Neuvasq Biotechnologies recently announced the presentation of new preclinical data demonstrating the therapeutic potential of targeting the Wnt co-receptors Gpr124 and Lrp6 to treat vascular retinopathies.
This research was delivered at the Association for Research in Vision and Ophthalmology (ARVO) 2026 Annual Meeting in Denver, Colorado.
Let’s start with the company.
Founded in 2021, Neuvasq is a biotechnology company advancing first-in-class Gpr124- and Reck-targeting antibodies designed to repair neurovascular dysfunction in patients with retinal vascular diseases.
Its background: The company is actually a spin-off from the Université libre de Bruxelles by molecular biologist Benoît Vanhollebeke PhD, whose research identified the role of Gpr124 and Reck in mediating Wnt7a/b signaling—specifically in the central nervous system (CNS).
- Side note: Neuvasq is also working on a second preclinical program focused on Wnt surrogate antibodies for neurological diseases like epilepsy and seizures and dementia.
And this novel antibody approach?
These next-generation multispecific antibody-based therapies target the Wnt/beta-catenin pathway to support the maintenance and repair of the blood-retina barrier (BRB), with the potential to slow, halt, prevent, or even reverse vision loss in retinal vascular diseases such as:
- Diabetic macular edema (DME)
- Wet age-related macular degeneration (AMD)
Give me some relevant background on CNS biology.
The CNS is a tightly controlled environment where specialized endothelial cells restrict the exchange of substances between the blood and CNS tissue (the brain, neural retina, and spinal cord).
Blood-CNS barriers include the BRB enabling normal vision and the blood-brain barrier (BBB) favoring normal neurological function.
And the BRB?
BRB formation and maintenance are regulated by the Wnt/β-catenin signaling pathway, and in endothelial cells of the CNS, this pathway is primarily activated by Wnt7a/b and Norrin ligands.
Plus: Wnt7a/b signal through a membrane receptor complex including two co-receptors:
- Gpr124 is a G protein-coupled receptor that regulates angiogenesis and vascular integrity. It is highly expressed in the endothelial cells of the blood-brain barrier (BBB) and BRB.
- Reck (reversion inducing cysteine rich protein with kazal motifs) is a membrane-bound protein that helps:
- Maintain the integrity of the BBB
- Support neuronal development
- Regulate extracellular matrix remodeling
Now tie it all together…
The BRB maintains the tightly regulated environment of the retina by controlling the exchange of molecules, fluids, and cells between the bloodstream and the parenchyma.
However: Vascular leakage can result in uncontrolled infiltration of blood-derived fluids, proteins, and immune cells into the tissue leads to edema, inflammation, oxidative stress, and neuronal damage, resulting in vision loss.
…. and that brings us to Neuvasq’s lead candidate.
Indeed. As a first-in-class bispecific antibody, NVQ401 is a highly potent Wnt surrogate antibody under development as an investigational treatment for vascular retinopathies like DME and wAMD.
Plus: To further expand the therapeutic profile of NVQ401,the company engineered NVQ501, a trispecific molecule, by combining β-catenin activation with anti-VEGF functionality—two clinically validated approaches.
And the preclinical findings on NVQ401?
NVQ401 was shown to be a highly potent activator of Wnt receptor signaling, with robust in vivo efficacy demonstrated across three relevant disease models, supporting the potential for quarterly dosing. Other discoveries:
- The drug reversed vascular endothelial growth factor (VEGF)-induced vascular permeability in human retinal cells
- In the oxygen-induced retinopathy (OIR) model, NVQ401 reduced both neovascularization and avascular areas
- Meaning: This early evidence supports NVQ401’s potential to protect against vascular leakage and abnormal vessel growth and to induce normal vessel growth in retinal diseases.
Any data on NVQ501?
The role of NVQ501 in preclinical models was assessed and compared to currently approved treatments as well as NVQ401.
The findings: NVQ501 potently activated β-catenin signaling in human retinal endothelial cells, and fully inhibited VEGF induction of PLVAP, a major mediator of retinal damage.
And in the OIR model, it showed enhanced efficacy versus the bispecific in reducing neovascularization, and unlike the parent anti-VEGF drug, demonstrated statistically significant reductions in avascular areas.
- Translation These data demonstrate that combining two clinically validated approaches, β-catenin activation with VEGF neutralization, has the potential to become a new standard of care.
So what are the next steps?
NVQ501 is currently advancing towards chemistry, manufacturing, and control (CMC) and IND-enabling studies, with an estimated timeline of 15 months to reach IND.
As always, stay tuned for updates on this!