Periodic Reporting for period 2 - PEPPER (Industrial-scale plant-based protein production in a cell-free platform)
Período documentado: 2020-12-01 hasta 2022-02-28
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.
• 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.
The goal of PEPPER is to bring LenioBio to a position of competitiveness and growth to be able to meet the current industrial demands of difficult to express (DTE) proteins for various biotechnology sectors (e.g. pharmaceutical and agricultural industries). To achieve this, LenioBio will scale-up the protein production capacity and product yield to be able to produce proteins at an industrial scale using a semi-automated platform, while complying to GMP protocols and FDA/EMA regulations for biopharmaceutical proteins.
PEPPER started in December 2019. The focus for this period was on i) expanding the team and nominating work package champions; ii) negotiating and signing of the contracts with the subcontractors; iii) expanding the laboratory space and identifying and purchasing of equipment. Further, we implemented a comunication plan for dissemination of project results and ensured data collection and storage in accordance with FAIR principles.
The team has been expanded in the first six months of PEPPER. Key personnel with expertise in plant molecular biology, bioprocessing and data management as well as operational support joined the team.
To scale the current ALiCE® process, potential equipment for each process step was identified, rented, tested, evaluated and if it fulfilled the requirements purchased. Due to the current COVID-19 pandemic there is the risk of delays for delivery and installation of equipment and delivery of consumables. However, we are confident that the pilot line will be installed in March/April 2021.
PEPPER started in December 2019. The focus for this period was on i) expanding the team and nominating work package champions; ii) negotiating and signing of the contracts with the subcontractors; iii) expanding the laboratory space and identifying and purchasing of equipment. Further, we implemented a comunication plan for dissemination of project results and ensured data collection and storage in accordance with FAIR principles.
The team has been expanded in the first six months of PEPPER. Key personnel with expertise in plant molecular biology, bioprocessing and data management as well as operational support joined the team.
To scale the current ALiCE® process, potential equipment for each process step was identified, rented, tested, evaluated and if it fulfilled the requirements purchased. Due to the current COVID-19 pandemic there is the risk of delays for delivery and installation of equipment and delivery of consumables. However, we are confident that the pilot line will be installed in March/April 2021.
After completion of the PEPPER project the cell-free production platform ALiCE® will be available at scale for applications in biopharmaceutical and alternative protein industry. The potential impact for biopharmaceutical applications is as follows: LenioBio will pursue research and development collaborations, licensing arrangements and other commercial opportunities with its partners and collaborators to leverage the value and benefits of its platform for their potential use in the development and manufacture of biopharmaceuticals. In particular, LenioBio believes the ALiCE® technology may help bring biologic drugs to market faster, in greater volumes, at a lower cost, and with new properties to drug developers and manufacturers and, hopefully, improve access and cost to patients and the healthcare system, but most importantly save lives.
For alternative protein applications (i.e. cultivated meat) scaling of our technology will have the following impact: It is becoming increasingly clear that our current methods of intensive animal farming in Europe are unsustainable. As well as being a major contributor to greenhouse gas emissions, livestock production systems occupy 28% of land in the EU and contribute disproportionately to soil acidification, water pollution, and air pollution. The negative impacts of meat consumption for animals, the environment, and human health are more pressing than ever. Our proposed solution to this predicament to accelerate the deveoplemt of cultured meat by enabling production of growth factors at large scale. As well as circumventing the need to slaughter animals, cultured meat will have a much lower environmental footprint than meat from animals, largely due to its relative input efficiency.
For alternative protein applications (i.e. cultivated meat) scaling of our technology will have the following impact: It is becoming increasingly clear that our current methods of intensive animal farming in Europe are unsustainable. As well as being a major contributor to greenhouse gas emissions, livestock production systems occupy 28% of land in the EU and contribute disproportionately to soil acidification, water pollution, and air pollution. The negative impacts of meat consumption for animals, the environment, and human health are more pressing than ever. Our proposed solution to this predicament to accelerate the deveoplemt of cultured meat by enabling production of growth factors at large scale. As well as circumventing the need to slaughter animals, cultured meat will have a much lower environmental footprint than meat from animals, largely due to its relative input efficiency.