Azafaros Announces Publication of Preclinical Efficacy Data with Nizubaglustat in GM2 Gangliosidosis

Azafaros, a company aiming to become a leader in lysosomal storage disorders (LSDs), focused on addressing especially neurological symptoms, today announced the publication of proof-of-concept preclinical data with its lead product, nizubaglustat, in GM2 gangliosidosis.

The data, published in the 7 January issue of the Journal of Inherited Metabolic Disease in collaboration with the laboratory of Dr. Jagdeep Walia, Department of Pediatrics, Queen's University, Kingston, Canada, reinforce nizubaglustat’s potential to address unmet needs in rare LSDs and build on existing preclinical and clinical evidence.

The preclinical study tested nizubaglustat in a mouse model in Sandhoff disease, a form of GM2 gangliosidosis with no approved treatments—alongside healthy control subjects. The research assessed how the drug’s exposure relates to its effects in the brain, demonstrating a significant increase in both survival (22%; 26 days) and assessments of movement and behavior at 16 weeks versus untreated Sandhoff diseased mice. Significant increases in survival were observed even at doses as low as 0.2 mg/kg/day, providing key proof-of-concept data for its potency and therapeutic potential.

Kyle Landskroner, Chief Scientific Officer at Azafaros, said the data highlights nizubaglustat’s clinical potential. “With the publication of these data in GM2, nizubaglustat is the only drug in development showing neurologic improvement in all three (GM2, GM1 and NPC) preclinical models, providing further support to the importance of the unique dual mode of action on both the non-lysosomal glucosylceramidase (NLGase) and glucosylceramide synthase (GCS) to improve neurological manifestations of lysosomal diseases,” he said.

“These published data provide more evidence of nizubaglustat’s dual mechanism of action and its ability to penetrate the brain, engage its targets, and modify disease-relevant outcomes,” said Stefano Portolano, Chief Executive Officer at Azafaros. “Importantly, the observed survival benefit and reduction in neuroinflammation further strengthen the therapeutic rationale currently being tested in our ongoing Phase 3 studies.”

Nizubaglustat is currently being evaluated in two Phase 3 registrational studies in patients with GM1/GM2 gangliosidoses and NPC.

The article can be found on PubMed, using the following link: https://pubmed.ncbi.nlm.nih.gov/41500827/

About nizubaglustat

Nizubaglustat is a small molecule, orally available and brain penetrant azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses and Niemann-Pick type C disease (NPC).

Nizubaglustat has received Rare Pediatric Disease Designations (RPDD) for the treatment of GM1 and GM2 gangliosidoses and NPC, Orphan Drug Designations (ODD) for GM1 and GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NPC, as well as Fast Track Designation and IND clearance for GM1/GM2 gangliosidoses and NPC from the US Food and Drug Administration (FDA). Additionally, nizubaglustat has been awarded Orphan Medicinal Product Designation (OMPD) for the treatment of GM1 and GM2 gangliosidoses by the European Medicines Agency (EMA) and Innovation Passport for the treatment of GM1 and GM2 gangliosidoses from the UK Medicines and Healthcare Products Regulatory Agency (MHRA).

About GM1 and GM2 gangliosidoses

GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides respectively, in the central nervous system (CNS). This results in progressive and severe neurological impairment and premature death. These diseases mostly affect infants and children, and no disease-modifying treatments are currently available.

About Niemann-Pick type C disease (NPC)

Niemann-Pick type C disease is a progressive, life-limiting, neurological, lysosomal storage disorder, caused by mutations in the NPC1 or NPC2 gene and aberrant endosomal-lysosomal trafficking, leading to the accumulation of various lipids, including gangliosides in the CNS. The onset of the disease can happen throughout the lifespan of an affected individual, from prenatal life through adulthood.

About Azafaros

Azafaros is a clinical-stage company founded in 2018 with a deep understanding of rare genetic disease mechanisms using compound discoveries made by scientists at Leiden University and Amsterdam UMC and is led by a team of highly experienced industry experts. Azafaros aims to build a pipeline of disease-modifying therapeutics to offer new treatment options to patients and their families. By applying its knowledge, network and courage, the Azafaros team challenges traditional development pathways to rapidly bring new drugs to the rare disease patients who need them. Azafaros is supported by leading healthcare investors including Forbion, Jeito Capital, Seroba, Pictet Group, BioGeneration Ventures (BGV), BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital.

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