Gyroscope Therapeutics, a retinal gene therapy company, has developed the Orbit subretinal delivery system (SDS). The technology is designed to deliver therapies to the retina without the need for invasive procedures, such as vitrectomies, which involve removing the gel-like substance within the eye, or retinotomies, which involve making a hole in the retina.
The company hopes that by combining medical devices that allow minimally invasive delivery with innovative gene therapies they can develop transformative therapeutic strategies. Gyroscope Therapeutics recently announced that the FDA has granted 510(k) clearance for the Orbit SDS.
The intended payload for the device is a gene therapy, which increases the expression of a gene involved in the complement system. The investigational therapy is designed to treat dry age-related macular degeneration, a condition which causes blindness and for which there are no approved treatments. The new treatment is intended to reduce an overactive immune response and inflammation within the eye. A clinical trial of this gene therapy is ongoing.
Here’s a very short video showing how the Orbit SDS system is applied:
Medgadget had the opportunity to talk to Mike Keane, Chief Technology Officer at Gyroscope Therapeutics, about the Orbit SDS.
Conn Hastings, Medgadget: What inspires you at Gyroscope Therapeutics?
Mike Keane, Gyroscope Therapeutics: I was one of the founders of Orbit Biomedical in 2018. We founded Orbit because we felt strongly that our new approach to subretinal delivery could enable the whole field of cell and gene therapy. Merging with Gyroscope in 2019 was an instrumental step in achieving our goals. We are now part of an amazing gene therapy company that combines gene therapy and device development expertise. Having inhouse device expertise puts us in a unique position to be able to advance our programs independently and also through partnerships. Being a part of this innovative company truly inspires me. The whole team is dedicated to fighting the devastating impact of blindness. Gyroscope was created to bring the right people and resources together to fundamentally help transform the lives of patients suffering from retinal disease. Our promise to patients is big – vision for life.
Medgadget: Please give us an overview of current approaches that are used to access the subretinal space, such as vitrectomies and retinotomies.
Mike Keane: To access the subretinal space, ophthalmologists typically preform a vitrectomy (a procedure that involves removing the vitreous, the gel-like substance that fills the eye) followed by creating a retinotomy (a hole in the retina).
Medgadget: How does the Orbit Subretinal Delivery System work? How is it different than the techniques mentioned above?
Mike Keane: The Orbit SDS is indicated for microinjection into the subretinal space at the back of the eye. The microinjection procedure is designed to avoid damaging the structure of the eye by preventing the need for a vitrectomy and eliminating the need to create a retinotomy in order to access the subretinal space.
Medgadget: Please give us an overview of the GT005 gene therapy. What is it intended to treat, and how does it work?
Mike Keane: At Gyroscope, we are developing gene therapy beyond rare disease. GT005 is an investigational one-time AAV-based gene therapy that is delivered under the retina and is intended to slow the progression of geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Dry AMD is a leading cause of permanent vision loss in people over the age of 50, and there are currently no FDA-approved treatments for this devastating condition.
Research suggests that when a part of the immune system called the complement system is overactive, it leads to inflammation that damages healthy eye tissues. The CFI protein regulates the activity of the complement system. GT005 is designed to restore balance to an overactive complement system by increasing production of the CFI protein. 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.
Medgadget: Is the Orbit SDS intended primarily for gene delivery, or could it be used to deliver a variety of therapeutics to the subretinal space?
Mike Keane: At this time the Orbit SDS is indicated for microinjection of Balanced Salt Solution (saline solution) into the subretinal space.
We are planning to evaluate delivery of GT005 using the Orbit SDS and anticipate starting to generate data delivering GT005 with the Orbit SDS in a planned future cohort in the ongoing Phase I/II FOCUS trial. Additionally, we plan to enter into licensing and collaboration arrangements involving the Orbit SDS with other companies who are developing gene and cell therapies to treat eye disease.
Medgadget: Please give us an overview of the FOCUS trial of your gene therapy.
Mike Keane: The FOCUS trial [NCT03846193] is a Phase I/II open label, dose-escalation trial assessing the safety and biological activity of GT005 administered as a single subretinal injection in patients with GA. We have completed enrollment in the dose-escalation cohorts of the study and are now expanding to additional cohorts, in the dose expansion phase. We anticipate starting to report initial data from FOCUS in 2021.
We also recently announced the first patient dosed in our Phase II, EXPLORE trial. EXPLORE is a Phase II trial evaluating the safety and efficacy of a single subretinal injection of GT005 in people who are aged 55 or older, have GA, and have specific mutations in their Complement Factor I (CFI) gene and low levels of the CFI protein in their blood. People being screened for the trial will be genotyped for the mutations. We plan to enroll approximately 75 patients at approximately 40 centers based in the United States, United Kingdom, Europe and Australia.
Additionally, we plan to initiate a second Phase II trial in 2020 that will evaluate GT005 in a broader group of people with GA.
Link: Gyroscope Therapeutics