San Diego, California

Co-founder and CEO Roy Lipski foresees his company’s fermentation-based technology supplying cannabinoids on a mass scale to Fortune 500 companies.

Photo courtesy Creo

THC, CBD, and other cannabinoids traditionally come from cannabis plants, starting with a seed or a clone. After harvest, companies extract cannabinoids from the plant material by means of a solvent — typically ethanol, carbon dioxide, or butane. From there, the oils can be further refined into isolates of single molecules, such as CBD, before being added into a variety of health and wellness or — as in the case of THC — recreational products.

But Lipski proposes totally bypassing the cultivation of plants. Instead, Creo will be using fermentation, in order to manufacture a host of legal cannabinoids. “It uses significantly less land, less water, less electricity, fewer pesticides and herbicides and other chemicals,” he says. “We supply cannabinoids in a way that is suited for mass-market applications, and in a way that causes less damage, less harm to the environment than traditional ways of extracting cannabinoids.”

For now, Creo (Latin for “to create”) is focusing on manufacturing some of the “rarer cannabinoids,” such as CBG and CBGA. And here’s how the company intends to produce large amounts of them: By taking the enzyme responsible for producing, say, CBG within a cannabis plant, and placing it within what Lipski calls a “proprietary bacteria strain,” through the use of metabolic engineering. Then, the CBG-creating bacteria will replicate in fermentation tanks within an industrial manufacturing setting, which Lipski likens to “a high-tech brewery.” After that, “there are a number of subsequent steps that are involved in separating and purifying the cannabinoid out of the, sort of, ‘soup’ that is the final product of the fermentation,” he says.

Lipski would neither confirm nor deny whether the proprietary bacteria strain that the company is utilizing is E. coli, as indicated within a report published by Raymond James called “Biosynthesis of Cannabinoids: Vanguard of the Bio Revolution.” (Creo’s primary investment partner, Genomatica, has developed a variety of products using E. coli, and the EPA has trumpeted Genomatica’s use of E. coli to make a cosmetic ingredient as “green chemistry.”)

Photo courtesy ExxonMobil and Genomatica

In terms of potential yields, Lipski says that growing hemp outdoors produces 0.5 percent by weight of CBG, whereas by using fermentation, Creo “can produce 5 percent by weight in 48 hours.” He adds, “You’re probably reducing the space requirement by a thousandfold: How much land you would need [for cultivation] versus the land for the fermentation facility?”

Lipski calls the CBG that results from fermentation “a natural ingredient, because it’s produced using life, using an organism — and absolutely identical, indistinguishable, from what is made in the natural plant setting.”

Additionally, the industrial method Creo employs — “the application of synthetic biology to therapeutic natural product biosynthesis,” as the publication Advanced Drug Delivery Reviews describes it — is becoming more common as a manufacturing practice. Lipski says of biosynthesis: “We make many of our vitamins this way. We make a host of medicines this way. We make many fragrances this way. We’re just bringing that established technology to the cannabinoid space.”

Who does Lipski see as customers for Creo’s CBG? For one, there could be the existing cannabinoid market, which might return isolated CBG — the “mother cannabinoid,” which converts into THC and CBD within the plant — back into hemp-based wellness products. And given CBG’s reported skin-moisturizing, antidepressant, and anti-inflammatory properties, there’s potential for its use by Fortune 500 makers of consumer packaged goods, in addition to nutraceutical or pharmaceutical companies.

But why would a major brand choose CBG produced by fermentation rather than cultivation? Lipski says, “If a big company like Procter & Gamble [or Johnson & Johnson] wants to put a cannabinoid in a toothpaste, they need to know there’s always going to be that ingredient available in the quantity that they need, at the price they can forecast, and with the purity and consistency that they demand in formulating a product.”

Photo courtesy ExxonMobil and Genomatica

Lipski, who studied Natural Sciences at Cambridge University, is a self-described “science entrepreneur.” who started an AI company in the ’90s. Then Lipski had what he describes as an “aha!” moment in 2015, when he realized that cannabinoids could theoretically be manufactured through biosynthesis.

Working with Dr. Ramon Gonzalez at Rice University in Houston, Lipski developed a proof of concept in the lab. Genomatica — a San Diego-based biotech company that develops industrial bioprocesses for customers — has been lending crucial assistance, in order to scale up production, and is the largest investor in Creo.

After a few years of R&D, Lipski says Creo “came out stealth mode in September [2020],” and expects to have its first CBG cannabinoids available by the end of Q1 2021. The company will manufacture cannabinoids at an undisclosed contract manufacturing facility in the Midwest, which Lipski says is cGMP-certified and FDA-registered.

CBG will just be the start. “We will be expanding our portfolio to include a whole host of rare cannabinoids over time — CBC, THCV, CBN, CDL. Those are the ones on the radar, right now.” He’s particularly intrigued by the potential of THCV for “mood stabilization and weight loss — it’s an appetite suppressant.”

“We’re working to be an enabler — to bring the benefits of this amazing class of compounds called cannabinoids to every household,” Lipski adds. “And we do that by taking the supply chain of cannabinoids out of the agrarian-agricultural landscape and into the 21st century modern world.”

Challenges: “The biggest challenge for us is education — having to create the market for these rare cannabinoids,” Lipski says. “It’s a chicken and egg situation: Because they haven’t been available, there hasn’t been a market; and because there hasn’t been a market, they haven’t been available.”

Photo courtesy ExxonMobil and Genomatica

Opportunities: “Our ambition is to help cannabinoids touch every household,” says Lipski, via relationships “with large multinationals, who can really create and get product out to large numbers of people.”

Creo has a developmental head start in comparison with a handful of other companies which are seeking to utilize biosynthesis to produce cannabinoids, according to the previously cited Raymond James report.

Needs: “I would say we’re always looking for good people,” says Lipski. “We’re building a team, we’re growing.”

He adds, “We’re blessed to have good amounts of capital.” So, the primary needs are “people and time,” as well as, “Good luck — always need good luck!”