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Ep #14 Transcript | Jeff Ubersax: Demetrix & Bioengineering Rare Cannabinoids

Full episode transcript below. Beware of typos!

Nick Jikomes

Jeff Ubersax, thank you for joining me. Great to be here. So can you start off by just telling us a little bit about your scientific background? And then what you're doing now? Sure. So

Jeff Ubersax 2:21

I have a PhD in biochemistry from the University of California in San Francisco, which is about two blocks away from where I am today, from which is in my house in San Francisco.

And, you know, I've always been fascinated with, you know, how cells do stuff and and how biology can make the world a better place. So I was at UCSF for a number of years for a PhD, and then went to Stanford, where I was really working at the interface between biology and how you can use kind of some of the new technology that's out there in DNA sequencing in automation tools and computing tools to make the biology stuff go a lot faster. Because ultimately, you know, I think what got me into science is that, you know, a lot of really cool things and great things for the world can happen with science, and how do you make science go faster, so that has more impact more quickly. And so pretty quickly realized that, you know, there was some cool science going on in industry outside of, you know, the academic world and knew a couple of the founders that a company called amorous bio technologies, and join them and boy in very early 2008, as a yeast strain engineer, and there was really interested in you know, how do you use yeast, which are super cool, to make products that the world needs and wants in a more sustainable way, in a more affordable way in a way that, you know, increases, you know, purity, safety, reproducibility, all the kinds of stuff that you want. And so it was there for a number of years, almost 10. And then one of the founders of amorous was Jay Keasling, he's a professor at UC Berkeley. They knew quite well. And he called me up one day and said, Would you like to have coffee?

And so had coffee with Jay and Jay said, you know, look, I have some really interesting results coming out of our lab on how you can get yeast to make this class of compounds called cannabinoids. I think it's really a great opportunity to start a new company and we'd love to have you come on board and what do you think? And so after a couple of weeks of agonizing said, Hey, this sounds like a fantastic new adventure. You know, it's an opportunity to kind of run a company and the way I thought it should be run and jump right into a class of, you know, super interesting compounds that, you know, they have, you know, a lot of opportunity to improve people's health and wellness and make the world a better place. And that's, you know, ultimately what, you know, Jay was in it for what I'm in for and what the matrix is about. So

The company that got started was called de metrics we've been around since September of 2017, at this point and are using yeast to make rare cannabinoids for all sorts of different applications in human health and wellness. And, you know, the more broad mission of the company is really to, you know, a lot of really cool and interesting and useful compounds are made in nature, in plants and other organisms that are present in really, really tiny amounts. And that through using biotechnology and fermentation, there's opportunities to make them much more available and useful throughout the world.

Unknown Speaker 5:41

So let's, let's talk about yeast. So what are yeast? And how do they How are they normally used by humans? Yes, great question. So he is Baker's, these same people using breadmaking, and beer making and winemaking. But they're also using a huge number of other products that people use around the world today. So Easter, these extremely cool microorganisms that people have been working with for, you know, over 100 years to this point. And so are you know, really, you know, their metabolism and genetics and genome and all that sort of stuff in the tools for editing them, and getting them to do new things are quite sophisticated and advanced. And so, you know, have been a focus of a number of companies, including ours for how do you put, you know, DNA from other organisms, right, this is one of the coolest things about biology to me was that, you know, DNA is universal. So DNA is like, you know, people call it the blueprints of life, right? It's really a string of letters of 80, G's and C's, that basically tell every organism how to do the things that it does, right and, and the cool thing about that is that you can figure out what parts that DNA do different things. And then you know, you can basically get that out of the organism or today, you can just order it, you submit an electronic file to somebody like twist or other companies, and they'll send you that string of DNA. And you can put it into other organisms, like yeast, and now there's yeast to the thing that the plant used to do. And so, you know, to give people a sense, like, you know, on the cannabinoid side, you know, yeast are tiny. So you know, some of the most beautiful structures that we've seen out of the plant world, or, in my opinion, at least, our trichomes, right, there are these, you know, beautiful kind of stocks have this beautiful globular head at the top. And they're they're full of oils, and all sorts of, you know, useful products that plants make, not just in cannabinoids, but a lot of plant products end up in the trichomes. And you can fit about 1000 new cells and every one of those trichomes, right, and so, one of the challenges with getting a lot of these rare natural products out of plants is that you need to grow a lot of that plant biomass to actually get enough of that product, to actually do stuff with it, even to study it to figure out what it does. And you know, you can imagine if you can take yeast that you know, where 1000s of them can fit in a single trichome, all of a sudden, you have an opportunity now to make a lot more of that product and make it a lot more kind of available for you know, all the things that need to happen to really understand what they do, and how they can be helpful to the world. Interesting. So, so yeast are single celled micro organisms. Yep. And basically, their job is in the world. And they've been used for, you know, 6000 years or more, to basically feed them sugar, and they produce carbon dioxide and alcohol. And that's how people have used them for a really long time. And, you know, they also make more cells. And so, you know, what we do basically, is change some of the DNA or put new things in there and modify some of the DNA that's in the cell to, to basically now take sugar, and not make ethanol, but make new products, right? And secrete them into, you know, the fermentation media that we grow them in, which is just, you know, like a nutritional broth. And then you can purify the product out of there at the end of the day, and, you know, in theory, be able to have, you know, higher purity products, more reproducible products, because you're not dealing with some of the, you know, other weather and rain and soil conditions of agriculture. So you can, you know, have more reproducible, more pure product at the end of the day. So the idea is yeast naturally eat sugar, and ethanol is a waste product. And we sort of just take that waste product, the ethanol and we use it to make out for beer and wine or use the carbon dioxide, right for your rising bread. Oh, yeah, as an example. And so you're saying that you guys can engineer yeast so that instead of producing ethanol and co2 as a waste product, they produce whatever you want, basically, that's the idea. And so, you know, that sounds super easy. It's actually really, really hard.

Jeff Ubersax 9:56

But basically, you know if you can understand how other organisms Like plants, or other microbes make products, then you know, what are the DNA parts that they need to, you know, instruct their selves to make those products, if you can identify what those DNA sequences are, you can recode them and put them into your yeast cell. And now that yeast cell will start making some of that product, right? Usually it's it starts at a very tiny amount. And it requires, you know, a bunch of work, and sometimes years of work to really get them to start making kind of commercially, you know, interesting amounts of that product. Right? So, at this point, you know, the world is probably made, you know, 1000 different compounds that plants make in yeast, right, but very few of them are not, you know, necessarily at the scale that you would want them to be at to make them kind of commercially relevant. Yeah, but, you know, that's really what there's a whole industry out there that some people would call synthetic biology or industrial biotechnology, that's really aiming at taking, you know, those T cells and making it so it's making you know, tiny amounts like milligrams to how's it, how do you get them to start making metric tons per year, which is what is really kind of necessary to make, you know, to have the impact on people in the world that kind of need to have

Nick Jikomes 11:14

it. So where the field is at, if I'm understanding is yeast cells, so Eastern SS can basically engineer yeast to produce any compound more or less, but they're not necessarily gonna produce that compound compound at a level at a scale that you want it. Yep, so all the work is, how do you get the yeast to produce a lot of something?

