Whether or not you partake in the $30 billion legal cannabis market, the legalization of cannabis in parts of the U.S. and Canada has helped to destigmatize and legalize the use of the cannabinoid family of chemicals for scientific research. This is opening the door to exploring its therapeutic potential for inflammation, pain, anxiety, and even cancer.
In the race to find the next great product in this family of plant molecules, Berkeley-based Demetrix announced today that it has commenced 15,000-liter demo-scale fermentation production of CBG, the first rare cannabinoid it will take to market. The company sees this as a big step towards the commercialization of rare cannabinoids for a range of safe, effective, and legal health and wellness products, from pharmaceuticals to skincare.
Demetrix CEO Jeff Ubersax says that CBG (also known as cannabigerol) is among the first cannabinoids in the chemical pathway that plants make. “This is a cannabinoid that most of the other cannabinoids are derived from,” says Ubersax. Based on its early testing of the molecule, Demetrix believes CBG has some interesting potential applications beyond current uses.
Rediscovering cannabinoids
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Most of us have heard about only two cannabinoids. THC is the psychoactive compound used for mind-altering recreation. CBD is a non-psychoactive cannabinoid that is thought to reduce pain, anxiety, depression, and a handful of other conditions.
CBD and THC make up most of the cannabinoid content in hemp and marijuana plants, but there are over 100 other “rare” cannabinoids found in these plants as well, present in such small quantities that you’d have to replace all the crops on Earth with cannabis to get enough substance to study.
That’s where companies like Demetrix come in. Using advances in computation, automation, and gene editing — a field we call synthetic biology — Demetrix is able to put the genes in baker’s yeast that enable it to ferment these rare cannabinoids in quantities that are sufficient to study.
By making these 100+ cannabinoids available, Demetrix and others are in essence creating a whole new family of natural potential therapies that are waiting to be discovered.
“The founding mission of Demetrix is to use science to make the world a better place,” Ubersax says. “We are producing small amounts of a number of different cannabinoids and testing them to determine what they are good for and whether they're going to be safe and effective for all sorts of different applications.”
Scaling up the technology
If there’s one aspect to Demetrix’s story that is most compelling, it’s how this relatively small startup has managed to build a fermentation platform to produce such a high volume of product in such a short period of time. Some of the more established players in this space have had a lot longer to get to where Demetrix is today.
“I think the big deal is that we've basically gone from zero to 15,000 liters in just under three years,” Ubersax says.
Ubersax believes that one of the keys to Demetrix’s success in scaling up so fast is that it began with the end in mind. Its engineers designed a production process for the 100,000-liter scale it ultimately wanted to achieve, then in a sense “scaled down” the process by orders of magnitude to demonstration and pilot scales.
At the 1,000-liter pilot scale, Ubersax says there’s enough volume of material that you can run through a more or less complete, miniaturized version of your full-scale production environment. This is where Demetrix did most of its testing. The purpose at the 10,000-liter demonstration scale — where Demetrix is now — is to finalize your microbial strain and ensure that fermentation and purification will scale to the next level.
Ubersax says you definitely do not want to test stuff at commercial scale, noting: “It's very expensive to be doing experiments at 100,000 liters.”
The business approach
In thinking about what kinds of cannabinoid products to develop, Ubersax shares three criteria. First, the compounds have to be safe, effective, and different from each other. Second, they will consider how difficult the molecule is to make. And third are the regulatory considerations.
“There’s a pretty complicated regulatory framework that's out there,” Ubersax says. He says Demetrix’s goal is not to try to disrupt the regulatory process, and he appreciates that regulators are human health and wellness. Instead, he says, “It's really, really important to work with [regulators] to be transparent and open about what we’re doing, and work with them to bring these molecules to the market.”
From a market point of view, what makes cannabinoids interesting is that they are both a high commodity product and a high-value product. They are used in health and wellness products, from pharmaceuticals to skincare.
“The best opportunity for any industry is to find things that have a high average selling price and where you can sell a lot of it,” says Ubersax. “Cannabinoids fall into that bucket, really, really well.”
The future is bright for the small and mighty
Ubersax is enthusiastic not just for Demetrix and the cannabinoids industry, but for all of synthetic biology.
“We are one of a bunch of other startups in the space that are, I would say, in a different game now,” he says. “Small teams can do a lot more than we used to be able to do. The technology is more mature. It’s still hard, and there’s still a lot of investment needed, but it's not on the scale of billions of dollars anymore. I’m really excited to see what this field is going to be able to do over the next couple of decades.”
Follow me on Twitter at @johncumbers and @synbiobeta. Subscribe to my weekly newsletters in synthetic biology. Thank you to Kevin Costa for additional research and reporting in this article. I’m the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta conference and weekly digest. Here’s the full list of SynBioBeta sponsors.
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