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AUTHOR: Heather Allman
PUBLISHER: CANNABIS LAW REPORT
As announced in January 2021, Creo became the first company to achieve demo scale production of rare cannabinoid CBGA.
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Creo becomes first company to achieve demo scale production of rare cannabinoid CBGA
San Diego, CA – January 28, 2021 – Creo, an ingredient company with a proprietary platform for producing natural rare cannabinoids without the cannabis plant, announced today that it has produced cannabigerol (CBG) and cannabigerolic acid (CBGA) through fermentation at 12,500-liter scale, with performance matching or exceeding expectations. Creo is the first fermentation-based cannabinoid company to successfully produce finished CBGA.
Rare cannabinoids such as CBG and CBGA (“CBG/A”) are being studied for a range of potential benefits; but they’re only found in small quantities in the plant and can be challenging to extract, making CBG/A hard to produce at scale. To enable broader access to CBG/A, Creo has partnered with biotech industry-leader Genomatica to create a patented fermentation technology platform that produces consistent high-quality, rare cannabinoids, sustainably, at scale, and at a higher purity level than traditional methods. Commercial production and supply are expected to begin in Q2 2021.
“With this demo run, Creo has cemented its leadership position in the emerging market for fermentation-based cannabinoids,” said Creo CEO, Roy Lipski. “This is a very significant milestone for Creo and a major step towards enabling cannabinoid ingredients to reach every household, through wellness, beauty, food and beverage products.”
According to a recent report on cannabinoids and the bio revolution by Raymond James, a financial services firm, the global market for cannabinoids produced by fermentation is estimated to grow from $10 billion in 2025 to $115 billion by 2040.
“We’re excited to be with Creo at the forefront of innovation in this fast-moving industry,” said Nelson Barton, Senior Vice President, Research and Development, Genomatica. “We’re glad to have demonstrated, yet again, Genomatica’s expertise in driving fermentation-based processes from idea to commercial readiness, and to showcase our technology delivering another performance product in health and wellness.”
Creo’s cannabinoids are produced in the USA, in an FDA registered, food cGMP-compliant facility. Creo’s global manufacturing partner has over 4,000 scientists, research chemists, engineers and plant operators dedicated to delivering for customers in a wide range of consumer and industrial markets.
With this January 2021 announcement, Creo successfully produced CBG and CBGA through fermentation at 12,500-liter scale, becoming the first fermentation-based cannabinoid company to successfully produce finished CBGA.
Creo’s promise of greater sustainability is why it makes its cannabinoid ingredients using one of the world’s oldest natural processes – fermentation. Fermentation requires less water, energy and land than the plant-based approaches typically used to extract cannabinoid ingredients.
Late April 2021, Cannabis Law Report interviewed Roy Lipski, CEO and President of CREO, and here is our insightful conversation about cannabinoids, sustainable fermentation, and the future potential of large scale minor cannabinoid production.
CLR: Please introduce yourself and tell us a little bit about what you do and where you work.
Roy Lipski: I’m Roy Lipski and I’m the CEO of Creo. Creo is a novel technology led ingredients business that is focused on the fastest growing ingredients market, which is that of cannabinoids. We have developed technology, in partnership with one of the leading biotech players in the field, a company called Genomatica, to produce cannabinoids naturally through fermentation, without the use of the cannabis plant.
We believe that this approach, while preserving all the benefits and properties of cannabinoids, will pave the way for these ingredients to really make it into the mainstream.
When I say mainstream, I’m talking about the sort of big consumer packaged goods players like Kraft Heinz, Johnson and Johnson, Procter and Gamble, Unilever, etc., who have been notable by their absence from the marketplace and we believe that the reason is because of two aspects.
One aspect is supply chain, as they need ingredients to have consistency, purity, scalability, reliability of supply, and price stability —all those kinds of things, which at the moment have been difficult to achieve.
The second aspect is legal clarity, and there is still the perception of legal uncertainty and risk associated with the cannabis plant that the biosynthetic process really sidesteps. So, any of these compounds made using biosynthesis without the cannabis plant are not scheduled substances; therefore, they’re treated under the law just like any other consumer good.
CLR: Can you tell me a little bit about your process to build up to that 12,500 liter scale.
