AL-S Pharma Reports New AP-101 Phase 2 Weight Data and Outlines Phase 3 Clinical Trial in ALS at 2026 NEALS Annual Meeting

AL-S Pharma Reports New AP-101 Phase 2 Weight Data and Outlines Phase 3 Clinical Trial in ALS at 2026 NEALS Annual Meeting

New Phase 2 post-hoc analyses demonstrate greater body-weight preservation with AP-101 compared with placebo in patients with ALS

Findings reinforce clinical relevance of body weight as a potential surrogate marker of clinical response; weight loss is closely associated with ALS disease progression and poorer outcomes

Planned confirmatory Phase 3 clinical trial expected to initiate in 2027

ZURICH, Switzerland — October 26, 2026 — AL-S Pharma AG (“AL-S Pharma” or “the Company”), a clinical-stage biotechnology company discovering and developing human antibodies that target misfolded proteins implicated in amyotrophic lateral sclerosis (ALS), today announced new analyses from its global Phase 2 clinical trial (AP101-02) evaluating the company's Phase 3-ready lead program, AP-101, in patients with sporadic ALS and superoxide dismutase 1 (SOD1)-ALS. The new findings demonstrate greater preservation of body weight in patients treated with AP-101 compared with placebo. Weight loss has been associated with shorter survival, while longitudinal changes in weight may reflect several aspects of disease progression, including nutritional status, metabolic changes, and muscle loss.

The results will be presented by Angela Genge, M.D., FRCP(C), eMBA, chief medical officer of AL-S Pharma, during the NEALS Affiliated Trial Session at the 2026 Network of Excellence for ALS (NEALS) Meeting taking place October 27–30, 2026, in Clearwater, Florida, and online.

"Preservation of body weight is particularly relevant in ALS, where weight loss is closely associated with disease progression and poorer outcomes," commented Dr. Genge. "These new analyses add an important clinical perspective to our Phase 2 findings, demonstrating a consistent trend toward greater weight preservation with AP-101 across different ALS patient populations. The new analyses provide additional evidence that rate of weight loss is an important additional measure of clinical response alongside established functional, respiratory, and survival outcomes. We are eager to progress the confirmatory Phase 3 study with the intention of delivering a critically needed new treatment option targeting misfolded SOD1 to people living with ALS."

New Phase 2 Analyses Demonstrate Greater Body-Weight Preservation with AP-101
New post-hoc analyses of the randomized, double-blind period of the AP101-02 clinical trial provide further insights into body-weight trajectories in patients with sporadic ALS and SOD1-ALS.

In the sporadic ALS cohort, mixed-model repeated-measures analyses showed a progressive separation in body-weight trajectories favoring AP-101, with an adjusted between-group difference of 2.25 kg at Week 24. In the SOD1-ALS cohort, the analysis demonstrated a 4.82 kg difference favoring AP-101 at the 21-day follow-up after the randomized treatment period (p = 0.0092). Additional post-hoc analyses examined participants with sporadic ALS according to baseline cerebrospinal fluid (CSF) levels of misfolded SOD1. Among participants in the highest tertile of baseline misfolded SOD1, AP-101 treatment was associated with greater preservation of body weight compared with placebo, with a 4.59 kg difference at the 21-day follow-up (p = 0.0010).

The global AP-101 Phase 2 clinical trial met its primary endpoint related to safety and tolerability. In addition to greater body-weight preservation in AP-101-treated participants, study findings provide additional evidence of clinically meaningful disease modification and prolonged survival. This is 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 in the per protocol population. Adverse events were found to be similar to those in the placebo group, with no reported antibody responses induced by AP-101.

Presentation Details

• Title: Learnings from the Phase 2 Study of AP-101 (AP101-02) and the Role of Weight as a Surrogate Marker of Clinical Response
• Presenter: Angela Genge, M.D., FRCP(C), eMBA, chief medical officer, AL-S Pharma
• Session: NEALS Affiliated Trial Session
• Date/Time: Wednesday, October 28, 2026, 11:05 a.m. ET
• Location: Ballroom

Planned NEALS-Affiliated Phase 3 Confirmatory Trial of AP-101 Featured in Poster Presentation
AL-S Pharma is advancing AP-101 toward AP101-03, a planned NEALS-affiliated, multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to evaluate the efficacy and safety of AP-101 in adults with ALS. The study is planned to enroll approximately 300 participants, randomized 2:1 to receive AP-101 at a dose of 2,500 mg intravenously every three weeks or placebo for 12 months, in addition to standard of care.

The planned primary analysis will employ a joint statistical model incorporating longitudinal changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) and survival-related events, defined as death or permanent assisted ventilation. This approach is intended to evaluate whether AP-101 has a significant effect on function and/or survival. Additional assessments will include body weight, respiratory function, King's staging, quality of life, safety, pharmacokinetics, immunogenicity, and CSF and plasma biomarkers. The inclusion of serial body-weight measurements will enable further prospective evaluation of the weight-preservation findings observed in the Phase 2 AP-101 clinical trial. Eligible participants will have an ALS diagnosis based on Gold Coast or revised El Escorial criteria, symptom onset within 24 months, and slow vital capacity of at least 60% at screening. Participants completing the 12-month double-blind treatment period may enter a further 12-month open-label extension.

The Phase 3 trial is planned to initiate in 2027. AP-101 has received Orphan Drug designations from the U.S. Food and Drug Administration, the European Medicines Agency, and Swissmedic.

Poster Details

• Title: Design of a Planned Phase 3 Confirmatory Trial of AP-101, a Human Antibody Targeting Misfolded SOD1 in ALS
• Presenter: Angela Genge, M.D., FRCP(C), eMBA, chief medical officer, AL-S Pharma
• Poster/Session: Poster 204; Session 2
• Date/Time: Thursday, October 29, 2026, 4:50-6:30PM ET
• Location: Opal Sands, Ballroom

About AP101-02
The AP101-02 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 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. 

AP101-02 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.

About Amyotrophic Lateral Sclerosis and SOD1
Amyotrophic 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.
Despite 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.
Misfolded 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.

About AL-S Pharma AG
AL-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.

Media Contact(s)

AL-S Pharma
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