KIO-301

KIO-301 is a small molecule molecular photoswitch under development for the treatment of inherited retinal diseases, including retinitis pigmentosa, choroideremia, and Stargardt disease. It is designed to restore vision in patients with profound vision loss by targeting surviving retinal ganglion cells (RGCs) after photoreceptor degeneration. KIO-301 preferentially enters RGCs via the P2X7 receptor, which is upregulated in diseased retinas. Once inside these cells, it localizes within voltage-gated potassium (Kv) and hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. In darkness, KIO-301 remains in a trans configuration that allows normal ion flow and keeps RGCs in an OFF state. Upon exposure to light, it undergoes a reversible isomeric shift to the cis configuration that blocks ion efflux through Kv/HCN channels—activating the RGCs and enabling them to send visual signals to the brain. This mechanism bypasses degenerated rods and cones and acts independently of specific genetic mutations causing retinal degeneration[1][2][5][6][8]. Clinical trials have shown preliminary evidence of restored light perception in patients with ultra-low or no vision due to retinitis pigmentosa[3].