Jeff Ubersax 11:36

Yeah, and, and, you know, there's lots of, you know, things underneath that, but you know, and what I'd say to kind of put a little bit more nuance on it is that there's certain types of chemistry that, you know, people like synthetic organic chemistry is really good at. And there's another type of chemistry that biology is really good at. And the type of chemistry that biology does is oftentimes very hard for what the synthetic organic chemists do. Right? And so what most people are doing are trying to harness that chemistry of cells and the chemistry of life, you might call it to make, you know, the products that are coming from other natural organisms like plants, right, or other microbes, like antibiotics is another good example of where, you know, people are insulin is another good example, right? where people have those are molecules that would be very expensive to make through synthetic organic chemistry. But that, you know, organisms in fermentation can do really well, because the chemistry is just really fits the chemistry of the cell really fits well into making those types of products.

Nick Jikomes 12:39

And so are you guys focused on cannabinoids specifically?

Jeff Ubersax 12:43

That's where we're starting. Yep. And, you know, I think that there's just, it feels to me like a once in a kind of career opportunity. With cannabinoids, because there's kind of been a convergence of, of, you know, regulatory changes, as well as you know, some of the science that's happened to understand how do plants make these products, and the combination of those two things have really opened up, you know, a potential for a very, you know, interesting class of natural products that haven't been really available or well studied, to be, you know, to study them to say, What can they do, how are they different and so I should step back and say one of the things we're really focused on is the rare cannabinoids right? So the major cannabinoids, most people are familiar with is THC and CBD. The plant makes no more than 100 other cannabinoids that haven't, you know, been studied nearly as much, but that because they've been present at such smelt small, small amounts in the plant. So what we've done is, you know, basically made some of those and then you know, are working to understand Okay, what do they do? What is their safety profiles look like? What are their efficacy profiles look like? How are they? How can we use these things in everything from you know, skincare products to foods and beverages to supplements to even pharmaceutical ingredients to you know, improve people's lives?

Nick Jikomes 14:03

Interesting. So before we get into the specifics on the cannabinoids, one more question about the basic biology I have an what I presume is an engineering problem with with this whole area and engineering challenge that you have to get around. So the plants have evolved to produce these cannabinoids for their own purposes, they put them or they they secrete them from the cells at the top of the trichomes. And there my understanding is they're actually purposefully away from the other plant cells because these compounds can be toxic actually. So do the yeast to tolerate them well, or do you have to engineer the yeast to to play well with the cannabinoids? Yeah,

Jeff Ubersax 14:42

so it's a bit of everything, right? So that's a great question actually. So you know, a lot of the work that we do is to, you know, do two things. One is to kind of make the plant parts like the enzymes and proteins from the plant that we're using a nice work In the yeast environment, right, because a yeast is looks very different than the tip of the tricon, right, it's just a very different, it's an oily thing versus, you know, a whole cell in a fermentation media. The second part is that we're also trying to engineer the yeast cell to look a little bit more like the trichome, right, like the plant cell, so that, you know, you kind of then are approaching the problem from both ends, to then make enough product that it's commercially relevant. And one of the, you know, challenges that you say, sometimes those products are toxic to the cell, I think, you know, the nice thing about contaminants is they're not super toxic to the cell. And even if there are, there are certain types of, you know, fermentation processes that you can put in place that help, you know, relieve that toxicity. And you can also evolve yourselves to be more resistant to whatever toxicity, you know, those compounds are causing, you know, the one thing I'll say, with cabinets in particulars, they're not particularly Oh, you know, super soluble in water. So you don't necessarily in the fermentations, you don't necessarily build up a whole lot of kind of like soluble cannabinoid, it tends to kind of, you know, aggregate out of the fermentation broth and be with the cells in a way that's a lot less toxic likely.

Nick Jikomes 16:14

And so why did you guys pick yeast? Is it just because of the genetic toolkit that's available for yeast? Or there? Could you do this in other mics? So

Jeff Ubersax 16:23

there, there are, there are other ways to do it, there are other organisms that people are working with. The reason we've chosen yeast is, you know, a couple of reasons. One is, you know, the toolset has been developed over the, you know, the decades is really outstanding, and it makes the engineering part really, really a lot more easy than it was, you know, even 10 or 20 years ago, and much easier than it is for some of these other organisms. The second part is that the type of chemistry that kind of has to go into making cannabinoids are things that other people have had success doing in yeast, right? So the class of enzymes that that are the plant uses to make these products have been, you know, similar types of enzymes have been used in yeast to make similar types of products. And so you know, there are other people that are doing it, and Nikolai, which is bacteria, there's other people doing it and algae. And, you know, our bet is on yeast and and we think that because of the prior success in the toolkit, and yeast, it's it's the, you know, a great choice for going forward with this product, or these types of products.

Nick Jikomes 17:27

So, which, which can avenues Have you guys started making first? Yep,

Jeff Ubersax 17:31

so the first one we made is kind of a, it's called canavero, geral or CBG. And so the plant actually makes cbga, the acid form of that, and that's actually what the yeast makes, and then you can get decarboxylated. So we're making, you know, in some ways, we're making both cbga and CBG. I think that, you know, beyond that, you know, we've got other products that are kind of in the development pipeline. And, and those are, you know, other minor cannabinoids where, you know, I think where we see them to be different than CBG, and providing different types of, you know, effects or impacts on people and what different applications they might be useful. And so that we're not necessarily just making you know, another CBG like molecule that does the same thing. Because it's not actually what the world needs the world, you know, we should be exploring the diversity of the plant and finding the parts that are doing different things for people so that we're bringing, you know, the most benefit out of the plant into people's lives. That's kind of how we think about

Nick Jikomes 18:30

it. And do we what do we what do we know about CBG? And cbga? At this point,

Jeff Ubersax 18:36

yep. So not as much as the world probably would like, or would need. And so you know, this is the issue with a lot of these rare cannabinoids is just, you know, first because the plant was a scheduled substance for so long, it was very hard to do some of the fundamental science of what do these things do. The second part is that it's very hard to get access to a lot of the rare cannabinoids because they aren't very, there's not much of them in the plant, and the chemistry to make them it's hard and expensive, like the human chemistry, right. But synthetic organic chemistry is hard and expensive to do. And so, you know, I think it's only in the last couple of years with kind of some of the changes on the regulatory front with the rare cannabinoids that are non psychoactive, that you know, there's an opportunity to use a combination of biology and chemistry to really start exploring what all these other cannabinoids kind of do, right? And so we've invested a lot of our own time and resources in doing the type of actual hardcore science that you need to do to understand what these things are going to do in your body and on your body. Right. And, and so what are their safety profiles look like? What are the efficacy, you know, where might they be useful in different types of products. And so some of these things are things like you know, G protein coupled receptor assez, or ion channel assez. To figure out you know, what type of receptor Are these things acting on in your body and how are different cannabinoids hitting different receptors in different ways, so that you can then you know, and that gives you both a sense of what their, you know, safety profile looks like because there's certain, you know, receptors in your body that you definitely don't want to be touching because they'll do really bad things. And there's other places where you'd say, Okay, this is, you know, looks like it's hitting a bunch of, you know, receptors that might be useful in things like inflammation or in things like, you know, anti inflammatory is one of the big areas that we're looking at. But you know, there's a whole bunch of other ones as well that we're, we've been investigating.

Nick Jikomes 20:42

So So you guys are doing like the receptor binding essays and all that stuff as well.

