Damien Perriman is Chief Commercial Officer at eXoZymes, where he leads the commercialization of cell-free bioengineering and next-generation biomanufacturing technologies. With more than 20 years of experience in industrial biotechnology, he has helped bring innovative, sustainable solutions to market across specialty chemicals, fuels, materials, nutrition, and personal care.
Human Transcribed
Damien Perriman:
So now that we're dealing with enzymes outside of the cell, we get to do this sequence of biological conversions in a way that sort of happens in nature but happens in this sort of engineering level control way. We went from idea to commercial scale manufacturing in less than two years now. In my career in biotech of the last 20 years, that's a really short and fast journey. I think the fastest I ever went before on a system, like five years to go from idea to commercial production. So two is astonishing.
Chai Nussbaumer:
What happens if you take an enzyme out of a living cell? You get an exozyme.
Micah Schweizer:
How does this change make manufacturing so much faster? And what could it help create?
Chai Nussbaumer:
In this episode, we're talking to an executive from eXoZymes with a capital X and Z. To learn more...
Micah Schweizer:
We'll find out how this technology works, how it achieves high purity yields, and hear about the Nobel Prize winner who pioneered cell-free biomanufacturing.
Chai Nussbaumer:
I'm Chai Nussbaumer.
Micah Schweizer:
And I'm Micah Schweizer. This is Balancing the Future from METTLER TOLEDO.
Chai Nussbaumer:
On this show, we explore the world of science and technology and the solutions transforming our lives.
Damien Perriman:
Good day, Chai. Thank you for having me, Damien Perriman and I'm chief commercial officer for a company called eXoZymes, a cell-free bioengineering company. My role is to help steward this technology to tackling some of every day's biggest material and chemical supply chain problems.
Chai Nussbaumer:
Could you walk us through how traditional medicines are manufactured?
Damien Perriman:
Yeah. See, the issue with a lot of traditional medicines and even sort of traditional materials throughout our entire ecosystem that humans rely on for everyday progress are generally sourced from petroleum-based feedstocks. And we've been using chemistry tools or converting that feedstock to useful materials that haven't really changed so that much in the last 100 years. And the way they draw upon resource is unsustainable for our environment, and the chemistry they use is often toxic or hazardous for the people that are involved in making these materials or in the localities where they are produced. Or often we draw upon natural resources for extracts that contain precious chemicals that are made by biology in a way that that ecosystem cannot or that habitat cannot sustain. The last hundred years, we've been able to fuel tremendous human progress, but it's not the way to move forward in the next 100 years.
Chai Nussbaumer:
So sustainability is a big touchpoint for your company, it sounds. Can you talk a little bit about some of the challenges such as compounds with medical potential, low yields, slow R&D, speed to market, for example?
Damien Perriman:
Yeah. So when we think about sustainability, it isn't just about finding a way to use renewable resources and lower our carbon footprint. And whilst that is important, it's not the only design consideration we have. When we think about sustainability, it's also about how do we find a system where we can draw upon raw materials that we can replenish, or how can we draw upon raw materials that aren't hazardous to that environment upon which they come from or where we're introducing them to? So sustainability is a very rounded concept in our minds in that regard. Much of the problem I think traditional chemistry has faced is, we're designing with the chemist goal in mind and not so much biology's goal in mind. And biology's really good at designing things that work in biological systems. So work with humans, work with plants, work with agricultural systems, and biology's really, really selective.
Biology is very good at saying, "This is the target I'm trying to solve or this is the stimulus I'm trying to eliminate, and how do I design a system that does that?" I think that's where biology inspiration is fueling a lot of new ideas from materials we can make in a better way right now. But Chai, I think much of the trouble we've been running into in the last 20 years as we've been working on this synthetic biology revolution is, biology can give us the inspiration, but biology doesn't scale up very well. Biology doesn't become an economic system particularly easily. And that's one of the things that the chemical industry has gotten very good at in the last 100 years is how to be profitable or how to deploy capital and build equipment that works at economic scale. And that hasn't been biology's experience.
