Periodic Reporting for period 1 - AlkaBurst2.0 (AlkaBurst2.0 – A game changing bioreactor for sustainable production of active pharmaceutical ingredients in a consistent, traceable and low cost approach)
Reporting period: 2022-11-01 to 2023-10-31
Alkion BioInnovations, a revolutionary biotech company, is developing a breakthrough biorefinery to produce top quality active pharmaceutical ingredients (API) and extracts in plant biomass in a sustainable and cost-effective way. Our core technology combines our disruptive patented automated bioreactor-AlkaBurst2.0 with unique knowhow on plant tissue culture, gene expression methods, culture media and extraction/purification methods. Our process offers high productivity and a low carbon footprint. The pharma industry is carbon intensive with recurring problems of access, quality & safety. Moreover, many critical APIs are outsourced to Asia to cut costs. AlkaBurst2.0 allows a local standardised production of safe & clean APIs in its automated process saving >75% time, 80% space, 97% electricity, 98% water. We first validated the production for natural vaccine adjuvants QS21/7, a range of cannabinoids & certain recombinant proteins such as the growth factor interferon beta 1A, all for the urgent and unmet market demand. With the €7.5M budget we build & validate our pilot and expect to generate €125M revenue by 2028 with 105 jobs created.
Producing active ingredients for modern medicine is currently: 1.Unsustainable: The upstream production chain is resource intensive (e.g. cannabinoids industry consumes 20 billion kWh of electricity and emits 15 million metric tons CO2eq per yr., e.g.2: ), generates lots of waste and has a limited scaling potential. Downstream processes are forced to use highly pollutive and expensive extraction methods due to adulterants and low quality raw product. 2.Costly with a long supply chain: 80% of our APIs production is outsourced to Asia to cut costs. This dependence makes Europe a victim of variations in the price and access of APIs. The EU needs a local production solution able to compete with Asian suppliers. 3.In need for better safety: Current production methods lead to frequent (>700 (USA), 27 (EU) in 2018) product recalls due to the presence of toxins or adulterants. 4.Under exploiting plant potential: Obtaining APIs from plants is currently limited by long cultivation cycles and very low yields (e.g. QS-21, a super-adjuvant for vaccine and immunotherapies, from the Quillaja Saponaria tree, has a 7-year regeneration, variable and low yields in the bark of the tree with cost of production up to $400k/g).
To tackle these problems, Alkion relies on their pioneering technology and know-how to develop a sustainable, cost effective and versatile platform for the bioproduction of high value active ingredients for pharmaceutical markets mainly, with a first focus on QS-21. The purpose is to offer a sustainable (low resources, carbon neutral), reliable, global and low-cost access to the adjuvant first and to other high-value compounds and extracts such as cannabinoids and some recombinant proteins. To reach this, the main objective of EIC project is to build an automated pilot biorefinery with 60 to 100 Alkaburst 2.0 (in-house large bioreactor) that will serve as a demonstrator before building the commercial biorefinery by 2025/2026. This includes the development of AI cutting robots and the improvement and validation of Alkaburst 2.0 adapted to the robots, an important biological R&D work for the improvement and adaptation of different strains to the process and of methods of purification, the pre-mass production of Alkaburst 2.0 and the validation of the overall process. The project also includes the refining of the business strategy and the pre-market launch with a dedicated team.
Producing active ingredients for modern medicine is currently: 1.Unsustainable: The upstream production chain is resource intensive (e.g. cannabinoids industry consumes 20 billion kWh of electricity and emits 15 million metric tons CO2eq per yr., e.g.2: ), generates lots of waste and has a limited scaling potential. Downstream processes are forced to use highly pollutive and expensive extraction methods due to adulterants and low quality raw product. 2.Costly with a long supply chain: 80% of our APIs production is outsourced to Asia to cut costs. This dependence makes Europe a victim of variations in the price and access of APIs. The EU needs a local production solution able to compete with Asian suppliers. 3.In need for better safety: Current production methods lead to frequent (>700 (USA), 27 (EU) in 2018) product recalls due to the presence of toxins or adulterants. 4.Under exploiting plant potential: Obtaining APIs from plants is currently limited by long cultivation cycles and very low yields (e.g. QS-21, a super-adjuvant for vaccine and immunotherapies, from the Quillaja Saponaria tree, has a 7-year regeneration, variable and low yields in the bark of the tree with cost of production up to $400k/g).
