Merus Initiates a Phase 1 Clinical Trial of MCLA-158, a Bispecific Antibody Utilizing ADCC-enhancing GlymaxX® Technology
Berlin, Germany, May 24, 2018 / B3C newswire / -- ProBioGen AG, a premier service & technology provider for complex therapeutic antibodies and glycoproteins, announced that the company achieved an undisclosed milestone payment from Merus N.V. (NASDAQ: MRUS) based on Merus’ use of MCLA-158, a bispecific antibody utilizing the GlymaxX® antibody-dependent cell-mediated cytotoxicity (ADCC)-enhancing technology in Merus’ Phase I clinical trial. The trial is in patients with solid tumors with an initial focus on metastatic colorectal cancer who will be administered MCLA-158, which uses ProBioGen’s GlymaxX® technology for greater cell-killing potential. GlymaxX® is a stable modification, applicable to any producer cell, leading them to produce antibodies without the sugar fucose. Such GlymaxX®-modified, afucosylated antibodies recruit and activate immune effector cells much more effectively, possess a much higher tumor cell killing activity and potentially require much lower doses with accordingly lower side effects.
Merus’ use of the GlymaxX® ADCC enhancement technology in MCLA-158 is the result of an agreement executed between ProBioGen and Merus in 2016. Under the terms of that agreement, Merus obtained non-exclusive rights to use the GlymaxX® technology for Merus’ Bioclonics® pipeline of bispecific antibodies designed to treat various forms of cancer to enhance their ADCC activity.
ProBioGen offers access to GlymaxX® royalty-free as part of cell line development service projects or as individual technology licenses.
ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity) activity is an important antibody function, leading to the selective killing of target cells, i.e. cancerous cells or pathogen-infected cells. Several therapeutic antibody drugs on the market rely on ADCC as a mechanism of action. ADCC enhancement has the potential to increase the therapeutic effect and/or to greatly reduce antibody dosage requirements, resulting in fewer side-effects and treatment costs.
ProBioGen developed the GlymaxX® technology to optimize antibody activity, notably the enhanced antibody-mediated cell killing or cancerous or infected cells (known as “ADCC” activity). GlymaxX® is based on the stable introduction into producer cells of a gene for an enzyme which blocks the cells’ fucose biosynthesis pathway and hence the formation of the sugar “fucose”. Consequently, no fucose is added to the antibody’s N-linked carbohydrate part of the in antibody producer cells. This absence of fucose in antibodies is known to greatly enhance ADCC.
As a unique feature, differentiating it from other approaches, GlymaxX® can be applied to both novel or already existing antibody producer cell lines, and entire antibody expression and discovery platforms. GlymaxX® does not negatively affect cellular productivity or other product characteristics. Furthermore, a GlymaxX® cell line can be flexibly used to produce differently fucosylated products, depending on the upstream process: In fucose-free medium the antibody is literally afucosylated. The same GlymaxX® cell line grown in fucose-containing medium however, uses the provided fucose and produces fully fucosylated antibody. Thus, one GlymaxX® cell line can by employed to produce several products: For instance ADCC-enhanced GlymaxX® antibodies or wildtype-like, fully fucosylated mAbs, e.g. for a parallel Antibody-Drug-Conjugate (ADC) project. Moreover, GlymaxX® has also been used by biosimilar-developing companies to adjust a specific fucose content in order to match the originators glycoprofile. Overall, GlymaxX® is simple, rapid, potent, and universally applicable to different CHO hosts and all other eukaryotic cell species. ProBioGen offers its GlymaxX® technology royalty-free and non-exclusively as a service or as an individual license.
About ProBioGen AG
ProBioGen is a premier, Berlin-based specialist for developing and manufacturing complex therapeutic glycoproteins. Combining both state-of-the-art development platforms, based on ProBioGen’s CHO-RiGHT® expression and manufacturing platform, together with intelligent product-specific technologies, yields biologics with optimized properties.
Rapid and integrated cell line and process development, comprehensive analytical development and following reliable GMP manufacturing is performed by a highly skilled and experienced team.
All services and technologies are embedded in a total quality management system to assure compliance with international ISO and GMP standards (EMA/FDA).
ProBioGen was founded 1994, is privately owned and located in Berlin, Germany.
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. Merus’ most advanced bispecific antibody candidate, MCLA-128, is being evaluated in a Phase 2 combination trial in two metastatic breast cancer populations. MCLA-128 is also being evaluated in a Phase 1/2 clinical trial in gastric, ovarian, endometrial and non-small cell lung cancers. Additional pipeline programs include MCLA-117, which is currently being studied in a Phase 1 clinical trial in patients with acute myeloid leukemia, and MCLA-158, a Biclonics® being studied in Phase 1 clinical trial in patients with solid tumors with an initial focus on metastatic colorectal cancer. Through its collaboration with Incyte Corporation, Merus is also developing a preclinical bispecific designed to bind to PD-L1 and a non-disclosed second immunomodulatory target.
Dr. Gabriele Schneider
Chief Business Officer
13086 Berlin, Germany
+49 (0)30 924 006-0