AL-S Pharma Reports Positive Results from Phase 2 Study of AP-101 for the Treatment of ALS, Supporting Plans for a Confirmatory Phase 3 Study

• Primary safety and tolerability endpoint met
• AP-101 prolonged survival and delayed need for ventilatory support after 12 months of treatment
• Functional stabilization and reduced neurofilament biomarkers observed in study participants with elevated misfolded SOD1

ZURICH, Switzerland, Dec. 5, 2025 /PRNewswire/ -- AL-S Pharma, a clinical-stage biotech company dedicated to the development of AP-101 for the treatment of amyotrophic lateral sclerosis (ALS) today presented its Phase 2 clinical study results on AP-101 at the 36^th International Symposium on ALS/MND in San Diego.

AP-101 is an investigational human antibody therapeutic selectively targeting misfolded SOD1 to disrupt the progressive spread of pathology in ALS.¹ The global phase 2 study with 73 participants met its primary endpoint related to safety and tolerability. Adverse events were comparable to placebo, and no AP-101-induced antibody responses were reported.

The analysis of an exploratory composite endpoint revealed that early treatment with AP-101 prolonged survival and delayed ventilatory support in comparison to study participants receiving placebo for 6 months followed by 6 months of treatment with AP-101. Positive treatment effects were observed in both the sporadic ALS cohort (p = 0.013) and the SOD1 mutation carrier cohort (p = 0.036). Effects on survival were accompanied by disease stabilization as measured by King's staging. Functional decline measured by ALSFRS-R was reduced in study participants with elevated misfolded SOD1 at baseline and in SOD1 mutation carriers. In addition, AP-101 treatment resulted in favorable neurofilament biomarker changes aligned with clinical benefit.

"We are very excited by the positive Phase 2 results for AP-101," said Angela Genge, MD, Chief Medical Officer of AL-S Pharma. "We are observing very consistent results across survival, function, and biomarkers in two independent cohorts within our study. Despite the statistical limitations of a Phase 2 study, the exploratory outcome data indicates that treatment with AP-101 results in a clinically meaningful treatment effect in both sporadic ALS as well as SOD1-ALS patients."

The Phase 2 study results with AP-101 are consistent with the hypothesis that targeting misfolded SOD1 is a disease-modifying approach in ALS.² AL-S Pharma is currently preparing for a confirmatory Phase 3 clinical study.

"We are deeply committed to advancing an urgently needed new treatment option for ALS. Together with our investigators, advisors, collaborators, and their clinical teams, we are pioneering a new disease-modifying approach by targeting misfolded SOD1 with a therapeutic antibody," said Michael Salzmann, PhD, Chief Executive Officer of AL-S Pharma. "We are grateful to all the trial participants and their families whose dedication made this study possible. We plan to engage with regulators on next steps in the coming months while we prepare for the confirmatory Phase 3 study."

The AP-101-02 study was a global, randomized, double-blind, placebo-controlled study evaluating safety, tolerability, pharmacodynamic markers, and pharmacokinetics of AP-101 in study participants with sporadic ALS (N=52) and mutant SOD1-ALS (N=21) over 6 months followed by a 6-months open-label extension and a safety follow-up period. Further information on the clinical study of AP-101 for ALS can be accessed on ClinicalTrials.gov (study number NCT05039099).

¹Maier M et al., Sci Transl Med. 2018;10(470).
²Marlow TR et al., Neurobiol Dis. 2025;216:107124.

About AP-101
AP-101 is an investigational human-derived antibody directed against misfolded superoxide dismutase 1 (SOD1) designed to inhibit the spread of SOD1 pathology in the CNS of ALS patients. AP-101 received orphan drug designations from FDA, EMA and Swissmedic. The Phase 2 study evaluated safety, tolerability, pharmacodynamic (PD) markers, and pharmacokinetics (PK) of AP-101 in patients with sporadic ALS and in patients with mutations in the SOD1 gene.

About AL-S Pharma AG
AL-S Pharma is a Swiss-based single-asset company founded and co-owned by Neurimmune and TVM Capital Life Science to develop AP-101. The company is fully financed by TVM Life Science Innovation I and Neurimmune. AL-S Pharma brings together a seasoned team of biotech and pharmaceutical leaders with expertise spanning drug discovery, translational research, and clinical development. Based on the successful Phase 2 data, AL-S Pharma is currently advancing AP-101 into late-stage development.

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www.al-spharma.com

Contact for Media

John Capodanno (US)
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+1 917 750-8649

Anne Hennecke (EU)
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Contact for AL-S Pharma
Dr. Michael Salzmann
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SOURCE AL-S Pharma AG