Mundipharma EDO GmbH data confirm EDO-S101 is effective in preclinical models of human glioblastoma June 1, 2015
Dr. Thomas Mehrling M.D., Ph.D.,
Mundipharma EDO GmbH
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Dr. Thomas Mehrling M.D., Ph.D.,
Mundipharma EDO GmbH
BASEL, SWITZERLAND – 1 June 2015:
Findings presented at the European Organization for Research & Treatment of Cancer (EORTC), European Association of NeuroOncology (EANO) and European Society for Medical Oncology (ESM0) 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 vitroexperiments 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-S101versus 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 centers 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 comments:
“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.”
For further information on Mundipharma EDO please visit www.mundipharma-edo.com
NOTES FOR EDITORS
Mundipharma EDO GmbH (“EDO”)
EDO is developing early stage assets in oncology for the Mundipharma network of independent associated companies and is committed to increasing the treatment options available for cancer patients, improving their quality of life through the early development of small molecules and biologics. EDO is currently investigating a new chemotherapy agent for haematological malignancies and solid tumours, and an antibody-drug conjugate for the treatment of ovarian cancer.
The company has utilised its worldwide clinical connections and partners to successfully license-in and develop competitively differentiated preclinical stage programs for a portfolio of biologic and small molecules in a number of therapeutic areas and disease indications. EDO’s approach enables the design of highly selective inhibitors and targeted medicines, supporting the company’s strategy of ensuring cost-effective and safety-enhanced drug development. As a privately-funded company with strengths in rapid decision-making, commercial flexibility and excellent execution, EDO is an ideal partner for biotech companies.
EDO’s demonstrated capability in early development, as well as its diverse pipeline, uniquely positions the company to develop multiple commercial opportunities for different therapeutic indications. EDO’s experienced management and scientific team, a broad network of scientific and clinical experts and partners around the world, are key drivers of the company’s success to-date. For future information, visit www.mundipharma-edo.com
For further information on Mundipharma’s network of independent associated companies please visit www.mundipharma.com
Glioblastoma multiforme (GBM) is a fast-growing brain or spinal cord tumor. These tumors arise from glial cells, normal cells that form the (supportive) tissue of the brain and spinal cord, are highly malignant, the cells reproduce quickly and they are supported by a large network of blood vessels.
Typically patients succumb to the disease approximately 15 months after diagnosis.[2,3] Treatment for glioblastoma multiforme remains challenging and no long-term treatments are currently available. Standard treatment is surgical resection, radiotherapy and concomitant adjunctive chemotherapy.
MGMT, a DNA repair gene, is shown to be a significant predictor of response to treatment. Glioblastoma patients who have had their MGMT gene shut off by a process called methylation also have prolonged survival rates.
The incidence of GBM is 2 to 3 per 100,000 people in the United States and Europe.
1. Festuccia C. The Alkylating Histone-Deacetylase Inhibition Fusion Molecule EDO-S101 is active in preclinical models of human glioblastoma independent from MGMT expression. http://www.ecco-org.eu/Events/EORTC_EANO_ESMO-2015
2. National Brain Tumor Society web site. Tumor Types. http://www.braintumor.org/brain-tumor-information/understanding-brain-tumors/tumor-types/#glioblastoma-multiforme. Accessed October 17, 2014 3. American Brain Tumor Association. (2012) Glioblastoma and Malignant Astrocytoma http://www.abta.org/secure/glioblastoma-brochure.pdf Accessed October 17, 2014.