CD137 and PD-L1 bispecific antibody with context-dependent T cell activation
UTRECHT, The Netherlands I April 01, 2019 I Merus N.V. (Nasdaq: MRUS) (“Merus”, “we”, “our” or the “Company”), a clinical-stage immuno-oncology company developing Biclonics®, innovative full-length human bispecific antibody therapeutics, and in collaboration with Incyte (Nasdaq: INCY), presented preclinical data from the MCLA-145 program at the American Association for Cancer Research (AACR) Annual Meeting 2019 in Atlanta, GA. Merus and Incyte presented two posters outlining preclinical data on MCLA-145, the Biclonics® program targeting CD137 and PD-L1, on Sunday, March 31.
“MCLA-145 data presented at AACR demonstrate potent triple action, designed to recruit and activate T cells through CD137 and prevent their exhaustion through inhibition of PD-1 for patients with solid tumors,” said Mark Throsby, EVP and Chief Scientific Officer of Merus. “Because the T cell activation is context-dependent, requiring PD-L1 expression in the tumor microenvironment, MCLA-145 has the potential to overcome known side effects of CD137 agonists currently in development.”
MCLA-145 Poster Presentations at AACR 2019:
I. An unbiased screen identifies a CD137xPD-L1 bispecific IgG1 antibody with unique T cell activation and binding properties
Abstract and Poster number: #541/5
Session: PO.IM02.16 – Therapeutic Antibodies 1
The poster outlines data demonstrating MCLA-145 binds to CD137 and PD-L1 with relative high affinity, and importantly, the activation of CD137 signaling specifically occurs in the presence of PD-L1 expressing cells through a ‘trans’ activation mechanism. MCLA-145 blocks the PD-1 checkpoint inhibition pathway resulting in T cell activation independent of CD137 agonist activity.
II. A bispecific Fc-silenced IgG1 antibody (MCLA-145) requires PD-L1 binding to activate CD137
Abstract and Poster number: #539/3
Session: PO.IM02.16 – Therapeutic Antibodies 1
The poster shows MCLA-145 induces CD137 signaling specifically in the presence of PD-L1 expressing cells, with signaling strength directly correlated to PD-L1 expression level. In preclinical studies, MCLA-145 was shown to induce cytokine secretion from T cells, to overcome the suppressive activity of M2 macrophages and Tregs, and to have antitumor activity associated with the recruitment of CD8+ T cells into the tumor microenvironment.
The clinical trial for MCLA-145 is expected to initiate in the second quarter of 2019. Copies of the posters are available on the Merus website in the events section, which can be accessed via the link here. Full abstracts of the presentations can be accessed on the AACR website at www.aacr.org.
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 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. Merus is developing MCLA-145 as part of a collaboration entered into with Incyte Corporation in December 2016 to potentially develop and commercialize up to 11 bispecific and monospecific antibodies from the Merus Biclonics® platform. Under the terms of the collaboration, Merus will retain all rights to develop and commercialize MCLA-145, if approved, in the United States, while Incyte has rights to develop and commercialize MCLA-145, if approved, outside the United States.
About Merus N.V.
Merus is a clinical-stage immuno-oncology company developing innovative full-length human bispecific antibody therapeutics, referred to as Biclonics®. Biclonics®, which are based on the full-length IgG format, are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information on the company and programs, please visit Merus’ website, www.merus.nl.
SOURCE: Merus
Post Views: 29
CD137 and PD-L1 bispecific antibody with context-dependent T cell activation
UTRECHT, The Netherlands I April 01, 2019 I Merus N.V. (Nasdaq: MRUS) (“Merus”, “we”, “our” or the “Company”), a clinical-stage immuno-oncology company developing Biclonics®, innovative full-length human bispecific antibody therapeutics, and in collaboration with Incyte (Nasdaq: INCY), presented preclinical data from the MCLA-145 program at the American Association for Cancer Research (AACR) Annual Meeting 2019 in Atlanta, GA. Merus and Incyte presented two posters outlining preclinical data on MCLA-145, the Biclonics® program targeting CD137 and PD-L1, on Sunday, March 31.
“MCLA-145 data presented at AACR demonstrate potent triple action, designed to recruit and activate T cells through CD137 and prevent their exhaustion through inhibition of PD-1 for patients with solid tumors,” said Mark Throsby, EVP and Chief Scientific Officer of Merus. “Because the T cell activation is context-dependent, requiring PD-L1 expression in the tumor microenvironment, MCLA-145 has the potential to overcome known side effects of CD137 agonists currently in development.”
MCLA-145 Poster Presentations at AACR 2019:
I. An unbiased screen identifies a CD137xPD-L1 bispecific IgG1 antibody with unique T cell activation and binding properties
Abstract and Poster number: #541/5
Session: PO.IM02.16 – Therapeutic Antibodies 1
The poster outlines data demonstrating MCLA-145 binds to CD137 and PD-L1 with relative high affinity, and importantly, the activation of CD137 signaling specifically occurs in the presence of PD-L1 expressing cells through a ‘trans’ activation mechanism. MCLA-145 blocks the PD-1 checkpoint inhibition pathway resulting in T cell activation independent of CD137 agonist activity.
II. A bispecific Fc-silenced IgG1 antibody (MCLA-145) requires PD-L1 binding to activate CD137
Abstract and Poster number: #539/3
Session: PO.IM02.16 – Therapeutic Antibodies 1
The poster shows MCLA-145 induces CD137 signaling specifically in the presence of PD-L1 expressing cells, with signaling strength directly correlated to PD-L1 expression level. In preclinical studies, MCLA-145 was shown to induce cytokine secretion from T cells, to overcome the suppressive activity of M2 macrophages and Tregs, and to have antitumor activity associated with the recruitment of CD8+ T cells into the tumor microenvironment.
The clinical trial for MCLA-145 is expected to initiate in the second quarter of 2019. Copies of the posters are available on the Merus website in the events section, which can be accessed via the link here. Full abstracts of the presentations can be accessed on the AACR website at www.aacr.org.
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 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. Merus is developing MCLA-145 as part of a collaboration entered into with Incyte Corporation in December 2016 to potentially develop and commercialize up to 11 bispecific and monospecific antibodies from the Merus Biclonics® platform. Under the terms of the collaboration, Merus will retain all rights to develop and commercialize MCLA-145, if approved, in the United States, while Incyte has rights to develop and commercialize MCLA-145, if approved, outside the United States.
About Merus N.V.
Merus is a clinical-stage immuno-oncology company developing innovative full-length human bispecific antibody therapeutics, referred to as Biclonics®. Biclonics®, which are based on the full-length IgG format, are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information on the company and programs, please visit Merus’ website, www.merus.nl.
SOURCE: Merus
Post Views: 29
