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R&D Focus

ITRI-E-(S)4046: A Novel ROCK Inhibitor for Glaucoma

ITRI-E-(S)4046 dual-target kinase inhibiter.

ITRI-E-(S)4046 dual-target kinase inhibitor.

Glaucoma is a common eye condition that induces optic nerve atrophy from elevated intraocular pressure (IOP) and may cause vision loss. According to the WHO, in 2020 more than 80 million people suffer from this disease, with blindness resulting in about 10 million cases.

Current treatment methods generally include eye drops or oral administration of drugs. However, 40% to 50% of patients develop drug resistance after receiving treatment for one to three years, and experience growing side effects such as dark circles under the eyes, sunken eyes, eye irritation, or pink eye symptoms. To improve the treatment, ITRI developed the dual-target kinase inhibitor designated ITRI-E-(S)4046, which in trials has shown greater effect on lowering IOP than current drugs on the market.

ITRI developed the new glaucoma treatment drug on its Integrated Platform for Ophthalmic Drug Development.

ITRI developed the new glaucoma treatment drug on its Integrated Platform for Ophthalmic Drug Development.

Division Director Dr. Jui-Mei Lu of ITRI’s Biomedical Technology and Device Research Laboratories pointed out that there are several drug treatments for glaucoma available on the market, which work by reducing the amount of aqueous humor created within the eye or target trabecular outflow. Around 50% of patients develop drug resistance after a year of treatment, and experience growing side effects.

“We applied ITRI’s targeted drug delivery system that was designed for tackling tumors to treat glaucoma,” said Dr. Lu. “Our team found from other research findings that Rho-associated Protein Kinase (ROCK) would cause the trabecular meshwork to contract, limit the flow of aqueous humor, and raise the patient’s IOP. Thus, we decided to use a kinase inhibitor that targeted ROCK as the basis to develop the new drug.”

The team tested more than 200 compound combinations on ITRI’s Integrated Platform for Ophthalmic Drug Development. This platform was established to provide a one-stop service for ophthalmic drug design, synthesis, pharmacodynamics, pharmacokinetics, toxicology, and pilot and GMP production. During preclinical trials, the team found a compound that not only inhibited ROCK but even suppressed MYLK4, another protein kinase that might affect the aqueous humor flow of the trabecular meshwork. Compared to current drugs, in vivo testing results have shown that ITRI-E-(S)4046 has 39 times greater effectiveness on inhibiting MYLK4, demonstrating ITRI’s formula as a dual-target glaucoma drug that has low hyperemia and only requires one application per day.

ITRI-E-(S)4046 has already been transferred to a biomedical company in Taiwan and is slated to enter phase I and II clinical trials this year. It is expected that the successful development of this drug with significant improvement in lowering IOP will offer glaucoma patients a new option of reduced side effects and dosage to improve their life quality. The technology received a gold medal at ITRI’s Outstanding Research Awards in 2022.