To tackle these problems, Alkion relies on their pioneering technology and know-how to develop a sustainable, cost effective and versatile platform for the bioproduction of high value active ingredients for pharmaceutical markets mainly, with a first focus on QS-21. The purpose is to offer a sustainable (low resources, carbon neutral), reliable, global and low-cost access to the adjuvant first and to other high-value compounds and extracts such as cannabinoids and some recombinant proteins. To reach this, the main objective of EIC project is to build an automated pilot biorefinery with 60 to 100 Alkaburst 2.0 (in-house large bioreactor) that will serve as a demonstrator before building the commercial biorefinery by 2025/2026. This includes the development of AI cutting robots and the improvement and validation of Alkaburst 2.0 adapted to the robots, an important biological R&D work for the improvement and adaptation of different strains to the process and of methods of purification, the pre-mass production of Alkaburst 2.0 and the validation of the overall process. The project also includes the refining of the business strategy and the pre-market launch with a dedicated team.
- We reached important R&D milestones : cannabinoids yields up to 7 - 8% and QS-21 yields up to 2% in precipitation;
- and significantly improved the processes for cost efficiency
- we scale up former and new strains with the new method in 4L bioreactors with replicability
- we adapted plant morphology to robots for automation (use of different biotic and abiotic parameters) with the expected results
- Bioengineering works: we managed the regeneration on cannabis plant and defined the strategy on QS for genetic transformation. Work on recombinant proteins is detailed in 1.3 session.
- We found the right partners for the robots and the improvement of Alkaburst 2.0 defined all steps and new specifications, and started the collaboration
- and significantly improved the processes for cost efficiency
- we scale up former and new strains with the new method in 4L bioreactors with replicability
- we adapted plant morphology to robots for automation (use of different biotic and abiotic parameters) with the expected results
- Bioengineering works: we managed the regeneration on cannabis plant and defined the strategy on QS for genetic transformation. Work on recombinant proteins is detailed in 1.3 session.
- We found the right partners for the robots and the improvement of Alkaburst 2.0 defined all steps and new specifications, and started the collaboration
Plant science, bioengineering: We have created a plasmid library which contains more than 100 different useful parts for further construction of the protein of interest. Combining with the efficient cloning techniques( GoldenBraid systems), we are able to create in a short time various recombinant proteins such as sweet protein, interferon or other proteins of interest.
We have established good expression systems in different plant species (tobacco, lettuce and camline) both in transient and stable expression. We also optimized the elements and parameters for highly expressing the recombinant protein, and we've already expressed various marker proteins and sweet protein.
Furthermore, we developed an innovative strategy for gene editing which allows us to precisely edit only a few base pairs on the genes which are existing naturally in camelina and transform them to a sweet protein. Thanks to this, we can produce the recombinant proteins which are subjected to new genomic techniques (non-GMO).
Hardware: 1/We are developing the world’s first AI-driven robots for in-vitro micropropagation. This will have an important impact on cost-efficiency for other industries that will thus be able to relocate in EU.
2/We adapt the bioreactors to consumption of CO2 by plant biomass as a replacement of sugar. This will lead to a more efficient, with less contamination risk, carbon-neutral to negative platform.
We have established good expression systems in different plant species (tobacco, lettuce and camline) both in transient and stable expression. We also optimized the elements and parameters for highly expressing the recombinant protein, and we've already expressed various marker proteins and sweet protein.
Furthermore, we developed an innovative strategy for gene editing which allows us to precisely edit only a few base pairs on the genes which are existing naturally in camelina and transform them to a sweet protein. Thanks to this, we can produce the recombinant proteins which are subjected to new genomic techniques (non-GMO).
Hardware: 1/We are developing the world’s first AI-driven robots for in-vitro micropropagation. This will have an important impact on cost-efficiency for other industries that will thus be able to relocate in EU.
2/We adapt the bioreactors to consumption of CO2 by plant biomass as a replacement of sugar. This will lead to a more efficient, with less contamination risk, carbon-neutral to negative platform.