On July 21, 2021 Merus N.V. (Nasdaq: MRUS), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the novel mechanism of action (MOA) of MCLA-145, the Company’s clinical stage Biclonics T-cell agonist (Press release, Merus, JUL 21, 2021, View Source [SID1234585023]). MCLA-145 binds with high affinity and specificity to PD-L1 and CD137. The unique immunostimulatory mechanism of action of MCLA-145 was published in Nature Communications on June 21, 2021, titled "A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context dependent T cell costimulation and checkpoint blockade."
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"Our recent Nature Communications publication is another example of the power and potential of our unique Biclonics platform technology allowing for high throughput functional screening to discover novel Biclonics —human, common light chain, IgG antibodies in the bispecific format—that can unlock innovative biology," said Cecile Geuijen, Chief Scientific Officer. "Preclinically, MCLA-145 has been observed to potently activate immune effector cells, only in the context of the tumor microenvironment, and can simultaneously block inhibitory signals in the same immune cell population."
MCLA-145 was identified by screening hundreds of bispecific IgG antibodies for immune activation via PD-L1 engagement among other characteristics. MCLA-145 was shown to potently activate T cells even in the presence of suppressive conditions. Furthermore, MCLA-145 was shown to enhance T cell priming and to promote long-term T cell immunity. These in vitro findings were translated to in vivo experiments where MCLA-145 anti-tumor activity was superior to the current standard immune checkpoint inhibitor comparators and linked to recruitment and intratumor expansion of CD8+ T cells.
MCLA-145 is currently being evaluated in a phase 1 open-label, multicenter dose escalation study, including a planned safety dose expansion phase, in patients with solid tumors. MCLA-145 is the first drug candidate co-developed under Merus’ global collaboration and license agreement with Incyte, which permits the development and commercialization of up to 11 bispecific and monospecific antibodies from our Biclonics platform. Merus retains full rights to develop and commercialize MCLA-145, if approved, in the United States; and Incyte holds full rights to develop and commercialize MCLA-145 outside the United States.
About MCLA-145
Discovered through an unbiased functional screening of multiple immunomodulatory target combinations, MCLA-145 is a Biclonics T-cell agonist that 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 potential to potently activate immune effector cells in the context of the tumor microenvironment while simultaneously blocking inhibitory signals in the same immune cell population.