In Vitro and In Vivo Efficacy of DLX1008
News Jun 10, 2015
Delenex Therapeutics AG has announced new pre-clinical data demonstrating the efficacy of its DLX1008 antibody fragment in in vitro as well as in vivo models of human glioma.
DLX1008 is a monovalent anti-VEGF-A antibody fragment that binds with 20-30 picomolar affinity to both human as well as mouse VEGF-A. VEGF-A is a key mediator of neo-angiogenesis promoting tumor growth by enhancing the supply of the tumor mass with nutrients and oxygen.
DLX1008 shows superiority to Avastin®, an anti-VEGF-A IgG antibody, and Lucentis®, an anti-VEGF-A Fab antibody fragment, in the inhibition of VEGF-A binding to VEGF-R1 in ELISA by a factor of around 10 and 15, respectively.
Glioblastomas are the most common primary malignant tumors of the central nervous system. Despite significant research efforts and a large number of clinical trials during the past decades, limited progress has been made to improve the lethal prognosis of this disease where angiogenesis mediated by VEGF-A is a hallmark.
A team led by Prof. Michael Weller from the Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Switzerland, demonstrated that DLX1008 is highly potent in an in vitro tube formation assay based on human cerebral microvascular endothelial cells.
In vivo, DLX1008 significantly improved survival in a mouse orthotopic U87 xenograft model and significantly inhibited tumor growth in a mouse subcutaneous U87 xenograft model compared to controls.
Prof. Weller said that "these data warrant further clinical development of DLX1008 in a biomarker-driven approach to glioblastoma. DLX1008 may provide improved efficacy in glioblastoma, because of its high affinity and small size, predicting enhanced tumor penetration".
"DLX1008 has now proven for a second time to be an excellent, highly potent antibody compound with demonstrated anti-tumor activity not only in Kaposi sarcoma, but in glioblastoma as well. Consequently, we will intensify our efforts to advance DLX1008 into clinical trials in oncological indications with a VEGF component," commented Titus Kretzschmar, PhD, Chief Scientific Officer of Delenex.
"Given the flexibility of the platform, in addition to advancing DLX1008, Delenex is also exploring supplementary approaches in immunotherapy for which our PENTRA®Bodies provide excellent opportunities," added Thomas Hecht, MD, Executive Chairman of Delenex.