Jeff Ubersax 20:46

Yep. Because you know, our floss. Like, I think that that's really, you know, sometimes you'll hear people talk about, like, the cannabinoid space is kind of like the Wild Wild West. And know, to some extent, that's true. And what's driving that is that there's not really a good understanding of what these things do and what they can do. And that the science, our philosophy is, like, No, we need to be using the science to understand what these things are, what they are good for, you know, that they're safe, to be able to have impacts that we think that we want to bring to the world and the world ultimately needs. Right so and interestingly enough, it's also very consistent with what you know, a lot of the regulatory regulatory regulators of this space want to see as well. So we work very closely with the FDA as an example to have, you know, to help them understand, you know, what we're doing, and help them understand how, you know, these products like cannabinoids in particular can be regulated under existing laws for how and regulatory frameworks for how, you know, natural products make their way into all sorts of products, whether it's consumer products or pharmaceutical ingredients, and you know, they are super important organizations right, because they're there to protect human health and wellness and and to you know, they've been very excited to see people actually doing the hardcore science and willing to work with them through their existing frameworks to do all the stuff that needs to be done to show these things are first safe for skincare applications like topical applications and then ultimately adjustables whether it's in the pharmaceutical side food and beverage or on you know, kind of supplement side they're excited to see people actually willing to engage with them and do that hard work to you know, really understand what these things do and what they're good for.

Nick Jikomes 22:41

And so because you guys are focused on the the minor cannabinoids, and you're not focused on THC, does that mean that you're largely free of the red tape that would come from doing anything with schedule one substance?

Jeff Ubersax 22:53

Yeah, so you know, and we started in 2017, kind of before the farm bill and so we also have a registration with the DEA right to work with schedule one substances because a lot of these things were schedule one substances A while back. And yeah, I think that you know, the, the change in the regulatory has been with the Farm Bill, that if you're making you know, cannabinoids, or Phyto cannabinoids that are, you know, have a THC content less than point 3%, then you're falling outside of the schedule on substances, aspect of, you know, THC in cannabis. And so it does free up a lot of that, you know, it's just much more, much easier to work with them and, you know, be regulated as other types of ingredients would be regulated through the FDA.

Nick Jikomes 23:41

And to the extent that you can talk about it, what, what other cannabinoids Have you started to look at, you mentioned, and I really liked the strategy you mentioned, you know, starting with CBG, but then also specifically trying to look at cannabinoids that are very likely to have relatively distinct pharmacological properties. Have you found any interesting?

Jeff Ubersax 24:01

Yeah, so I'll speak in general terms first. So you know, the way that most of these molecules have an impact on your body is that they bind different receptors or other proteins in your cells. And you know, what kind of dictates which of the things they're binding to is the shape of the molecule, right? So in general, we look at kind of different scaffolds that cannabinoids make, right? So there's like the kind of natural Endocannabinoid scaffold which is like these long chain kind of loopy things. And then there's, you know, CBG, which has like a phenolic ring and then two tails hang off. And then there's, you know, CBD and THC, which are, you know, ring structures that are sometimes double rings. And then there CBC as well, which has, you know, another type of double ring structure. And those we kind of classify as different scaffolds, right. And so, those different scaffolds are a big part of what drives how they interact differently in your body, right? So when we were We're looking at it, you know, a couple years back, we said, you know, like, what are the kinds of different scaffolds that we should be thinking about? And how do we, you know, think that we might be able to approach making them through, you know, fermentation and biotechnology, and and then, you know, test them to see what they're, they're good in different for. So, you know, the structures is part of what we use in deciding to go after the products, but ultimately, we make them and then we test them in some of these more functional assays like gpcr receptors, or ion channels or other kind of functional acids, like in vitro functional assays to say, you know, how are they the same? And how are they different? And that kind of drives? Then we go, okay, we kind of think about, okay, how hard are these things to make, and if they're, you know, super duper hard, and they require, you know, a couple different, you know, 15, different enzymatic steps, then a bunch of those enzymes aren't identified from the plant on how those things are made, we say, you know, that would be really hard for us to approach can be really expensive. So maybe we'll leave that one for later. And focus on ones where, you know, keeping the end in mind, they have to be affordable, and something that we can make, to have, you know, to bring them to the market. That's kind of one of the things that we need to think about. So that's one of the first kind of filters for how we think about which ones to go after. And then after we have, you know, that we say, Okay, and then what do they actually do? And how are they the same or different, we try to find ones that are different from each other that still have, you know, interesting applications in, in human health and wellness. And that's kind of how we think about filtering it down from, you know, 100 100 plus different cannabinoids in the plant to these are the product 1234 that we're going to go after.

Nick Jikomes 26:38

And for, you know, in terms of CBG, or whatever one is the best optimized to be produced the most from the cells. Can you give us a sense for scale? How much CBG? Can you produce? Compare? I say, the plant?

Jeff Ubersax 26:53

That's a really good question. So let me think about the best way to answer that one for a second. So, you know, one of the, let's dive in a little bit and talk about fermentation, because that kind of is the first place to start, right? And so what do we do with fermentation, right? So ultimately, it starts with a single yeast cell, right? That you've, you've generated, through, you know, advanced molecular genetic techniques, you've put in, you know, a bunch of these plant things, and you've also optimized the host cell. So the cell to you know, as I said earlier, kind of look more like, you know, the trichome, or plant cell, and those enzymes that you put in look more like the kinds of things that Easter used to seeing, but still do the same thing that doing the plant. So you start with a single cell. And then you have to grow that, right, the single use cell doesn't make a lot, it's tiny, right? It's, it's, you can't see it without a microscope, it's about 10 microns big, it's not very big cell. And so you put it on a plate on your dish, and it grows into a colony, a colony is no, a whole bunch of sounds like 10, to the eight cells, or 10, to the 10 cells, you can then scrape that and you put it in a flask, that flask kind of grows up over time. So you get sugar, you give it oxygen, it eats the sugar, it makes ethanol, carbon dioxide, and also more cells, right. So you keep growing it bigger and bigger and bigger. And then you reach a scaler class flasks, no longer work, which is you can't make no 100,000 liter flask, they just couldn't do it. And so then people move over to what are called fermenters, or bio reactors. And these are just larger vessels that supply you know, air sugar. And that's basically it and nutrients to the cells to allow them to continue to grow and now start produce your mouth producing your molecule. And so, you know, the way that this works is that in the laboratory that we have in Berkeley, we go up to about 10 litres of fermentation production, right. And, you know, the typical way that people kind of think about how much product you're making out of these fermenters is by talking about something called tighter. So tighter is the, like, the grams of your product that you've made per liter of your fermentation, right? And so, typically, in the biotechnology space, you know, people have brought products to the market that are anywhere from you know, the titers are anywhere from like one gram per liter, up to, you know, over 100 grams per liter, right? So, a leader is about 1000 grams. So if you're at, you know, if you're at, you know, 100 grams per liter 10% of your fermenter is your product, right? That's a lot. There aren't actually that many products that are kind of in that space. Most of them are down in the cult, though. I don't know like the one to 25 gram per liter range is typically where people would be. And so from that, you can say, Okay, if I had, you know, 1000 liter fermenter and my titers were at 10 grams per liter. I'm making you know, Basically 10 kilograms in that 1000 liter fermenter. And that's just what's in the kind of fermentation broth, the next step that you have to then do is you have to purify it out, right? And that's tricky and hard, and oftentimes something that people don't think a lot about, it's like, how do you get this back out of the fermentation broth. And so that's what we call downstream purification, or DSP. And that typically has an efficiency anywhere from, you know, 25%, all the way up to, you know, 80, or 90%, in the best kind of fermentation. So, if you're, let's just say you're 50%, that means 50% of the product that's in that fermentation bath, you're able to recover, the rest kind of goes down the drain, right, and so from again, from that 1000 liter fermenter, if you're at 10 grams per liter, you're making you know, 10,000 grams, which is 10 kilograms, and then you've got 50% recovery at the end of the day, you're only making you're making about five kilograms per 1000 liters, right. And so,

Nick Jikomes 30:59

so there's two basic steps here, just to make sure I'm following. So if you were thinking analogously, to the plant world, someone would be growing a bunch of plants and that plant would be producing trichomes that produce cannabinoids, you guys are putting yeast cells into giant tubs, essentially, giving them sugar, giving them oxygen, the yeast are then growing, multiplying, kicking out a fair amount of cannabinoids as well. So so the giant tubs of yeast are analogous to growing a plant basically. And the second step is getting the cannabinoid from, you know, purifying it from those cells, which would be analogous to doing a plant extraction. That's right.

