Abstract
Purpose :
KIO-301 is an azobenzene photoswitch compound known to block voltage-gated ion channels, including hyperpolarisation-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium channels during exposure to visible light. KIO-301 is taken up selectively by viable retinal ganglion cells (RGCs) downstream of degenerated photoreceptors, rendering RGCs photoresponsive. KIO-301 delivered intravitreally in patients with retinitis pigmentosa (RP) may restore functional vision. Safety data and patient reported outcomes from the first blind human to receive a single low-dose of KIO-301 are reported.
Methods :
As part of an ongoing, 6 subject (12 eyes) phase I/II dose-escalating study (ABACUS) of the safety, tolerability and efficacy of KIO-301 administered intravitreally to patients with non-syndromic late-stage RP (NCT05282953), subjects undergo general ophthalmic examination at 4 hours, 1 day, and 1, 2 and 4 weeks post injection. Safety lab assessments are performed at baseline and 29 days. A subject-reported effectiveness survey is administered at four timepoints post-injection over the same 29-day period. The initial subject had advanced RP with bilateral bare light perception.
Results :
There were no reported adverse events, including ocular adverse events, over the course of 29 days. The ocular examination remained unchanged from baseline. A 4-hour post-injection EKG did not demonstrate any change nor did any clinical chemistry or hematology laboratory values at 29 days. The subject-reported outcome indicated an improvement in the ability to perceive contrast between light and dark at Day 7 and 29 post injection and perceived improvement in overall functional vision.
Conclusions :
Small molecule photoswitch compounds have shown promise in the ability to restore vision in RP animal models. This case study, as part of an ongoing, larger clinical trial, documents the first-in-human report of safety and tolerability of KIO-301 in this late-stage RP population. Early signs of patient reported effectiveness are encouraging and support additional patients and dose escalation.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.