Roy: Well, it’s been a journey!
Creo was actually founded almost exactly five years ago by myself and Professor Ramon Gonzales, who is a leading bioengineering researcher in academia. We spent about 14 months doing a proof of concept of this idea at Rice University.
At that point, the technology moved out of the university and we teamed up with a biotech leader here in San Diego called Genomatica. Since 2017 until today, we’ve been developing and perfecting and scaling up that technology.
Now, in January of this year, we announced a 12,500 meter scale demonstration of the technology, the product being produced at one of our manufacturing partners who are a large multinational chemicals and ingredients manufacturer, in their FDA-registered, cGMP compliant, kosher certified food grade facility.
The journey from the earliest stages at Rice University, working in shake flasks to demonstration scale, was a scale up of 200,000 times.
Ultimately, we’ve already done the majority of the heavy lifting, having scaled up to where we are now, to commercial demonstration. Initial commercial production —something we see happening around late summer this year— is only a 2x increase in scale from here.
CLR: That is still very impressive. CBG is extremely helpful for me, so the fact that it’s on such a large scale —and you’ve done it in a very interesting way— is truly fascinating. Can you tell me more about the fermentation process?
Roy: Precision fermentation is really a high tech way of controlling the conditions around some micro organism, typically a bacteria or yeast, which you’ve bred or selected or in some other way modified to make a compound interest.
Now, what’s very interesting about this approach is that the compounds that you make are produced by using biology. They are natural, and they behave exactly the same way they would if you were to extract them from a plant.
They have the advantage of being produced at scale in a controlled environment, which means you can really guarantee purity, consistency, and scalability.
Now, this technology was really pioneered by a company called Genetec in the 1970’s. The first big step on the global stage was with Eli Lilly in the 1980’s, who, for the first time, produced human insulin from a bacterium, in fermentation, which was a lifesaver for diabetics.
Until then, we were using insulin that was extracted from the dead bodies of pigs, and, unfortunately, that was not identical to human insulin, so all kinds of other health issues emerged. For the first time, being able to produce human insulin in this way, really was a boon for diabetics.
More recently, this process has come into notoriety with companies like Impossible Foods and Beyond Meat, who are using a fermentation process to produce an ingredient called haem, which is like the precursor of hemoglobin in the blood; it’s what makes blood red, but it turns out it also is what makes meat taste like meat.
Now that they’ve discovered that interesting fact, they’re producing it without having to grow and kill animals —all using a fermentation process.
Ultimately, this is a technology base that really is coming to the fore. It’s part of the larger macro trend that is happening at the moment. We’re entering the century of biology.
Technologies like fermentation will play an important role in helping us achieve a sustainable and environmentally responsible society that is able to produce ingredients that we otherwise get from petrochemicals, or through intensive agricultural processes.
These fermentation technologies have a much smaller environmental footprint. We’re just part of that revolution here at Creo.
CLR: That is a great revolution to be part of because it’s very interesting the way fermentation requires less water and less energy. Can you talk about the CBGa produced by Creo and why you chose CBGa to focus on for this first full scale batch produced?
Roy: CBGa is the mother of all cannabinoids. It’s the cannabinoid from which all other cannabinoids are derived. It plays a really important role in this whole bio process.
Unfortunately, it’s still pretty rare, generally because in most normal hemp and marijuana plants, it gets converted to either CBD or THC.
We felt that CBGa is a really important cannabinoid compound that has huge potential, which is still under-exploited because of its relative rarity.
I know that with time people will breed plants with higher levels of CBGa, but it’s still on the rarer side of the marketplace, so that’s why we felt there was a unique opportunity here to bring CBGa to market.
It is quite difficult to preserve the acid form of the cannabinoids as they decarboxylate into the neutral forms such as CBG, CBD and THC in the plant extraction process.
With the fermentation approach we have, we can do things in the purification which preserve this acid form. Therefore, we can actually bring two products to market for the price of one as we can also choose to heat that CBGa we make and convert some of it CBG.
CBGa is interesting because the acid forms tend to perform differently to the neutral forms of the cannabinoids.
For example, THCa is actually non intoxicating; you can’t get high on it. It is believed amongst some researchers, not least of whom is Professor Mechoulam —the pioneer of cannabinoid science— that the acid forms actually have enhanced therapeutic properties compared to the neutral forms.
