Mundipharma EDO GmbH data confirm EDO-S101 unique mechanism of action and significant activity in models of relapsed/refractory multiple myeloma and other haematological malignancies January 15, 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 – 15 January 2015:
Findings presented at the American Society of Hematology congress in San Francisco in December 2014 suggest that EDO-S101 may be a useful anti-myeloma agent for relapsed/refractory patients, as a single agent, and particularly in combination with a proteasome inhibitor.
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.
The data confirm the simultaneous activity of EDO-S101 as an alkylator and HDAC inhibitorin vitro and in vivo. Moreover, while the HDAC inhibition activity was very similar to vorinostat and the alkylating capacity to bendamustine, it appeared that the combined functions in one molecule showed superior activity in various models compared to the single agents, in both myeloid and lymphoid malignancies.[1,2]
- In vitro experiments demonstrated a synergy between EDO-S101 and proteasome inhibitors, which was associated with induction of pIRE1, the key regulator of the unfolded protein response (UPR). This elevation of pIRE1 and induction of UPR have recently been shown to be linked to overcoming proteasome inhibitor resistance in human multiple myeloma.[1,3]
- Meaningful activity was demonstrated in a Vk*MYC mouse model that is a clinically and biologically faithful model of untreated Multiple Myeloma. The response was sustained for more than 3 months in mice receiving only two doses of EDO-S101, one week apart.
- Significant activity was demonstrated in very aggressive, multi-drug resistant Vk12653 transplant model of relapsed/refractory Multiple Myeloma in which EDO-S101 was the only drug in this model of many, that has been identified with single agent activity. The investigators have indicated that EDO-S101 is suitable for prioritization for rapid clinical development.
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 of new anti-myeloma agents including the Hematology Group at the University of Salamanca, Spain, the Experimental Oncology Group from Sankt Gallen, Switzerland and the Comprehensive Cancer Center, Mayo Clinic Scottsdale, Arizona.
Phase I studies in liquid and solid tumors are planned to start in 2015.
Dr. med. Thomas Mehrling M.D., Ph.D.,
Managing Director of Mundipharma EDO GmbH comments:
“We are very pleased about the data presented at the ASH conference, which is testimony to the great progress we were able to make in researching this interesting drug. It is particularly encouraging to see the activity in refractory models, where the drug seems to be able to break through resistance. The year 2015 will be most exciting for us as we are getting ready for our first in human study and will be able to find out if the drug holds promise in human disease.”
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.edoncology.com
Multiple Myeloma is a cancer of plasma cells in the bone marrow affecting approximately 20,000 new patients each year. This cancer usually responds to immune system-stimulating drugs, but eventually overcomes them and is rarely cured. Patient survival rate is generally up to 5 years. More effective treatment options are urgently needed.
References: 1. Kraus, M., EDO-S101, a New Alkylating Histone-Deacetylase Inhibitor (HDACi) Fusion Molecule, Has Superior Activity Against Myeloma and B Cell Lymphoma and Strong Synergy with Proteasome Inhibitorsin Vitro. Blood 2014 124 (21). https://ash.confex.com/ash/2014/webprogram/Paper69945.html 2. López-Iglesias, A.A., The Alkylating Histone Deacetylase Inhibitor Fusion Molecule Edo-S101 Displays Full Bi-Functional Properties in Preclinical Models of Hematological Malignancies. Blood 2014 124 (21). https://ash.confex.com/ash/2014/webprogram/Paper72121.html 3. Leung-Hagesteijn, C., Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma. Cancer Cell 2013. 24: p. 289–304. 4. Chesi, M., Identification of Novel Therapeutic Targets in the Clinically Predictive Vk*MYC Mouse Model of Multiple Myeloma. Blood, 2014 124 (21) https://ash.confex.com/ash/2014/webprogram/Paper70113.html 5. SEER Stat Fact Sheets: Myeloma.