Merus Begins Phase 2 Trial Dosing for Petosemtamab in Advanced mCRC

UTRECHT, The Netherlands and CAMBRIDGE, Mass., Dec. 16, 2024 – Merus N.V., a clinical-stage oncology company listed on Nasdaq under the symbol MRUS, is making strides in the fight against cancer with their innovative multispecific antibodies, known as Biclonics® and Triclonics®. Recently, the company achieved a significant milestone by dosing the first patient in their phase 2 clinical trial. This trial is focused on evaluating the effectiveness of petosemtamab as a monotherapy for patients with heavily pretreated metastatic colorectal cancer (mCRC), particularly those who have undergone at least third-line therapy (3L+).

Petosemtamab, also known as MCLA-158, is a specialized Biclonics® antibody that targets the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). This bifunctional approach is designed to provide multiple mechanisms of action, including the obstruction of EGFR-dependent signaling pathways, binding to LGR5 to facilitate EGFR internalization and degradation within cancerous cells, and enhanced immune responses through antibody-dependent cell-mediated cytotoxicity (ADCC) and cellular phagocytosis (ADCP).

The phase 2 trial, which is open-label, aims to assess both the safety profile and antitumor efficacy of petosemtamab in patients who have previously undergone anti-EGFR treatments. Eligibility for the trial requires participants to lack specific mutations as identified by circulating tumor DNA next-generation sequencing (ctDNA NGS), notably KRAS and NRAS mutations. This rigorous selection criteria ensures that the treatment is administered to those most likely to benefit from this therapeutic strategy.

John de Kruif, Ph.D., the Chief Technology Officer at Merus, expressed optimism about the potential of petosemtamab to improve treatment outcomes for patients with heavily pretreated mCRC. He noted that petosemtamab was developed following an extensive screening process of over 500 bispecific antibodies, which were tested for their ability to selectively inhibit cancer-derived organoids as opposed to those derived from normal tissue. Notably, in preclinical models of colorectal cancer, petosemtamab has consistently demonstrated superior activity compared to cetuximab, a well-established therapy in the treatment of mCRC.

Merus N.V. is dedicated to advancing the field of oncology through the development of cutting-edge antibody therapeutics. Their platform, which includes Multiclonics®, encompasses full-length human bispecific and trispecific antibodies that are produced using established industry methodologies. These therapeutics have been shown to possess characteristics akin to conventional human monoclonal antibodies, such as extended half-life and reduced immunogenicity, in both preclinical and clinical settings.

The company remains focused on leveraging its unique technologies to deliver improved therapeutic options for patients with cancer. As their phase 2 trial progresses, Merus and its team are hopeful that the data will support the efficacy of petosemtamab, potentially paving the way for new treatment strategies for individuals battling advanced colorectal cancer. Through their relentless pursuit of innovation, Merus aims to make a meaningful impact on the lives of those affected by this challenging disease.