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

GT005 Continues to be Well Tolerated with Encouraging Biomarker Results in Patients with Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

New Data from Phase I/II FOCUS Clinical Trial Reflect Additional Patients and Longer Follow-Up

LONDON--()--Gyroscope Therapeutics Holdings plc (“Gyroscope”), a clinical-stage gene therapy company focused on diseases of the eye, 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 today 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 today by Szilárd Kiss, M.D., Associate Professor in Ophthalmology and Director of Clinical Research in the Department of Ophthalmology, Weill Cornell Medical College.

These data build on the positive interim results we shared earlier this year, reinforcing GT005’s potential to restore balance to an overactive complement system and continuing to show an encouraging safety profile,” said Nadia Waheed, M.D., MPH, Chief Medical Officer, Gyroscope Therapeutics. “It’s an exciting time in complement research, and we believe a 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 enrol our Phase II clinical trials evaluating the potential of GT005 to slow progression of the devastating vision loss that GA inflicts.”

GA is a leading cause of permanent vision loss for people aged 55 and older, and there are no approved treatments.1,2 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.

The presentation will be made available on Gyroscope’s website at

About GT005

GT005 is designed as an AAV2-based, one-time investigational gene therapy for GA secondary to AMD that is delivered under the retina. GT005 aims to restore balance to an overactive complement system, a part of the immune system, by increasing production of the CFI protein. Complement overactivation can lead to inflammation that damages healthy tissues, 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 CFI production could reduce inflammation, with the goal of preserving a person’s eyesight.

In addition to FOCUS, Gyroscope is evaluating GT005 in two Phase II clinical trials. EXPLORE [NCT04437368] and HORIZON [NCT04566445] are Phase II, multicentre, randomised, controlled, assessor-outcomes masked trials evaluating the safety and effectiveness 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 enrolling people who have GA secondary to AMD and carry rare variants in their CFI gene associated with low levels of CFI. HORIZON is enrolling a broader group of people who have GA secondary to AMD.

About Dry Age-Related Macular Degeneration (AMD) and Geographic Atrophy (GA)

Dry AMD is a leading cause of permanent vision loss in people over the age of 55 and is a devastating diagnosis.1 There are currently no approved treatments for dry AMD, which is the most common form, impacting approximately 85-90% of people with AMD.2 As dry AMD advances, it leads to GA, an irreversible degeneration of retinal cells, causing a gradual and permanent loss of central vision. This disease can severely impact a person’s daily life as they lose the ability to drive, read and even see the faces of loved ones.

About Gyroscope: Vision for Life

Gyroscope Therapeutics is a clinical-stage gene therapy company developing gene therapy beyond rare disease to treat diseases of the eye that cause vision loss and blindness. Our lead 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), a leading cause of blindness. GT005 has received Fast Track designation from the U.S. Food and Drug Administration for the treatment of people with GA.

Supported by leading life sciences investors, Gyroscope has built a global organisation combining discovery, research, drug development, a manufacturing platform and surgical delivery capabilities. Headquartered in London with locations in Philadelphia and San Francisco, our mission is to preserve sight and fight the devastating impact of blindness.

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

1 National Eye Institute. Age-Related Macular Degeneration. Page last reviewed June 22, 2021. Accessed September 28, 2021.
2 American Macular Degeneration Foundation. What is Macular Degeneration? Accessed September 28, 2021.


Kate Archer
Director, Corporate Affairs
Gyroscope Therapeutics

Release Summary

Gyroscope Therapeutics announces positive interim phase I/II data for investigational gene therapy GT005 at Retina Society Annual Scientific Meeting.


Kate Archer
Director, Corporate Affairs
Gyroscope Therapeutics