Basel, Switzerland (Press Release) – Mundipharma EDO GmbH (Early Development in Oncology) has announced the initiation of a first-in-human clin­i­cal trial of its inves­ti­ga­tional drug can­di­date EDO-S101. A first in class, fusion molecule - S101 is cur­rently being developed for the treat­ment of re­lapsed-refractory (RR) haematological malig­nan­ces. This phase 1 study is designed to eval­u­ate the safety and tolerability of ascending doses of EDO-S101 and will be conducted at several sites across the United States and Europe.

EDO-S101 is the first rep­re­sentative of the A-DAC principle, a new ap­proach in chemo­ther­apy that uses fusion tech­nology to combine an alkylating agent with a pan-histone deacetylase inhibitor (HDAC) to simultaneously damage DNA and block damage repair. The com­bi­na­tion of the two dif­­fer­en­t modes of action has the poten­tial to overcome resistance to­wards other conventional chemo­ther­a­pies. EDO-S101 combines the active structures of bendamustine and vorinostat, two molecules that have been well estab­lish­ed in the treat­ment of haema­to­logical malig­nan­cies, to produce a novel single agent with efficacy char­ac­ter­istics superior to those of the parent com­pounds given in com­bi­na­tion.[1],[2]

Dr. Thomas Mehrling, CEO, Mundipharma EDO GmbH commented: "Today EDO forges ahead with even greater momentum fol­low­ing this important mile­stone of a first-in-human trial. EDO-S101 is making sig­nif­i­cant progress in its clin­i­cal devel­op­ment journey and we are passionate about its poten­tial to treat patients with re­lapsed-refractory haemato­logical malig­nan­ces, who are in dire need of new treat­ment options. The pri­mary goal of this first clin­i­cal trial is to eval­u­ate the safety and tolerability of EDO-S101 and its phar­ma­co­ki­netic profile. These data will be used to estab­lish­ the recommended dose which will then be further eval­u­ated for safety and efficacy."

Preclinical experiments dem­onstrated that EDO-S101 exerts sig­nif­i­cant activity against haemato­logical malig­nan­cies in­­clud­ing multiple myeloma (MM)[1],[3], acute myeloid leukemia (AML)[1],[4], mantle cell lym­phoma (MCL)[2], ABC type diffuse large B-Cell lym­phoma (DLBCL)[3] as well as hodgkin lym­phoma (HL)[3]. In addi­tion, the molecule is active in pri­mary resistant cells as well as in cells that have acquired resistance.[5]

About Mundipharma EDO GmbH

Mundipharma EDO has col­lab­o­rated with its world­wide clin­i­cal connections and partners to suc­cess­fully license-in and develop competitively dif­fer­en­ti­ated pre­clin­i­cal stage pro­grammes for its com­pounds across 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.

About the study

The Phase 1 multi-centre, clin­i­cal trial will assess the safety and tolerability of EDO-S101 admin­istered in­tra­venously once in a 28-day cycle. The study will enroll patients with re­lapsed refractory haemato­logical malig­nan­cies for which there are no avail­able ther­a­pies and it is designed as a two stage trial. The key objectives of stage one are to determine a maximum tolerated dose and phar­ma­co­ki­netic profile, while in stage two the recommended dose will be further eval­u­ated for safety and pre­lim­i­nary anti-tumor activity in selected haematological malig­nan­cies. Please refer to http://www.clinicaltrials.gov for addi­tional clin­i­cal trial details.

About re­lapsed refractory haematological malig­nan­cies

Despite recent im­prove­ments in the treat­ments of haematological malig­nan­cies, patients who have re­lapsed or refractory disease remain a clin­i­cal chal­lenge due to limited effective treat­ment options.

For example, almost all patients with MM who survive initial treat­ment will eventually relapse and will require further ther­apy. The patient survival rate for MM up to five years is 48.5%.[6]

Relapse in HL occurs in a small proportion of patients; approx­i­mately 5% to 8% of those presenting with limited stage disease and 15% to 20% of those with ad­vanced stage disease.[7]

In the majority of patients with AML who achieve a com­plete remission (CR), the leukaemia will recur within 3 years. In general, the prognosis of patients after relapse is poor and treat­ment options un­sat­is­fac­tory.[8]

References

1. 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
2. López-Iglesias, A.A., preclinical antimyeloma activity of EDO-S101 (bendamustine-vorinostat fusion molecule) through DNA-damaging and HDACi effects. 15th International Myeloma Workshop. 23−26 September 2015. Rome, Italy.
3. 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 Inhibitors in Vitro. Blood 2014 124 (21). https://ash.confex.com/ash/2014/webprogram/Paper69945.html
4. Mundipharma EDO GmbH Data on file.
5. 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
6. SEER Stat Fact Sheets: Multiple Myeloma, S.S.F.S
7. Connors J. M. Hodgkin lymphoma: special challenges and solutions Hematol Oncol 2015;33:21-24.
8. Döhner H. et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet Blood 2010;115:453-474.

Source: Mundipharma EDO.