Jul 8 2013
VBL Therapeutics, a clinical-stage biotechnology company committed to the development of novel treatments for immune-inflammatory diseases and cancer, announced today the publication of pre-clinical data for VB-201 in the journal of Atherosclerosis. The manuscript reports that VB-201 can broadly inhibit monocyte chemotaxis, with up to 90% efficacy in vitro. Molecular analysis revealed that the effect of VB-201 was not restricted to a specific chemotactic ligand or receptor. In vivo, oral treatment with VB-201 reduced monocyte migration in a peritonitis model and inhibited atheroma development in ApoE-/-mice, without affecting cholesterol or triglyceride levels.
“We are excited to share these mechanistic and pre-clinical results with the cardiovascular and immunology community”
VBL's findings highlight a novel role played by native and synthetic phospholipids in regulating monocyte chemotaxis. The data provide further evidence for the involvement of phospholipids as key signaling molecules in inflammatory settings and demonstrate their potential therapeutic applicability.
For open access to the manuscript please see: http://authors.elsevier.com/sd/article/S0021915013003699
VB-201 is rationally designed, oxidized but non-oxidative phospholipid analog. It is the first in a new class of drug candidates called Lecinoxoids, which have been rationally designed to be orally available anti-inflammatory medicines. The published manuscript details some of the studies performed by VBL to better understand the molecular mechanism and properties of VB-201, and to explore its potential for treatment of Atherosclerosis and other immune-inflammatory diseases.
Previously, VBL has shown that VB-201 limited inflammatory cell infiltration into the CNS and restricted Th1 cell polarization, leading to ameliorated severity of experimental autoimmune encephalomyelitis (EAE) in this MS model (Mendel et al., J Neuroimmunol. 2010). In this study, VBL scientists report anti-atherogenic activity of VB-201 and provide mechanistic insight to VB-201-mediated inhibition of monocyte chemotaxis in vitro and in vivo. Two different models were employed in this study to test the hypothesis that VB-201 may inhibit monocyte chemotaxis in vivo. In a thioglycollate-induced mouse peritonitis model, VB-201-treatment resulted in dose-dependent inhibition of macrophage accumulation in the peritoneum. In the second model, VB-201 inhibited atherosclerosis development in ApoE knockout mice with clear evidence of reduced lesional macrophage staining.
Over the past few decades, prevention and treatment of atherosclerosis has been mostly focused on regulation of cholesterol and blood-pressure. Nevertheless, numerous recent studies have emphasized that inflammation plays a significant role in atherosclerosis, and this key vector has not been adequately met thus far. The current findings demonstrate for the first time in vivo inhibition of monocytes migration by an oral phospholipid-based small molecule. VB-201 reduces macrophage accumulation and decreases experimental atherosclerotic lesion development without affecting the cholesterol or triglyceride levels.
"We are excited to share these mechanistic and pre-clinical results with the cardiovascular and immunology community," said Eyal Breitbart, PhD, VBL's VP for R&D. "VBL's intensive research of native anti-inflammatory mechanisms has led us to the development of the Lecinoxoid pipeline of small molecules, which unlike current drugs in the atherosclerosis field, do not affect the lipid profile but rather modulate the inflammatory process in this disease. Due to its MOA, VB-201 may add significant value to atherosclerosis patients on top of statins."
VBL Therapeutics has recently announced that a Phase 2 sub-study of VB-201 in moderate to severe psoriasis patients with cardiovascular risk has successfully achieved its primary endpoint demonstrating a statistically significant reduction in vascular inflammation, which was measured by PET-CT.
"We are currently evaluating VB-201 in two Phase 2 clinical trials to treat psoriasis and Inflammatory Bowel Disease after demonstrating proof of efficacy in a recently completed phase 2 study in moderate-to-severe psoriasis patients with cardiovascular risk," said Professor Dror Harats, M.D., chief executive officer of VBL. "The pre-clinical findings reported in this manuscript seem to be well translated to humans, as the clinical data we have gathered so far consistently demonstrate the potential of VB-201 as a safe, novel oral therapeutic option for chronic immune-inflammatory diseases."
SOURCE VBL Therapeutics
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