Our lives are currently unthinkable without the use of recombinant proteins. Particularly in the biopharmaceutical sector, where protein drugs have saved millions of lives. The pharmaceutical industry has been witnessing a shift from molecular to protein-based drugs because of their high specificity, enhanced efficacy, affinity and solubility and low incidences of toxicity. As a result, the market for recombinant pharmaceutical proteins is expanding rapidly. Nearly all pharmaceutical companies with a market capitalization value of more than €10 billion have reported that their revenue share from such products is growing faster than that from small-molecule drugs. Currently, there are over 400 marketed recombinant products (peptides and proteins), and another 1,300 undergoing clinical trials. However, the problems with the existing protein production systems are numerous:
• Aging and inefficient expression technology for discovery, clinical trials materials, and large-scale production
• Time-consuming and expensive cell line development and optimization cycles for each step
• Post-translation reactions are difficult, often incomplete or heterogeneous (e.g. the glycosylation in CHO)
• Large-scale production consists of very complex infrastructure for the manufacturing processes, designed and optimized for one single protein.
The consequences of these problems are also numerous;
• 10-12 years of development before drugs are authorized and commercialized
• 20% of proteins cannot be expressed at all in the cell, or the yield is so low further development is abandoned. These potential candidates are “collecting dust” in archives.
• From phase I, about 90% of the candidates do not make it to market. Each failed candidate wasted the high investment in the optimization and scale-up of the cell expressing the protein candidate before the clinical trials are conducted.
• Due to the high and costly failure rate, pharmaceutical developers have become very risk-avert, which inhibits new drug development.
As a result, out of approximately 10.000 known diseases, only 5% have registered treatments available. Drug development aims to address this need for more treatments. Also dwindling drug pipelines, the lack of potential blockbuster drugs and the anticipated expirations of patents for existing drugs are forcing the pharmaceutical industry to look for new tools that increase the productivity of drug research, accelerate the drug discovery process, promote more efficient manufacturing processes, and reduce R&D expenditures. The complexity for protein production becomes particularly evident for proteins that are difficult to express; i.e. i) existing cell-free platforms produce no or very low quantities of these proteins, are very difficult to scale up and ii) cell-based expression platforms require time-consuming optimization processes to produce and purify significant quantities of these proteins. The development of many potential promising protein candidates is currently abandoned because of the inability to produce them in large-scale, due to the very low yield of target proteins (“lost children”). Up to 20% of proteins are being discarded already during the discovery phase because they cannot be expressed efficiently at all in cells (Ref: LenioBio Protein Drug candidates for trails
market research).
Cell-free technologiescan offer a solution to accelerate the protein development, but cell-free protein expression at the gram and kilogram scale, an essential starting requirement for biotherapeutic drug development, has been hampered by the lack of scalable systems adaptable to standard bioreactor configurations at large scale. LenioBio offers the patented and innovative ALiCE® eukaryotic cell-free platform, which represents the best of both technologies (cell-free and cell-based), developed for consistent high-yield protein synthesis at any scale with simplified downstream purification processes.
ALiCE® provides solutions to these problems by offering unique solutions during each stage of drug development for “difficult to express” proteins.