Jeff Ubersax 31:37

And in the fermentations, these products, at least for this product class are outside of the cell already, but they're they typically because their solubility in water is so low and growing water, you know, you need to they're associated with kind of cancer cells or, you know, kind of lipids with carbohydrate cell walls, that's what cells or T cells have. So that looks more like what the cabinet looks like. So canavalia kind of sticks around in that, like in like the the non soluble phase, which includes cells and your product. And so you can basically do like a, what's called a liquid solid centrifugation, where you centrifuge, which is just the spin to separate the liquid phase from the solid phase. And then you almost have something that like you think is very analogous to the plant world, which is like we've got, you know, plant biomass, and we've got cannabinoid, how do we get that out. And so, you know, the DSP process in many cases is with some sort of extraction, oil extraction, or, you know, there's a whole bunch of different ways you can get it out of there, that you can then do, you know, further purification on down the line through crystallization are other types of tools.

Nick Jikomes 32:45

And in the plant world, you know, when you're growing the plants, harvesting them, and especially if you're doing extractions, for making concentrated products, you often have to worry about things like residual solvents from the extraction process, you have to worry about pesticides, maybe that were used to help facilitate growth of the plant, is there anything like that, that you have to worry about when you're engineering these compounds to come out of yeast?

Jeff Ubersax 33:08

Right, so that's one of the coolest things about fermentation is a you don't have to deal with a lot of the kind of pesticides or you know, heavy metals or other types of stuff that come through with that, certainly, like, you know, organic, like residual solvents and stuff like that is something that everybody should be concerned about that that is something that anybody who's doing any type of purification process, whether it's, you know, from, you know, cannabis plants, hemp plants or from you know, you know, even making you know, pharmaceutical ingredients oftentimes use, you know, organic extractions during, you know, the chemical synthesis. So, you know, residual solvents is always something that everybody is going to be paying attention to, it's something that Yeah, we pay attention to, I think the advantage of doing it from yeast is that typically, you know, kind of like the product being made to, you know, the bio mass is just a lot greater, and you're not extracting a lot of the other things that you typically extract during like a plant extraction, like polyphenols and waxes and a whole bunch of other stuff, like yeast just doesn't have that. And so the product that you get at the end of the purification process, you know, when we first got into this, and we start talking about cannabinoids, you know, we were talking about, you know, you know, basically high purity product, and, you know, people would be like, you know, our product is pure. And they'd be like, Well, what does that mean? Because cannabinoid world, pure oftentimes means you know, greater than 90%, we might call it pure and greater than 98, or 99%, then you have an isolate. And we're like, well, then we have an isolate. What we're used to in the fermentation world is, you know, purity over is typically over 98 or 99% pure, we just call it pure, and that's what we're used to calling it. So entering into the plant word where there's both this purity and isolette word was confusing to us at first, but we really quickly adapted to that. And so we basically make product at the end of the day that's, you know, greater than 98 99% pure out of these fermentations.

Nick Jikomes 34:58

And can you give us a sense for time So when you're growing the plants, I'm not a grower, but you're talking about months of time to go from seed to plant to harvest, and do the whole thing. What's the timeframe for this type of approach?

Jeff Ubersax 35:10

Yeah, so it's usually about a week to go from, you know, that kind of single seller colony all the way up to, hey, we've got, you know, typically we think about when you're talking about commercial scale production, we're typically talking about 100,000 meters or so and so to give you a sense of scale, you know, 100,000 liter fermenters, probably, about, you know, 20 to 30 meters tall. So it's, it's big. Yeah, it's a lot of volume. And, you know, so what we get out of that end of day, you know, is hundreds of kilograms of product that you then run through the purification process, and you know, that end to end process, typically, you know, the fermentation might take a week, and then the purification takes another week. And sometimes, you know, that's about the then there might be shipping and logistics and all that sort of stuff. It's generally like a one to two week process.

Nick Jikomes 36:04

Wow. And what is, what is pure cannabinoid look like?

Jeff Ubersax 36:08

So it depends on the cannabinoid is the answer. So like, pure CBG, looks like a white crystal, which is very, very cool. There's others that look more that are hard to get crystals, are they they're more oils. And so it just depends, again, on the shape, and the structure of the molecule oftentimes, you know, drives the chemical, what that looks like, in its pure form, but CBG I mean, that was one of the coolest things for us is that, you know, one of the hard things for science is that, you know, what you do, oftentimes doesn't have like a physical or tangible thing that you can touch and say, I did that, right. It's more esoteric, it's more like, Hey, I learned something new, that nobody else in the world maybe have known before. And that's fun and rewarding in its own way. But to actually go from, you know, a scientist, like a project where we started, you know, from no lab in 2017, like nothing we were working out, you know, somebody's dining room. And, you know, to a point where, you know, three years later, we were running, you know, 15,000, liter fermentations. And making, you know, kilograms of product that you could actually see, they're like buckets of products that are, you know, highly pure crystal and CBG. Like, that is super rewarding to say, we actually made that, that's pretty cool.

Nick Jikomes 37:21

Yeah. Now, that is cool. And so you make so there's the fermentation step, there's the purification step, you end up literally, in the case of CBG, with buckets of crystal, the kilogram quantities, where does it go from there? What types of places? What types of companies? Are you guys actually selling the product to? Is that people doing clinical research? Is that people making consumable products? Is it all the above?

Jeff Ubersax 37:43

Right? So what I'll say about that is we're not actually selling product yet, right? So developing the tech, we're developing the fermentation, the purification, technology, and starting to build those commercial relationships, right. And a big part of this is understanding, you know, what we have and what it's good for, and, you know, doing all the safety trials, so actually, this first kilograms of product are things that we, you know, are using to do all the types of safety studies that folks like the FDA require us to do, right. So some of these are, you know, typically, when you talk about fermentation ingredients coming to the market, the way that they come to the market is through, you know, a couple different pathways with the FDA. So if you're going into food and beverages, you generally are doing what's called a general generally recognized as safe notification with the FDA. And that requires, you know, a large amount of toxicology and safety studies first, where you're doing kind of long term studies at reasonably high doses, typically in rodents, like rats, to show that, you know, if I do 90 or 180 days of high dose treatments of these things, that those rats aren't going to be, you know, having, you know, tumors or other types of things that really prove that these things are safe. And so, you know, that takes a significant amount of product and is where a lot of companies would typically bring some of their first, you know, kilograms that they're making. The second part I would say is that, you know, we have gotten to the point where we're sending samples, though, of these products out to the samples range from, you know, call a gram to, you know, hundreds of grams of product to, you know, all sorts of kind of the first applications that many people are talking about going for is topical applications in skincare and consumer products, because, you know, the, the regulatory threshold for those is kind of the easiest to get through. It's basically you have to do no irritation of skin and eye testing, as an example, right. And those are relatively straightforward, short term studies, not you know, half a year type of studies. And so that's, you know, where we've started and so have been prioritizing samples going out to, you know, very large, you know, global conglomerates. All the way down to, you know, smaller independent brands that are, you know, it really interested in the cannabinoid space.

