Merus Announces the Journal Publication of Petosemtamab Mechanism of Action
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Insights
Merus' journal publication validates petosemtamab's triple mechanism of action, supporting promising clinical data in head and neck cancer.
The publication in the journal "Cancers" represents an important scientific validation for petosemtamab, Merus' bispecific antibody targeting both EGFR and LGR5. This peer-reviewed article details the drug's three distinct mechanisms of action: EGFR ligand blocking, receptor internalization/degradation in LGR5+ cells, and Fc-mediated immune system activation through ADCP and enhanced ADCC.
The scientific rationale outlined in this publication is particularly significant because it targets LGR5+ stem cell-like cancer cells, which are frequently implicated in cancer growth, treatment resistance, and recurrence across multiple solid tumor types. This provides mechanistic support for the previously reported robust clinical responses in both first-line PD-L1+ recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) when combined with pembrolizumab, and as monotherapy in second-line or later r/m HNSCC.
The concurrent advancement of petosemtamab through multiple clinical development pathways demonstrates Merus' confidence in this therapeutic approach. The company has two Phase 3 trials ongoing in r/m HNSCC (first-line and second/third-line) expected to be substantially enrolled by year-end, alongside a Phase 2 trial in metastatic colorectal cancer (mCRC) evaluating petosemtamab both in combination with chemotherapy and as monotherapy. Initial clinical data for the mCRC program is expected in H2 2025.
This publication strengthens petosemtamab's scientific foundation at a critical time as the company advances its late-stage clinical trials, potentially positioning this bispecific antibody as an important new treatment option for multiple cancer types with significant unmet needs.
UTRECHT, The Netherlands and CAMBRIDGE, Mass., May 15, 2025 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (“Merus”, “the Company”, “we”, or “our”), an oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics®, Triclonics® and ADClonics®), today announced publication on the mechanism of action of petosemtamab, a bispecific antibody targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G (LGR5), in the scientific journal “Cancers”, a MDPI publication, available here.
“LGR5+ stem-cell-like cells within a tumor, are frequently reported to be a central contributor to cancer growth, treatment resistance, and recurrence in CRC and other solid tumors,” said Cecile Geuijen, Ph.D., Senior Vice President and Chief Scientific Officer. “This publication outlining the scientific rationale for petosemtamab, a bispecific targeting EGFR and LGR5, underpins the strong previously reported phase 2 interim clinical data in both 1L PD-L1+ r/m HNSCC in combination with pembrolizumab and as a single-agent in 2L+ r/m HNSCC.”
Petosemtamab employs three distinct mechanisms of action: EGFR ligand blocking, EGFR receptor internalization and degradation in LGR5+ cells, and Fc-mediated activation of the innate immune system by antibody-dependent cellular phagocytosis (ADCP) and enhanced antibody-dependent cellular cytotoxicity (ADCC).
Petosemtamab has demonstrated substantial clinical activity in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) as reported in our 2024 press releases, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC (May 28, 2024) and Merus’ Petosemtamab Monotherapy Interim Data Continues to Demonstrate Clinically Meaningful Activity in 2L+ r/m HNSCC (Dec. 7, 2024). Phase 3 trials are ongoing in both first-line (1L) programmed PD-L1+ (CPS≥1) and second/third-line (2/3L) r/m HNSCC with both trials expected to be substantially enrolled by year end.
A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L metastatic colon cancer (mCRC), and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in second half of 2025.
The publication is available on the Publications page of our website.
About Merus
Merus is an oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® 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. For additional information, please visit Merus’ website, and LinkedIn.
About Petosemtamab
Petosemtamab, or MCLA-158, is a Biclonics® low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.
About Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) describes a group of cancers that develop in the squamous cells that line the mucosal surfaces of the mouth, throat, and larynx. These cancers begin when healthy cells change and grow in an unchecked manner, ultimately forming tumors. HNSCC is generally associated with tobacco consumption, alcohol use and/or HPV infections, depending on where they develop geographically. HNSCC is the sixth most common cancer worldwide and it is estimated that there were more than 930,000 new cases and over 465,000 deaths from HNSCC globally in 2020.1 The incidence of HNSCC continues to rise and is anticipated to increase by
1 Sung et al. CA Cancer J Clin, 71:209-49, 2021; 2 Johnson, D.E., Burtness, B., Leemans, C.R. et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6(1):92, 2020
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding the content and timing of clinical trials, data readouts and clinical updates for our product candidate, MCLA-158 or petosemtamab; the specific biology and characteristics for therapeutic applications; the potential of the mechanism of action, design, activity and efficacy of petosemtamab as described in the publication; the potential role of LGR5+ stem-cell-like cells to cancer growth, treatment resistance, and recurrence; the impact, if any, of prior reported clinical data for petosemtamab on future development; the plan for both phase 3 H&N trials to be substantially enrolled by year end; and expectation to provide initial clinical data for petosemtamab in mCRC in the second half of 2025. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the volatility in the global economy, including global instability, including the ongoing conflicts in Europe and the Middle East; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.
These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended March 31, 2025, filed with the Securities and Exchange Commission, or SEC, on May 7, 2025, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.
Multiclonics®, Biclonics®, Triclonics®, and ADClonics® are registered trademarks of Merus N.V.
Investor and Media Inquiries: Sherri Spear Merus N.V. SVP Investor Relations and Strategic Communications 617-821-3246 s.spear@merus.nl Kathleen Farren Merus N.V. Director IR/Corp Comms 617-230-4165 k.farren@merus.nl
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