Kiora Pharmaceuticals has received Investigational New Drug (IND) approval to initiate a Phase 2 clinical trial, named ABACUS-2, to evaluate KIO-301 for vision restoration in patients with retinitis pigmentosa. The trial, a significant step forward in addressing this unmet medical need, will enroll patients with ultra-low vision or no light perception, regardless of the underlying gene mutation associated with their condition.
ABACUS-2 Trial Design
The ABACUS-2 trial is designed as a 36-patient, multi-center, double-masked, randomized, controlled, multiple-dose study. Patients will be randomized in a 2:1 ratio to receive either KIO-301 intravitreally or a control treatment. Treatment will be administered to both eyes. Participants will receive either a high dose (100 micrograms) or a low dose (50 micrograms) of KIO-301. Following three consecutive doses administered six weeks apart, patients will be followed for three months. After this phase, patients in the control arm may elect to cross over to the active arm.
The trial will be conducted across five centers within Australia. Primary endpoints will focus on safety and tolerability. Key efficacy assessments include functional vision, visual acuity (measured by the Berkeley Rudimentary Vision Test), visual fields (measured by perimetry), and a validated ultra-low vision quality-of-life questionnaire.
Addressing Unmet Needs in Retinitis Pigmentosa
"There are unfortunately no approved therapies for patients with retinitis pigmentosa," said Eric Daniels, M.D., Chief Development Officer at Kiora. The company engaged with European and US regulators to incorporate their expectations and guidance for approvable endpoints. Both regulatory bodies emphasized the need to measure a therapy's effect on everyday functional vision.
KIO-301: A Novel Approach to Vision Restoration
KIO-301 is a small molecule that functions as a light-sensitive photoswitch, potentially restoring vision in patients with reduced sight due to inherited retinal diseases. The compound is activated by light and deactivated in its absence. It targets retinal ganglion cells (RGCs), specialized cells in the retina located downstream of degenerated rods and cones. Inside RGCs, KIO-301 confers light-sensing capabilities by altering ion flow, enabling RGCs to facilitate visual processing. This process is reversible, allowing RGCs to be turned on and off in the presence and absence of light.
"What makes KIO-301 compelling is that it appears, based on the Phase 1b data, to have potential for meaningful vision restoration," said Dr. Céline Olmiere, Head of Théa Open Innovation. "Further, because of its unique mechanism of action, it has the potential to work across all 150-plus underlying gene mutations associated with retinitis pigmentosa and other inherited retinal diseases."
Collaboration and Endpoint Validation
Kiora is collaborating with Théa Open Innovation, with support from the Choroideremia Research Foundation, to validate functional endpoints for ABACUS-2. This collaboration aims to design a standard endpoint for investigational therapies for inherited retinal diseases, increasing the likelihood of success in a potential single Phase 3 trial for market approval in the US and Europe.