Nick Jikomes 40:09

And can you give us a sense for like the cost effectiveness, I would imagine that this is probably where you're aiming to make it much more cost effective, just in terms of speed and literal costs to make, you know, a kilogram of product compared to growing plants and extracting from the plant,

Jeff Ubersax 40:25

right. So the way we think of cost is really about, you know, it needs to be at a cost that makes it available and affordable for the applications that it's going into, right. And so a lot of that's kind of driven by, you know, the efficacy of it as well, like, you know, people are basically like, at the end of the day, people are paying, if you're, if you're in the non pharmaceutical space, so if you're in consumer products, as an example, people are paying, you know, for the, the effect of that thing, right, so, and they're paying, you know, dollars, perfect. Yeah, that's one way to think about it. And so, you know, most, you know, in the consumer product space, like, if you're talking about kind of like medium to high end cosmetics that might sell, you know, call it in the 60 to $100 range, you know, most brands are only going to pay at most, like $5 of that 100 is going to be the ingredients that they use, right. And so you've got to be able to have, you know, be able to, you know, generate, you know, an effect that's positive for the consumer, in that $5 kind of range. Right. So that's how we think about pricing. And so, you know, for a lot of these products, yeah, the rare ones are really hard to get from plants CBG, you know, there are definitely very smart talented plant breeders out there that are, you know, starting to, I think make, you know, hemp strains that are making significantly more CBG and the prices that's coming down. And so, you know, we've got to be competitive with that, at least is kind of the way we think about it.

Nick Jikomes 41:57

Interesting. So, any other cannabinoids, you can tell us about specifically that you think are interesting that, you know, not necessarily either ones that you guys have produced, or that you're thinking about producing? You know, off the top of my head, you mentioned some of the big ones. So CBG CBC, people are talking a lot about CBN, which isn't actually produced by the plant. And then there's these new ones that I've been starting to hear about, that are present at very low quantities, but potentially have very high, like receptor binding affinities, like th MP, are you guys looking at any of those? Yeah, so

Jeff Ubersax 42:29

a lot of those other ones are kind of tinkering around, like, with the tail of the phenomenon, right? You think of the two ring structures, it's got a little tail that hangs out. And, like DHCP is a different length tail, basically. And yeah, that does seem to impact, you know, both the affinity for different receptors and the diversity of receptors that these things have, again, it's changing the shape of the molecule in a way that, you know, I think, to us, at least initially was a little bit surprising that you just change it a couple carbons at the end of that tail and you have a much tighter binding thing but that's one of the things biology salies full of surprises, there's a lot of stuff you don't even know you don't know. And so there's definitely a lot of interest in both inside the matrix and in the field in general and how other variants of you know, even some of the common ones like CBD CBG THC, how those different variants might change how they interact with your body, right, and so we've definitely like the, you know, 10 plus different cannabinoids, we've tested in a bunch of these assays. Some of them are definitely some of those variants that have changes on that talanx and yeah, I mean some of those are present in really small amounts in the plant and it makes them you know, particularly hard to get through the agricultural kind of supply chain and are places where we think there's there's real opportunity, there's another kind of flip side to this that we can also do that that's you know, allows us to make kind of what we call new to nature cannabinoids to so one of the things that we can do with yeast fermentations is we can feed them not just sugar but some other precursors to kind of the cannabinoid pathway that and those some of those precursors might be things that aren't found in nature that chemistry can make right human chemistry can make and so then you end up with a contaminated scaffold that has no let's say it has a tail that has you know, some non natural structure to it that you were able to put into it because you can feed yeast these chemical precursors that you could never feed a plant right and so we can make new to nature cannabinoids as well that you know are you know mostly going to have applications in the pharmaceutical space and not so much in like consumer space but are also something that you know we're pretty excited about being able to do

Nick Jikomes 44:50

so you you're literally engineering you know Frankenstein yeast, but then you can also give them precursor molecule so that you're creating brand new, never before seen cannabinoids.

Jeff Ubersax 45:01

Yeah, we don't like calling them Frankenstein. That, you know, a lot of the products and this goes back to, you know, a great question that we often get is, you know, I think it's really important to understand that, you know, there are a number of products in the world today that people use that are coming from, you know, highly engineered microbes that people have worked on for, you know, a long time to get to make products that are, you know, without that technology really wouldn't be available to people. So I think one of the, you know, my favorite kind of nuance to talk about is like, they're called human milk oligosaccharides, right. So these are, you know, sugar molecules that are found only in human mother's breast milk, right, and they're thought to have been shown to have a role in the developing immune system by supporting, you know, beneficial, like microbiome and the infant's gut, and then also have indications that they're also important for brain development, right. And so these are now made through by there's both made and being developed by some of the biggest companies out there, like BASF, DSM, DuPont, and others, are making these human milk oligosaccharides through fermentation, and including them in infant formula two now, you know, provide benefits to infants that used to only be available through through breastfeeding, and now available through through formula, right. So, you know, that's a good case where, you know, if people are saying, hey, these are Frankenstein, yeah, Easter bacteria, people be like, Oh, no way, like, keep me away. But they have you know, they're not that scary. They're, they're not things that you know, if they get out into the wild are going to take over the wild population, because, you know, basically what we're doing is, in the case of yeast, right, Eastern normally make taking sugar, to make carbon dioxide, ethanol, and Marcel's what our job is, it's kind of like that's on the strain engineering side is to make those cells make less ethanol makes, you know, and make more of your product. And oftentimes, that comes at the cost of them making fewer cells as well. And so the interesting thing about that is, if you were to, you know, kind of compete in a growing experiment, these engineer geese versus a wild yeast, they would that wild use just crushes it like, Yeah, no, after a couple, you know, even days, you would not even be able to detect any of your, you know, engineer geest in the worst case scenario. So, and this is, I think, where a lot of these companies, including us take the responsibility to, you know, we're here to try to make the world a better place, we, you know, are very conscientious and work with the regulatory agencies to help them understand what we're doing both on whether the molecules we're making, but you know, how biotechnology in general is generally a very safe activity that doesn't, you know, have dangers that if one of these things gets out, you know, the world's gonna get high on THC, because there's ESL out there making THC that everybody's just inhaling or whatever.

Nick Jikomes 48:09

So how did you how did you first get into East biology?

