Vision restoration using a light-responsive small molecule photoswitch (KIO-301) in advanced retinitis pigmentosa: the ABACUS-1 phase 1/2 clinical trial

A small, azobenzene, photoswitch molecule (KIO-301) that renders retinal ganglion cells responsive to light was investigated for safety and activity in a first-in-human, phase 1/2, open-label, dose-escalation clinical trial in individuals with advanced retinitis pigmentosa. KIO-301 was delivered by intravitreal injection to 12 eyes of 6 participants. The primary endpoint was safety. Secondary endpoints included assessment of functional vision, visual acuity, kinetic visual field, functional magnetic resonance imaging (fMRI) and participant reported outcomes. There were no drug-related adverse events. A participant with no light perception at baseline recovered light perception by 2 days post injection. Visual function, including navigational ability, displayed a trend of improvement. By day 2-14 post injection the fMRI signal to visual stimuli in the primary visual cortex was enhanced and decayed over the ensuing 3 weeks. Participant-reported quality of life improved. The excellent safety profile and evidence supporting proof-of-principle has motivated a larger, randomized controlled trial.