CAMBRIDGE, Mass. — Amylyx Pharmaceuticals, Inc. announced new early safety and tolerability findings from Cohort 1 of its Phase 1 LUMINA trial evaluating AMX0114 in people with amyotrophic lateral sclerosis. The company also shared progress on biomarker analyses related to target engagement. The data were presented at the 36th International Symposium on ALS/MND, held December 5–7 in San Diego.
According to the company, AMX0114 was generally well-tolerated among the first 12 participants enrolled in LUMINA, with no treatment-related serious adverse events reported. Based on these results, Amylyx plans to open enrollment for the second cohort in Canada later this month and in the U.S. in January.
Sabrina Paganoni, M.D., Ph.D., principal investigator of the LUMINA trial and an investigator at the Sean M. Healey & AMG Center for ALS at Mass General Brigham, said the early findings support continued advancement of the program. “LUMINA is a first-in-human study, and we are encouraged by these data as we continue to advance AMX0114 as a potential treatment for this rapidly progressive disease with high unmet need. The safety and tolerability analysis allows LUMINA to proceed with its next cohort of participants, which is critical given that this community has no time to wait,” she said.
The LUMINA study (NCT06665165) is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose trial assessing AMX0114, an investigational antisense oligonucleotide designed to target calpain-2, a calcium-activated protease associated with axonal degeneration in ALS. The trial is evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics, along with a broad panel of ALS biomarkers, including changes from baseline in neurofilament light chain levels. Amylyx expects to report Cohort 1 biomarker results in the first half of 2026.
Camille L. Bedrosian, M.D., Chief Medical Officer at Amylyx, said the company is encouraged by the early safety profile. “We appreciate the partnership with LUMINA sites and participants to achieve complete enrollment of the first cohort. In addition, we are pleased that to date no drug-related SAEs or dose-limiting toxicities were observed, which represent important early steps in this study,” she said. Bedrosian added that preclinical work with AMX0114 showed strong, dose-dependent reductions in calpain-2 protein levels, along with improved neuronal survival and reductions in extracellular neurofilament light chain. “We look forward to presenting cohort 1 biomarker data at a medical meeting in the first half of next year,” she said.
