On October 7, 2021 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 that clinical data on MCLA-158, including clinical responses observed in advanced head and neck squamous cell carcinoma (HNSCC) and preclinical data on zenocutuzumab (Zeno) at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Merus, OCT 7, 2021, View Source [SID1234590973]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Andrew Joe, Chief Medical Officer at Merus, said, "We are encouraged by the early evidence of clinical activity of MCLA-158 in patients with advanced, previously treated HNSCC, further validating the potential of our Biclonics platform. With Zeno, our preclinical research continues to reinforce the mechanisms by which Zeno is capable of potently inhibiting the growth of NRG1 fusion cancers."

MCLA-158 (petosemtamab)
The reported data are from the ongoing phase 1 dose expansion cohort that is investigating the safety, tolerability, and anti-tumor activity of MCLA-158 monotherapy in advanced HNSCC.

Observations in the presentation include:

Enrollment of 10 patients with advanced HNSCC, as of the safety and efficacy data cutoff date of August 9, 2021, with median age of 65 (range 50-77) years, and who were treated with a median of 2 lines of prior therapy.
Seven patients were evaluable for an interim efficacy analysis by investigator assessment (three patients were enrolled <8 weeks from the cutoff date).
Three of seven patients achieved partial responses, with one achieving complete response after the data cutoff date. Tumor reduction was observed in all seven patients.
The safety profile of MCLA-158 was based on 29 patients with advanced solid tumors who were treated at 1500 mg every two weeks across the phase 1 trial.
The most frequent adverse events (AEs) were infusion related reactions; 72% any grade, 7% grade ≥ 3.
Mild to moderate skin toxicity (3% grade ≥3).
The Company is planning its next update on the MCLA-158 trial in 2022.

Zeno
Observations in the preclinical presentation include:

The bispecific HER2/HER3 antibody Zeno blocked cell growth 100 fold more potently than the bivalent HER3 antibody derived from Zeno, in an NRG1 driven growth assay.
Zeno potently blocked NRG1-fusion mediated downstream signaling and growth in vitro and in vivo.
Zeno induced both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) mediated killing of cancer cells in a dose-dependent manner.
As of September 1, 2021 more than 80 patients with NRG1 fusion cancers have been treated with Zeno monotherapy in our phase 1/2 eNRGy trial and Early Access Program. (www.nrg1.com).
About MCLA-158
MCLA-158, or petosemtamab, 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, MCLA-158 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.

About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.