SUPPRESTEM Consortium Led by Merus Receives €6 Million FP7 Grant from the European Union
May 27, 2013
Development of Therapeutic Bispecific Antibodies (Biclonics™) Targeting Treatment-resistant Cancer Stem Cells Using Patient-Derived Organoid Screening Tools
Utrecht, The Netherlands, May 27, 2013 – Merus B.V., a biopharmaceutical company focusing on innovative human antibody therapeutics, today announced that it has been granted funding from the European Union’s FP7 program. Merus is leading the SUPPRESSTEM consortium which was granted a total of about €6 million to develop novel antibody-based therapeutics targeting cancer stem cells for the treatment of colorectal cancer as well as patient-derived organoid-based screening tools to aid drug discovery. The consortium includes The Hubrecht Institute (The Netherlands), OcellO B.V. (The Netherlands), Fundacio Privada Institut de Recerca Biomedica (Spain), and The Wellcome Trust Sanger Institute (UK).
Specifically, the consortium is addressing mechanisms that lead to the development of treatment resistance and tumor escape in colon cancer, a problem that has hampered the development of efficient therapeutics in the past. Furthermore, it is pioneering the application of patient-derived tissue in drug discovery to address the high clinical failure rate in cancer drug research. It is hoped that the SUPPRESSTEM results will have broad application in cancer drug development.
“Metastatic colorectal cancer is still largely incurable,” said Mark Throsby, COO of Merus. “Chemotherapy-resistant cancer stem cells have recently emerged as a major cause of treatment failure. To target cancer stem cells, we need treatments able to address multiple targets simultaneously - particularly those in the Wnt pathway.”
In the SUPPRESSTEM consortium, Merus will develop Biclonics™ antibodies which will both modulate the Wnt pathway and address growth factor receptors to specifically inhibit cancer stem cells with minimal toxicity on healthy tissue. Functional screening of these stem cell-targeting bispecific antibodies for specific inhibitory activity and for selecting lead candidates will be done using organoids.
“The likelihood of clinically translating these efforts will be enhanced because testing will be performed on relevant human tissue material (both tumor and normal), using organoid technology and novel imaging readouts," said Prof. Hans Clevers, former director of the Hubrecht Institute, who discovered the organoid culture system. The genomes of paired colon cancer tissue organoids and normal tissue organoids from each patient will be sequenced.
"The in-depth analysis of the phenotype and genotype of responsive organoids from patient material that will be used to identify lead products in SUPPRESSTEM will also have important implications for future drug discovery efforts and increase our knowledge on cancer genetics,” added Prof. Mike Stratton, Director of the Sanger Institute.
“The overarching goal of the consortium is to increase the success rate of cancer treatment not only by developing more advanced drugs, but also by improving the predictive capacity of drug screening models for cancer,” said Ton Logtenberg, CEO of Merus. “The consortium aims to provide a novel drug product, using organoid technology as a patient-specific drug screening approach for clinical validation that ultimately will greatly improve the life of cancer patients.”
Biclonics™ are full-length bispecific IgG antibodies encoded by a common light chain (cLC) and two different heavy chains. Using a proprietary CH3 dimerization technology, the two different heavy chains and the cLC are expressed in a single cell to efficiently assemble into Biclonics™. As a result, thousands of different Biclonics™ can be rapidly screened in functional assays. Biclonics™ have excellent stability and pharmacokinetics and are produced at >99% purity in manufacturing cell lines such as CHO cells, providing yields of >2.5 grams/liter.
Due to their ability to bind to two different epitopes on a single or on multiple target antigens, bispecific antibodies can exert more potent biological activities than conventional therapeutic antibodies. They bind to target cells more specifically, making them ideal for application in drug conjugate technologies, and can be applied to redirect immune effector cells such as T cells or NK cells for potent target cell killing.
About Merus B.V.
Merus is a biotechnology company building a pipeline of innovative human bispecific antibodies (BiclonicsTM) and single cell-derived combinations of antibodies (Oligoclonics®) for cancer therapy. Through the use of a common antibody light chain and CH3 heterodimerization technology, these full-length IgG antibody therapeutics can be robustly produced at high yields from a single clonal manufacturing cell line using standard approaches. Biclonics™ and Oligoclonics® bind to multiple disease-associated targets such as growth factor receptors expressed by tumor cells. Synergy is achieved by addressing multiple pathways/mechanisms simultaneously, thereby eliminating tumor cells more efficiently and preventing treatment escape.
Merus meets a significant need in the oncology field: the supply of bispecific antibodies and single-cell derived antibody combinations with improved clinical efficacy to address the limited potency of conventional antibodies.
For further information, please visit our website at www.merus.nl
Dr. Ludger Wess or Ines-Regina Buth
Tel. +49 (0)40 88 16 59 64 / +49 (0)30 2363 2768
S. Margetson - s.margetson(at)merus.nl
3584CH Utrecht, The Netherlands
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