About glaucoma
Glaucoma is the second leading cause of blindness in the world. It is mainly because the fluid, the aqueous humor, in the eyeball cannot be drained normally. This causes an increase in intraocular pressure (IOP), leading to damage to the optic neuropathy, and then optic nerve atrophy. There are no symptoms in the early stage. In the moderate to severe stages, the patient begins to lose peripheral vision due to damage to the optic nerve. If not treated immediately, the visual field will slowly shrink from the edges until the central vision disappears. This is a chronic and irreversible optic neuropathy process.
The causes of glaucoma vary and are mainly divided into two categories. One is increased IOP, and the other is poor blood circulation of the optic nerve. High-risk factors include elevated IOP caused by high myopia or hyperopia, age older than 40 years, family history of glaucoma, long-term use of steroids, anti-epileptic drugs, or psychiatric drugs, systemic chronic diseases such as diabetes, cardiovascular disease, and hypo-/hypertension, etc., other eye diseases such as intraocular inflammation, eyeball trauma, or intraocular surgery, etc.
According to WHO (2019), there will be approximately 76 million glaucoma patients in 2020, which is estimated to grow to 95.4 million patients by 2030. It is estimated that the overall number of patients will grow at a compound annual growth rate (CAGR) of 2.3% between 2020 and 2030. According to the Ophthalmology Department of Taichung Veterans General Hospital, there are currently approximately 80 million people with glaucoma worldwide, including more than 340,000 glaucoma patients in Taiwan.
Development of Rho Kinase (ROCK) Inhibitors
Rho kinase (ROCK) is a serine-threonine-specific protein kinase belonging to the AGC (PKA/PKG/PKC) family. It primarily regulates cell shape and movement by regulating on the cytoskeleton. Due to its broad biological functions, ROCK has been explored for various medical applications.
For instance, ROCK inhibitors can promote the relaxation of trabecular meshwork muscle tissue in the eye, thereby increasing aqueous humor outflow and effectively lowering intraocular pressure (IOP) for Glaucoma patients. Additionally, studies have shown that ROCK plays a role in corneal cell migration and distribution, accelerating corneal wound healing. Beyond ophthalmology, ROCK has been implicated in regulating inflammatory responses, tissue fibrosis, immune reactions, and even cancer therapy, highlighting its clinical potential.
BRM411 Ophthalmic Solution Mechanism of Action:
Glaucoma treatment primarily focuses on lowering intraocular pressure (IOP) through medications, laser therapy, or surgery, aiming to slow the degeneration of optic nerve function. Current pharmacological treatments include prostaglandin analogues (PGA), beta-blockers, adrenergic agonists, and carbonic anhydrase inhibitors. However, these therapies often cause side effects such as dark circles, iris pigmentation changes, eyelash growth, and ocular redness. Long-term use may lead to drug resistance in some patients, reducing the efficacy of IOP-lowering treatment and patients’ adherence. Newer drugs approved in the U.S., such as Aerie’s Rhopressa and its combination Rocklatan, are small-molecule targeted therapies that selectively inhibit Rho-associated protein kinase (ROCK) and increase aqueous humor outflow via the trabecular meshwork (TM). Nevertheless, these drugs show limited efficacy in patients with IOP above 26 mmHg, and over 50% of patients experience ocular redness, limiting market expansion.
Allgenesis Biotherapeutics, in collaboration with ITRI, is developing BRM411, an ophthalmic solution that lowers IOP by modulating aqueous humor outflow through ROCK inhibition, a mechanism already validated by approved drugs overseas. BRM411 employs dual ROCK/MYLK-4 inhibition and demonstrated significant IOP-lowering efficacy in Phase 2 clinical trials, while reducing mechanism-related class effects and exhibiting a favorable safety profile. As the global patient population rapidly grows, the demand for new therapies continues to rise. BRM411 effectively controls IOP, including in patients with high IOP, and requires only once-daily bedtime dosing, reducing daytime ocular redness and improving patient compliance. With its dual-target design, BRM411 can control very high IOP (>26 mmHg), offering glaucoma patients an additional therapeutic option upon approval. Furthermore, Allgenesis plans to leverage its ROCK inhibitor platform to develop treatments for corneal repair and endothelial corneal dystrophy, addressing significant unmet clinical needs.
