This Company Figured Out How to Make CBD from E. Coli - Culture | MERRY JANE
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This Company Figured Out How to Make CBD from E. Coli

InMed Pharmaceuticals is making bacteria-bred cannabinoids “identical to those found in nature,” sans chemicals or even cannabis.

by Randy Robinson

by Randy Robinson

Lead image via iStock Photo. All other images courtesy of InMed Pharmaceuticals

In 1978, the biotech firm Genentech made a revolutionary breakthrough: they genetically modified the bacteria E. coli to produce human insulin. Diabetics require the insulin protein to absorb blood sugar into tissues, including the brain; without insulin, they may slip into a coma and die. Prior to 1978, insulin for diabetic patients came from pig or bovine pancreases, a costly, inefficient, and inhumane method for procuring an otherwise life-saving molecule. Insulin was much more expensive before it was derived from genetically modified E. coli, and the risk of running out of supply always loomed over the heads of patients prior to its mass production via bacteria. This technology was subsequently licensed to Eli Lilly, who built a $1 billion manufacturing facility to meet the needs of diabetic patients worldwide.

Today, one company has taken this idea of producing chemicals from E. coli and translated it to cannabis. InMed Pharmaceuticals, a Canadian firm, recently announced they have manufactured CBD and many other plant-based cannabinoids without ever planting a single cannabis seed.

Eric A. Adams is the CEO of InMed. A former chemistry student, he's spent his entire professional career at cutting-edge biotech and pharmaceutical companies around the world. "When I saw the technology that InMed has, I knew right away that it was going to be something big," says Adams. "The science behind the company is a real game-changer." MERRY JANE spoke to Adams over the phone to find out more about how InMed's technology works – and what they plan to do with it.

This interview has been edited for length and clarity

MERRY JANE: Can you explain how this technology works?
Eric A. Adams:
There are three pillars to our technology at InMed. The first pillar is a bioinformatics database we use to match the potential therapeutic effects of each individual cannabinoid with the respective diseases. We can also go backwards; take any disease, and we'll decipher if there's a cannabinoid that is active against it. That's one of the foundations we have that allows us to expedite our early-stage research and target identification.

The second pillar is the biosynthesis. If we look through the list of 90-plus cannabinoids, and we determine, "Hey, number 85 may work against prostate cancer," that's interesting, but no one can economically make number 85, and you can't extract it from the plant because it's in such a small amount – it could cost you hundreds of thousands of dollars per gram.

Also, with many of these cannabinoids, you can't synthesize them. You can't go into a chemistry lab and just start mixing things until you get them, because there are so many different isomers of some of these compounds. It's difficult to isolate the right isomer [the correct molecular shape that is biologically active].

InMed has created a fermentation process where we can manufacture any one of the over-90 cannabinoids, and we think the cost is going to be very competitive with whatever else comes along. The final cannabinoids made with this biosynthesis process are identical to those found in nature. This really is the pathway to opening up the entire spectrum of cannabinoids to be looked at in terms of their therapeutic value.

The third pillar is our drug development programs – led by INM-750 (epidermolysis bullosa) and INM-085 (glaucoma). We have several other drug candidates in our pipeline for indications such as pain, neurodegenerative diseases, cancer, and others.

How does the biosynthesis for cannabinoids happen?
It's a pretty complicated process that we're working to make easier. You have the specific gene sequence that encodes any one of these given cannabinoid compounds. But you have to fuse it with other gene sequences so the E. coli can actually read it, and so you can also maximize the over-expression [over-production] of these cannabinoids in the bacteria itself.

What we've done is recreate all the different plant biosynthesis pathways inside of the E. coli, so our products are identical to what the plant makes, which is important from efficacy and safety standpoints. There are no additional isomers produced by our technology. The gene we insert only produces the cannabinoid isomer made by the plant.

Besides economics, what other advantages does InMed's technology offer?
Any time you're involved in an agricultural undertaking, you have a lot of limitations on the scalability of what you're doing. Not only do you have to buy more property, you have these plants exposed to the elements – grown outdoors or in a greenhouse – and you have all these pesticides you have to use to ensure a high-yield crop. The pesticides can treat for bugs, they can treat for other plants, they can treat fungi – and there's a whole list of things you have to protect against when you're a grower, and you're trying to isolate your cannabinoids from plant material.

