Indications: Retinitis pigmentosa, late-stage dry AMD, including geographic atrophy and glaucoma

Mechanism of action: neuroprotective, antioxidant

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 retinitis pigmentosa (RP), age-related macular degeneration (AMD), and glaucoma.

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 go blind. 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 1 of more than 90 genes.

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 may further restrict the number of patients eligible for viral gene therapy. By preventing oxidative stress, EYS611 helps slow the progression of RP, buying patients valuable time, regardless of the genetic mutation they have.

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 in all RP subtypes, independent of the underlying genetic mutation. As such, it may provide a treatment option for more patients with RP, at an earlier stage in their disease.

Preclinical experiments show that EYS611 can help preserve retinal structure and function in multiple animal models, including rat models of inherited RP.

Eyevensys is also investigating the potential benefit of EYS611 for the treatment of late-stage dry AMD, including geographic atrophy and, possibly, glaucoma. Evidence suggests that dysregulation in iron homeostasis contributes to the cumulative oxidative damage, causing the progression of these diseases. Excess iron has also been shown to activate the complement cascade and inflammation—both pathways involved in AMD.