Data confirm EDO-S101 is effective in human glioblastoma models

Findings presented at the European Organization for Research & Treatment of Cancer (EORTC), European Association of NeuroOncology (EANO) and European Society for Medical Oncology (ESMO) congress in Istanbul demonstrate that EDO-S101 is effective in models of human glioblastoma irrespective of methyltransferase (MGMT) status and in combination with radiotherapy (RT).

EDO-S101 is a first in class fusion molecule that combines the DNA damaging effect of bendamustine with the pan-histone deacetylase inhibitor (HDACi) vorinostat, with the aim of increasing the efficacy of the alkylator through the HDACi-mediated chromatin relaxation.

EDO-S101 was tested in models of human MGMT negative and positive glioblastoma. Tumour volumes were measured to calculate time to progression (TTP) and imaging was employed to estimate overall survival time.

The bi-functional properties of EDO-S101 were demonstrated in vitro through hyperacetylation, HDAC inhibitory activity, cell cycle arrest and apoptosis. These in vitro experiments also provided evidence that EDO-S101 has anti-angiogenic and radio-synthesising activity in human brain cells. Pharmacokinetic evaluation of EDO-S101 showed excellent CNS penetration (~16.5%) and high CNS concentrations (Cmax: ~11.2 uM).

Time to progression was significantly increased with EDO-S101 versus RT or temozolamide (TMZ) and the combination of both, irrespective of MGMT expression. EDO-S101 + RT also resulted in superior TTPs versus TMZ + RT. Overall survival was higher with EDO-S101 versus TMZ and RT alone, but lower than RT + TMZ.

The effectiveness of EDO-S101 in models of human glioblastoma supports further investigation in patients. Phase I studies in haematological and solid tumours are planned to start later this year.

Experiments to evaluate the pharmacological activity and the mode of action of the molecule were conducted in collaboration with several reference centres renowned for preclinical and clinical studies in early asset oncology, including the Department of Applied Sciences and Biotechnologies at the University of L’Aquila and the Department of Cancer Biology at the Mayo Clinic, Jacksonville, Florida.

Dr. med. Thomas Mehrling M.D., Ph.D., Managing Director of Mundipharma EDO GmbH commented: “We are very pleased with the data presented at the conference, which is testimony to the great progress we have been able to make in researching this interesting drug. It is particularly encouraging to see this activity in models of human glioblastoma, where the drug seems to be able to arrest the cell cycle irrespective of MGMT status and in combination with radiotherapy. The rest of the year will be most exciting for us as we are getting ready for our first in human study and will be able to explore if the drug holds promise in human disease.”