- Preclinical proof-of-concept data in GM2 gangliosidosis demonstrated survival benefit, functional improvement and target engagement
- Results are published in the 7 January issue of the Journal of Inherited Metabolic Disease
- Nizubaglustat is currently in Phase 3 registrational studies in GM1/GM2 gangliosidoses and Niemann-Pick type C disease (NPC)
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/