So what we're trying to tackle here at eXoZymes, and the reason why I joined is, working in the sort of new cell-free approach where we're using biology as the inspiration, but using the enzymes of biology, those tools that actually do the conversion, do the work, we're working with them specifically in an engineering setting. And so now we get to scale our systems up as though we were just performing traditional chemistry. So we get all of that sort of benefit of those efficient systems for scale up that previously just weren't available to us in biology, in synthetic biology.
Chai Nussbaumer:
So let's talk about the solutions. Could you explain what an exozyme is?
Damien Perriman:
Yeah, no, of course. So an exozyme is taking the enzyme that exists within a biological system, and generally it's regulated by a cell, a microorganism or some type of living system. But the enzyme's job is to really take a raw material and convert it into something that's biologically valuable to that system or maybe to us as we've looked to that compound and the way it could benefit humanity. When we take that enzyme and we convert it into an exozyme, what we do is we use our tools of bioengineering combined with our tools of artificial intelligence and large language models to optimize the way that enzyme could function without the cell, right? So that enzyme can function as a catalyst in a bioreactor, in a way that we can control in a sort of engineering level way, all of the things that happen inside that bioreactor. And that's what's needed to scale efficiently is that engineering level control. So that's an exozyme. It's just an enzyme that functions outside of a cell in an environment that we've designed.
Chai Nussbaumer:
And are there any safety concerns during production?
Damien Perriman:
Yeah. So now that we're dealing with enzymes outside of the cell, we get to do these sequence of biological conversions in a way that sort of happens in nature, but happens in this sort of engineering level control way. The biological approach to making many chemicals often avoids much of the toxicity that you see in chemical-based systems. We're not dealing with raw materials that can be hazardous. We can select for raw materials that are available to us in nature, which are often much safer and much easier to source. And then being in this bioreactor where we've got control over every input, every environmental feature, that allows us to have really strict control over what's produced, how quickly and what we can recover. It's been incredible. We've been able to engineer systems now that make ingredients for nutraceutical supplements, ingredients that have wellness impact, and we can produce them very, very quickly. We can scale them up very, very quickly, which gives us that chance to create impact very, very quickly.
Chai Nussbaumer:
And how are your production methods different than traditional pharmaceutical manufacturing?
Damien Perriman:
Yeah, so a lot of the way things get manufactured today, either by traditional chemical synthesis, so you get a petrochemical of some type and you could have 18, upwards of 20 reactions to get to the target product that you want. Yields are often really, really, really low because sometimes chemistry can produce a diversity of things, multiple enantiomers or multiple side reactions. So when you get to your final product, you've actually had to waste a lot of material to get there. And then when you go into a traditional fermentation system, which is often used for also producing various materials, those systems take a very long time to run.
It could take upwards of three days to complete a fermentation run to get to a relatively small amount of product, and you've got to separate a lot of spent biomass, you've got to separate a lot of dead cells that have been involved in that production. Those are some of the issues that have hampered production. When we go into a cell-free system, we convert high amounts of raw material to end product. We're getting upwards of 90% conversion of everything we put into the final product, so not a lot of waste. And our systems run very, very quickly. We can do multiple transformations. We call it a cascade where you've got multiple enzymes working together to start at a raw material and finish at a target product. We can complete that in four hours.
Chai Nussbaumer:
Wow.
Damien Perriman:
Not three days, but four hours. So that very, very rapid production system, it just changes the economics of what you're producing. And once you change the economics and you can start making these materials available to people that need them in a way that they can afford to use them.
Chai Nussbaumer:
Yeah, that's phenomenal. So what class of compounds have you produced so far?
Damien Perriman:
Yeah, so we've produced a whole range of cannabinoids as we've been looking for the role that cannabinoids can play in influencing the endocannabinoid system as it could influence drug discovery. So that's been a really exciting space for us to get into these sort of non-psychoactive cannabinoids that have real health hypotheses, really substantiated health benefits. We also worked with a compound called N-trans-caffeoyltyramine, which in both pre-clinic and in human clinical studies has this positive effect on metabolic health, the cellular energy and cellular efficiency. We were able to scale that up super quick. We went from idea to commercial scale manufacturing in less than two years now.
Chai Nussbaumer:
Wow. Yeah.
Damien Perriman:
In my career in biotech of the last 20 years, that's a really short and fast journey.
