Our lead program in lysosomal storage diseases

Lysosomal storage diseases such as Gaucher, Tay-Sachs, Fabry, Sanfilippo or Pompe disease, are a group of rare inherited metabolic disorders caused by lysosomal function defects. Lysosomes are cellular compartments filled with a variety of enzymes that are involved in the turn-over and degradation of proteins, polysaccharides, nucleic acids, or lipids. For example, dysfunctions in the aforementioned enzymes in the brain of patients can result in the cytotoxic accumulation of degradation products, resulting in severe symptoms including developmental delays, seizures, respiratory infections, loss of vision and hearing, and cognitive functions.

In recent years, it appeared that several enzymes involved in glucosylceramide metabolism are relevant targets for drug development. Moreover, and in contrast to the clinical dogma of compound selectivity, it is hypothesized that the most effective compounds should inhibit a combination of glucosylceramide processing enzymes, or alternatively one of these in combination with unrelated glycoprocessing enzymes (see Ghisaidoobe et al., 2014, J Med Chem).

In our most advanced program, the lead candidate AZ-3102 is a first-in-class, disease-modifying small molecule aiming to treat these rare lysosomal storage diseases. This orally available azasugar compound was designed to interfere with the metabolism of glycolipids and to uniquely affect several key disease pathways through a dual mode of action with the potential to reduce harmful metabolite accumulation and to ameliorate lysosomal function. It belongs to a library of novel patented compounds discovered by internationally recognized experts in the field, Professor Hans Aerts, PhD, Professor Hermen Overkleeft, PhD, Professor Stan van Boeckel, PhD, and their co-workers currently at the Leiden Institute of Chemistry, Leiden University.

Our drug discovery program

Next to our lead program, we have embarked in a medicinal chemistry drug discovery program with the goal to identify and develop new orally available small molecules to expand our pipeline into another family of rare metabolic indications.