Amylyx Pharmaceuticals Announces First Participant Dosed in Phase 2 Study of AMX0035 for the Treatment of Wolfram Syndrome

Amylyx Pharmaceuticals has announced that the first participant has been dosed in the HELIOS study, a Phase 2 clinical trial of AMX0035 for the treatment of Wolfram syndrome (WS). HELIOS is an exploratory open-label proof of biology study assessing the effect of AMX0035 safety and tolerability, and various measures of endocrinological, neurological and ophthalmologic function. Amylyx anticipates topline results from HELIOS in 2024.

Researchers from the Washington University School of Medicine in St. Louis, in collaboration with Amylyx, recently published preclinical data exploring the potential of AMX0035 as a novel therapeutic approach for WS. These data were published in the peer-reviewed Journal of Clinical Investigation Insight, characterizing a pathogenic variant in the WFS1 gene (WFS1 c.1672C>T, p.R558C), identifying a platform for further genotype-phenotype analysis, and providing initial proof-of-concept for the therapeutic development of AMX0035 in WS. The study demonstrated that iPSC-derived WS models can provide a model of genotype-phenotype relationships that correlate with clinical observations. The study highlights related to AMX0035 included:

• Administration of AMX0035 improved WFS1 protein expression, increased insulin secretion, and inhibited cell death in β cells with the WFS1 c.1672C>T, p.R558C variant. AMX0035 also prevented cellular death in patient-derived neuronal progenitor cells. Gene enrichment analysis revealed that treatment with AMX0035 ameliorated organelle dysfunction, mitophagy, endoplasmic reticulum (ER) stress, and apoptosis.
• Furthermore, AMX0035 delayed the onset of the diabetic phenotype in vivo in the Wfs1-knockout mouse model of Wolfram syndrome.

“WS is a rare, progressive, and often fatal neurodegenerative disease. Preclinical data showed that a combination treatment of two chemicals, namely AMX0035, may restore cellular functioning in a cellular model of WS,” said Fumihiko Urano, MD, PhD, Principal Investigator of the HELIOS clinical trial, and Professor of Medicine and of Pathology and Immunology in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine. “There continues to be a significant unmet need for people living with WS and we look forward to building upon our preclinical findings as part of HELIOS to explore the safety, tolerability, and preliminary clinical activity in people living with WS.”

“The WS community is in critical need of treatments to potentially improve their outcomes and standard of day-to-day living,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. “We believe AMX0035 has scientific potential in several neurodegenerative diseases. We look forward to continuing to work to study AMX0035 in additional populations, including WS, and advancing progress in collaboration with the WS community including clinicians, researchers, and those living with the disease and their caregivers.”

Amylyx announced that the FDA granted orphan drug designation to AMX0035 for the treatment of Wolfram Syndrome in November 2020. The FDA may grant this designation to drugs and biologics intended to treat a rare disease or condition affecting fewer than 200,000 persons in the U.S. Orphan designation qualifies a company for certain benefits, including financial incentives to support clinical development and the potential for seven years of market exclusivity in the U.S. upon regulatory approval.