Merus Announces Publication in Nature Cancer on the Unique Mechanism of Action of Petosemtamab (MCLA-158)

UTRECHT, Netherlands and CAMBRIDGE, Mass., April 25, 2022 (GLOBE NEWSWIRE) — Merus AG (Nasdaq: MRUS) (“Merus”, “the Company”, “we” or “our”), a clinical-stage oncology company developing innovative full-length multispecific antibodies (Biclonics® and Triclonics®), announced today the publication of a preclinical report on petosemtamab (Peto, MCLA-158: LGR5 x EGFR Biclonics®) in the journal nature cancer. The post will be available at 11 a.m. ET today. The report describes the use of the company’s Biclonics® platform to perform large-scale functional screening of bispecific antibodies resulting in the selection of Peto, a bispecific antibody targeting Epidermal Growth Factor Receptor (EGFR) and repeat rich in leucine containing the protein G-coupled receptor (LGR5). Peto has shown potent growth inhibition of colorectal cancer (CRC) organoids, blockade of metastasis initiation and tumor outgrowth in preclinical models of different tumor types. Peto specifically triggered EGFR degradation in LGR5-expressing organoids, while showing minimal toxicity toward normal LGR5-expressing organoids.

In October 2021, Merus reported first interim clinical data in an ongoing Peto trial in patients with head and neck squamous cell carcinoma (HNSCC).

“This publication demonstrates the potential of our Biclonics® platform to generate a large number of diverse panels of antibodies, undertake high-throughput functional screening of bispecifics in format, and identify drug candidates that possess specific biology and characteristics for therapeutic applications,” said Cécile Geuijen. , Ph.D., Senior Vice President and Chief Scientific Officer. “We are encouraged by the preclinical and clinical data we have obtained to date, and we look forward to further clinical development of Peto.”

The results published in nature cancer further describe Peto’s results in preclinical solid tumor models, including the following highlights:

  • Peto exhibits unique therapeutic properties such as potent growth inhibition of KRAS mutant CRC organoids, blockade of metastasis initiation, and inhibition of tumor outgrowth in preclinical models of different tumor types
  • Peto shows superior growth inhibition compared to cetuximab, an EGFR inhibitor used for the treatment of metastatic CRC and HNSCC, in subcutaneous xenografts generated from inoculation of C31M, a CRC organoid derived from patient carrying a KRAS G12D mutation
  • Unlike cetuximab, Peto triggers EGFR internalization and degradation via LGR5
  • peto watch live anti-tumor activity in other tumor types that express LGR5 such as esophageal squamous cell carcinoma, gastric carcinoma and HNSCC

Peto is currently participating in a multicenter, open-label, phase 1 study in patients with solid tumors. Merus is planning a clinical update for the second half of 2022.

Merus is the sponsor of the Peto clinical trial and certain preclinical work described in the nature cancer the article was generated in collaboration with the suppresSTEM consortium, among other institutions and organizations cited in the publication.

About Petosemtamab (Peto, MCLA-158)
Peto is an ADCC-enhanced Biclonics® human IgG1 designed to bind to cancer stem cells (CSCs) expressing G protein-coupled receptor 5 containing leucine-rich repeats (Lgr5) and epidermal growth factor receptor (EGFR). In preclinical models, Peto binding triggers EGFR degradation in LGR5+ CSCs and is thought to have two different mechanisms of action. The first is to block cancer cell growth and survival pathways. The second exploits the recruitment and enhancement of immune effector cells to directly kill cancer-initiating cells that persist in solid tumors and can cause relapses and metastasis.

About Merus SA

Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapies, called Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to exhibit many of the same characteristics as conventional human monoclonal antibodies, such as a long half-life and low immunogenicity. For more information, please visit Merus’ website and follow Merus on Twitter and LinkedIn.

Forward-looking statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements in this press release that do not relate to historical facts should be considered forward-looking statements, including, without not limited to, statements regarding the content and timing of clinical trials, data readouts, and clinical updates for our product candidate, MCLA-158 or Peto; the potential of our Biclonics® platform to generate a large number of diverse panels of antibodies, undertake high-throughput functional screening of bispecifics in format and identify drug candidates that possess specific biology and characteristics for therapeutic applications; the potential for the design, potency and efficacy of Peto as described in preclinical studies and the impact, if any, on development and clinical evaluation; the progress of the phase 1 trial for Peto and the update expected in the second half of 2022. These forward-looking statements are based on management’s current expectations. These statements are not promises or 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 future results, performance or achievements. expressed or implied by the forward-looking statements. 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 revenues; the long and costly process of clinical drug development, the outcome of which is uncertain; the unpredictable nature of our efforts to develop early-stage marketable drugs; potential delays in patient enrollment, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the possibility that such third parties may not perform satisfactorily; impacts of the COVID-19 pandemic; we may not identify suitable Biclonics® or bispecific antibody candidates in our collaborations or our collaborators may not perform well in 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 patentability rules and regulations; we may not prevail in any lawsuits for infringement of third-party intellectual property; our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented, or held to be generic or determined to infringe other trademarks; and risks related to our ceasing to qualify as an emerging growth company and a small reporting company in 2022.

These and other important factors discussed under “Risk Factors” in our Annual Report on Form 10-K for the period ended December 31, 2021, filed with the Securities and Exchange Commission, or SEC, on February 28 2022, 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. These forward-looking statements represent management’s estimates as of the date of this press release. Although we may choose to update these forward-looking statements at some time in the future, we assume no obligation to do so, even if subsequent events change our views, except as required by applicable law. These forward-looking statements should not be taken to represent our views as of any date subsequent to the date of this press release.

Multiclonics®, Biclonics® and Triclonics® are registered trademarks of Merus NV


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Merus N.V.
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