Al-S Pharma reports Phase 2 AP-101 data in ALS showing biomarker and survival signals alongside safety findings from a global study presented at ENCALS 2026.

AL-S Pharma AG has presented Phase 2 findings for AP-101 at the European Network to Cure ALS 2026 Congress, highlighting biomarker changes and exploratory survival outcomes in patients with ALS, including both sporadic disease and those with SOD1 mutations.

AP-101 is described as a first-in-class, Phase 3-ready antibody designed to selectively bind misfolded superoxide dismutase 1 (SOD1), a toxic protein species linked to motor neuron degeneration. The company states the aim is to reduce propagation of misfolded SOD1 and support clearance mechanisms that may slow disease progression.

The Phase 2 AP-101-02 study enrolled 73 patients across multiple regions including Europe, North America and Asia. Participants received either intravenous AP-101 or placebo every three weeks, followed by an open-label extension phase in which all participants received active treatment.

The primary endpoint focused on safety and tolerability, which the company reports was met. AP-101 was generally well tolerated, with adverse events comparable between treatment and placebo groups, and no reported treatment-induced antibody responses.

More notable from a development perspective were biomarker and exploratory efficacy signals. The company reports reductions in serum neurofilament light chain (NfL) and cerebrospinal fluid phosphorylated neurofilament heavy chain (pNfH) after six months of treatment. These markers are widely used as indicators of neuroaxonal injury in ALS research.

Exploratory analyses also suggested potential effects on disease progression. A prespecified composite endpoint indicated delayed need for ventilatory support and prolonged survival compared with placebo followed by open-label treatment. Signals were reported in both sporadic ALS and SOD1 mutation carrier subgroups, with reported p values of 0.013 and 0.036 respectively.

Disease stabilisation was additionally described using King’s staging, while functional decline measured by ALSFRS-R appeared reduced in patients with elevated baseline misfolded SOD1 and in SOD1 mutation carriers.

In a company statement, Angela Genge, chief medical officer at AL-S Pharma, said: “While ALS is a highly diverse disease, these data reinforce the central role of misfolded SOD1 as a therapeutic target in ALS. The consistency observed across multiple biomarker and clinical measures provide strong rationale for continued development of AP-101 as a potential disease-modifying therapy.”

The data will now support progression into a confirmatory Phase 3 programme, which the company expects to initiate in the first quarter of 2027. AP-101 has received orphan drug designations in the US, EU and Switzerland.

Alongside the data presentation, AL-S Pharma hosted a scientific symposium at ENCALS focused on ALS biology, genetics, biomarker interpretation and trial design. Academic speakers discussed evolving perspectives on the distinction between sporadic and genetic ALS, the interpretation of neurofilament dynamics in trials, and the potential role of misfolded protein biology beyond known mutations.

Overall, the dataset adds to growing interest in neurofilament-linked biomarker responses as early indicators of therapeutic activity in ALS, though the findings remain within the context of a Phase 2 study and require confirmation in larger controlled trials.