TEL AVIV, Israel, May 11, 2017 (GLOBE NEWSWIRE) -- VBL Therapeutics (Nasdaq:VBLT) today announced new preclinical data indicating that treatment with ofranergene obadenovec (VB-111) augments the anti-tumor activity of a PD-L1 blocker in lung cancer and melanoma models. The data will be presented tomorrow, May 12, in a poster session at the 20th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), taking place in Washington, DC.
Immunotherapy with checkpoint inhibitors demonstrates remarkable efficacy in several cancers; yet, only a low percentage of patients seem to benefit from this class of treatment when given as a monotherapy. Several studies have shown that response rates are increased when checkpoint blockade is combined with other anti-cancer treatments. VB-111 is a biologic agent that is being currently studied in a Phase 3 clinical trial for recurrent glioblastoma (rGBM). VB-111 specifically targets angiogenic endothelial cells and promotes antitumor immune response. In the study to be presented at ASGCT, VB-111 was evaluated in combination with an anti-PD-L1 checkpoint inhibitor in lung and melanoma cancer models, indications for which PD-1 blockers are already marketed.
VBL's data show that treatment with either VB-111 or anti-PD-L1 reduced tumor burden in mice induced with Lewis lung carcinoma (LLC), by 42% and 51% versus saline control, respectively; however, the combination of both agents resulted in an amplified effect (67% reduction versus control; p≤0.001), and similar results were seen in a melanoma model. In addition, treatment with VB-111 and anti-PD-L1 enhanced infiltration of CD8+ cells to lung tumors. A copy of the poster will be available on VBL’s website, beginning May 12.
"An important observation from our pre-clinical data in the LLC model was that the combination of VB-111 at a dose of 109 viral particles (VPs)/mouse, which is equivalent to the human therapeutic dose, with a PD-L1 blocker, yielded a tumor burden reduction similar to treatment with 1011 VPs/mouse, a 100-fold higher dose," said Eyal Breitbart, Ph.D., Vice President of Research and Operations at VBL. "Therefore, a combination with a checkpoint inhibitor may achieve much better anti-tumor activity than VB-111 alone,” added Dr. Breitbart.
VB-111 is currently studied in the pivotal Phase 3 GLOBE trial in rGBM, comparing VB-111 in combination with Avastin® (bevacizumab) to Avastin alone, which is being conducted in the US, Canada and Israel. Enrollment in the study, 256 patients in total, was completed earlier this year, five months ahead of schedule. The study is proceeding under a Special Protocol Assessment (SPA) granted by the FDA, with full endorsement by the Canadian Brain Tumor Consortium (CBTC). The Company expects to report interim data from the GLOBE trial in Q3-2017, with top-line results from the full dataset expected to be available in early 2018.
VBL plans to launch a Phase 3 study for VB-111 in combination with chemotherapy for platinum-resistant ovarian cancer in the second half of 2017. Launch of an exploratory clinical study on VB-111 in combination with a checkpoint inhibitor in lung cancer is also expected by year-end 2017.
About Ofranergene Obadenovec (VB-111)
Ofranergene obadenovec is a unique biologic agent that uses a dual mechanism to target solid tumors. Based on a non-integrating, non-replicating, Adeno 5 vector, ofranergene obadenovec utilizes VBL's proprietary Vascular Targeting System (VTS™) to target the tumor vasculature for cancer therapy. Unlike anti-VEGF or TKIs, ofranergene obadenovec does not aim to block a specific pro-angiogenic pathway; instead, it uses an angiogenesis-specific sensor (VBL's PPE-1-3x proprietary promoter) to specifically induce cell death in angiogenic endothelial cells in the tumor milieu. This mechanism retains activity regardless of baseline tumor mutations or the identity of the pro-angiogenic factors secreted by the tumor and shows activity even after failure of prior treatment with other anti-angiogenics. Moreover, ofranergene obadenovec induces specific anti-tumor immune response, which is accompanied by recruitment of CD8 T-cells and apoptosis of tumor cells.
Ofranergene obadenovec completed a Phase 2 study in rGBM, which showed a statistically significant improvement in overall survival in patients treated with ofranergene obadenovec through progression, compared to either patients treated with ofranergene obadenovec followed by bevacizumab alone, or to historical bevacizumab data. In a Phase 2 trial for recurrent platinum-resistant ovarian cancer, ofranergene obadenovec demonstrated a statistically significant increase in overall survival and 60% durable response rate (as measured by reduction in CA-125), approximately twice the historical response with bevacizumab plus chemotherapy in ovarian cancer. In a Phase 2 study in recurrent, iodine-resistant differentiated thyroid cancer, ofranergene obadenovec met the primary endpoint demonstrating disease stabilization with a positive safety profile, along with a dose-response and evidence of an overall survival benefit. Ofranergene obadenovec has received Fast Track Designation for recurrent glioblastoma in the U.S. and orphan drug status for glioblastoma in both the U.S. and EU.
About VBL
Vascular Biogenics Ltd., operating as VBL Therapeutics, is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class treatments for cancer. The Company’s lead oncology product candidate, ofranergene obadenovec (VB-111), is a first-in-class, targeted anti-cancer gene-therapy agent that is positioned to treat a wide range of solid tumors. It is conveniently administered as an IV infusion once every two months. It has been observed to be well-tolerated in >200 cancer patients and we have observed its efficacy signals in an “all comers” Phase 1 trial as well as in three tumor-specific Phase 2 studies. Ofranergene obadenovec is currently being studied in a Phase 3 pivotal trial for recurrent Glioblastoma, conducted under an FDA Special Protocol Assessment (SPA).
Forward Looking Statements
This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to”, “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions. These forward-looking statements include, but are not limited to, statements regarding the clinical development of ofranergene obadenovec (VB-111), including our expectations regarding the timing of results from the GLOBE study, our plans for our Phase 3 study of VB-111 in platinum-resistant ovarian cancer, our plans for an exploratory clinical study of VB-111 in combination with a checkpoint inhibitor in lung cancer, and the therapeutic potential of, and clinical results for, VB-111. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, and the risk that historical clinical trial results may not be predictive of future trial results. In particular, results from our pivotal Phase 3 clinical trial of ofranergene obadenovec (VB-111) in rGBM may not support approval of ofranergene obadenovec for marketing in the United States, notwithstanding the positive results seen in prior clinical experience. A further list and description of these risks, uncertainties and other risks can be found in the Company’s regulatory filings with the U.S. Securities and Exchange Commission, including in our annual report on Form 20-F for the year ended December 31, 2016. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. VBL Therapeutics undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Avastin® (bevacizumab) is a registered trademark of Genentech Inc.