TEL AVIV, Israel and SAN DIEGO, March 16, 2012 – VBL Therapeutics, a clinical stage biotechnology company committed to the development of novel treatments for immune-inflammatory diseases and cancer, today 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 associated with atherosclerotic lesions as measured by PET-CT imaging. VB-201 is a first-in-class, oral disease-modifying agent selected from a series of proprietary oxidized phospholipid analogs pioneered by the company in the Lecinoxoid molecular class. The compound is being developed as an oral controller medicine for chronic immuno-inflammatory disease and atherosclerosis inflammation.
The results were presented today at 4:00 p.m. P.S.T during the Late-Breaking Research Symposium at the American Academy of Dermatology 70th Annual Meeting in San Diego. The oral presentation titled “Safety and Efficacy of VB-201, a Novel Immune-modulator, on Inflammation of Atherosclerotic Disease in Patients with Moderate to Severe Plaque Psoriasis: A Phase 2 Randomized Placebo Controlled Trial” was given by Alexa Boer Kimball, M.D., M.P.H., vice chair, department of dermatology; director, clinical unit for research trials in skin; vice president, Massachusetts General Physicians Organization at Massachusetts General Hospital; and principal investigator of the study.
The findings validate the compound’s novel mechanism of action for the control and attenuation of chronic immuno-inflammatory diseases via the highly selective modulation of components of the innate immune system. Central to the overall mechanism of action for VB-201 are the targeted antagonism of cell-surface Toll-Like Receptor (TLR)-2 and TLR-4 co-receptor CD-14, and the inhibition of chemokine-mediated migration of monocytes to inflamed tissue. The study data support the growing scientific evidence that these mechanisms are important in regulating inflammation in atherosclerosis. VB-201 is a first-in-class, specific, orally-available innate immunity controller drug.
“The Phase 2 data are promising and demonstrate an anti-inflammatory effect of VB-201 on psoriasis patients with atherosclerosis within a short time period,” said Dr. Kimball. “VB-201 is the first drug we aware of to demonstrate a reduction in the inflammation associated with atherosclerosis through this pathway. These data are especially important given the growing evidence linking cardiovascular events and elevated mortality in patients with chronic inflammation, including patients with psoriasis. This study serves as a proof of concept for this compound’s novel mechanism of action and demonstrates an anti-inflammatory effect on two systemic inflammatory conditions simultaneously—atherosclerosis of the vascular wall and psoriasis.”
In the pre-defined cardiovascular sub-study, PET-CT scans were used to evaluate the effect of VB-201 on the suppression of active inflammation in atherosclerotic lesions. PET-CT has been validated as an imaging tool for measuring vascular inflammation related to atherosclerosis and has been shown to predict cardiovascular events. VB-201 produced a statistically significant, dose-responsive mean reduction of 12.7 percent of the inflammation associated with vascular endothelial lesions (80 mg dose group, p=0.04) over the 12-week dosing period. Patients already maintained on statin therapy received additional responses in the range of 10 to 68 percent reduction in vascular inflammation. A dose response was seen across quintiles of VB-201 through blood levels (p=0.037).
In the overall Phase 2 study, VB-201 demonstrated an excellent safety and tolerability profile. There were no treatment-related serious adverse events observed, and the overall rates of adverse events were similar across the VB-201 drug and placebo dosing arms. Statistically significant improvements in the psoriasis efficacy endpoints, Physician Global Assessment and Patient Global Assessment (p=0.019), were achieved. A statistically significant dose response in Psoriasis Area and Severity Index (PASI) was demonstrated across quintiles of VB-201 through blood levels (p= 0.04). Overall, improvement in psoriasis measures did not reach a plateau, with a continued widening of the separation between the treatment and placebo groups at the 12-week termination point of the trial.
“We are excited to reveal that the favorable experimental data in the atherosclerosis models has translated into proof of concept in humans,” said Yael Cohen, M.D., vice president, clinical development at VBL. “We believe that these data suggest that VB-201 is an excellent candidate for both the control of primary chronic immuno-inflammatory disease as well as the reduction of the elevated cardiovascular risk accompanying the primary disease. It’s encouraging to see the psoriasis efficacy measures did not plateau at the conclusion of the 12-week trial and, as a result, an additional trial with higher dosage and longer duration is underway.”
About Chronic Autoimmune/inflammatory Diseases and Cardiovascular Risk
With millions of patients worldwide, chronic autoimmune/inflammatory diseases represent some of the largest clinical challenges and unmet medical needs in medicine. Physicians and the clinical literature now report that patient mortality is related to increased cardiovascular events occurring as sequellae to the chronic pro-inflammatory status of the patients, including those that are maintained on statins and anti-inflammatory biological drugs. In particular, atherosclerotic cardiovascular disease has recently been recognized as a major cause of morbidity and mortality in psoriasis patients. There is a widespread need for a specific, targeted and safe oral controller medication for long-term management of these autoimmune/inflammatory diseases.
About the VB-201 Phase 2 Study and Cardiovascular Sub-Group Study
The Phase 2 double-blind, randomized, dose-ranging, placebo-controlled study enrolled approximately 185 patients with moderate to severe psoriasis. Patients received either 20 mg or 80 mg of VB-201 or placebo once-daily for 12 weeks. The study was conducted at multiple centers in the United States, Germany and Israel. Additionally, based on encouraging preclinical results, a sub-study including several of the participating U.S. sites was conducted during the Phase 2 trial to evaluate the effect of VB-201 on atherosclerosis in psoriasis patients. PET-CT scans of the great vessels of the chest and neck measured the level of inflammation within atherosclerotic plaques, which is known to trigger vessel occlusion.
VB-201 is a proprietary, first-in-class, orally-available, specific innate immunity disease-modifying medicine in development for the effective treatment of chronic immuno-inflammatory diseases. VB-201 offers the potential to deliver long-term control of a spectrum of immuno-inflammatory indications with a favorable safety profile.
Preclinical data have demonstrated VB-201’s prolonged response and the product has successfully completed five Phase 1 clinical trials involving 140 healthy subjects under a U.S. investigational new drug (IND) application. These Phase 1 trials demonstrated that VB-201 was well tolerated with a favorable safety profile. VB-201 has potential application across a range of inflammatory diseases including psoriasis, rheumatoid arthritis, atherosclerosis and inflammatory bowel disease.