Jeff Ubersax 48:14

Oh, that's a great question. So. So when I was I was an undergraduate student at the University of North Carolina, and I was in an undergraduate lab there that worked on these things called motor proteins. And so one of the another really cool things in cells is that, you know, there there's tons of these little machines, like enzymes, like proteins are in there, a class of them are just little machines that actually like use what's called ATP, which some people call like the current energy currency of the cell. It's, it's just adenosine triphosphate, to generate to use the energy stored in that molecule to actually change shape and move, right. So there's like motor proteins like dining and conditions and other things, actin motors, that that, that actually change shape and move as they take in ATP and then make it into ADP or either ADP or a MP and release that phosphate. The phosphates contain really high energy bonds. And I was always fascinated by how enzymes in cells, like do the things that they do, and how does that work. That sounds so cool. And so that kind of drove me to look when I was going to grad school to say, you know, where are some of the, you know, best places in the world that kind of study those types of things. And UCSF is one of those and gotten to UCSF and you do these things called rotations where you rotate through a bunch of different labs. And, and try to get a feel for how that science is done in that lab and what your interests really where they lie and everything. And so went through a couple different labs. One of them happened to be a yeast lab that was studying how T cells grow and divide and had some really cool technology for ways to kind of really start understanding that In the cells and yeast was just so much fun, it's so easy to deal with compared to some of the other things. So I also worked in like a Drosophila lab, which is fruit flies, fruit flies are really hard to take care of, it turns out, like, you've got to, you know, feed them and you know, it, you feed them actually, you know, like grapefruit juice with yeast blended into it. And they're just, they're hard to deal with, they're, you can't freeze them, because, you know, if you freeze them, they die, get deep freeze them. And yeast was just so convenient. And has, you know, so many, like, there's been just a tremendous number of kind of fundamental discoveries, about cancer, about all sorts of things how biology works in these model organisms, like yeast. And it was just, it just seemed like a great tool to understand how some of the science works. And so got started on that as a grad student, and then when I went to do a postdoc, we worked on both human cells, and also were called xenopus oocytes, which are frog eggs, and frog eggs are some of the biggest kind of single cells that you can actually see they're millimeter size scale things, but they're still single cells. And, you know, human cells and other kind of higher mammalian cells are just harder to deal with the nice too, they grow a lot slower. So a human cell divides about once a day, whereas the cell divides once every 90 minutes. And so you can just do a lot more with yeast. And so then I heard about, you know, through some grad school, folks, connections and postdoc connections, that there's, you know, companies out there in the world that are actually using yeast to make products that can make the world a better place, I was like, that sounds like a lot of fun, I should go see what that's about, and checked it out, and was really quickly hooked and said, this is this is fun, I, this is why I want to do

Nick Jikomes 51:50

so. So it was actually in graduate school, that you started to understand that you were interested in industry, it was more

Jeff Ubersax 51:57

Yeah, I mean, it's a mix of grad school and post secondary in grad school, it's time, you know, was, and this is, you know, a thing that I think it's still evolving, there's, there's a lot of at the time, you know, it was focused on training you to be, you know, a professor, and, you know, some of the alternative careers that might people might pursue, whether it's like law or industry, or science policy, or a whole bunch of other things were a lot less emphasized than they are today, which I think is a great thing. And it really came when I was a postdoc, you know, kind of seeing, you know, when your postdoc, you're doing an independent research project in somebody else's lab, and usually the path there is that you then, you know, start your own lab at a different university doing some of that work. And just seeing, you know, the job searches and how competitive it was, you know, we would see, you know, 250 applicants for a single, yeah, you know, position as a professor, and, you know, then you get down to 10, people that are interviewing and one person who's actually getting the job. And it was also, you know, also a bit, you know, isolating in academia, because it's like, it's your project, it's your thing, there are other people around you that are working on similar stuff, but not identical. And then I got, you know, kind of a friend, a postdoc in the lab, his name is Zack surber, you know, went and joined amorous, because he knew some of the founders, they're really, really well. And they kind of enticed him and I said, you know, he was like you should come to and I said, Well, you go try it out and see how it is. And I think that was like, in September 2007. And, you know, by October, November, I interviewed at amorous and was like, Yeah, that sounds like a fun thing to try. So that was, it was a good opportunity to, you know, see how and I think the thing that most people found as a moving industry is it's now it's not your project. It's the project of no 10s 20s or even 100 people that are working on the same thing. And that makes the science go a lot faster. And it's a lot more collaborative. And there's a lot more kind of idea exchange. And so it's also sometimes more applied. And so the stuff like the output of all that, at the end of the day is like real, tangible benefits to people, which, you know, basic science has real tangible benefits to but they're, they're hard to touch. They're not as tangible, right. So, a lot of people found that find that really rewarding and myself included.

Nick Jikomes 54:31

Do you are you this you're the CEO? Yep. I'm

Jeff Ubersax 54:34

a CEO of two metrics.

Nick Jikomes 54:36

So you know, you have the scientific background of then you spent a number of years in, in the private sector. So that's sort of your your two pronged training for being a CEO. Does it? Did you ever imagine yourself becoming someone like this? Or do you think it's does it feel weird being a scientist running a company or is it actually a natural fit in some ways

Jeff Ubersax 54:57

so a bit of all of that, actually. So, you know, I think that there are certainly the job I have today is very different than I necessarily thought it would be right. And, you know, some of the, you know, the personal challenges of being, I think a scientist CEO, is that you don't actually get to do a lot of the science anymore. Like, I haven't been in lab in a really long time. And people in the lab probably shouldn't let me in the lab at this point. Because I don't know where anything is, or, or so I've kind of, you know, that's, that's different. But you know, and, you know, to a certain degree, being able to do some of that lab work and, you know, getting excited about, you know, hey, I set this experiment up tomorrow, I get to see the results, is something that I definitely miss, right. But the parts that I think are exciting is that, you know, you're also like, as you know, a CEO, or even, you know, a senior leader in the company, you're able to, you know, a lot of the hard parts of getting science in industry done is actually related to, you know, how do you get teams of people to work together, and then across different teams, to drive the science and technology forward as fast as possible. And the people aspect of that was just fascinating to me, like, people, each person's individual puzzle, like, how do you best, you know, get them, you know, to, to do their best work and get them to be able to do things that they never even thought that they could do. Like, that side of it kind of really drew me towards, like, hey, the people side of this stuff is just as interesting and oftentimes just as hard as a science that we're trying to do. And that a lot of, you know, I do now it's like, you know, organization and team and how you get these people working together, and how to, you know, say, connect, you know, what they're doing in the lab to, you know, the impacts that they're having on the broader business, like that stuff is hard, and challenging and fun. And so that part's, you know, really rewarding, and very different than I imagined doing.

Nick Jikomes 57:09

I think that's the answer to what my next question was going to be, which is, you know, what's the, what's the most interesting, you know, so much of science is driven by what you're interested in, I was gonna ask you, what is the most interesting part of your job? That's not the science?

Jeff Ubersax 57:23

That's not the science? Yeah, I mean, boy, there's a lot of interesting things. I think that especially being in the cannabinoid space, there is just like, I find it so exciting to try to, you know, to be able to talk about the science of, you know, what we do, and also what cannabinoids are, and what they can do. And, you know, there's a lot that's not known, and that's the stuff that we're starting to understand this stuff, the world starting to understand about what these things are good for, and how they're going to have positive impacts for people talking about that stuff. And, you know, both, you know, so helping, you know, talk about that, and educate regulators, investors, you know, consumers, big CPG companies, like all that sort of stuff is is fun, like, ability to talk about science in a way that people can kind of grasp some of the basics that aren't necessarily scientists and see why it's cool, and why it's exciting to get people excited about that is also something that's super fun and rewarding.

Nick Jikomes 58:31

Interesting, so what do you have any general advice that you would give to like graduate students or postdocs who are in academia, that might be thinking about moving into the biotech world or anything like that?

Jeff Ubersax 58:43

Yep. So my first thing would be is try it. So there are a lot of universities now are starting to have like, you know, industry internships that they provide for grad students, and sometimes postdocs to, that is a fantastic opportunity to try it and get a taste of what it's like. And so, you know, I would encourage people to, you know, the things I think most people hooked on the science that goes on in industry or in industry positions, in general is, you know, that you're, it's a lot less of, and this is also a big transition that people have to make, it's not like your project anymore. It's like, it's like, there's five or you know, 10 or 100 people that are working on the same thing. And that makes the science go a lot faster. But you know, it's also means that you've got to let go of this feeling like this is my yeast strain, or this is my experiment. It's, it's not there's lots of people that touch that now. And so it's like, the things that I do have a lot more kind of impact, which is both good and also something that you know, people need to learn about. And so experiencing what industry life is like is kind of the best way to get a taste for that. To understand if that's what you want to do, there are so many other places where scientists can have impact in the world, though, that I would also encourage each individual person to think about what are the types of things I'm interested in. And if I don't even know, ask people about what are the places that I can go after graduate school or after a postdoc, because they range from, you know, going to Washington DC, and doing science policy to, you know, going to a law firm or going to law school and talk about, you know, intellectual property or other types of law. There's, you know, there's just so many different applications of, you know, the training that you get as a grad student on how to think analytically and scientifically about problems, then you can have impacts in all sorts of places and the more you try, the more likely you are to find the place that you find is the right spot for you.

