Clinical Pipeline

MCLA-128 is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics^® that targets the HER3 pathway. The bispecific antibody docks on HER2, abundantly expressed on tumor cells, and subsequently efficiently blocks heregulin-stimulated growth of tumor cells by binding to HER3. MCLA-128 is designed to overcome the inherent and acquired resistance of tumor cells to HER2-targeted therapies using two mechanisms: 1) blocking growth and survival pathways to stop tumor expansion and 2) recruitment and enhancement of immune effector cells to eliminate the tumor.

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MCLA-117 is a Biclonics^® that binds to CD3, a cell-surface molecule present on all T cells, and CLEC12A, a cell surface molecule present on Acute Myleoid Leukemia (AML) cells and stem cells. MCLA-117 is designed to recruit and activate T-cells to kill CLEC12A-expressing AML tumor cells and stem cells, which may prevent recurrence of the tumor.

MCLA-158 is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics^® for the treatment of solid tumors, including the potential treatment of colorectal cancer, that binds to cancer stem cells expressing leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptor (EGFR). MCLA-158 is designed to use two different mechanisms of action. The first blocks growth and survival pathways in cancer stem cells. The second involves the recruitment and enhancement of immune effector cells to directly kill cancer stem cells that persist in solid tumors and cause relapse and metastasis.

MCLA-145 is a Biclonics^® T-cell agonist discovered through an unbiased functional screening of multiple immunomodulatory target combinations. MCLA-145 binds with high affinity and specificity to human PD-L1 and CD137 in preclinical models. The unique immunostimulatory profile of MCLA-145 derives from the ability to potently activate immune effector cells in the context of the tumor microenvironment while simultaneously blocking inhibitory signals in the same immune cell population

MCLA-129 is a Biclonics^® binding to EGFR and c-MET for the treatment of solid tumors. EGFR is an important oncogenic driver in many cancers; the upregulation of c-MET signaling has been associated with resistance to EGFR inhibition. MCLA-129 has two distinct mechanisms of action. First, Merus’ Dock & Block^® mechanism of action blocks the signaling of EGFR as well as c-MET, with the potential to inhibit tumor growth and survival. Second, MCLA-129 utilizes GlymaxX^® antibody-dependent cell-mediated cytotoxicity (ADCC)-enhancement technology designed for greater cell-killing potential. Because the Dock & Block^® and ADCC mechanism of action is based on the co-expression of EGFR and c-MET, it is expected to have less toxicity compared to agents targeting EGFR alone.