Site-directed Enzyme Enhancement Therapy (SEE-Tx) is a platform that allows identifying a new generation of pharmacological chaperones, which are non-competitive with the natural substrate and which have improved drug-like properties.

Using the three-dimensional structure of proteins and proprietary computational technology, we identify and exploit previously uncharacterized binding sites. Those sites are druggable, but do not bind the substrate. In consequence, the pharmacological chaperones we find are drug-like and non-inhibitors, hence offering a wider therapeutic window.

Minoryx applies this innovative technological platform to discover pharmacological chaperones for Lysosomal Storage Disorders, a group of Inborn Errors of Metabolism with a high unmet medical need.

The cause of many rare diseases is a protein malfunction due to a mutation on the wild-type sequence. This mutation causes a decrease in the protein’s stability, which is degraded by the quality control system of the cell. The absence of functional protein is the primary cause of these diseases and pharmacological chaperones aid the recovery of such functionality, thus preventing further development of the diseases.

Through its proprietary technological platform (SEE-Tx), Minoryx has identified a novel series of non-competitive pharmacological chaperones which are able to stabilize misfolding mutations and restore protein’s enzymatic activity. The mechanism has been validated with GLB1, the enzyme involved in lysosomal storage diseases GM1-gangliosidosis and Morquio B.

These new compounds are binding on a novel site identified through SEE-Tx and reduce the accumulation of toxic substrate in fibroblasts. Contrary to pharmacological chaperones targeting the active site, they do not inhibit GLB1.

Additionally, Minoryx found good quality hits for several other lysosomal storage diseases, which are currently in optimization phase.

In the field of metabolic diseases, most pharmacological chaperones described to date are analogues of the natural substrate. Such kind of molecules show poor selectivity and reduced therapeutic window due to the inhibition of the target enzyme at higher concentrations. Also, their drug-likeness is poor, which means that they may not reach the site of action.

Through its proprietary technological platform (SEE-Tx) Minoryx develops non-competitive (allosteric) chaperones which are not limited by such constraints.