Dutch startup VectorY Therapeutics has been given the green light by the FDA for a phase 1/2 trial of a drug against a target implicated in up to 97% of amyotrophic lateral sclerosis (ALS) cases.
VTx-002 is described as a first-in-class vectorised antibody targeting molecular pathways involving TAR DNA-binding protein 43 (TDP-43), a protein involved in DNA repair that has emerged in recent years as a possible driver of the nerve damage seen in ALS.
The VTx-002 antibody is delivered by an adeno-associated virus (AAV) vector and produced continuously within target cells after a one-shot administration into the cisterna magna (CM) of the brain.
Misfolded forms of TDP-43 seem to aggregate and become toxic in people with both inherited and spontaneous forms of ALS, potentially making it a therapeutic target for the majority of patients.
Amsterdam-headquartered VectorY’s drug discovery platform is designed to overcome the challenges of developing antibodies that can target intracellular proteins, rather than those that are expressed on the surface of cells, and the phase 1/2 trial will be an important test of that concept.
It is focusing on misfolded proteins involved in neurodegenerative diseases, with antibodies designed to avoid the properly folded forms and so minimise side effects.
Current therapies have shown limited efficacy in slowing down the progression of ALS, a fast-developing, fatal disease that typically leads to death in two to five years, and in some cases – i.e. Biogen’s Qalsody (tofersen) – are limited to use in patients with specific mutations.
VTx-002 is not expected to be suitable for ALS patients whose disease is caused by SOD1 genetic mutations, who can be treated with Qalsody, as well as cases linked to FUS mutations.
The planned phase 1/2 trial, called PIONEER-ALS, will take the form of an open-label, dose-escalation study looking at two dose levels of VTx-002 and is expected to enrol 12 adults with ALS.
The primary objective is to evaluate VTx-002 safety and tolerability. However, the trial will also track biomarkers, including neurofilament light chain (NfL), a widely used surrogate marker for neuronal damage in ALS, and TDP-43 pathway-related measurements, as well as clinical endpoints.
PIONEER-ALS will assess survival along with measures of ALS symptoms, including respiratory function and hand strength.
“The FDA’s clearance to proceed with our phase 1/2 study marks a pivotal milestone for VectorY, as we strive to transform the neurodegenerative disease landscape with our novel vectorised antibodies that are specifically designed to address the well-established biology driving disease manifestations,” said Jim Scibetta, the biotech’s chief executive.
VectorY raised $138 million in a Series A round two years ago, co-led by EQT Life Sciences and Forbion, in one of the largest European biotech financings of 2023.
