EYS611

Lead Indication: Geographic atrophy (GA) secondary to dry AMD

Planned future indication: Retinitis pigmentosa

Mechanism of action: iron chelation, antioxidant, neuroprotection

EYS611 encodes the human transferrin protein, a natural iron transporter involved in the control of iron levels in the eye. Iron is needed for retinal cell metabolism, but excess free iron causes oxidative stress and is extremely toxic to the retina. Iron overload is associated with a number of degenerative retinal diseases, including AMD, retinitis pigmentosa (RP), and glaucoma.

Eyevensys is investigating the potential benefit of EYS611 for the treatment of late-stage dry AMD, including geographic atrophy. Geographic atrophy (GA) is a chronic degeneration of the macula. This progressive disease results in central vision loss because of the loss of retinal pigment epithelial cells. Typically, the condition is bilateral, and the initial central vision loss, caused by the development of scotomas, expands over time. Due to the manner in which GA progresses, patients may maintain BCVA while simultaneously experiencing significant loss of visual function.

More than 5 million people are affected worldwide with GA, and approximately 10-20% of all patients diagnosed as legally blind as a result of AMD have been affected by GA. And GA is on the rise—the diagnoses are expected to continue to increase as older populations of developed countries continue to rise. There is no cure for GA. Although recently approved inhibitors of the complement cascade, overactivated in AMD conditions, do show a modest reduction in the rates of GA lesion growth, they necessitate intraocular injections every 4 weeks.

Given that AMD is a multifactorial disease, any effective treatment must address multiple pathological pathways. Evidence suggests that dysregulation in iron homeostasis contributes to the cumulative oxidative damage, causing the progression of AMD. Excess iron has also been shown to activate the complement cascade, inflammation, lipid peroxidation, and ultimately lead to ferroptosis, a newly discovered programmed cell death pathway that cause the death of retinal pigment epithelium (RPE) cells and subsequent loss of photoreceptors in AMD.

Preclinical experiments conducted across various disease models show the beneficial effects of Transferrin to remove iron, reduce oxidative stress, preserve the integrity of the RPE, and prevent retinal degeneration and vision loss. We believe EYS611 holds the potential to effectively address the complex pathophysiological pathways involved in GA/dry AMD, all the while requiring re-treatment only every 6 to 12 months.

1
genes can carry a mutation that results in retinitis pigmentosa

RP is a group of rare, inherited conditions that affect the light-sensitive cells in the retina. Symptoms often begin in early childhood, initially affecting night vision and the ability to adjust to lighting changes. Over time, vision becomes more restricted; most patients eventually progress to blindness. The speed at which vision is lost varies considerably from one individual to the next. This is because RP can result from mutations in any one of more than 90 genes and different mutations cause differences in the severity of disease. Corrective viral vector gene therapies are being developed for some forms of RP, but these help only a tiny minority of patients with RP. Pre-existing immunogenicity to viral vectors may further restrict the number of patients eligible for viral gene therapy. By preventing oxidative stress, EYS611 helps slow the progression of vision loss in RP patients, regardless of the patient’s genetic mutation.

EYS611 combines plasmids encoding for human transferrin delivered to the ciliary muscle using the proprietary Eyevensys Electrotransfection System. EYS611 is a much less invasive gene therapy approach than viral vector gene therapies administered directly to the retina, and it is intended for the treatment of the entire retina with all RP subtypes, independent of the underlying genetic mutation. As such, it may provide a treatment option for more patients at an earlier stage in their disease.