 patients showed that GT005 continues to be well tolerated without any serious treatment-related adverse events. There was no evidence of clinically significant GT005-induced inflammation. Biomarker data from 13 patients, ranging from approximately seven months after treatment to almost two years, continued to demonstrate sustained increases in vitreous complement factor I (CFI) levels from baseline in the patient. majority of patients, as well as sustained decreases in downstream proteins associated with activation of the complement system. A new analysis showed no increase in systemic levels of CFI circulating in the blood, suggesting that the effects of GT005 remain localized in the eye as expected.

These data are presented today by Szilárd Kiss, MD, Associate Professor of Ophthalmology and Director of Clinical Research in the Department of Ophthalmology at Weill Cornell Medical College.

“This data builds on the positive intermediate results we shared earlier this year, enhancing the potential of GT005 to restore balance to a hyperactive complement system and continuing to show an encouraging safety profile, ”said Nadia Waheed, MD, MPH, Chief Medical Officer, Gyroscope Therapeutics. “This is an exciting time in further research, and we believe that one-time gene therapy has the potential to be a long-term solution for people with geographic atrophy. We continue to collect data from FOCUS and register our Phase II clinical trials evaluating the potential of GT005 to slow the progression of devastating vision loss inflicted by GA.

GA is one of the leading causes of permanent vision loss in people aged 55 and over, and there is no approved treatment.1.2 An overactive complement system is considered to be a key factor in AMD, and CFI is a natural regulator of overactivity in the complement system.

Update of interim data from the Phase I / II FOCUS trial

TO CONCENTRATE [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 administered to patients in Cohorts 1-4 using the standard Transvitreal procedure and Cohorts 5-7 using the exclusive Gyroscope Orbit.MT subretinal delivery system.

Data have been reported on patients in cohorts 1 to 4.

Safety data from 28 patients showed:

  • There was no dose-related trend in the frequency or type of adverse events and no serious adverse events related to GT005.

  • As previously reported, there was one possible adverse event related to GT005, which was a suspicion of moderately severe choroidal neovascularization during a patient’s six-month follow-up. This has been successfully treated with anti-vascular endothelial therapy (VEGF).

  • There were 16 adverse events considered to be related to the surgery; the majority of them were mild (mild n = 12; moderate n = 4).

Biomarker data were reported in 13 patients who received GT005 at least 29 weeks prior to analysis:

  • Eleven of 13 patients treated with GT005 had increases in CFI levels, with an average increase of 122% from baseline (p = 0.002).

  • Of the 11 patients with increased CFI levels, all had sustained increases from baseline at their most recent endpoint (week 29 or beyond), with two of these patients exhibiting increases sustained at nearly two years (one at 84 weeks and one at 100 weeks).

  • There were sustained decreases in glassy levels of key proteins associated with complement activation (Ba and C3 degradation proteins: C3b and iC3b).

  • An average 46% decrease was observed in Ba protein levels from baseline (n = 11; p = 0.001); and, a mean decrease of 46% was also observed in C3 degradation proteins from baseline (n = 13; p = 0.001).

  • Increases in CFI levels and decreases in Ba and C3 degrading proteins have been observed in patients with rare variants of the CFI gene as well as those in the wider GA population.

The presentation will be available on the Gyroscope website at

About GT005

GT005 is designed as a unique, experimental AAV2-based gene therapy for GA secondary to AMD that is administered under the retina. GT005 aims to restore the balance of an overactive complement system, part of the immune system, by increasing the production of the CFI protein. Overactivation of complement can lead to inflammation that damages healthy tissue, and it has been strongly correlated with the development and progression of AMD. The CFI protein regulates the activity of the complement system. It is believed that increasing the production of CFI could reduce inflammation, in an effort to preserve a person’s eyesight.

In addition to FOCUS, Gyroscope is evaluating GT005 in two Phase II clinical trials. TO EXPLORE [NCT04437368] and HORIZON [NCT04566445] are Phase II, multicenter, randomized, controlled, masked evaluator trials evaluating the safety and efficacy of GT005 administered as a single subretinal injection. The primary endpoint for both trials is progression of GA over 48 weeks (measured by change in GA area from baseline). EXPLORE is recruiting people with GA secondary to AMD and carriers of rare variants of their CFI gene associated with low levels of CFI. HORIZON is recruiting a larger group of people with GA secondary to AMD.

About age-related dry macular degeneration (AMD) and geographic atrophy (GA)

Dry AMD is one of the leading causes of permanent vision loss in people over 55 and is a devastating diagnosis.1 There is currently no approved treatment for dry AMD, which is the most common form, affecting about 85-90% of people with AMD.2 As dry AMD progresses, it leads to GA, an irreversible degeneration of retinal cells, causing gradual and permanent loss of central vision. This disease can seriously affect a person’s daily life as they lose the ability to drive, read and even see the faces of those close to them.

About the Gyroscope: Vision for Life

Gyroscope Therapeutics is a clinical-stage gene therapy company that develops gene therapy beyond rare diseases to treat eye diseases that cause vision loss and blindness. Our main investigational gene therapy, GT005, is currently being evaluated in phase II clinical trials for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), one of the main causes of blindness. GT005 has received Fast Track designation from the United States Food and Drug Administration for the treatment of people with GA.

Backed by leading investors in the life sciences, Gyroscope has built a global organization combining discovery, research, drug development, a manufacturing platform and surgical administration capabilities. Based in London and with offices in Philadelphia and San Francisco, our mission is to preserve sight and combat the devastating impact of blindness.

For more information visit: and follow us on Twitter (@GyroscopeTx) and on LinkedIn.

1 National Eye Institute. Macular degeneration. Page last revised on June 22, 2021. Accessed September 28, 2021.

2 American Macular Degeneration Foundation. What is Macular Degeneration? Accessed September 28, 2021.

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