Study underscores potential for VBL Therapeutics VB-111 as broad-spectrum cancer therapy

VBL Therapeutics today announced positive results from preclinical and Phase 1 studies evaluating the company's lead anti-cancer agent, VB-111 - a first-in-class, targeted biological agent shown to work via dual-action, anti-angiogenic and vascular disruptive mechanism of action - in metastatic cancer. Preclinical data evaluating VB-111 in a comprehensive set of in vivo studies employing the Lewis Lung metastasis mouse model showed the compound to be safe and specific, with a 90% reduction in tumor burden of lung metastases after only one injection. A Phase 1 study involving 27 patients with advanced stage solid tumors demonstrated that VB-111 was well-tolerated with no dose-limiting toxicities, and promising efficacy signals. These results were presented at the American Association for Cancer Research (AACR) 101^st Annual Meeting 2010, taking place this week in Washington, D.C.

“The preclinical findings coupled with the safety and tolerability VB-111 demonstrated in the Phase 1 patient study support the continued clinical evaluation of the compound in specific tumor types of advanced metastatic cancer, and underscores the potential for VB-111 as a broad-spectrum cancer therapy.”

VB-111 is the first dual-action, anti-angiogenic and Vascular Disruptive Agent (VDA) to use the company's proprietary platform technology, its Vascular Targeting System (VTS™), for cancer therapy. VB-111 is an IV-administered VDA that works in a manner akin to a "biological knife" to destroy tumor vasculature by cutting off the blood vessels feeding the tumor. The targeting mechanism is confined to the tumor, without damage to normal tissue blood vessels.

Preclinical data evaluating VB-111 in a comprehensive set of in vivo studies employing the Lewis Lung metastasis mouse model showed the compound to be safe and specific with activity only in the metastatic lesion themselves. VB-111 induced a dose dependent reduction of 90% in tumor burden of lung metastases with one injection and similar efficacy in other tumor models. In this same model, VB-111 showed better efficacy as compared to sunitinib (Sutent®) 40 or 80 mg/kg. An additive effect was reached when mice were treated with VB-111 and doxorubicin 2.5mg/kg.

"The mechanism behind this dual-action, anti-angiogenic agent is truly unique, potentially allowing for enhanced specificity and activity," said Pierre Triozzi, M.D., Solid Tumor Oncology Department, Cleveland Clinic, and the principal investigator in the Phase 1 trial. "The preclinical findings coupled with the safety and tolerability VB-111 demonstrated in the Phase 1 patient study support the continued clinical evaluation of the compound in specific tumor types of advanced metastatic cancer, and underscores the potential for VB-111 as a broad-spectrum cancer therapy."

The Phase 1 clinical trial, conducted at The Cleveland Clinic and The University of Texas Health Science Center at San Antonio, evaluated the safety, PK, immune and tumor responses of a single, intravenous administration of VB-111. The trial enrolled 27 patients with progressing, advanced solid tumors, with no existing curative therapy, and adequate organ function and performance status. There were six cohorts of patients evaluated in this trial; cohorts one to five included three patients each, and cohort six was expanded to 12 patients. Patients had frequent clinical and laboratory safety evaluations. Tumor response was evaluated on day 28 and day 56.

VB-111 was found to be safe and well tolerated in these patients. No dose-limiting toxicities were observed, and the maximal tolerated dose has yet to be reached. Viral distribution, cytokine and antibody response data supports repeat dosing at three to six-week intervals. Both stable disease (SD) and partial response (PR) were observed in the trial. On day 56 evaluation, three of the 15 patients in cohorts one to five had SD; among the 12 patients in cohort six, four had SD on day 56, and one patient (with papillary thyroid carcinoma) had a PR persisting for 12 months post dosing.

"VB-111 is a first-in-class vascular disruptive agent and the lead oncotherapeutic borne out of our innovative, proprietary Vascular Targeting System platform technology. VB-111 was designed to target cancer tumors with a precision and specificity not seen with currently available targeted therapies, which are often associated with off-target safety issues and side-effects," said Professor Dror Harats, M.D., chief executive officer of VBL. "The results we've seen with VB-111 thus far underscore the potential of this innovative therapy to be utilized as a broad-spectrum anticancer agent. We are pleased to be sharing this research with the medical community here at AACR, and are excited to initiate Phase 2 development of VB-111 later this year."

VBL is expected to launch Phase 2 clinical trials in 2010 in thyroid cancer, as well as in a second indication later this year.