VectorY Therapeutics has announced the dosing of the first participant in its Phase I/II PIONEER-ALS clinical trial evaluating VTx-002, a first-in-class vectorised antibody therapy designed to target TDP-43 pathology in people living with Amyotrophic Lateral Sclerosis (ALS). The first dose was administered at the Sean M. Healey and AMG Centre for ALS at Mass General Brigham, a leading center for neurodegenerative disease treatment and research.

VTx-002 is engineered to address one of the central pathological drivers of ALS—abnormal aggregation of TDP-43, a protein implicated in up to 97 percent of ALS cases. The therapy is designed to enable sustained antibody expression within the central nervous system using a vector-based delivery platform. By holistically targeting TDP-43 pathology, VTx-002 aims to reduce protein aggregation, correct mis-splicing abnormalities and restore normal nuclear function. The investigational therapy has recently received US FDA Fast Track Designation to support expedited development and review.

The PIONEER-ALS study is a multicentre, open-label, dose-escalation Phase I/II trial that will evaluate two dose levels of VTx-002 in approximately 12 adults with ALS across sites in the US, Europe and the UK. The primary objective is to assess safety, tolerability and pharmacokinetics, along with exploratory measures of efficacy.

Secondary and exploratory endpoints include changes in Neurofilament light chain (NfL) levels and novel TDP-43 pathway-related biomarkers, as well as clinical measures such as the ALS Functional Rating Scale-Revised (ALSFRS-R), slow vital capacity, hand-held dynamometry and survival outcomes.

Olga Uspenskaya-Cadoz, Chief Medical Officer of VectorY, described the initiation of dosing as a milestone for the company and the ALS community, highlighting the urgent need for disease-modifying therapies in a condition that remains universally fatal with limited treatment options.

Global Coordinating Investigator James Berry, MD, MPH, Chief of the Division of Motor Neuron Diseases and Director of the Neurological Clinical Research Institute at Mass General Brigham, noted that the study represents an innovative approach aimed at a key pathological hallmark of ALS and expressed optimism about exploring VTx-002’s potential impact.

VectorY plans to continue enrolling participants in the PIONEER-ALS trial across multiple international clinical sites.

ALS affects more than 30,000 people in the United States, with over 5,000 new cases diagnosed annually. Median survival after diagnosis is typically two to three years, underscoring the significant unmet medical need. Beyond VTx-002, VectorY is advancing a broader pipeline of vectorised antibody therapies targeting neurodegenerative diseases, including Huntington’s disease, Alzheimer’s disease and frontotemporal dementia.