Chai Nussbaumer:
It is.
Damien Perriman:
I think the fastest I ever went before on a system, like five years to go from idea to commercial production. So two is astonishing.
Chai Nussbaumer:
Yeah, absolutely. So what levels of purity are you achieving with the molecules you produce?
Damien Perriman:
That's a great question, Chai. And I'm going to start by saying, if you were to look to natural extraction as a means to getting to a really sort of biologically precious material, purity is your biggest battle, right? Because there's always a mixture of other bioactive compounds that exist around it. Plants aren't single-minded. Microbial systems are not single-minded. They are trying to balance a very complex set of needs that they have, so they make many things. If you want to get access to the thing in there that is really, really important to you, you've got to start separating all the other stuff.
And it's that separation cost that becomes really, really expensive to try and get to your target purities. But still, in much of the world of supplements, if you're dealing with extracts, you're dealing with purity levels that are like 10%, maybe 50% if it's a particularly high value bioactive. And so then what the producer has to do is demonstrate all the other stuff that wasn't needed but was too expensive to separate, isn't going to cause some type of reaction that's unsafe to humans. When we use a cell-free system, we're hitting 99.6, 99.8% purity.
Chai Nussbaumer:
Wow.
Damien Perriman:
So not much other stuff. And that's because the enzymes have one job. They have a singular focus and that's to make the target product that we've designed it to make. And that's what I mean by the value of that engineering control is to be able to be very specific to what comes out and our purity levels are like pharmaceutical grade, and we get there very, very efficiently. And so that means we can go to our partners and say, "You don't have to worry about all the other crap because it's not there, and you can expect every single batch you get from a cell-free system is going to look exactly the same as the previous one." So that reliability and that consistency is also super important.
Micah Schweizer:
Hey, Chai.
Chai Nussbaumer:
Hey, Micah.
Micah Schweizer:
Chai, have you heard of Eduard Buchner? He was a German biochemist who could be considered the father of cell-free biomanufacturing. He won the Nobel Prize for chemistry in 1907.
Chai Nussbaumer:
Wow, interesting. What did he do?
Micah Schweizer:
He ground and pressed brewer's yeast to produce a clear cell-free liquid, then he added sugar, and then the liquid began releasing bubbles of carbon dioxide. His conclusion was that you didn't need living cells to make fermentation happen.
Chai Nussbaumer:
Yeah, you can really see the connection to exozymes. Today though, we have much more control over how chemicals are made.
Micah Schweizer:
That's right. And we also have access to much more computing power, and now of course, AI can play a role too.
Damien Perriman:
We use AI up and down and sideways in our company. I think where I saw the biggest impact coming into eXoZymes about a year and a half ago was the way they used AI in designing experiments, and then the way they fed experimental information back into AI to improve that design. It enabled this group to go superfast. I mean, to go from idea to proof of concept on a compound in two to three months, and my previous experience was like, that's a 12 to 15 month journey.
That's AI shining itself out, being able to predict better experimental outcomes and have those experimental outcomes land closer to those predictions, being able to simulate a lot of what could happen, but then also to learn and sort of understand how certain functions or certain results can be connected back to raw experimental data gives us a lot more sort of predictability throughout the full process design.
I'd say AI is becoming more and more important in SynBio or in the chemical industry at large. We recently got a grant from the Department of Energy to participate in their Genesis program, which was exactly that idea of how do we use AI to double the productivity of American biomanufacturing?
Chai Nussbaumer:
And why did eXoZymes choose not to trademark the exozyme concept?
Damien Perriman:
Well, it was a good debate and I think we saw the word exozymes all lowercase as just a new scientific principle, as a new way of just describing enzymes that function outside the cell. So why should we own that? That should be available to everyone because it's a very convenient word for describing enzymes in this way. And we think if cell-free becomes more and more ubiquitous to production, as we believe fervently it will, then everyone should be using exozymes. So we chose very deliberately not to trademark exozymes. Our company name is eXoZymes, but we get a little cute with the X and the Z, right? Exozymes should be ubiquitous for how we use various tools of production.
Chai Nussbaumer:
And let's dive a little bit into the future. What's next for eXoZymes as a company and for the broader exozyme concept?