Nick Jikomes 1:00:48

Speaking of IP, I imagine a lot of the value for a company like this comes from the IP you guys are generating. And I would guess that a lot of it has to do with the methods you're developing for how a particular E string can be engineered to tolerate and produce a particular type of compound. Is that accurate? Yeah, so

Jeff Ubersax 1:01:06

there's kind of like three big buckets for how to think about IP from this type of company. So one is, you know, the individual enzymes and pathways that you use to make these products in the cells, right? So that's one that's kind of one level. The second level is kind of like methods of production. So there's like, you know, fermentation based IP, there's downstream purification based IP, and then last buckets, kind of like the applications IP. So once you have a product, what can you use it for? And so I think everybody, you know, all biotech companies are valued to certain degree off their intellectual property. And it's a big focus of us and others to think about all three of those buckets.

Nick Jikomes 1:01:47

And then can you take us back, you touch on a little bit back to the origin story for that company? So so another scientist invites you out for coffee, presumably, he had developed, you know, techniques, specifically well suited to the production of cannabinoids. But what sort of happened after that? How did you come up with the name? How did you decide to actually put it together?

Jeff Ubersax 1:02:07

So Good question. So So Jay Keasling, who's a professor at UC Berkeley, you know, has is one of the kind of pioneers and one of the really well known kind of folks that are, you know, basically engineering yourself to make natural products. So, his lab is, was probably really well known for making artemisinin, which is a anti malarial compound that's used all over the world and was funded by one world health and basically was funded to, you know, make that at cost to decrease and stabilize the price of artemisinin. And so he's always been interested in saying, you know, what are kind of the the natural products that exist out there that could be beneficial to people? And how can I use my lab to, you know, seed, you know, figure out whether some of these technologies can be used to make these things commercially relevant. And so, you know, around 2016, I think in Jays lab, this is right around the time that CBD was going through phase three clinical trials in epidiolex. And Jay, I think, looked at that and said, you know, hey, here's another plant based molecule that's being used as a pharmaceutical ingredient, and, you know, is probably going to be relatively expensive as most plant products are. And, you know, wouldn't it be interesting to see if we can get yeast to make that? Right? And so that's kind of a Genesis in his lab. And he had a couple of students and postdocs working on that say, Okay, how do we get used to make these these products, and they found, you know, they kind of found some of the, you know, a couple, one, in particular missing enzyme and pathway, but, you know, is the thing that makes CBG or cbga from the plant, it's a parental transferase. And so that was, you know, one of the key discoveries that they made at the time was, they could all of a sudden get, you know, call it, you know, hundreds of milligrams of CBG, the cell where people before, were probably making, you know, a milligram or less, right, so all of a sudden, they found this thing, you know, the way we talk about this, or Jay would talk about this sometimes, too, is that, you know, what was in the kind of space before was kind of like, you know, you know, called a moped or something like that scooter. Right. And that what they had found was the jet engine that was really required to kind of get used to make new things at a higher or commercially interesting level, put it that way. And so that's what he kind of, you know, when Jay had coffee said, you know, like, we've we found what we think is a missing enzyme here. And think that you know, cannabinoids, in general are, you know, a broad class of compounds that are, you know, very, very interesting and things that need to be studied more and be made more available, so we could even study them. And, you know, people will say, Well, you know, what got you interested in the cannabinoid Space Center, how did you think about this Before he made the jump, and for me, it was like, you know, I heard stories and people you know, they go to, you know, Amsterdam or other places and go into coffee houses and talk to people and see, you know what their experiences are. And that was helped help them see that there's potential here. And for me, it was like, you know, the National Academies of Sciences had just released like a 500 page report about the potential therapeutic uses of cannabinoids and what the, you know, some of the science evidence was for them being effective in those indications. And, lo and behold, you know, there's a lot of opportunity here, there's a lot of implications for what these things can do. And there's just more science that needs to get done before these things can come to the market. But it's a huge opportunity to have, you know, positive impact in the world. And why wouldn't you try to jump on that?

Nick Jikomes 1:05:46

Do you ever so when you're doing a lot of the the work downstream of the actual cannabinoid production when you're looking at receptor binding activity and acids like that? Do you ever, you know, there might be a kind of conflict? I would imagine where in academic science, you sort of like, get to tell everyone everything? Yeah. But in industry, you don't necessarily get to do that. So are there times where are there discoveries that you guys make that you publish in an open access way or anything like that?

Jeff Ubersax 1:06:15

So I would say that there are stuff that we will eventually publish? Yes, but we're not at that point yet. And yes, that is frustrating at times. But this is, I think, classic, like, a lot of folks that are in industry feel this way, because oftentimes people in industry, you know, make discoveries, or invent technology that then you know, a couple years later comes out through academia or other places and gets talked about as like, Hey, here's the giant breakthrough that we made. And the companies are like, yeah, we knew about that already. And it's frustrating not to be able to say that. Yeah. But that's, you know, the nature is it's a competitive industry. And, you know, there are lots of people that are trying to do this at this point. And so we do, we're thoughtful about what we say and what we don't say. And yeah, that that's, that can be extremely frustrating sometimes, because it's like, you're no, I always want to err on the side of transparency, because otherwise it comes off as, hey, you're hiding something here. And that never feels good to me. And it's also something that, you know, I don't think benefits, you know, the cannabinoid industry in general, like the more transparency and openness and clarity that people can provide about what these things can do and how they're safe and what, where they're effective. I think that's what the general space needs more of anyway.

Nick Jikomes 1:07:28

So how did you guys come up with the name of the matrix? What does that mean? So Jay,

Jeff Ubersax 1:07:31

Keasling, came up with that one, so it's after diameter, who's the who's the, let's see, diameter is the Greek god of the harvest. Right? And so, you know, the idea here was that plants make a whole lot of really interesting, rare, natural products. And wouldn't it be cool to start a company that was focused on making those more available to the world. And it just so happened that the first class of products that looked really interesting, were the cannabinoids?

Nick Jikomes 1:07:58

Interesting, so anything, you know, what are you most excited about? That's on the horizon? What would you say are the next sort of critical steps for this company?

