– IND Accepted in April by the U.S. FDA for MCLA-158 –

UTRECHT, The Netherlands I May 24, 2018 I Merus N.V. (Nasdaq:MRUS), a clinical-stage immuno-oncology company developing innovative bispecific antibody therapeutics (Biclonics®), today announced that the first patient has been dosed in a Phase 1, first-in human clinical trial of MCLA-158 in patients with solid tumors with an initial focus on metastatic colorectal cancer. The trial will be conducted in Europe, where several Clinical Trial Applications (CTAs) have been approved to date. The Company also announced the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for MCLA-158, which was accepted by the FDA in April 2018. With this acceptance, Merus plans to open additional sites for this trial in the United States.

MCLA-158 is designed to bind to cancer stem cells expressing leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptors (EGFR). MCLA-158 was identified from a large library of bispecific antibodies targeting molecules belonging to the Wnt and receptor tyrosine kinase signaling pathways as part of work performed by the suppresSTEM consortium, a project that was funded by the European Union. Functional evaluation of patient-derived colorectal tumors, including those harboring RAS and/or PI3K mutations, demonstrated that MCLA-158 was more effective at inhibiting tumor growth and promoting apoptosis than an approved targeted therapy comparator for metastatic colorectal cancer, cetuximab. In preclinical studies, Merus also observed that the growth inhibitory activity of MCLA-158 was greater for colon tumors compared to normal colon tissue, consistent with its good safety profile in non-human primates.

“The commencement of our Phase 1 clinical trial of MCLA-158 is an important milestone for the advancement of our pipeline of bispecific antibodies obtained from our Biclonics® technology platform,” said Ton Logtenberg, Ph.D., Chief Executive Officer. “We believe MCLA-158 has the potential to address features that limit currently approved colorectal cancer-targeted therapies, including issues with off-target toxicity and inability to target tumor stem cells, and thus, potentially treat a broader population of patients more effectively.”

The Phase 1, open-label, multicenter clinical trial of MCLA-158 consists of two parts, a dose escalation and a dose expansion. The dose escalation part is intended to determine the appropriate dose of MCLA-158. The dose expansion part will evaluate the safety and tolerability of the defined dose of MCLA-158 in patients with solid tumors. The dose escalation and expansion parts of the trial will also examine the preliminary antitumor activity of single-agent MCLA-158. 

About Merus N.V.

Merus is a clinical-stage immuno-oncology company developing innovative full-length human bispecific antibody therapeutics, referred to as Biclonics®. Biclonics®, which are based on the full-length IgG format, are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. Merus’ most advanced bispecific antibody candidate, MCLA-128, is being evaluated in a Phase 2 combination trial in two metastatic breast cancer populations. MCLA-128 is also being evaluated in a Phase 1/2 clinical trial in gastric, ovarian, endometrial and non-small cell lung cancers. Additional pipeline programs include MCLA-117, which is currently being studied in a Phase 1 clinical trial in patients with acute myeloid leukemia, and MCLA-158, a Biclonics® being studied in a Phase 1 clinical trial in patients with solid tumors with an initial focus on metastatic colorectal cancer. Through its collaboration with Incyte Corporation, Merus is also developing a preclinical bispecific antibody designed to bind to PD-L1 and a non-disclosed second immunomodulatory target. For additional information, please visit Merus’ website, www.merus.nl.

About suppresSTEM

The suppresSTEM consortium consisted of Merus N.V. as coordinator, The Hubrecht Institute (The Netherlands), OcellO B.V. (The Netherlands), Institute for Research in Biomedicine (IRB, Barcelona Spain), and The Wellcome Trust Sanger Institute (UK). The research leading to the results described here received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement n° 601876. In May 2013 the consortium 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 as a European Union’s FP7 program. Specifically, the consortium was focused on 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 pioneered the application of patient-derived tissue in drug discovery to address the high clinical failure rate in cancer drug research.

SOURCE: Merus