The company presented topline Phase I/II first-in-human results at the 127th AAO annual meeting in San Francisco, demonstrating significant improvement in visual field, in concordance with trended improvements in visual acuity and functional vision.
Kiora Pharmaceuticals announced topline results of a Phase I/II clinical trial demonstrating proof-of-concept that KIO-301, the company’s first-in-class small molecule, has the potential to meaningfully improve vision in patients with retinitis pigmentosa (RP) who are living with ultra-low vision or complete blindness.
According to a company news release,1 the ABACUS study is a first-in-human, open-label, multi-site, single dose-escalating clinical trial for Kiora’s intravitreal (IVT) molecular photoswitch. The results were presented as a late-breaking presentation at the American Academy of Ophthalmology annual conference (AAO 2023) during the Retina Subspecialty Day by Russell N. Van Gelder, MD, PhD, professor and chair, Department of Ophthalmology, University of Washington, School of Medicine.
Although the study was not powered to primarily assess efficacy, the following topline observations were reported in line with proof-of-concept for this novel class of light-restoring small molecules:1
In addition to the objective data, patients reported positive changes in their vision over the course of the 28-day study.1
"I have been blind and living in complete darkness for over 10 years and was resigned to never seeing again. During my time on this trial, under the care of Robert Casson, MD, and his team, it has changed that reality, and in fact gave me the ability to once again see light for about a month,” Chris Edwards, a trial participant, said in a statement. “I look forward to future clinical trials and hope this therapeutic may eventually help all of those in need.”
According to the news release, under the direction of co-principal investigators, Drs Casson (University of Adelaide, Department of Ophthalmology) and Van Gelder, the ABACUS trial included 6 patients who were administered KIO-301 in each eye for a total of 12 eyes assessed. Half of the patients enrolled were the most severely affected by RP, having either no ability to perceive light (no light perception), or barely perceive light.
The remaining 3 were able to perceive light but live with ultra-low vision, clinically diagnosed as being able to perceive hand motion or count fingers, but incapable of reading even the largest letter on an eye chart. Each eye received a single IVT injection of either 7.5 (n=3), 25 (n=6), or 50 µg (n=3) of KIO-301. Assessments were performed at baseline (prior to KIO-301 injection) and several timepoints over 28 days post-treatment.
While safety/tolerability was the primary endpoint of the trial, visual acuity, kinetic visual field, and functional vision changes were also assessed. To understand if activity within the visual cortex of the brain changed due to treatment, functional MRI was also included in the trial.1
“This new technology offers hope to patients living with late stage inherited retinal diseases. The mechanism of action and trial data firmly support KIO-301’s continued development, potentially filling a major unmet need in the search for treatments for these patients,” Van Gelder said in the news release. “Based on shared pathology between RP and other inherited retinal diseases, we believe there is an opportunity to explore KIO-301 for several other indications including choroideremia and Stargardt’s disease.”
According to the company, KIO-301 is a small molecule, referred to as a molecular photoswitch, potentially conferring light-sensing capabilities to special types of retinal neurons called Retinal Ganglion Cells (RGCs). In healthy eyes, light detection is performed by photoreceptors (rods and cones). In RP, mutations in any of 150 known genes lead to eventual death of photoreceptors, typically starting in the teenage years. Moreoer, the company noted this photoreceptor death first results in difficulty seeing in dark environments, progressing to a narrowing of one’s field of vision, and eventually leading to complete blindness.1
The death of photoreceptors allows KIO-301 to selectively enter RGCs. Once inside the cell, KIO-301 localizes within specific voltage-gated ion channels involved in regulating neural signaling. When light hits these RGCs, KIO-301 alters its shape to change the flow of current, thereby activating the cell, and resulting in signaling the brain. When light is removed, KIO-301 reverts to its lower energy shape, stopping the signaling to the brain. In this way, the molecule acts as a light switch within the eye.
"We would like to express our sincerest gratitude to the patients, families, and caregivers for their participation in the ABACUS trial,” Eric Daniels, MD, Chief Development Officer of Kiora, said in the news release. “First-in-human studies are about safety and looking for signals of efficacy. In consultation with our scientific and medical advisors, data generated in this first-in-human study strongly support Kiora continuing to a sham-controlled, multi-dose Phase II clinical trial in 2024. We will share the results of ABACUS and design of ABACUS II with the U.S. FDA in the fourth quarter to ensure alignment as we look to expand our clinical development into the U.S. and EU.”