ATS907 and ATS8535 are Rho kinase (ROCK)-selective inhibitors in development as next-generation topical eye drop
therapies for reduction of elevated intraocular pressure (IOP) in primary open angle glaucoma and ocular
Unlike prostaglandins, which reduce IOP by increasing outflow through the secondary uveal-scleral aqueous
clearance route, ROCK inhibitors reduce IOP via a novel mechanism of action. Inhibition of ROCK, which modulates
the intracellular contractile state of cells in the trabecular meshwork, appears to enhance conventional (primary
route) outflow of aqueous humor directly through the trabecular meshwork.
Since both ocular tolerability and efficacy are mediated by ROCK, one of the key challenges in their development
is managing ocular tolerability and efficacy. Unlike other ROCK inhibitors that are in development, ATS907 and
ATS8535 have pro-drug like properties that are expected to provide a wider therapeutic index by allowing for rapid
conversion into a more potent metabolite within the ocular tissue following topical administration. This conversion
occurs within the anterior chamber of the eye where the trabecular meshwork resides, making ATS907 and ATS8535
excellent ocular drug candidates for glaucoma.
In animal models, ATS907 was shown to significantly reduce IOP following topical administration and was well
tolerated. ATS907 entered clinical development in the first quarter of 2012 in a Phase 2a clinical study in
patients with primary open angle glaucoma or ocular hypertension.
ATS8535 has successfully completed initial preclinical and formulation development activities, and has been
declared a development candidate.