AMSTERDAM & BOSTON--(BUSINESS WIRE)--VectorY Therapeutics, a leader in vectorized antibody therapies for neurodegenerative diseases, announced today that the U.S. Food and Drug Administration (FDA) has cleared the company to proceed with the PIONEER-ALS Phase 1/2 Trial of VTx-002. VTx-002 is a first-in-class vectorized antibody targeting TDP-43 pathology in amyotrophic lateral sclerosis (ALS).
TDP-43 pathology drives up to 97 percent of ALS cases. VTx-002, VectorY’s lead vectorized antibody program, delivers an engineered antibody designed to selectively target toxic species of TDP-43. By binding only to pathological forms, the therapeutic aims to reduce TDP-43 aggregation, correct mis-splicing abnormalities, and restore normal nuclear function. The VTx-002 antibody is produced continuously within target cells following a single intracisterna magna (ICM) administration of its genetic payload, delivered via an AAV5.2 capsid, a vector with a well-established clinical safety profile.
“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 vectorized antibodies that are specifically designed to address the well-established biology driving disease manifestations” said Jim Scibetta, chief executive officer. “We are collaborating with PIONEER-ALS Global Coordinating Investigator James Berry, MD, PhD, chief of the Division of Motor Neuron Diseases and director of the Neurological Clinical Research Institute (NCRI) at Mass General Brigham, and with the ALS patient advocate and physician community, as we actively work towards trial initiation."
The PIONEER-ALS Phase 1/2 Trial of VTx-002 in ALS
PIONEER-ALS, an open label, dose-escalation Phase 1/2 clinical study, will evaluate two dose levels of VTx-002 and is expected to enroll 12 adults with ALS. The primary objective of this study is to evaluate VTx-002 safety and tolerability. To optimize the path to pivotal clinical development, secondary and exploratory endpoints include assessment of the post-treatment Neurofilament light chain (NfL) and novel TDP-43 pathway-related biomarker trajectories, as well as clinical endpoints, including ALSFRS-R, slow-vital capacity, hand-held dynamometry and survival.
About ALS and VTx-002
ALS is a universally fatal neurodegenerative disease with no cure and only limited symptomatic treatment options. In the United States, more than 5,000 new cases of ALS are diagnosed each year, and more than 30,000 people are currently living with the disease. Median survival is 2–3 years after a diagnosis, and someone is either diagnosed with or dies from ALS every 90 minutes. The disease has an incidence comparable to major indications such as multiple sclerosis, yet far lower prevalence reflecting a persistent disease burden and urgent unmet medical need.
This IND clearance will make VTx-002 the first therapeutic in clinical development directed at the complete spectrum of TDP-43 pathology in ALS, simultaneously targeting gain of toxicity and loss of function. These pathological mechanisms are present in up to 97% of ALS patients, not including patients with pathology resulting from SOD1 or FUS genetic mutations.
In preclinical studies, VTx-002 has demonstrated robust activity, including reversal of cryptic splicing events of mRNAs encoding for stathmin-2, UNC13A, and multiple other genes critical for motor neuron survival. In addition, VTx-002 has shown prevention of toxic aggregate formation, and transcriptomic restoration towards healthy motor neuron profiles. The therapy has shown a favorable safety profile in non-human primate studies, consistent with that observed by clinically validated and commercialized therapeutics delivered by AAV5.
About the VectorY Vectorized Antibody Platform
VectorY’s proprietary vectorized antibody platform is designed to overcome the challenges of targeting intracellular, misfolded proteins that underlie neurodegenerative disease biology. The technology utilizes antibody fragments engineered for high specificity for toxic proteins, while sparing wild-type proteins, delivered to disease-affected regions in the CNS via a one-time, safe AAV5-based vector. The technology enables continuous intracellular therapeutic expression, allowing for sustained activity. VectorY has also developed a scalable, high-yield proprietary manufacturing platform that meets commercial production requirements.
About VectorY Therapeutics
VectorY Therapeutics is dedicated to changing the trajectory of neurodegenerative diseases by developing precision-targeted, durable therapies that have the potential to arrest and ultimately reverse disease progression. With deep expertise in neurobiology, antibody engineering, and AAV-based delivery, VectorY is building a pipeline that includes VTx-002 targeting TDP-43 in ALS, VTx-001 targeting oxidized phospholipids in ALS, VTx-003 targeting mutant HTT and TDP-43 in Huntington’s disease, VTx-005 targeting phosphorylated tau in Alzheimer’s disease, and VTx-004 targeting TDP-43 in frontotemporal dementia (FTD).
Contacts
VectorY Therapeutics B.V.
E-mail: info@VectorYtx.com
Tel: +31 20 226 8020
Instinctif Partners (Media)
Julian Walker / Tim Pearson
E-mail: VectorY@instinctifpartners.com
Tel: +44 207 802 2657
