At Amylyx, we’re charting new territories with rigorous science. Our approach stems from our commitment to advancing science and innovating our way to novel treatments. We are tackling several of the industry’s unanswered questions, one data point at a time, to develop a deeper understanding of the scientific pathways driving our diseases of focus and leveraging diverse modalities to make targeting those pathways possible.
Avexitide is a first-in-class, glucagon-like peptide-1 (GLP-1) receptor antagonist with Breakthrough Therapy and Orphan Drug designations for the treatment of hyperinsulinemic hypoglycemia. Post-bariatric hypoglycemia (PBH), a condition characterized by hyperinsulinemic hypoglycemia, is thought to be caused by an excessive GLP-1 response leading to persistent, recurrent, and debilitating hypoglycemia and impaired quality of life. Avexitide is an injectable that was designed to bind to the GLP-1 receptor on pancreatic islet beta cells and inhibit the effects of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilize blood glucose levels. This may allow individuals with this condition to experience the benefits of bariatric surgery without the significant glycemic variability and hypoglycemia characteristic of PBH. GLP-1 hypersecretion is believed to play a critical role in PBH, and we therefore see a clear link between avexitide’s proposed mechanism of action and the mechanism of disease in hyperinsulinemic hypoglycemia.
AMX0035 is an oral, fixed-dose combination of two small molecules, sodium phenylbutyrate (PB) and taurursodiol (TURSO, also known as ursodoxicoltaurine outside of the U.S.). AMX0035 is designed to mitigate neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, two cellular processes central to neuronal cell death and neurodegeneration. AMX0035 has demonstrated clear biological activity in preclinical and clinical studies, leading us to target diseases in which ER stress and mitochondrial dysfunction are known contributors, including Wolfram syndrome and progressive supranuclear palsy (PSP).
AMX0114 is an Amylyx-developed, intrathecally administered antisense oligonucleotide (ASO) designed to target calpain-2, a protein involved in axonal degeneration and neurofilament biology. Activation of calpain-2 has been identified as a critical effector of axonal degeneration, also known as Wallerian degeneration, which is a key contributor to the clinical presentation and pathogenesis of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Calpain-2 cleaves neurofilament light chain (NfL), a broadly researched biomarker for axonal degeneration in ALS, and TAR DNA-binding protein 43 (TPD-43), a protein associated with ALS. The AMX0114 program reflects our continued commitment to ALS and our broader R&D strategy to explore differentiated scientific approaches tailored to the diseases in which we can have the greatest impact.
None of the above therapies has been proven safe or effective by any regulator and further evaluation is necessary.