By inhibiting the DHODH enzyme, the proliferation of overactive immune cells that contribute to pathological inflammation can be reduced. DHODH makes for an ideal target because of its dependence on proliferating highly active cells. However, systemic use of DHODH inhibitors does not provide an adequate amount of drugs into the eye and hence the need for an ophthalmic-specific formulation of a potent DHODH inhibitor.
Clinical proof-of-concept of the potential for the KIO-100 family of compounds has been demonstrated in multiple studies. This includes a first-in-human, open-label, phase-1 clinical trial, which investigated the use of KIO-104 for treating Uveitis, an intraocular inflammatory disease. Results, which were reported in October 2022, showed that a single intravitreal injection of KIO-104 decreased intraocular inflammation in a dose-dependent fashion, and improved visual acuity significantly during the duration of the study. The drug was well tolerated, with no serious side effects on intraocular tissues or other adverse events observed.
Separately, clinical proof-of-concept was similarly demonstrated in a study reported in April 2022. The results of the vehicle-controlled, randomized clinical trial in patients with ocular surface inflammation demonstrated safety and tolerability of KIO-101 as well as statistically significant improvements in conjunctival hyperemia in the 0.15% KIO-101 arm compared to vehicle control. Conjunctival hyperemia was a key inclusion criterion for the enrollment of patients with ocular surface inflammation and is a recognized clinical sign in patients with ocular surface inflammation and associated dry eye.
