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AP-101: Targeting misfolded SOD1 to halt ALS progression

AP-101 is a Phase-3 ready human antibody designed to selectively deplete toxic, misfolded forms of superoxide dismutase 1 (SOD1) while preserving the normal, protective function of healthy SOD1. By targeting only the pathological conformations, AP-101 aims to interrupt a key driver of ALS progression without lowering total SOD1 levels.

How AP-101 is designed to work

AP-101 is designed to inhibit the progressive spread of SOD1 pathology in the central nervous system by binding toxic misfolded SOD1 and helping the body’s immune system clear these harmful proteins. The approach is based on growing evidence that misfolded SOD1 contributes to ALS biology beyond hereditary SOD1 mutation disease.

Phase 2 results

The global Phase 2 clinical trial evaluating AP-101 in ALS (AP-101-02) was completed in 2025 and met its primary endpoint related to safety and tolerability. Phase 2 findings presented at key medical congresses in 2026 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.

In a prespecified analysis of an exploratory composite endpoint, early treatment with AP-101 prolonged survival and delayed ventilatory support compared with study participants receiving placebo for six months followed by six months of AP-101. Positive treatment effects were observed in both the sporadic ALS cohort and the SOD1 mutation carrier cohort. 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.

About AP-101-02

The 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 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. 

AP-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.

Regulatory status and next step

AP-101 has received Orphan Drug designations from the U.S. Food and Drug Administration, the European Medicines Agency and Swissmedic. AL-S Pharma is advancing AP-101 into a confirmatory Phase 3 clinical trial in ALS aimed to initiate in 2027.

AP-101 is investigational and has not been approved by any regulatory authority.
AP-101-02 phase 2 trial design and execution
AP-101-02 phase 2 trial sites

    AL-S Pharma Early/Expanded Access Policy

    AL-S Pharma is working with urgency and compassion to develop AP-101, an investigational therapy for amyotrophic lateral sclerosis (ALS). Our goal is to develop a treatment that may significantly improve outcomes for people living with this devasting disease.

    Before an investigational therapy can be approved and made broadly available, it must be studied in well-controlled clinical trials. These trials help understand the safety of the investigational therapy, whether it may help patients, and whether its potential benefits outweigh its risks.

    Early or expanded access is a potential pathway for patients diagnosed with a serious and/or life-threatening disease or condition to gain access to an investigational drug for treatment outside of a clinical trial when no comparable or satisfactory alternative therapy options are available, all of which must be done while adhering to regulatory health authorities’ guidelines.

    In these instances, a patient’s treating physician can request an investigational drug prior to regulatory approval, where allowed by local laws and adherence to regulatory health authorities’ guidelines. Any such request must be reviewed in the context of patient safety, available clinical data, regulatory requirements, and the ability to provide the investigational medicine without compromising ongoing clinical development.

    Currently, AP-101 is not available through an early or expanded access program. At this stage, AL-S Pharma believes that participation in clinical trials is the best way for patients to access AP-101.

    As the AP-101 clinical program progresses, AL-S Pharma will continue to evaluate early access and may reconsider how to make AP-101 available in the future.

    «As a principal investigator in the AP-101 trial, I’ve seen firsthand the importance of targeting underlying disease mechanisms in ALS. Misfolded SOD1 represents a compelling therapeutic target, and the clinical evaluation of AP-101 marks a meaningful step toward bringing new treatment options to patients.»

    Caroline Ingre, MD, PhD
    Trial Investigator