Our Mission: Better technology for better health

LimmaTech Biologics aims to revolutionize treatment options for the most urgent medical needs by providing better technologies for the manufacturing of biopharmaceuticals. To achieve this, we are developing a novel, game changing production platform that enables full control of glycosylation of therapeutic glycoproteins, whilst at the same time being highly cost-effective.


The Problem

Therapeutic Proteins or Biologics such as monoclonal antibodies, enzymes, and hormones are the major products of the biotechnology industry today, generating worldwide sales of more than USD 250 billion per year. Such biologics are often glycosylated, and this glycosylation is crucial for therapeutic efficacy. Glycosylation determines functionality such as receptor binding and tissue targeting, pharmacokinetics, stability, and folding, to name only a few. However, efficient and controlled glycosylation remains the key challenge in biologics manufacturing. LimmaTech Biologics is developing a technology platform that masters the control of therapeutic activity by controlling glycosylation.


LimmaTech’s Solution: CustomGlycan Platform

In our quest to resolve the shortcomings of traditional technologies, we have developed a protein expression technology that allows full control of glycosylation.

We selected a fast growing, unicellular protozoan organism for this purpose. It has robust growth and encodes a human-like glycosylation system that is amenable to modification. This means that the type of glycosylation can be defined by the user, and is then determined by manipulating the genetic configuration of the cell line. Using our proprietary genetic engineering techniques, we created cell lines that produce several target proteins with customized and homogeneous glycosylation patterns. In addition to providing customized and uniform glycosylation, the CustomGlycan Platform allows cost-effective production, enabling expansion into novel therapeutic areas that are currently inaccessible due to the high costs of manufacturing.


Glycosylation Control

In traditional mammalian cell lines, a wide variety of divergent glycosylation reactions can occur, where addition of certain side branches can result in an entirely different set of subsequent modifications, ultimately leading to a highly diverse array of end products produced by a single cell. The complexity of this process means glycosylation is highly dependent on growth conditions and external stimuli that are difficult to control. The host employed in the CustomGlycan technology expresses a unique, short, human-like N-glycosylation pathway that is ideally suited to engineering to deliver precise human glycosylation patterns. Diverging pathways complicating the situation as in mammalian cells are absent. Furthermore, additional genetic elements can be added to achieve a customized pathway, resulting in the desired glycan structure for a given application.

To demonstrate the versatility of the platform, we performed several proof of concept studies with hormones and monoclonal antibodies and confirmed the broad applicability as well as the glycoengineering potential:

  • Glycan site occupancy of 100% is reliably achieved
  • Over 94% homogeneity of glycosylation
  • 30× increased ADCC of CustomGlycan Platform-produced antibodies


Simplified Manufacturing

Compared to current mammalian cell production systems, the CustomGlycan Platform offers many advantages during the manufacturing process:

  • No risk of functionality changes due to micro- and macroheterogeneity of glycans between lead selection and upscaling
  • No need for virus clearance
  • No need for complex media
  • No need for complex and expensive manufacturing infrastructure

In addition to the improved product characteristics, the CustomGlycan Platform promises to reduce production costs due to its low-cost media and ease of fermentation. With its short generation time, the CustomGlycan Platform rapidly reaches high cell densities, accelerating cell line development and subsequent production steps.


Fast Track to Glyco-Optimized Therapeutics

The CustomGlycan Platform addresses limitations of state-of-the-art technologies by overcoming glycosylation heterogeneity and simplifying manufacturing.

Unprecedented genetic engineering approaches developed at LimmaTech rapidly create novel host cell lines. Integration of heterologous genes is site-specific, resulting in monoclonal cell lines that do not require extensive clonal screening. Regulatory sequences flanking the transgene further contribute to ensuring consistent expression of the glycoengineered therapeutic. The short generation time of the CustomGlycan cell lines further reduces the development timelines of target biopharmaceuticals:

  • Initial lead candidates can be produced for preclinical assays within a few weeks
  • Initial cell lines are stable and directly used for yield optimization
  • 2-3× accelerated seed and inoculum production
  • Reduced GMP times

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