Firm claims ROCK inhibitor AMA0076 reduces IOP but is enzyme-inactivated at nontarget sites to reduce side effects such as hyperemia.

Belgian kinase drugs firm Amakem raised €18 million in a Series A round of financing with a syndicate of life science investors. The funds will be used to further develop Amakem’s lead preclinical-stage glaucoma candidate AMA0076 to clinical proof of concept stage, and advance its ophthalmology drug pipeline.

AMA0076 is a Rho Kinase (ROCK) inhibitor that in vivo models have shown is highly effective in reducing intraocular pressure (IOP) but without causing hyperemia, a dose-limiting side effect associated with all other ROCK inhibitor candidates, Amakem notes. Administered as eye drops, AMA0076 penetrates the cornea, where it increases the outflow of aqueous humor from the eye through the trabecular meshwork to reduce IOP. However, outside the aqueous humor environment, AMA0076 is converted into an inactive form and is eliminated, preventing off-target activity and reducing side effects such as hyperemia.

The drug has been developed using Amakem’s Localized Drug Action platform, which has been designed to generate novel kinase inhibitors that are rapidly inactivated outside the target organ through the action of specific enzymes. Each kinase inhibitor drug candidate thus combines kinase specificity with enzymatic conversion specificity. 

The Localized Drug Action Platform was initially developed by researchers at Devgen, who established Amakem in 2010 to commercialize the technology. Amakem claims the platform can be applied to a range of kinase inhibitors for indications where local administration is viable, such as to the eye, skin, gastrointestinal tract, and ears, and via local injections. Focused primarily on exploiting the platform to develop drugs for ophthalmic indications, the firm has also demonstrated proof of concept in models of COPD and asthma.

Amakem has an ongoing collaboration with the Ophthalmology Research Center of the University Leuven Hospital, focused on development of Localized Drug Action-based kinase inhibitors for treating a range of ophthalmic conditions including glaucoma.

The firm’s lead COPD candidate, AMA0247, is a selective ROCK inhibitor that has been developed to be stable in extracts of smoker’s lung, but rapidly converted to inactive metabolites in plasma. In November 2010 the firm was awarded €1.28 million by the Flemish government agency for Innovation by Science and Technology to support the COPD program. 

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