TEL AVIV, Israel – VBL Therapeutics, a clinical-stage biotechnology company committed to the development of novel treatments for immune-inflammatory diseases and cancer, announced today the online publication of mechanistic data for VB-201 in the journal of Clinical and Experimental Immunology. The manuscript reports that VB-201, VBL's lead anti-inflammatory small molecule, inhibits toll-like receptor (TLR) 2 and TLR4 signaling in human and mouse monocytes and dendritic cells, leading to profound anti-inflammatory effect in vivo.
For access to the manuscript please see: http://www.ncbi.nlm.nih.gov/pubmed/24116867
VB-201 is rationally designed, oxidized but non-oxidative phospholipid (OxPL) analog. It is the first in a new class of drug candidates called Lecinoxoids, which have been 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 immune-inflammatory diseases as Atherosclerosis, Psoriasis, Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis and more.
TLRs are a class of immune receptors that act as sensors of pathogens and danger signals. TLRs are implicated in multiple chronic inflammatory conditions. VBL's new data demonstrate that VB-201 binds directly to TLR2 and CD14, the TLR4 co-receptor, to impair downstream cues and cytokine production. Accordingly, treatment with VB-201 resulted in reduced secretion of IL-12/IL-23p40 and IL-6.
A growing body of evidence suggests that Ox-LDL and Ox-PLs can convey their pro-inflammatory activity through TLRs. VBL’s findings highlight a novel role played by synthetic Ox-PL in specific regulation of TLR2 and TLR4 signaling. Notably, oral treatment with VB-201 constrained atherosclerosis progression in a rabbit model even without affecting lipid profiles. Furthermore, VB-201 had an effect additive to that of atorvastatin. This observation suggests that administration of VB-201 in parallel to statins, targeting inflammation and cholesterol abundance, respectively, may be conducive for the treatment of atherosclerosis. The data strengthen the efficacy VB-201 in inflammatory settings.
“We are excited to share these innovative results with the immunology community, said Eyal Breitbart, PhD, VBL’s VP for R&D. “VBL’s intensive research on anti-inflammatory mechanisms has led us to the development of the Lecinoxoid pipeline of small molecules, which modulate the underlying pathway that leads to inflammation in many immune inflammatory diseases. Moreover, Due to its MOA, VB-201 may add significant value to atherosclerosis patients on top of statins.”
The company is currently evaluating VB-201 in two Phase 2 clinical trials to treat psoriasis and Ulcerative Colitis after demonstrating proof of efficacy in a recently completed phase 2 study in moderate-to-severe psoriasis patients with cardiovascular risk. “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” said Professor Dror Harats, M.D., chief executive officer of VBL.
VB-201 is a proprietary, first-in-class, orally-available, specific innate immunity disease modifying medicine in development for the effective treatment of chronic immune-inflammatory diseases. VB-201 offers the potential to deliver long-term control of a spectrum of immune-inflammatory indications with a favorable safety profile. VB-201 has completed Phase 2 study in patients with moderate-to-severe psoriasis and a sub-study in patients with cardiovascular risk which have successfully achieved its primary endpoint demonstrating a statistically significant reduction in vascular inflammation. Altogether, the product has successfully completed five clinical trials involving more than 400 subjects under U.S. investigational new drug (IND) applications. These trials demonstrated that VB-201 was well tolerated with a favorable safety profile. VB-201 has been progressed into two more Phase 2 clinical trials in patients with psoriasis and patients with inflammatory bowel disease. VB-201 has potential applicability across a range of inflammatory diseases including atherosclerosis, psoriasis, and inflammatory bowel disease.