AL-S Pharma announces positive topline results from Phase 2 study of AP-101 for the treatment of amyotrophic lateral sclerosis (ALS)

• Phase 2 of AP-101 in sporadic ALS and mutant SOD1-ALS met its primary safety and tolerability endpoint
• Clinically meaningful changes in outcome measures and stabilization of biomarkers were observed
• Data will be presented at upcoming scientific conferences and AL-S Pharma plans to engage with regulatory authorities later this year
• AP-101 is a first-in-class investigational human antibody targeting misfolded SOD1, a pathological hallmark of ALS

ZURICH, Sept. 4, 2025 /PRNewswire/ -- AL-S Pharma today announced positive topline results from the Phase 2 clinical study evaluating AP-101, a potential first-in-class, disease-modifying treatment for amyotrophic lateral sclerosis (ALS). AP-101 is a monoclonal antibody targeting misfolded SOD1, a key pathology in both sporadic ALS and mutant SOD1-ALS.¹ AP-101, in addition to standard of care, met its primary endpoint related to safety and tolerability. Clinically meaningful changes in exploratory clinical outcome measures related to survival and non-invasive ventilation, as well as stabilization of clinical disease-staging and neurofilament biomarkers, were observed following 12 months of treatment. Results will be shared with regulatory authorities, presented at upcoming ALS conferences, and submitted for publication in a peer-reviewed scientific journal.

"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, AL-S Pharma. "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."

"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," said Peter Andersen, Professor and Senior Consultant Neurologist, Umea University, Sweden, and Principal Investigator for the AP-101 Phase 2 study. "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".

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.

SOD1 pathology has been proposed to be a disease driver in both genetically determined SOD1-ALS as well as in sporadic ALS.^2,3 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.

AL-S Pharma's Phase 2 study is a multicenter, randomized, double-blind, placebo-controlled study evaluating safety, tolerability, pharmacodynamic markers, and pharmacokinetics of AP-101 in both 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. Further information on the clinical study of AP-101 for ALS can be accessed on ClinicalTrials.gov (study number NCT05039099).

In 2016, Neurimmune and TVM Capital Life Science co-created AL-S Pharma to develop AP-101. AL-S Pharma has executed its innovative clinical plan for AP-101 in collaboration with an international network of ALS experts.

Presentation Details

36^th International Symposium on ALS/MND
Title: 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
Presenter(s): Prof. Dr. Angela Genge (McGill University – Montreal, Canada)
Session Type: Oral Presentation
Date: December 5, 2025

2025 Annual NEALS Meeting
Title: Baseline characteristics and analysis of misfolded SOD1 target levels in a Phase 2 proof-of-concept study to evaluate the human antibody AP-101 in sporadic ALS and genetically determined SOD1-ALS
Presenter: Prof. Dr. Angela Genge (McGill University – Montreal, Canada)
Session Type: Poster at Science Symposium
Date: October 2025 (additional details to be announced)

¹Maier M et al., Sci Transl Med. 2018;10(470).
²Forsberg K et al., PLoS One. 2010;5(7):e11552.
³Trist BG et al., Brain. 2022;145(9):3108-3130.

About AP-101
AP-101 is an investigational human antibody directed against misfolded superoxide dismutase 1 (SOD1) and was discovered by Neurimmune's Reverse Translational Medicine^TM (RTM^TM) 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. The Phase 2 study completed by AL-S Pharma evaluated the safety, tolerability, pharmacodynamic (PD) markers, and pharmacokinetics (PK) of AP-101 in patients with sporadic ALS and 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 is led by an experienced management team and the Board of Directors comprises Guy Rouleau, director of McGill University's Montreal Neurological Institute (MNI) and Hospital, Chair Department of Neurology and Neurosurgery, McGill University, Hubert Birner, Managing Partner, TVM Capital Life Science, Munich, Marc Riviere, General Partner, TVM Capital Life Science, Montreal, Christoph Hock, CMO of Neurimmune, and Jan Grimm, CSO of Neurimmune.

Follow AL-S Pharma on LinkedIn.

About Neurimmune
Neurimmune is a biopharmaceutical company translating human immune memory into antibody therapeutics. Neurimmune develops drug candidates for CNS and related protein aggregation diseases including Alzheimer's disease, amyotrophic lateral sclerosis and ATTR cardiomyopathy. With its Reverse Translational Medicine^TM technology, Neurimmune discovered the anti-ATTR antibody cliramitug (formerly NI006, ALXN2220) for ATTR cardiomyopathy, the anti-SOD1 antibody AP-101 for ALS and the anti-NogoA antibody NG004 for spinal cord injury, programs being currently evaluated in clinical trials.

For further information, please visit www.neurimmune.com. Follow Neurimmune on LinkedIn.

About TVM Capital Life Science
TVM is a leading international venture capital firm focused on investing in life science innovations. The company has a highly experienced transatlantic investment team and approximately $900 million under management. TVM's portfolio focuses on therapeutics and medical technologies from North America and the EU that represent differentiated first-in-class or best-in-class assets with the potential to transform standard of care. With its early-stage investments, TVM follows several key principles, which include increasing capital efficiency, streamlining development timelines and soliciting buyer input at the time of investment. This strategy has been validated through successful exits such as AurKa Pharma, Inc. and Acanthas Pharma, Inc.

For further information, please visit www.tvm-capital.com. Follow TVM on LinkedIn.

Contact for Media

John Capodanno (US)
[email protected]
+1 917 750-8649

Contact for AL-S Pharma
Dr. Michael Salzmann
[email protected]

SOURCE AL-S Pharma AG