AMA0076 is Amakem’s lead product candidate and targets glaucoma. Based on Amakem’s ‘Localized Drug Action’ platform, AMA0076 is a highly potent Rho kinase (ROCK) inhibitor that has been designed to allow for high localized dosing in the eye combined with low systemic exposure. AMA0076 is aimed at providing better patient outcomes than other ROCK inhibitor based treatments currently in development because its improved side effect profile enables higher dosing, leading to better efficacy.. Amakem is currently advancing AMA0076 through preclinical development.
AMA0076 has been shown to cause a profound reduction in intraocular pressure (IOP) in several in vivo models of glaucoma. Applied as eye drops, AMA0076 effectively penetrates the cornea to where it acts by increasing the outflow of aqueous humor from the eye through the trabecular meshwork and thereby reduces IOP. Outside the aqueous humour, AMA0076 is designed to be rapidly converted into an inactive form which is eliminated from the body. This unique feature is aimed at preventing off-target activity and reducing important side effects such as hyperemia.
ROCK inhibitors reduce IOP through a novel mechanism of action by improving the outflow of aqueous humor through the trabecular meshwork, the main outflow mechanism in the human eye (conventional outflow). Other drug treatments either reduce the production of aqueous humor or facilitate the outflow via the uveoscleral pathway. However, facilitating the outflow through the most important pathway has the potential to provide a much better level of IOP reduction.
In an acute model of glaucoma, AMA0076 was shown to prevent IOP rise with a clear dose response relationship. AMA0076 also reduces IOP over the entire six hour period in another validated model. Comparative studies of AMA0076 against existing first line treatments for glaucoma, the prostaglandins, have shown it to produce greater IOP lowering effects in acute models of glaucoma.
All other ROCK inhibitors in development for glaucoma have hyperemia as a major dose limiting side effect, with cardiovascular safety issues also identified as a potential major risk. AMA0076 has shown no systemic side effects in the models tested so far and did not cause hyperemia at a dose that produced a profound reduction in IOP. Other ROCK inhibitors have been shown to reduce IOP in both the treated and untreated eye in preclinical models, suggesting significant systemic concentrations may be reached. In contrast, AMA0076 is rapidly degraded to an inactive metabolite in the blood and therefore does not affect other organs.