In this instalment of The Cell Base's ‘Start-up spotlight,' we speak to Josh Robinson, CEO of Cocoon Bioscience, a Spanish biotech company that produces speciality enzymes and growth factors using insects in their chrysalis stage as bioreactors.

Can you tell us about Cocoon Bioscience and the inspiration behind starting the company?

Cocoon Bioscience is a biotech company based in Spain, which produces recombinant proteins and enzymes for the food and life science industries.   Founded in 2022, we use a unique technology to produce our proteins, which has performance, scaling and affordability advantages – we use insects as natural bioreactors as opposed to the traditional means of producing recombinant proteins, which is done in big, stainless-steel bioreactors with genetically modified bacteria or yeast.   

The technology powering Cocoon, the Crisbio platform, was initially developed by our legacy company Algenex, as a way to make vaccines for animal health.  After the sale of Algenex to a large pharma company in 2022, Cocoon was spun out to pursue other industries that have significant bottlenecks in product development that could be solved with the proteins made with Cocoon’s technology.

What inspired the development of Cocoon’s insect-based bioreactor technology, and how did it come about? 

Necessity is the mother of all innovation.  The use of insect cells to produce proteins and vaccines has been demonstrated and commercially pursued for over three decades, with US Food and Drug Association-approved vaccines.  However, insect cells still need the expensive capex of stainless-steel bioreactors and high operating costs involved in the media designed to mimic the living system of the insect cells and the monitoring systems to ensure no contamination takes place, the pH is right, the oxygen levels are right, etc.  (It is worth noting that insect cells do not need to be genetically modified – a baculovirus, i.e. a virus specific for insects, can be used to make recombinant proteins).   

In order for our legacy company to be able to commercial vaccines from insect cells, they need to get better at scaling and reduce costs.  The inspiration came when they realized that insect pupae in their chrysalis state are immobile, low cost, easily infected with a baculovirus, and contain billions of insect cells. 

What were the key challenges in scaling Crisbio and how did you overcome them?

There are three challenges that we needed to overcome with some creative innovation in order to scale Crisbio to the industrial scale.   First, we need to be able to rear 15 million insects or more in a contained environment in a way that we can have them in a continuous lifecycle from egg to full grown moth, so that we always have a starting supply of bioreactors.   Our entomology team spent years understanding the environmental conditions and sensory factors that allow us to build a repeatable, robust process for rearing our insects.  

The second challenge was inoculating the cocoons with the baculovirus without damaging the insect.   We had to build a custom, first-of-its-kind automation platform in order to achieve this, spending over a year engineering and prototyping all aspects.   The final challenge was scaling the purification of our proteins from the insects.  For this, we took inspiration from the pharmaceutical industry, which has refined methods for decades of purifying a target protein out of a fermentation lysate – we just had to make a few tweaks to adjust for the fact that our lysate is crushed insects, not fermentation media. 

How does your method produce cost-effective growth factors, compared to traditional bioprocessing?

By eliminating both the high capex involved in purchasing stainless steel bioreactors, and the high operating expense involved in fermentation media and monitoring systems for fermentation, we have a much cheaper upstream process for production.   And with our automated platform, the people needed to run the full process is quite low, contributing to our more affordable process.   In addition, our process is linearly scalable – if something works in one insect, it will work in 100 or a million, so we don’t need to invest heavily in scaling production. 

How does the regulatory landscape for insect-based recombinant proteins differ from conventional methods?

There isn’t a vast difference in either the food regulatory space or the pharmaceutical regulatory space.   The products need to meet the quality specifications for both our method and conventional methods in terms of impurities, toxicities, allergens, etc.   One key that helps is that we don’t genetically modify our insects – if we did, that would send us down a more complex and unprecedented regulatory pathway that we are glad to avoid. 

Can you explain how your growth factors like FGF-2 and PDGF support muscle and tissue development in cultured meat?

Growth factors are like the ‘blue prints’ for the animal cells that growth into cultivated meat.  Without growth factors, cells won’t multiply and proliferate – the growth factors name is quite literal, it attaches to the cells and instructs them to grow.  They are only needed in minute quantities, on the order of 1 milligram of growth factor for 1 kilogram of cultivated meat produced.  However, with conventional fermentation, growth factors can represent over 50% of the total cost of producing cultivated meat – a critical cost bottleneck that Cocoon is using our technology to address.

What challenges do you anticipate as you scale production to 20kg annually? 

At the moment, don’t anticipate any major challenges to come – we have already demonstrated scaling for our first products to 50-litre scale.  In order to reach the 20 kg targeted annual capacity, all we would need to do is execute with the team and protocols we have in place.  The one thing we will need to do is expand our downstream purification equipment – right now, we have sufficient equipment to produce 3-4 kilograms per year and will be purchasing the equipment to expand in the near future. 

How do you ensure the quality, safety and sustainability of your recombinant proteins?

Quality and safety at the highest levels are table stakes for working in the food and pharma industries.  The design of our industrial facility was done to ensure that we are compliant with both good manufacturing production practices for pharma and compliant with the Food Safety Modernization act.   We have seen validation of the quality and safety of the platform through the European Medicines Agency's approval of an injectable vaccine for our legacy company in 2021.  

Sustainability is also core to our mission.   While we want our products to help empower a more sustainable production of meat with cultivated meat, we also want to make sure we are sustainable in how we produce our proteins.   From our initial estimates, the CO2 emissions of our process may be up to 90% lower than the standard processes; however, we plan to do a much more detailed life cycle analysis of our entire operation and facility in the upcoming year to fully understand the environmental footprint of our products and how it compares to the current standards.

What's next for Cocoon Bioscience?

In addition to expanding our capacity and sharpening our pencils around our environmental footprint, we plan to continue to expand our product portfolio in the upcoming year, offering a full range of growth factors, including development of aquatic species growth factors for cultivated seafood.   We are also looking to deepen the collaborations with our existing partners to ensure that our products can have as large of an impact as possible on our target industries.

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