Damien Perriman:
I use this word repeatable development engine. It's something I talk a lot to our partners and to our investors about. And honestly, it's a term that gets batted around by a lot of companies in their early days as they try and demonstrate that they have the potential to create lots of impact. We all aspire to it, right? If we develop a tool base that's effective, why don't you just keep using those tools? But there's a difference between the aspiration of having a toolbox that's valuable and actually having a toolbox that's valuable, and that difference is delivering.
So us taking N-trans-caffeoyltyramine to market is the demonstration that we can deliver, and being able to do that in two years is a step change. It's a big step change from what's been done before. So now we've earned the right to start thinking about how do we use the tools again, and how do we take all of those experiences and the team that we built up over time as we did the NCT experience, and how do we think about the next chemical target that we go after?
So what we've been doing for the last couple of months actually is we've been taking people back into early stage discovery and we've asked the question, take everything we learned on NCT. What is the next best set of chemical targets we should be throwing ourselves against? Where is the next hard to make natural product? Where is the next human condition that hasn't been well served or well met? And how do we design a pathway to make a chemical that could unlock that opportunity and what does it look like?
And so we're using AI not just to think about how to design a system for a target product, but we're also using AI to how will we put that product into the market? Where are those unmet needs? Where do we see clinical results that actually don't go anywhere because they can't make the product that they've identified as being potentially really, really valuable? That for us unlocked the thesis of quite a number of targets we could go after.
So that's really, really exciting. And we told our investors back in our last quarterly investor call that by the end of the year, we'll have some proof of concepts done on some future chemicals that will be our development focus in '27 and '28 and onwards. Our goal is idea to commercial scale. Let's do that. Every two years we've got a new product hitting the market. That's going to be incredible pace of innovation.
Chai Nussbaumer:
And you mentioned briefly about the partnership with the US Department of Energy, the Genesis Mission. Can you tell us a little bit more about that work?
Damien Perriman:
Yeah, look, it's exciting the way industry at large is embracing AI to enhance biomanufacturing efficiency or manufacturing efficiency in its totality. The DOE Genesis Mission is exactly that. How do you double productivity of manufacturing within the United States as its target? So they've got their national labs to team up with industry partners on projects that can help unlock those tools to double productivity. We're working with the Berkeley Lab and we're focused on building digital twins. These are systems that we can actually simulate the way a bioreactor would function in an AI setting, right? So that allows us to predict experiments going into a reactor, how they would behave, but then to use that data coming out of the reactor to feed back into that system to make it more and more powerful in the way that it creates that prediction. We think this is going to really speed up the R&D effort even further, which I think would be a great boon for industry.
Chai Nussbaumer:
Are there any molecules or fields that you're hoping to target in the future or near future?
Damien Perriman:
Oh, yeah. I mean, I'll be careful what I say here because we're not yet public on our next field of chemical targets and we've got-
Chai Nussbaumer:
Okay.
Damien Perriman:
... many an investor waiting on bated breath to go, "Tell us what they are." I don't want to scoop them here on this podcast as much as that would be fun, but I'll talk about some of the indications we want to be in. We think women's health is a really important frontier to move into. We're understanding a lot more about women's health today than we did before, and we're looking for materials that can make a real impact in that space, mood, sleep, pain. These are all indications that we think are really, really important.
With our first compound, N-trans-caffeoyltyramine, I mean that's tackling weight and mitochondrial dysfunction, cellular energy. Building upon that I think is a great opportunity in the world of GLP-1s. We're looking for companions now for GLP-1s, things that people can take before they become obese, things people can take after they come off GLP-1s. Those are, I think, really important categories to serve. And we will take cannabinoids into drug discovery. We got a $2 million NIH grant this year to support exactly that kind of effort. Theres a lot of indications we're looking at that I think could really benefit from well-made, economic, efficient, super pure, superfast to market products that unlock a lot of those benefits.
Chai Nussbaumer:
Well, Damien, it's been such a pleasure speaking with you and it's very exciting to hear where eXoZymes is headed in the near future. So thank you so much for your time.
Damien Perriman:
Thanks for having me on the show, Chai. I appreciate it.
Chai Nussbaumer:
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