Dutch biotech scores €25M in small molecule bet to tackle lysosomal storage disorders
While a host of biotech companies work on gene and enzyme replacement therapies for certain lysosomal storage disorders, a Dutch player is aiming to slot in its small molecule approach across a range of these rare inherited metabolic disorders.
The company — Azafaros — founded in 2018 based on science developed from Leiden University and Amsterdam University Medical Center has secured €25 million in Series A financing as it works on shepherding its lead experimental drug into the clinic.
The drug, dubbed AZ-3102, is designed to work via a dual mode of action — by diminishing metabolite accumulation and enhancing lysosomal function.
There has been a lot of attention for gene therapy in lysosomal storage disorders — but some efforts have shown no benefit and there are some challenges such as the risk of immunogenicity, noted Azafaros chief Olivier Morand in an interview with Endpoints News. “But still, it obviously has a lot of potential.”
Lysosomal storage disorders are inherited metabolic diseases characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies. Lysosomes are like the stomach of the cell, in charge of digesting complex components like proteins, polysaccharides, nucleic acids, or lipids and breaking them down into simpler units. When this process doesn’t occur, a sort of a traffic jam ensues — which can culminate in a reservoir of toxicity in different organs such as the liver, spleen, heart, kidney, skin, bones and brain.
Altogether, there are roughly 50 such disorders — including Tay-Sachs, Fabry, Hunter and Sanfillipo — each characterized by different symptoms resulting from the toxic accumulation of a certain metabolite. For example, toxic accumulation in the brain can lead to developmental delays, seizures, respiratory infections, loss of vision and hearing, and cognitive function.
“I think the recurrent notion is that these diseases are very complex and very severe,” Morand noted. “So having several treatment modalities and combining them may be the way to go for a solution.”
In contrast to gene or enzyme replacement therapy developers, Azafaros’ small molecule effort has the potential for use across several indications, he added, without disclosing how long it will take AZ-3102 to be ready for clinical testing.
The Series A round was led by Forbion, with participation from BioMedPartners and founding investor BioGeneration Ventures.
Months ago, Merck shelled out up to $576 million to swallow Calporta, which has been working on small molecule agonists of TRPML1 — designed to restore calcium efflux and normalize lysosomal function — to treat lysosomal storage disorders, as well as neurodegenerative diseases.
Meanwhile, Sangamo Therapeutics has tested its gene editing zinc finger technology in patients with two lysosomal storage diseases. Lentiviral gene therapy developer Avrobio also is in the early stages of assessing the potential of its technology across different lysosomal storage diseases.