VBL Therapeutics, a clinical-stage biotechnology company committed to the development of novel treatments for cancer and immune-inflammatory diseases, has received the US Food and Drug Administration (FDA) Fast Track designation to its lead oncology drug VB-111, for prolongation of survival in patients with Recurrent Glioblastoma Multiforme (rGBM).

GBM is an aggressive form of brain cancer which carries a very poor prognosis with current therapy. VB-111 was already granted Orphan Drug status for GBM in the US and in Europe.

VB-111, given as a simple IV infusion, is a novel gene-therapy drug that targets endothelial cells in the tumour vasculature, acting as a "biological knife".

Based on a non-replicating adenoviral vector, VB-111 harbors a proprietary promoter which regulates transcription of a Fas-Chimera transgene, leading to targeted cell-death of endothelial cells in tumour-feeding blood vessels, with no harm to normal vasculature and non-cancerous tissues in the body. VB-111 is the first agent based on transcriptional targeting of tumour endothelium to be assessed in a clinical trial.

VBL has recently published phase I/II results for VB-111 in the journal of Clinical Cancer Research. The phase I/II trial for VB-111 demonstrated safety and tolerability in patients with advanced metastatic cancer at a single administration. Notably, tumour response and superior overall survival were found in the 1x1013 VPs cohort compared to sub-therapeutic doses. The data confirmed pre-clinical findings in animal models and validated VB-111's mechanism of action, resulting in a targeted expression of the Fas-Chimera transgene selectively in tumour vasculature.

The company has recently presented results from phase II clinical study in patients with recurrent glioblastoma at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago in June 2013. Data from the trial evaluating the effect of VB-111 on 28 patients with recurrent Glioblastoma Multiforme (rGBM) demonstrate that VB-111 was safe and well tolerated with repeat doses of up to 1x1013 VPs. Tumor responses and significant attenuation of tumor growth rate were seen. Overall survival was 12 months, which is at least 3 months longer compared to historical data in rGBM with the standard of care with chemotherapy and/or anti-angiogenic agents.

“The Fast Track designation is another significant milestone reached in our programme for approval of VB-111 as a unique drug for rGBM. We are very pleased that the FDA recognized the potential for this novel therapy to treat this serious and devastating cancer" said Dror Harats, MD, VBL’s chief executive officer. “Building on the promising data from our phase 2 trial, we plan ahead for a pivotal trial with VB-111 for rGBM under the Fast Track programme which should expedite the development of VB-111.”

In addition to GBM, VB-111 is also evaluated in multi-dose Phase 2 clinical trials for differentiated thyroid cancer and ovarian cancer.

VB-111 is a novel IV-administered anti angiogenic agent that utilizes VTS™, VBL’s proprietary platform technology to target endothelial cells in the tumour vasculature for cancer therapy. VB-111 contains a non-replicating adenovector, a proprietary modified murine pre-proendothelin promoter (PPE-1-3x) and a Fas-Chimera transgene. The modified promoter specifically targets the expression of the Fas-Chimera transgene to angiogenic tumour blood vessels, leading to their apoptosis. VB-111 is the first agent based on transcriptional targeting of tumour endothelium to be assessed in a clinical trial.

VB-111 has successfully completed a phase I/II “all comers” clinical trial, which demonstrated multiple cases of objective tumour response and disease control and excellent safety and tolerability. VB-111 has been advanced into tumour specific, repeat-dose trials in glioblastoma, thyroid cancer and ovarian cancer.