Gyroscope Therapeutics Announces Positive Interim Data from Phase I/II FOCUS Trial of Investigational Gene Therapy GT005

Interim Data Showed GT005 Was Well Tolerated in Patients with Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

Majority of Patients Treated with GT005 Had Increases in Complement Factor I (CFI) Levels, with an Average Increase of 146% Compared to Baseline Interim Data Demonstrated Potential for Single Administration of GT005 to Down-Regulate Overactive Complement System, a Key Driver of AMD

Gyroscope Therapeutics Limited, a clinical-stage gene therapy company focused on diseases of the eye, today announced 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 (GA) secondary to age-related macular degeneration (AMD). Interim results showed GT005 was well tolerated and resulted in sustained increases in vitreous Complement Factor I (CFI) 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.

“Our investigational gene therapy, GT005, is designed to restore balance to an overactive complement system and reduce inflammation by increasing production of the CFI protein. We are excited by these early results from the FOCUS trial that showed GT005 has been well tolerated to date, increased CFI levels in a durable manner and caused down-regulation of an overactive complement system,” said Dr. Waheed. “These results give us confidence that a one-time treatment with GT005 may have the potential to slow progression of geographic atrophy, and this is being evaluated in our ongoing Phase II clinical trials.” 

“There is strong evidence that an overactive complement system is a key driver of dry AMD,” said Arshad Khanani, M.D., M.A., Director of Clinical Research at Sierra Eye Associates, Clinical Associate Professor at the University of Nevada, Reno School of Medicine, and an investigator in the FOCUS trial. “The recently released data from the FOCUS trial suggest the potential of a one-time gene therapy with GT005 to regulate an overactive complement system. It is encouraging that GT005 generated sustained increases in CFI in a majority of the patients, even in some patients treated more than a year ago. We continue to look forward to learning more about GT005 as a potential treatment for GA in the ongoing Phase II clinical trial programme.”

Interim Data from the 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).  

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 (VEGF) 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).

Dr. Waheed’s 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 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 dampen the system’s overactivity and reduce inflammation, with the goal of preserving a person’s eyesight.

As of December 2020, 22 patients had been dosed with GT005 in the FOCUS trial across Cohorts 1 to 5. Dosing in Cohorts 1, 2, 3 and 5 is complete. Patients continue to be enrolled in the dose expansion Cohort 4, which is planned to enrol up to 20 patients. 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.

Gyroscope is also evaluating GT005 in two Phase II clinical trials. EXPLORE [NCT04437368] and HORIZON [NCT04566445] are Phase II, multicentre, randomised, controlled 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. EXPLORE is enrolling people who have GA secondary to AMD who have rare variants in their CFI gene. 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 50 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.


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.