Jeff Ubersax 1:08:07

Yeah, so you know, recently we announced moving to, you know, full scale commercial production, which is over 100,000 liters, and, you know, getting that working and running and making, you know, so at that kind of scale, companies in the space, you know, would be making, you know, kind of metric tons per year of product, that's when you start actually having impacts in the world, right? Everything before that, is just, you know, it's it's, it's the the footwork, the hard work that you have to do to get to that point, but that's the point at which, you know, you're starting to make enough product that's going to get its make its way into the consumers hands and actually start having the impact that you want it to have in the world. And that I think, is, you know, hugely exciting. And it's also a big challenge, right? So getting fermentation scale up to work as a whole, like, there's, you know, decades and decades of experience people out there who have, you know, tried to do that, it's hard, it takes a lot of work, and it's something that we're, you know, just really focused on. So getting that to work is really important. And then on the other side of that is both kind of lining up the customers that are going to be able to buy that much product, right? So we want to be able to sell everything we make, and so, you know, finding and getting, you know, those commercial discussions to the point where people are then willing to, you know, sign supply contracts and such to do that. offtake is also you know, one of the big focuses of the company over the next year. And, you know, I think that, you know, speaks to the quality of our the strategy of like, if you can approach companies with some of the basic science of what these things do and how what applications they're good for, and Provide them real scientific data that says like these are what these things are going to be good for and how they're better than some of the ingredients you're already using today. And how they're more sustainably produced, how they're, you know, all the all the all the advantages of fermentation, it makes that commercial approach so much easier and gets them engaged so quickly. And that's kind of, you know, where we are today. And, you know, so from a year from now, when I say, you know, what, where do we want to be, it's, you know, that manufacturing facilities up and running and humming and doing really well, and we've got people, you know, buying the product, and we've been through, you know, all the safety and regulatory stuff that we need to with the FDA. And we've also, you know, continued to do innovation inside the company to bring no additional cannabinoids up to the point where they're ready to go into that manufacturing facility. Like, that's kind of that's, that's the thing that's exciting. And we look forward to over the next couple of years.

Nick Jikomes 1:10:52

How big are you guys? How many people work here?

Jeff Ubersax 1:10:54

So right now we're, you know, over just a little over 60 people, okay, well, and so, you know, still, I would say, moderately small, but, you know, continuing to grow, you know, in 2017, we're started off is like, four, then five and 11. And so, you know, one of the biggest challenges for any company is growing from 11 to 60. comes with a lot of changes. Yeah. And that's, you know, people that, especially people, they're in the early days, you know, they're used to knowing everything that happens everywhere. And when you're 60, people, you can't do that anymore. And that's, you know, having people let go of some of that and adapt to that is, you know, is one of the natural challenges that every company that grows, has to go through what,

Nick Jikomes 1:11:42

what percentage of the employees are like, bench scientists like doing doing

Jeff Ubersax 1:11:47

a good question science. So I would say about 40 of the 60 are in, you know, on the science or, you know, manufacturing side of things, which is still a lot of process development. And then, you know, the other 20 are a mix of in some of those 20, you know, we have, because what we do is involves, in the lab, at least a lot of automation and computing tools, we have a bunch of software engineers that, you know, work both on with the r&d team, but they work elsewhere with manufacturing team and other where other places as well. So it's a real mix of different disciplines. So we're even within the r&d team, you know, we've got, you know, people that are yeast geneticists, we've got people who are, you know, what we would call like metabolic engineers who kind of understand broader physiology of how cells work. We've got, you know, high throughput screening groups that are, you know, how do you measure how much you know, yeast cells are making these products in really high throughput? We've got analytical chemists that are there to say, you know, how do we measure in high throughput, how much cannabinoid and other products these cells are making. We've got fermentation engineers, downstream purification engineers, there's just a whole broad swath of kind of technical experience that spans biotechnology, automation and computing. And, you know, it's, it's, it's exciting to and also there's challenges in getting all this disciplines to kind of work together. And that's, you know, one of the things that makes it fun and exciting to

Nick Jikomes 1:13:17

how much were you guys impacted by COVID

Jeff Ubersax 1:13:23

Personally, I think there's you know, personal and professionally right so personally, you know, COVID changed our lives just dramatically. So I've got two kids 1619 and they you know, more than a year ago with the school shut down and then we you know, basically the California in the Bay Area went into a shelter in place so shut down everybody I think on the 17th of 2020 and so we were all then trying to you know, work from home and teach from home and you know, do a whole bunch of other stuff at home and deal with all the stress and concern and I'm you know, what's going to happen here that was just you know, tremendously unbalancing for everybody. And you know, professionally we're, you know, definitely shut down the labs and shut down everything for a while. And you know, then it was about you know, in the summer of last year how do you start stuff back up safely and how you know, our approach has been you know, that people that can work from home and do their work from home have to work from home the people that can you know, go in the lab and need to do you know, actual lab work and bench work to you know, keep making progress. Those are the folks that we want in there and how do we organize the space and how do we organize you know, schedules so that we minimize overlap with people and do this in a safe way that everybody in the whole organization feel safe with was you know, took time but we got there and you know, haven't had any COVID cases inside or transmission inside, and so have I'm really fortunate from that front. But it definitely has, especially on the science side has changed. And one of the cool things about science is you're in the lab, there's other people there, you have a cool result. And you can turn to the person right next to you and say, Hey, here's a cool result. What do you think this means, and there's like a transit, there's like, no kicking around of ideas. And that's how a lot of innovation kind of comes about. And when everything's more structured, and people aren't in the labs, as much as they were before, a lot of that communication, like kind of disappeared, and people felt that it's like, I don't have like that critical mass are those people that I can kick around those ideas with anymore. So it's been about how you figure out how to use zoom and other tools to kind of like, bring that back in a way that people get that, you know, feeling. It's still not quite the same. But you know, people have found ways everything's become more scheduled, and kind of like, but all that stuff is still starting to happen. And has started happening and is important in keeping pushing the science for

Nick Jikomes 1:16:04

interesting. Well, any final thoughts? You want to leave people with? Jeff, before we stop?

Jeff Ubersax 1:16:10

Oh, that's a good question. I mean, I think that, you know, what would I say So? So? I think on a couple of fronts, I think it's important, one of the things you touched on, you know, is what advice do you have for people in graduate school, or in, you know, as postdocs are even considering going to graduate school, I mean, science, the training that you get in graduate school, and science in general, is just super cool. And if it's something that you're interested in, you know, there's so many different areas like science is so big and broad, that, you know, you will find a place and you should try it, and do it. Because it's, it's, you know, super rewarding, you know, to be first feeling like you're discovering something for the first time ever, and nobody else in the world knows it. And you're now like a world expert in something. And that is what graduate school is all about, is making you that world expert in that thing, and teaching you how to, you know, design experiments and, you know, test ideas, and get to kind of deepen human understanding of the natural world. And that is super cool. And I would definitely encourage people to do that. That said, like, there's what you do after graduate school is, you know, there's a whole bunch of different opportunities and people should, you know, try as many of those different things to find the one that works for them. And industry might be is right for a lot of people, and it's probably not right for everybody. And so try things out and find the place that feels right to you. And that, you know, you get out of bed every day and say, This is cool, I want to keep doing this. On the, you know, cannabinoid side, I'd say no, but what we're trying to do is, you know, take, you know, basically open the world up to the science and opportunity of cannabinoids and say, you know, this is what they are, this is what they can do, they haven't been studied before somebody needs to do sit down and really do a lot of the hard work of understanding science. And that's what's going to ultimately, let these things have impact in the world that, you know, a lot of people actually think they can. And it's exciting to be part of that. And we think it's a huge opportunity. And it's, you know, amazing to think about how you can use biotechnology and yeast in particular, to make these things more available and then use that availability to try that science forward and eventually make its way into people's hands as things that actually improve their lives. So you know, for me, what I find rewarding is you know, science can have science has positive impacts in the world. We've seen it with COVID with COVID vaccines. There's just so much stuff that science around this and it's just so exciting and people should try it.

Nick Jikomes 1:19:01

Awesome. Well, thanks for joining me, Jeff. This was really interesting. Absolutely. I look forward to see seeing what you guys come up with the next few years.

Jeff Ubersax 1:19:08

Yeah, no, this is super fun discussion. I really appreciate you taking the time to do this is fun.


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