AL-S Pharma announced positive topline results from its Phase 2 clinical study evaluating AP-101, a potential first-in-class, disease-modifying treatment for amyotrophic lateral sclerosis (ALS). The monoclonal antibody targeting misfolded SOD1 met its primary endpoint related to safety and tolerability while demonstrating clinically meaningful changes in exploratory clinical outcome measures.
Study Design and Patient Population
The multicenter, randomized, double-blind, placebo-controlled study evaluated safety, tolerability, pharmacodynamic markers, and pharmacokinetics of AP-101 in patients with sporadic ALS (N=52) and patients with mutant SOD1-ALS (N=21) over 24 weeks followed by a 24-week open-label extension and a safety follow-up period. The study is registered on ClinicalTrials.gov under study number NCT05039099.
"This is the first Phase 2 study to assess a SOD1-targeted therapeutic in both sporadic ALS and in ALS patients with mutations in the SOD1 gene," said Peter Andersen, Professor and Senior Consultant Neurologist at Umea University, Sweden, and Principal Investigator for the AP-101 Phase 2 study. "The study allowed us to rigorously assess patient safety, pharmacokinetics, and early signals of biological activity."
Clinical Outcomes and Biomarker Results
Following 12 months of treatment with AP-101 in addition to standard of care, clinically meaningful changes in exploratory clinical outcome measures related to survival and non-invasive ventilation were observed. The study also demonstrated stabilization of clinical disease-staging and neurofilament biomarkers.
"The completion of the trial marks an important step in evaluating the therapeutic potential of AP-101 for broad use in patients with ALS," Andersen noted. "The results support the hypothesis that misfolded SOD1 protein plays a more general role in ALS."
Targeting SOD1 Pathology in ALS
ALS is a fatal neurodegenerative disease characterized by loss of both upper and lower motor neurons. Symptoms typically begin focally with spread in a contiguous anatomical pattern, leading to muscle weakness, respiratory issues, swallowing and speaking difficulties, and ultimately to death. Very limited therapeutic options are available for this devastating condition.
SOD1 pathology has been proposed to be a disease driver in both genetically determined SOD1-ALS as well as in sporadic ALS. Pathological, genetic and preclinical evidence suggest that SOD1 misfolding and the formation of neurotoxic SOD1 species drive cell death in the motor system. AP-101 is a first-in-class antibody therapeutic targeting misfolded SOD1.
Drug Development and Regulatory Status
AP-101 is an investigational human antibody directed against misfolded superoxide dismutase 1 (SOD1) and was discovered by Neurimmune's Reverse Translational Medicine™ (RTM™) technology. The antibody has been designed to inhibit the spread of SOD1 pathology in the cerebrospinal fluid and spinal cord of ALS patients. AP-101 received orphan drug designations from FDA, EMA and Swissmedic.
"We are excited by the topline Phase 2 results of AP-101 for ALS, a devastating degenerative disease for which new treatments are urgently needed," said Michael Salzmann, PhD, Chief Executive Officer of AL-S Pharma. "We are grateful to the participants, their families and the international network of ALS experts who made this trial possible."
Next Steps and Regulatory Engagement
Results will be shared with regulatory authorities, presented at upcoming ALS conferences, and submitted for publication in a peer-reviewed scientific journal. AL-S Pharma plans to engage with regulatory authorities later this year.
The company will present detailed findings at the 36th International Symposium on ALS/MND in December 2025, with Prof. Dr. Angela Genge from McGill University delivering an oral presentation titled "Top-line results of the Phase 2 proof-of-concept study of AP-101, a first-in-class human antibody targeting misfolded SOD1 in amyotrophic lateral sclerosis."
Company Background
AL-S Pharma is a Swiss-based single-asset company founded and co-owned by Neurimmune and TVM Capital Life Science in 2016 to develop AP-101. The company is fully financed by TVM Life Science Innovation I and Neurimmune, and has executed its innovative clinical plan for AP-101 in collaboration with an international network of ALS experts.