All of those are real limiting factors, and you can't underestimate the role of pesticides. Every jurisdiction in the world has strict regulations for pesticides that are used on plants meant for human consumption. You're going to be limited in your exportation ability of these plants, because in some countries you're not allowed to have any trace of any pesticides.

These are some of the major issues facing cultivation, and InMed's biosynthesis process doesn't have any of these. We can scale our operation as big or as small as we need. We can make any of the 90-plus cannabinoids at an incredibly low cost. It's a superior process in many ways compared to other biosynthesis approaches, and especially against cultivation.

How do you plan to sell these E. coli-derived cannabinoids? Will these be sold as research chemicals, or infused into products for consumers?
The reason we started the program initially was that we wanted to unlock the potential of all these minor cannabinoids for pharmaceutical applications. If you're looking at THC or CBD, there are lots of sources that are plant-derived where you can get those. But once you get past the few prominent cannabinoids like THC or CBD, it gets prohibitively expensive. We started this program just for our own research purposes, so we had a low-cost supply of cannabinoids we could use for our pharmaceutical products.

But now that we have established this process and are starting to scale it up, we've been approached by a lot of companies who are interested in either buying the technology outright or accessing it, where we would become a supplier of raw materials for their products. I think, ultimately, this technology may represent a stand-alone business opportunity. As it evolves, we're going to have to seriously look at that opportunity.

What cannabinoids can InMed's E. coli make?
We won't divulge which cannabinoids we have made, but it's important to know that there's four different branches of the cannabinoid family that are in the biosynthesis process. We've been able to establish that we can manufacture any of those four "gateway" cannabinoids that lead to the differentiation of the other ones. We're well positioned to manufacture any of the cannabinoids that occur naturally in the cannabis plant.

When do you anticipate these cannabinoids will hit the market, either B2B or general sales?
The first goal is to have them biosynthesized for our own internal R&D purposes, and that will take place over the next year. We want to be able to manufacture enough research-grade material to meet our own research purposes. I think over the course of the next year, we're going to be deciding exactly how we want to ramp this up from a commercial standpoint. A lot of decisions will be made based on the research outcomes but also what we anticipate our needs will be, and certainly as we learn more about the market potential.

Canada is one of the few countries that can export its cannabis outside of national borders. Will your cannabinoids be exportable as well?
Every country is going to be different regarding how they control cannabinoids. In several countries, if it's not THC, the level of control is much lower. Every jurisdiction is different, and they each have different laws. In Canada, all cannabis is going to be completely legal as of July 1, 2018. So, I don't think there's one set answer as to, "Can we move these compounds from one jurisdiction to another?"

One of the things about InMed is that we do not use THC in any of our products. THC does a number of incredibly unique and interesting things in the human body, one being its psychoactivity. When we treat someone with a specific disease, it's not our goal to get them high, it's our goal to treat their underlying disease. What we found in our research, wherever THC is active, there's probably another cannabinoid that's more active and doesn't have the side effect [of psychoactivity].

And that's really where we think the industry needs to go. CBD has a vast array of effects on the human body, and it's not psychoactive. So why all the controversy? It's a topic I'm sure your readers are well educated on.

Do you believe Canada's lax regulations regarding cannabis has made research at InMed much easier?
Cannabinoid science has come a long way in the last decade. GW Pharma has paved the road for companies to move into the area and establish new therapeutics using cannabinoids. There are some jurisdictional advantages to being in Canada, but there are some drawbacks as well. For instance, there are not as many patients here as there are in the US for running large clinical trials. But, I think the regulatory pathways are a little more defined in Canada, things as simple as moving research products from point A to point B here and in other jurisdictions like Europe and Australia and Israel make it a little easier to conduct research.

I think the US will turn a corner. With the right regulations in place, you're going to see the cannabinoid sciences take off in the US in a big way, as well.

For more on InMed Pharmaceuticals, visit their website here

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Randy Robinson

Based in Denver, Randy studied cannabinoid science while getting his degree in molecular biology. He writes about science, pot, politics, and pop culture. Find him on Twitter @Randy_Robinson_ or Facebook @RealRandyRobinson



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