On April 25, 2022 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported publication of a preclinical report on petosemtamab (Peto, MCLA-158: LGR5 x EGFR Biclonics) in the journal Nature Cancer (Press release, Merus, APR 25, 2022, View Source [SID1234612919]). The publication will be available at 11:00 a.m. ET today. The report describes the use of the company’s Biclonics platform to perform a large-scale functional screen of bispecific antibodies resulting in selection of Peto, a bispecific antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G protein-coupled receptor (LGR5). Peto displayed 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 organoids expressing LGR5, while showing minimal toxicity towards normal LGR5-expressing organoids.
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In October 2021, Merus reported early, interim clinical data in an ongoing trial of Peto in patients with head and neck squamous cell carcinoma (HNSCC).
"This publication demonstrates the potential of our Biclonics platform to generate large numbers of diverse panels of antibodies, undertake high throughput functional screening of in-format bispecifics, and identify drug candidates that possess specific biology and characteristics for therapeutic applications," said Cecile 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 look forward to the further clinical development of Peto."
The results published in Nature Cancer further describe Peto’s results in preclinical models of solid tumors, 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 relative to cetuximab, an EGFR inhibitor used for treatment of metastatic CRC and HNSCC, in subcutaneous xenografts generated from inoculation of C31M, a patient-derived CRC organoid bearing a KRAS G12D mutation
Unlike cetuximab, Peto triggers EGFR internalization and degradation through LGR5
Peto shows in vivo anti-tumor activity in other tumor types that express LGR5 such as esophageal squamous cell carcinoma, gastric carcinoma and HNSCC
Peto is currently enrolling in a phase 1 open-label, multicenter study in patients with solid tumors. Merus is planning a clinical update for the second half of 2022.
Merus is the sponsor of the clinical trial, investigating Peto, and certain preclinical work described in the Nature Cancer paper was generated in conjunction with the suppresSTEM consortium, among other institutions and organizations cited in the publication.
About Petosemtamab (Peto, MCLA-158)
Peto is an ADCC-enhanced human IgG1 Biclonics designed to bind to cancer stem cells (CSCs) expressing leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptor (EGFR). In preclinical models, Peto binding triggers EGFR degradation in LGR5+ CSCs and is designed to have two different mechanisms of action. The first entails blocking of growth and survival pathways in cancer initiating cells. 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 relapse and metastasis.