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<\/a><\/a>\nAP-101 is an investigational human-derived antibody that selectively targets the misfolded, toxic form of superoxide dismutase 1 (SOD1) to disrupt the progressive spread of ALS. The goal of this approach is to help slow the spread of misfolded SOD1 in the nervous system of people living with ALS and support the body\u2019s natural ability to clear it.1<\/sup><\/p> \n\u201cWhile ALS is a highly diverse disease, these data reinforce the central role of misfolded SOD1 as a therapeutic target in ALS,\u201d said Angela Genge, M.D., FRCP(C), eMBA, chief medical officer of AL-S Pharma. \u201cThe consistency observed across multiple biomarker and clinical measures provide strong rationale for continued development of AP-101 as a potential disease-modifying therapy. We are focused on the continued advancement of the AP-101 clinical program and bringing a much-needed new treatment option to people living with ALS.\u201d<\/p> \nThe global AP-101 Phase 2 clinical trial met its primary endpoint related to safety and tolerability. Recent findings provide additional evidence of clinically meaningful disease modification and prolonged survival supported by reductions in key neuroaxonal injury biomarkers, serum neurofilament light chain (NfL) and cerebrospinal fluid phosphorylated neurofilament heavy chain (pNfH) after six months of treatment. Adverse events were found to be similar to those in the placebo group, with no reported antibody responses induced by AP-101.<\/p> \nThe prespecified analysis of an exploratory composite endpoint indicated that early treatment with AP-101 prolonged survival and delayed ventilatory support when compared to study participants receiving placebo for six months followed by six 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\u2019s staging. Functional decline measured by ALSFRS-R was reduced in study participants with elevated misfolded SOD1 at baseline and in SOD1 mutation carriers.<\/p> \nAL-S Pharma is advancing AP-101 into a confirmatory Phase 3 clinical trial of AP-101 in ALS aimed to initiate the first quarter of 2027. AP-101 received Orphan Drug designations from the U.S. Food and Drug Administration, the European Medicines Agency, and Swissmedic.<\/p> \nAL-S Pharma ENCALS Symposium: \u201cBeyond \u201cSporadic\u201d ALS: Genetics, Biomarkers, and the Misfolded SOD1 Pathway.\u201d<\/b><\/p> \nModerated by Dr. Genge, AL-S Pharma\u2019s symposium brought together internationally recognized leaders in ALS research to examine how advances in disease biology are reshaping clinical investigation and therapeutic development. Designed for neurologists, physician-scientists, clinical trialists, and industry professionals in drug development, the session connected emerging insights in genetic architecture, biomarker interpretation, and protein misfolding biology to the practical realities of ALS diagnosis, stratification, and trial design.<\/p> \nA moderated panel discussion, \u201cTranslating ALS Biology into Better Trials,\u201d featured Prof. Leonard van den Berg, Ph.D., Prof. Andrea Malaspina, M.D., Ph.D., and Prof. Julian Grosskreutz, M.D. They discussed how emerging insights in ALS genetics, biomarker interpretation, and misfolded protein biology can be translated into better trial design, patient stratification, and therapeutic development.<\/p> \nAbout AP-101-02<\/b><\/p> \nThe AP-101-02 clinical trial (NCT05039099) was a global, randomized, double-blind, placebo-controlled Phase 2 study evaluating the safety, tolerability, pharmacodynamic markers, and pharmacokinetics (PK) of AP-101 in 73 patients with sporadic ALS and in patients with mutations in the superoxide dismutase 1 (SOD1) gene. Study participants with sporadic (n=52) or mutant SOD1<\/i> ALS (n=21) were stratified and randomized 2:1 to intravenous AP-101 or placebo every three weeks. Key assessments included survival and ventilation endpoints, slow vital capacity, neurofilament levels, misfolded SOD1, PK, and anti-drug antibodies. After 24 weeks all participants entered a 24-week open-label extension with continued AP-101 treatment, followed by a 16-week safety follow-up period.<\/p> \nAP-101-02 was conducted in the U.S., Canada, the U.K., European Union, and South Korea. More information about the clinical trial can be accessed on www.clinicaltrials.gov<\/a>.<\/p> \nAbout Amyotrophic Lateral Sclerosis and SOD1<\/b><\/p> \nAmyotrophic lateral sclerosis (ALS) is a relentless and progressive neurodegenerative disease that affects the motor neurons of the brain and spinal cord. Symptoms vary from person to person. Some forms of ALS begin with limb weakness, while others start with bulbar symptoms. All forms ultimately lead to loss of independence and a markedly shortened lifespan. Median survival remains three-to-five years, and diagnosis is often delayed.<\/p> \nDespite this diversity, many patients share common downstream pathologies involving axonal injury, inflammation, and protein misfolding. Superoxide dismutase 1 (SOD1) is a protective enzyme that helps cells manage oxidative stress. In ALS, structural changes can cause SOD1 to lose its proper function and misfold, taking on toxic conformations that disrupt cellular function. Such misfolded SOD1 can injure motor neurons, damage mitochondria, and impair axonal transport. Pathology can spread by the seeding of SOD1 misfolding.<\/p> \nMisfolded SOD1 represents a powerful therapeutic opportunity. Across different presentations of ALS, misfolded SOD1 can amplify axonal injury and accelerate disease progression, making these toxic conformations an important target for intervention.<\/p> \nAbout AL-S Pharma AG<\/b><\/p> \nAL-S Pharma is a clinical-stage biotech company developing AP-101 for the treatment of amyotrophic lateral sclerosis (ALS). Founded and co-owned by Neurimmune and TVM Capital Life Science, AL-S Pharma brings together a seasoned team of biotech and pharmaceutical leaders with expertise spanning drug discovery, translational research, and clinical development. AL-S Pharma is based in Zurich, Switzerland. For more information, visit www.al-spharma.com<\/a>.<\/p> \n1<\/sup>Maier M et al., Sci Transl Med. 2018;10(470).<\/p> \nInvestor Contact<\/strong><\/p> \nAL-S Pharma\n \nMedia Contact(s)<\/strong><\/p> \nAL-S Pharma\n\n