Gyroscope Therapeutics Initiates Phase 2 Program Evaluating its Investigational Gene Therapy for Dry AMD

Source: Gyroscope Therapeutics

Gyroscope Therapeutics announced the initiation of its phase 2 program evaluating its investigational gene therapy, GT005, for the treatment of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). GT005 is a one-time AAV-based gene therapy that is delivered under the retina. The goal of the phase 2 clinical trial program is to determine if GT005 has the potential to slow the progression of GA.

Gyroscope plans to conduct two phase 2 trials evaluating GT005 in people with GA. The first, called EXPLORE, is enrolling people who have a mutation in their Complement Factor I (CFI) gene [NCT04437368]. The first patient to receive GT005 in EXPLORE was enrolled and dosed by Arshad M. Khanani, MD, at Sierra Eye Associates in Reno, Nevada.

“Geographic atrophy is a devastating diagnosis, as there are no approved treatments for this gradual and irreversible loss of vision,” Dr. Khanani, Director of Clinical Research at Sierra Eye Associates and Clinical Associate Professor at the University of Nevada, Reno School of Medicine, and an investigator in the EXPLORE trial, said in a company news release. “We are excited to participate in this trial evaluating GT005 for the potential to slow progression of geographic atrophy. We believe one-time gene therapies could be a major advancement in the field of retinal disease.”

GT005 is designed to restore balance to an overactive complement system, a part of the immune system, by increasing production of the CFI protein. An overactive complement system has been implicated in the development of AMD. The CFI protein regulates the activity of the complement system. It is believed that increasing CFI production will dampen the system’s overactivity and reduce inflammation, with the goal of preserving a person’s eyesight.

Research has found that approximately 3% of people with dry AMD have certain CFI mutations that correlate with low CFI levels in the blood and a higher risk of developing AMD.1 Gyroscope estimates that more than 100,000 people with GA in the United States and EU5 European countries may have these mutations.1,2,3,4 The EXPLORE trial will evaluate GT005 in this group of people with mutations in their CFI gene.

Research has also shown that a small supplementation of CFI can normalize complement activity in the blood,5 suggesting GT005 may also be applicable for a broader group of people with GA, according to Gyroscope Therapeutics. It is estimated that approximately one million people in the United States alone have GA.4 Gyroscope therefore plans to initiate a second phase 2 trial in 2020 that will evaluate GT005 in a broader GA population.

“We are excited about the potential of GT005 for people with dry AMD. Research suggests GT005 may be best suited for people with certain mutations in their CFI gene. However, evidence also suggests it may have potential for a broader population of people with geographic atrophy,” said Nadia Waheed, MD, MPH, Chief Medical Officer of Gyroscope. “We have designed our clinical program to evaluate these groups in two distinct phase 2 trials, with the goal of determining which patients GT005 may be most appropriate for and to further our understanding of the role of the complement system in AMD.”

About the EXPLORE Trial

EXPLORE is a phase 2, multicenter, randomised trial evaluating the safety and efficacy of GT005 administered as a single subretinal injection.

EXPLORE is enrolling people who are aged 55 or older and have a clinical diagnosis of GA secondary to dry AMD and who have a mutation of the CFI gene. People being screened for the trial will be genotyped for the mutations. Trial participants will be randomised to one of three treatment arms: GT005 dose 1, GT005 dose 2 or a control arm. Participants in the control arm will receive current standard of care. The primary endpoint of EXPLORE is progression of GA over 48 weeks. The study will also evaluate GT005 for various safety and tolerability measures. Gyroscope plans to enroll approximately 75 patients at approximately 40 centres based in the United States, United Kingdom, Europe and Australia.

Gyroscope will announce details about the second phase 2 trial of GT005 at a later date.


1 Kavanagh D, Yu Y, Schramm EC, et al. Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels. Hum Mol Genet. 2015;24(13):3861-3870.
2 Data on File.
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5 Lachmann PJ, Lay E, Seilly DJ, Buchberger A, Schwaeble W, Khadake J. Further studies of the down-regulation by Factor I of the C3b feedback cycle using endotoxin as a soluble activator and red cells as a source of CR1 on sera of different complotype. Clin Exp Immunol. 2016;183(1):150-156.
6 Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–116.
7 National Eye Institute. Age-Related Macular Degeneration. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration. Accessed July 16, 2020.
8 Centers for Disease Control and Prevention. Age-Related Macular Degeneration. https://www.cdc.gov/visionhealth/basics/ced/. Page last reviewed June 3, 2020. Accessed August 4, 2020.

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