Proteases are enzymes that cleave other proteins (matrix proteins, cell surface receptors, hormones or other proteases), which are then either activated or inactivated. In effect, proteases are the tools by which the cell can interact with or modify the surrounding tissue environment. Homeostasis relies on a delicate balance between the amount of activated proteases and their naturally occurring inhibitors. Defects in the regulation of specific proteases play a major role in tissue degenerative diseases such as diseases of the lung, bowl and cancer. Understanding and exploiting the role of specific proteases may enable the development of effective therapeutic drugs against diseases involving unregulated protease activity.

RedHill Biopharma Ltd. is developing MESUPRON (upamostat), an orally administered protease inhibitor with several potential mechanisms of action for inhibition of tumor invasion and metastasis.

About MESUPRON

MESUPRON has undergone several Phase I and Phase II clinical studies, including a Phase II proof-of-concept study in locally advanced unresectable pancreatic cancer, in combination with first-line chemotherapeutic agents.

The biochemical studies conducted during 2016 by the Aarhus team have identified a small subset of proteases which may represent likely in vivo targets of inhibition by MESUPRON. The continued research collaboration for 2017 will focus on finalizing the identification of the most likely molecular targets of MESUPRON and to develop antibody-based strategies for the detection of these targets in patient samples. Currently, two proteases are in the research collaboration pipeline for antibody development, with more possible candidate proteases to follow.

Further evaluation of MESUPRON, together with Aarhus University, may allow for selection of appropriate sub populations of patients towards potentially demonstrating the activity of MESUPRON in planned clinical trials. The non-clinical studies with MESUPRON are intended to add to the clinical data from previous Phase I and Phase II studies, and may allow RedHill to take a precision medicine approach going forward. 

RedHill is planning to conduct a Phase I study of the safety, efficacy and dose evaluation of MESUPRON in combination with chemotherapy in patients receiving adjuvant chemotherapy for resected pancreatic cancer. The Phase I study is expected to be initiated in the second half of 2017 in up to four sites in Germany.

The Aarhus laboratory

The Danish research team consists of M.Sc. Emil Oldenburg and Ph.D. Christine R. Schar, the latter responsible for the daily management of the laboratory facility dedicated to the RedHill effort. The direction of the research is managed on a consultant basis by Ph.D. Jan K. Jensen, who until recently held the position of Associate Professor at Aarhus University. The research laboratory is located at the Department of Molecular Biology and Genetics, Aarhus University in the Science Park (Gustav Wieds vej 10C, Aarhus) and occupies a part of the former research laboratories of Jan K. Jensen and the late Professor Peter A. Andreasen. Prof. Andreasen was instrumental in the startup of the collaboration with Redhill Biopharma after being approached by the company in the summer of 2015. The current research team draws upon the accumulated knowledge from the research of Profs. Jensen and Andreasen on biochemical and biophysical analysis of proteases, receptors and inhibitors as well as development of non-natural inhibitors based on antibodies, camelid nanobodies, RNA aptamers and peptides.

About RedHill Biopharma Ltd.
RedHill Biopharma Ltd. is a specialty biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally administered, small molecule drugs for the treatment of gastrointestinal and inflammatory diseases and cancer.

In 2014, RedHill acquired the exclusive worldwide development and commercialization rights to MESUPRON (upamostat), excluding China, Hong Kong, Taiwan and Macao, from Germany’s WILEX AG for all indications. Wilex AG completed several clinical studies with upamostat for different indications, including two Phase II proof-of-concept studies, one for pancreatic cancer and one for metastatic breast cancer.

For further information, please contact

Project Manager Jan K. Jensen
Department of Molecular Biology and Genetics
Aarhus University, Denmark
jkj@mbg.au.dk - +45 4111 2177