GlycoEra leverages its control over natural glycan-mediated pathways to advance novel drugs using its propriety platform. GlycoEra develops first in class therapeutics with customized and highly homogenous human-glycans assembled onto glycoproteins in a site-specific manner.
Glycosylation is the process in which a carbohydrate is attached to a protein. As an enzymatic process attaching glycans to proteins, or other organic molecules, glycosylation produces one of the most fundamental components found in cells along with DNA, RNA, and proteins.
Glycobiology and Glycoimmunology fields are quickly evolving due to rapid increases in understanding of the roles of glycans in immunology, and dramatic advances in glycan analytics and engineering cellular glycosylation.
Emerging studies demonstrate that glycans play predominant roles in immune regulation and cell functions, beyond being structural and folding factors. Glycans, therefore, enable unique functions by engaging different carbohydrate-binding receptors to induce diverse pathways such as modulating immune cells, triggering endocytosis and signaling. Hence, glycan-receptor interaction can be exploited to develop therapeutics with novel modes of action, opening a new front in combating diseases.
Examples of glycan-mediated modes of action enabled by GlycoEra’s Custom Glycan Platform
GlycoEra fosters and employs in-depth knowledge of in vivo engineering complex carbohydrate structures and is at the forefront of the development of novel glycoengineering platforms. GlycoEra’s CustomGlycan Platformis the only in vivo technology offering unparalleled controlled glycan structure design capabilities, enabling several glycan-mediated functions. This opens a new era in developing novel drugs.
Controlled glycosylation of Rituximab produced by the CustomGlycan Platform.
Comparison of N-glycan profiles of Rituximab expressed in the CustomGlycan Platform using the “G0 cell line” to the market products MabThera (Chinese Hamster Ovarian, CHO expressed) and Gazyvaro, an improved anti-CD20 mAb (CHO expressed, GlycArt platform). CustomGlycan Platform G0 cell line produces 100% G0 N-glycan,. The antibodies produced in CHO cell lines contain mostly heterogeneous complex N-glycans. N-glycan structures are indicated: ■: N-acetylglucosamine; ●: mannose
Fast cell line development using a proprietary modular genetic toolbox.
GlycoEra is continuously extending its CustomGlycan Platform glycoengineered cell line repertoire offering unique and highly abundant glycosylation features. These plug-and-play cell lines can be used to extend glycan enabled modes of action validated through GlycoEra’s product candidates.
Advanced CustomGlycan Platform cell lines available to date.
Available cell lines expressing specific human N-glycan structures G0, G2 and G2S2. The wild-type (wt) cell line expresses Man3GlcNAc2 (M3) form. Corresponding N-glycan fingerprints (liquid chromatography traces) indicate the relative abundance of N-glycan species in a given cell line.
Short generation time allows process acceleration.
Due to the short generation time of about seven hours, seed generation for main culture inoculation is drastically reduced. Typically, inoculi are ready within 48 hours and allow for a 50x volume increase per step.
The CustomGlycan Platform is compatible with extended process times of up to at least 28 days of stable growth and productivity. Thus, batch sizing cannot only be influenced by fermenter size, but also by time.
Fermentations rely on a simple and low cost GMP compatible media promoting reproducible growth.
The product can be easily recovered from the remarkably clean supernatant through industry standard separation, clarification and concentration processing. The following downstream process is compatible with standard processes employed by manufacturers.
The platform has been demonstrated to be capable to produce glycoengineered monoclonal antibodies with high titers. So far, up to 1.5 g/l with a defined N-glycan structure in a 10 day process has been achieved.
Schematic CustomGlycan Platform fermentation process.
As a consequence of the considerably faster growth speed, the CustomGlycan Platform processes enable shorter process times and ultimately less facility occupation. Lower media cost and faster strain development (time from DNA to stable monoclone) add up to the list of advantages.