KIO-301

These therapies selectively target specialized neurons called retinal ganglion cells (RGCs), turning them into light-sensing cells. RGCs play a central role in the pathway that connects the eye to the brain.

In healthy eyes, light is first converted to electrical signals via the rods and cones (photoreceptors) and transmitted through RGCs to the vision perceiving part brain (visual cortex). In many inherited retinal diseases including retinitis pigmentosa, choroideremia, and Stargardt disease, rods and cones degenerate and die off, affecting an individual’s ability to perceive light. While photoreceptors degenerate in inherited retinal diseases, RGCs are preserved. As such, they represent a target cell to bypass degenerated photoreceptors, perceive light, and signal the brain.

Specifically, inside RGCs, molecular photoswitches change shape depending on the presence or absence of light. In the absence of light, they are in an “off” position. In the presence of light, they change shape, turning to an “on” position that triggers the RGC to signal the brain.

Inherited Retinal Diseases Lead to Loss of Vision

Healthy Vision

Healthy Vision

• Rods and cones, the photoreceptors of the retina, process light and relay an electrical signal to downstream cells.
• One of these cell types, retinal ganglion cells (RGCs), transmit the signal to the visual cortex.
• The visual cortex is the part of the brain where vision is perceived.

Damage from Retinitis Pigmentosa

Damage from Retinitis Pigmentosa

• Retinitis Pigmentosa (RP) results in progressive degeneration and loss of function of rods and cones.
• This causes continuous impairment of vision that often leads to blindness.
• Importantly, in RP and other inherited retinal diseases, the RGCs remain viable.

KIO-301: A Molecular Photoswitch Designed to Restore Vision

Without Light

Without Light

• When photoreceptors die, RGCs undergo some remodeling, including expressing specific proteins that allow KIO-301 to selectively enter the cell with ion channels.
• Without light, KIO-301 remains in its linear “off” (trans) position.

With Light

With Light

• With light, KIO-301 is activated and bends into its “on” (cis) formation.
• This physically blocks ion channels and activates the cell to transmit signals to the visual cortex.