According to a new announcement, AL-S Pharma’s AP-101, a monoclonal antibody targeting misfolded SOD1, met its primary safety and tolerability end point in a phase 2 study of both patients with sporadic amyotrophic lateral sclerosis (ALS) and mutant SOD1-ALS. The company is planning to present the full data at upcoming scientific conferences, as well as engage with regulatory authorities later this year on determining next steps for this agent.1
This randomized, double-blind, placebo-controlled trial included 52 patients with sporadic ALS and 21 patients with SOD1-ALS who were evaluated for a 24-week treatment period, followed by a 24-week open-label extension and a safety follow-up period. While no specifics of the data were released, AL-S Pharma noted that the drug was safe, and led to clinically meaningful changes in outcome measures and stabilization of relevant biomarkers.
To date, tofersen (Qalsody; Biogen) remains the only FDA-approved treatment for patients with SOD1-ALS, which make up about 15-20% of familial ALS cases and roughly 2% of all ALS cases overall. AP-101, discovered using Neurimmune’s proprietary Reverse Translational Medicine (RTM) technology, is designed to selectively bind to misfolded and aggregated forms of SOD1, leaving the normal SOD1 untouched. This targeted binding is intended to promote clearance–likely via phagocytosis–of the pathological proteins, potentially slowing motor neuron death.
“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,” Michael Salzmann, PhD, chief executive officer at AL-S Pharma, said in a statement. “We are grateful to the participants, their families and the international network of ALS experts who made this trial possible, and we look forward to sharing results from the study at the International Symposium on ALS/MND.”
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Topline results from the study are expected to be presented at the 36th International Symposium on ALS/MND on December 5, 2025, while he baseline characteristics and analysis of misfolded SOD1 target levels are expected at the 2025 Annual NEALS Meeting. The phase 2 study, which began in 2021, primarily focused on safety and tolerability, but also included other outcomes such as half-life, area under the drug concentration, cerebrospinal fluid (CSF) levels in neurofilament light and phosphor-neurofilament heavy chain levels.
The phase 2 study included those with ALS whose symptoms began within the past 24 months, while having documented progressive motor impairment and evidence of motor neuron dysfunction. Those with familial cases required a confirmed pathogenic SOD1 mutation to be included.
Additional requirements for the study included an SVC greater than 50, limited ventilatory support use, stable riluzole or edaravone regimens if spplicable, adequate venous access, and acceptable lablvalues. Exclusions applied to those recently in other trials, requiring tracheostomy or at least 4 hours/day of noninvasive ventilation, with other causes of neuromuscular weakness, significant comorbidities, pregnancy or nursing, prior SOD1 antisense therapy within six months, or prior stem cell therapy.
“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. The study allowed us to rigorously assess patient safety, pharmacokinetics, and early signals of biological activity,” Principal investigator Peter Anderson, PhD, professor and senior consultant neurologist at Umea University, in Sweden, said in a statement. “The completion of the trial marks an important step in evaluating the therapeutic potential of AP-101 for broad use in patients with ALS. The results support the hypothesis that misfolded SOD1 protein plays a more general role in ALS.”
REFERENCES
1. AL-S Pharma announces positive topline results from Phase 2 study of AP-101 for the treatment of amyotrophic lateral sclerosis (ALS). News release. AL-S Pharma. September 4, 2025. Accessed September 4, 2025. https://www.prnewswire.com/news-releases/al-s-pharma-announces-positive-topline-results-from-phase-2-study-of-ap-101-for-the-treatment-of-amyotrophic-lateral-sclerosis-als-302545686.html
2. A Study to Evaluate, Safety, Tolerability, Pharmacodynamic (PD) Markers and Pharmacokinetics (PK) of AP-101 in Participants With Amyotrophic Lateral Sclerosis (ALS). Clincialtrial.gov. Updated August 19, 2025. Accessed September 4, 2025. https://clinicaltrials.gov/study/NCT05039099, in Sweden, said in a statement. “The completion of the trial marks an important step in evaluating the therapeutic potential of AP-101 for broad use in patients with ALS. The results support the hypothesis that misfolded SOD1 protein plays a more general role in ALS.”