VectorY Doses First Patient in TDP-43–Targeting ALS Trial

VectorY Therapeutics, a Netherlands-based biotech company, has dosed the first participant in a Phase I/II clinical trial evaluating VTx-002, a first-in-class vectorized antibody designed to target pathological transactive response DNA-binding protein 43 kDa (TDP-43) in people with amyotrophic lateral sclerosis (ALS). The multicenter study (PIONEER-ALS) marks the first clinical evaluation of a therapy intended to holistically address TDP-43 pathology, a defining molecular hallmark in the majority of ALS cases, according to the company in a Feb. 9, 2026 announcement (1).

The first participant was treated at the Sean M. Healey & AMG Center for ALS at Mass General Brigham, located in Boston, which is serving as the lead study site. The trial is enrolling adults with ALS across sites in the United States, Europe, and the United Kingdom and is designed to evaluate the safety, tolerability, pharmacokinetics, and exploratory efficacy of VTx-002.

“ALS is a fatal neurodegenerative disease with no cure and only limited symptomatic treatment options available,” said Olga Uspenskaya-Cadoz, MD, PhD, chief medical officer, VectorY Therapeutics, in a company press release (1). “The initiation of dosing in the PIONEER-ALS trial is a significant milestone for VectorY as we strive to transform the neurodegenerative disease landscape with novel disease-modifying approaches.”

Why target TDP-43 in ALS?

TDP-43 aggregates abnormally in up to 97% of ALS patients and is associated with neuronal dysfunction, mis-splicing of RNA, and loss of normal nuclear function (2). Despite its central role in disease biology, TDP-43 has remained a challenging therapeutic target. VectorY’s approach uses a vector-based delivery platform designed to enable sustained, localized antibody expression within the central nervous system (CNS), with the aim of addressing multiple aspects of TDP-43 pathology.

“This trial marks the first ever clinical evaluation of a therapy designed to holistically target TDP-43 pathology in ALS, and thereby reduce TDP-43 aggregation, correct mis-splicing abnormalities, and restore normal nuclear function, and we are excited to advance this novel potential therapeutic strategy to a community of patients who are actively looking for hope,” said Dr. Olga Uspenskaya-Cadoz in the release.

How is the ALS study designed?

PIONEER-ALS is an open-label, dose-escalation Phase I/II study evaluating two dose levels of VTx-002. The trial is expected to enroll 12 adults with ALS. In addition to primary endpoints focused on safety and tolerability, the study includes assessments of pharmacokinetics and exploratory efficacy.

Secondary and exploratory endpoints are intended to support downstream clinical development and include post-treatment changes in neurofilament light chain, trajectories of novel TDP-43 pathway-related biomarkers, and multiple clinical measures. These include the ALS Functional Rating Scale-Revised, slow vital capacity, hand-held dynamometry, and survival.

“There remains a critical need for disease-modifying therapies in ALS,” said James Berry, MD, MPH, global coordinating investigator for the study and chief of the Division of Motor Neuron Diseases at Mass General Brigham, in the release (1). “VTx-002 is engineered to enable sustained, localized delivery of an antibody targeting pathological TDP-43, a hallmark of ALS, with the goal of addressing a central driver of disease progression.”

What does this study mean for ALS drug development?

ALS remains universally fatal, with median survival of two to three years following diagnosis and limited treatment options that primarily address symptoms. More than 30,000 people in the United States are currently living with the disease, underscoring the urgent need for therapies that target underlying biology rather than disease manifestations alone (3).

“The initiation of this study reflects an innovative approach aimed at one of the most important pathological features of the disease,” Dr. Berry said in the release. “I look forward to leading this exploration of VTx-002 and its potential to impact people living with ALS.”

VectorY expects to continue enrolling participants in the PIONEER-ALS study and advancing its broader pipeline of vectorized antibody programs across neurodegenerative diseases.

References

1. VectorY Therapeutics.VectorY Therapeutics Announces First Participant Dosed in Phase 1/2 PIONEER-ALS Clinical Trial of VTx-002 in People with Amyotrophic Lateral Sclerosis (ALS). Press Release. Feb. 9, 2026.
2. Brown, A. L.; Wilkins, O. G.; Keuss, M. J.; et al. TDP-43 Loss and ALS-risk SNPS Drive Mis-Splicing and Depletion of UNC13A. Nature 2022, 603 (7899), 131–137. DOI: 10.1038/s41586-022-04436-3
3. CDC. About the National ALS Registry. CDC.gov. Nov. 12, 2024 (accessed Feb. 10, 2026).