BERLIN—ProBioGen AG, a specialist in contract development and manufacturing of complex glycoproteins, and Vancouver, British Columbia-based Zymeworks Inc., a global antibody therapeutics development company, have signed an agreement under which ProBioGen will complete cell line development of a Zymeworks bispecific antibody product candidate, applying its GlymaxX technology to enhance antibody-dependent cell-mediated cytotoxicity (ADCC).
According to an NIH-authored article carrying the provocative and hopeful suhead “Light at the end of the tunnel,” with 23 approvals in the United States and other countries and four approvals outside the U.S., antibodies are now widely recognized as therapeutic molecules. “The therapeutic and commercial successes met by rituximab, trastuzumab, cetuximab and other mAbs have inspired antibody engineers to improve the efficacy of these molecules. Consequently, a new wave of antibodies with engineered Fc leading to much higher effector functions such as antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity is being evaluated in the clinic, and several approvals are expected soon. In addition, research on a different class of antibody therapeutics, bispecific antibodies, has recently led to outstanding clinical results, and the first approval of the bispecific antibody catumaxomab, a T cell retargeting agent that was approved in the European Union in April 2009. This review describes the most recent advances and clinical study results in the field of bispecific antibodies, a new class of molecules that might outshine conventional mAbs as cancer immunotherapeutics in a near future.”
ProBioGen’s chief scientific officer, Dr. Volker Sandig, commented: “We have been working productively with Zymeworks for some time already and look forward to contributing to the success of Zymeworks’ Azymetric bi-specific antibody platform. Our proprietary CHO expression platform is ideally suited for the expression of bispecific antibodies with high purities and expression titers. The implementation of our innovative GlymaxX technology for enhanced cancer cell killing underlines the flexibility of our expression platforms’ toolbox approach.”
“We believe that biotherapeutics developed using the Azymetric platform have the potential to create game-changing treatment options for patients with unmet medical needs,” added Dr. Ali Tehrani, Zymeworks’ president and CEO. “Our productive partnership with ProBioGen and their highly skilled team will help advance one of Zymeworks’ therapeutic programs into the clinic. The incorporation of the GlymaxX technology is one of the key components in enhancing the efficacy of this therapeutic candidate.”
ProBioGen’s CEO, Dr. Wieland Wolf, noted: “We are very pleased to work with Zymeworks as a biopharmaceutical company with worldwide recognition for their innovative and potentially life-changing therapeutic candidates. Given our established working relationship, we are confident that together we will help move highly efficacious bi-specific antibody therapeutics towards clinical validation.”
ProBioGen is a specialist for developing and manufacturing complex therapeutic glycoproteins. Combining both state-of-the-art development platforms 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, and is privately owned and located in Berlin.
Zymeworks is a privately held biotherapeutics company that is developing best-in-class Azymetric bispecific antibodies and antibody drug conjugates for the treatment of oncology, autoimmunity and inflammatory diseases. The company’s novel Azymetric and AlbuCORE platforms, and its proprietary ZymeCAD structure-guided protein engineering technology, enable the development of highly potent bi-specific antibodies and multivalent protein therapeutics targeted across a range of indications. Zymeworks is focused on accelerating its preclinical biotherapeutics pipeline through in-house research and development programs and strategic collaborations. According to Dr. David Poon, the company’s senior director of external R&D and alliances, Zymeworks hopes to be in the clinic by “2017-ish.”
The GlymaxX technology, developed by ProBioGen, prevents the addition of the sugar “fucose” to the N-linked antibody carbohydrate part by antibody producing cells. The absence of fucose enhances antibody-dependent cell-mediated cytotoxicity. The GlymaxX technology is based on the stable introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis. Moreover, GlymaxX cell lines can be two cell lines in one: they can either produce afucosylated antibodies, or, by adding fucose to the medium, stably produce fully fucosylated antibodies. The GlymaxX technology is universally applicable, simple and potent, and can be rapidly applied to any existing antibody producer cell line, any new cell line development or to entire expression platforms. ProBioGen offers this technology royalty-free to third parties.