CLR: Tell me a little bit more about what you found in this journey, regarding these enhanced therapeutic properties.
Roy: I’ll be honest with you, we are singularly focused on bringing these ingredients to market, rather than doing the fundamental science on their efficacy and therapeutic capabilities.
We see our role as creating abundance around all of these cannabinoids, which then seed the industry and the research and all the things that go around this.
Being a science guy, I’ve kind of geeked out on all the sciences out there, and if you go on our website, we’ve got a very useful education hub, where we’ve pulled together all of the science around CBG, and to some extent, other rare cannabinoids.
There’s a growing body of research out there that shows that CBG has different properties to CBD. It’s being nicknamed “the skin color” – because it has wonderful properties for beauty, anti-aging, skin inflammation, irritation, and other kinds of skin conditions, so that’s where we think CBG can each really play a unique roles.
CLR: You’re right. I think that CBG as an ingredient by itself is just at the cusp of a very nascent industry and yet, this is what Creo is all about now.
Roy: Yes! To some extent, I would say that the way I think about this is that we are simply at the tip of the iceberg. The real market is still to come.
I fully respect all of those who have pioneered the industry to date, but the real scale is still to come, when the big consumer packaged goods companies get on board. What we’ve seen so far is really only the beginning of what I think will be a world in which cannabinoids literally touch every household in some form or another.
CLR: I agree that the minor lesser cannabinoids —or the lesser known cannabinoids— like CBN CBG, and CBC are going to start becoming more and more household names and household brands across the globe, as you mentioned.
Roy: We’re starting with CBG, but we plan to bring a portfolio of different cannabinoids to market, ones that really enable this cannabinoid revolution that I think is just waiting to happen.
CLR: Since you did work with a team of people on this, because obviously it was not just an individual effort, what advice would you offer to other leaders in the space to help their teams and brands thrive, on whatever project they may be working on?
Roy: Keep in mind that the closer we get to this being just an ingredient, the broader the reach of these products, and the more this is normalized to just another ingredient.
We all understand and respect the history and the origins of this, and how the real movement of pioneers fought against the scheduling of cannabis. But the next stage is, in my opinion, that this will become just another ingredient, no stigma.
When it becomes boring and unremarkable, and not very avantgarde, that’s when it really hits its potential.
In a way, that’s kind of how we want to think about this: too much choice is confusing to consumers, and it’s difficult for companies to maintain focus to make their idea or plan a reality.
Focus on making that goal or idea a reality and everything else will follow.
CLR: Excellent advice, because we’re far past the age of stigma being attached to cannabis. As you said, it can just become another normalized ingredient —a move which would not only benefit Creo, but also the whole planet if we could truly open up the fields of research and technology in this industry. This is just the tip of the iceberg. Anything else you’d like to add?
Roy: I would say that we don’t see what we’re doing at Creo as competing with the plant. I believe that there will always be a market for cannabis, because the cannabis plant is a unique cocktail of hundreds of different compounds, all together, which give it a unique flavor, smell, and experience. Bottom line, the product is not going away.
However, there will be other applications where we’re looking for the cannabinoids as just another ingredient, without caring where it came from. Like sugar in my. You’re happy as long as it’s in there.
That’s where I see biotechnology really coming into play, but actually needing to work very much in synergy with the plant people, to increase awareness, and grow the market for each other. So I really don’t think of the two approaches as competing.
CLR: That’s the key here: collaboration and complimentary behaviors, not competitiveness. I think that synergy you’re speaking of spreads into so many areas that the cannabis plant touches on.
Roy: Actually there’s even ways for the two approaches to work directly together.
One of the real challenges with plant production is variable consistency, particularly around these minor cannabinoids. One of the reasons that cannabis and hemp plants produce cannabinoids is actually as an adaptation to dealing with harsh conditions, in particular ultraviolet light. So. the composition of cannabinoids in the plant is strongly affected by their growing conditions, and in particular, the minor cannabinoid percentages, which can really jump all over the place from harvest to harvest, from plant to plant, from strain to strain.
