VST Bio First-in-Class drugs are dual-acting
Developing First-in-Class drugs (antibodies), that target novel pathways selectively regulating vascular permeability and inflammation in cardiovascular disease, including acute ischemic stroke
Developing First-in-Class drugs (antibodies), that target novel pathways selectively regulating vascular permeability and inflammation in cardiovascular disease, including acute ischemic stroke
VST-Bio First-in-Class drugs are dual-acting, and simultaneously pathways that regulate injury-induced inflammation and vascular permeability, without affecting normal vascular function.
Originally regarded as a common bystander effect of tissue injury, researchers now understand that vascular permeability (loss of vascular integrity, or ‘vascular leakage’) is detrimental to a cascade of events, including the deposition of local inflammatory cells and free radical formation, that further expand tissue damage (for instance in ischemic stroke). Through this infiltration of damaging inflammatory monocytes and oxidative stress, together with swelling of the tissue (edema), cerebral damage expands in the first 7 days after the onset of stroke. VST Bio proprietary antibodies aim to restore vascular function and prevent the expansion of cerebral damage in the first days after the onset of symptoms.
Our lead indication is stroke, but these two mechanisms underly many critical care diseases such as traumatic brain injury (TBI), myocardial infarction (MI), septic shock, ARDS, COVID-19, and others.
In stroke, inflammation after ischemic stroke rapidly disrupts the blood–brain barrier (BBB), increasing vascular permeability, which drives vasogenic edema and strongly predisposes to hemorrhagic transformation, especially after reperfusion therapies. In sepsis, ARDS, and COVID-19, increased vascular leak leads to interstitial and alveolar edema, impaired oxygen diffusion, reduced organ perfusion, and the need for vasopressors and mechanical ventilation.
Stroke: Our data in rodent and NHP models of stroke confirm that a single iv bolus of VST antibody is safe, blocks vascular leakage, and reduces cerebral damage by 50-80%, even when the mAb therapy is initiated late after stroke onset.
MI: Anti-Sdc2 therapy in rodent AMI models has demonstrated a reduction in MI size, prevention of pathological myocardial remodeling, progression to heart failure, and prevention of ventricular arrhythmogenesis (VT/VF).
Sepsis: Anti-Sdc2 therapy improved survival, better bacterial clearance, and reduced serum IL-6, TNF, and IL-1β
The human VB-001 antibody can safely
- Normalize vascular leakage (as seen after VEGF activation)
- Prevent inflammatory monocyte infiltration
- Reduce oxidative stress of reperfusion injury
- Reduce hemorrhagic transformation
- Reduce swelling of the brain in the acute phase of stroke (i.e. edema
formation) and prevents intracerebral pressure build-up - Leading to limitation of overall cerebral damage due to stroke
But more importantly
- Conventional (standard-of-care) therapy for ischemic stroke is only
effective when given within the first hours after onset of stroke - Since vascular leakage is a phenomenon that continues over the days after
stroke onset, the VB-001 antibody therapy is effective to reduce ongoing
cerebral damage in the first days after onset of stroke. - Reduction of cerebral damage will lead to expedited functional recovery
from ischemic stroke and a reduction of long-term neurological symptoms
in treated patients
Our Product: VB-001
A bolus of VST proprietary humanized antibody to revert vascular dysfunction and prevent ongoing cerebral damage in ischemic stroke patients.
VST BIO technology uses fully human antibodies against syndecan-2 to target the immune system and the vasculature to selectively block inflammation and injury-induced vascular leak, without affecting normal immune and vascular function.
We have developed an IV formulation of a humanized antibody that specifically normalizes vascular dysfunction and prevents ongoing tissue damage (by edema formation, inflammation and oxidative stress) leading to better tissue perfusion and limitation of ongoing cerebral damage in acute cardiovascular disease, like ischemic stroke.
The therapy can be given in the acute phase of the disease up to several days after onset of the ischemic stroke. Improved tissue perfusion and reduction of cerebral damage will lead to expedited recovery and reduction of persisting neurological symptoms
PUBLICATIONS & PRESENTATIONS
- Anti-inflammatory mechanisms of anti-sdc2 mab vb-001 contributing to neuroprotection after ischemic stroke. Federico Corti, J. Zhang, P. Perrotta, E. Ristori, C.A. Hernandez, J.W. Berman, K. Zsebo, M. Simons
- The role of vascular permeability in outcome after ischemic stroke. M. Simons
- Delayed Therapy with Humanized Anti-SDC2 MAB prevents formation of vasogenic edema and promotes Neuroprotection in non-human primates with ischemic stroke. Federico Corti, M. Weed, E. Nisbett, V. Chaseau, M. Lawrence, E. Ristori, J. Zhan, Z.W. Zhuang, D.A. Cheresh, K. Zsebo, M. Simons
- Anti-Syndecan-2 Human Monoclonal Antibody for treatment of stroke-associated edema. Federico Corti, E. Ristori, J. Zhang, Z.W. Zhuang, D.A. Cheresh, K. Zsebo, H. Duckers, M. Simons
- Anti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV. Corti F, et. Al., Transl Vis Sci Technol. 2025
- Syndecan-2 selectively regulates VEGF-induced vascular permeability F. Corti, E. Ristori, F. Rivera-Molina, D. Toomre, J. Zhang, J. Mihailovic, Z. W. Zhuang & M. Simons 2022
- Targeting VEGF-induced vascular permeability Mark Richards and Lena Claesson-Welsh. Nature and Cardiovascular Research, 2021
- N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization Federico Corti, Yingdi Wang, John M Rhodes, Deepak Atri, Stephanie Archer-Hartmann , Jiasheng Zhang , Zhen W Zhuang, Dongying Chen, Tianyun Wang, Zhirui Wang, Parastoo Azadi, Michael Simons 2019
- The Janus Face of VEGF in Stroke Samuel J Geiseler, Cecilie Morland 2018
- Vascular endothelial growth factor: a neurovascular target in neurological diseases Christian Lange, Erik Storkebaum, Carmen Ruiz de Almodóvar, Mieke Dewerchin, Peter Carmeliet 2016
SYNOPSIS
VB-001 has the potential to reverse vascular dysfunction that drives ongoing cerebral damage following acute ischemic stroke.
Leading to accelerated recovery and reduction of persisting neurological symptoms
VB-001 has a simple critical path for development and regulatory approval.
Antibody Therapeutics have been shown to have a favorable safety profile and CMC manufacturing and regulatory path of this non-conjugated antibody therapy is well established and straightforward
VB-001 is designed for deep market penetration
Our formulation is designed for use in patients with ischemic stroke that present early (within 4-6 hrs. after onset) and late after onset of stroke symptoms (after 6 hrs, and even in first days after onset of stroke symptoms)
VB-001 is a Candidate for Breakthrough Designation.
New MOA and the ability to reverse the underlying pathological process even when patients present late at the medical center (more than 6 hrs. after onset), offers a new avenue for stroke patients, who are now not eligible for conventional medical therapy, designate this new therapeutic antibody therapy for Breakthrough Designation
VB-001 has established proof of safety & efficacy
Demonstrated in both small and large NHP animal models.