Fermentation produced cannabinoids, and especially rare cannabinoids, actually allow producers to make cannabis extracts with a consistent profile of these rare cannabinoids by essentially adding some in, in order to bring the levels up to a consistent level.
I can see many opportunities for the two fields to work together by allowing producers to produce extracts that have consistent profiles.
CLR: There’s a lot of opportunities to allow those producers to produce the extracts and see that consistency, because I think consistency is the major key here in this space that we’re talking about.
Roy: I mean why is McDonald’s so successful? It’s not because they produce great food, we all know that. It’s because you go into McDonald’s, anywhere in the world and you know exactly what you’re going to get.
CLR: Exactly. You just know, every time you go in, consistency and hopefully safety as well.
Roy: Safety. That’s an important point too.
CLR: I think that’s lost a lot of times when people are talking about cannabis the plant, or any of the minor cannabinoids — that consistency and safety get lost in the fight for accessibility.
Do you feel that they all three can kind of go hand in hand: consistency, accessibility, and safety? We always talk about accessibility, but I don’t feel that they’re mutually exclusive. What good is accessibility if we don’t have that consistency and that safety?
Roy: Right! There are a number of key factors here.
- Firstly, consistency allows you to have a predictable product experience. It allows the product manufacturer to put out a consistent experience for his customers. Consistency is really important, particularly as you move more and more into minor cannabinoids.
- Secondly, alongside that comes purity, because you could be consistently impure. That’s not a good thing. You want to be consistently pure, meaning that you don’t have impurities in the profile and the product is the same every time. What’s in there is not going to be dangerous or harmful to your health; it’s typically the impurities that are really the focus we’ve seen with cannabis. With cannabis, there are risks around fertilizers, pesticides, herbicides, or other substances making their way into the final product. So that’s the second pillar.
- Thirdly, accessibility, or as we call it, abundance. It’s about making it available. Accessibility comes from availability. It needs to be cheap enough that people can afford to make products with it and customers can afford to buy it. Generally speaking, the lower the price of the product hits the more applications open up for it. If CBG was cheap enough, you could use it as a daily household item.
This effectively comes into play with price points – that’s number one.
Number two is channels to market, and this is where you can get these products into mainstream channels and you’re going to reach more people.
It’s got to be safe, and it’s got to have a consistent product experience, yes, and you’ve got to have as broad a reach as possible.
CLR: That’s where availability or abundance comes in because of the supply and demand. If you’re trying to provide a product as an everyday ingredient and we’re trying to normalize it, we must have that availability and abundance that you’re talking about.
Roy: Exactly. I’ve been in the business of commercializing world class science for 25 years.
Unfortunately, in the world that we live today, most great inventions never make it into the real world, and it’s a tragic loss.
My particular focus has been on science and scientific innovation, but crossing the chasm between potential and actual realization is a huge deal.
It’s one thing having a compound like CBG or CBC or THCV, that has massive potential to improve people’s lives; however, if people don’t actually get access to it, that potential is for nothing.
Ultimately, the job that we — and everyone in this industry— has to do now is to find a way to get the benefits of these compounds to the largest number.
To do that, as I said, we need to access the mainstream channels and we need to have a price point that is affordable —not only for people in first world countries and rich, developed nations, but all over the planet.
CLR: Right. I think that’s exactly the direction we need to go because we need to think of cannabis as a global endeavor, and it sounds like you at Creo are doing a great job of that. Thank you so much for your time.
Roy: Thank you very much for the great questions.
Creo is an ingredient company that produces rare and novel cannabinoids using the age-old natural process of fermentation, coupled with cutting-edge technological innovation. Founded in 2016 and based in California, Creo’s mission is to enable the creation of cannabinoid products that help people everywhere while doing less harm to the planet. Creo’s technology partner and major shareholder is industry-leading biotech firm Genomatica. To learn more, visit www.creoingredients.com.
Genomatica is harnessing synthetic biology to remake the world of everyday products and materials through the power of clean manufacturing. The company is developing more sustainable, higher-performance key ingredients for everyday products, using plants and waste rather than fossil fuels or other non-sustainable sources like palm oil. Genomatica has already commercialized ingredients to make better plastics, spandex and personal care products, and is working on nylon, household cleaners and more. To learn more, visit www.genomatica.com.