The Future of Biomanufacturing | Michael Heltzen, eXoZymes

In this episode of Biotech Bulls & Breakthroughs, John sits down with Michael Heltzen, CEO of exoZymes, to discuss the revolutionary move toward cell-free biomanufacturing. Discover how exoZymes is using AI to bypass the limitations of living cells, engineering "super-enzymes" through brute-force evolution, and bringing high-purity natural compounds like NCT to the mass market.

eXoZymes Inc.
https://www.biopharmcatalyst.com/company/EXOZ#/

📲 Follow Michael Heltzen and eXoZymes: https://www.linkedin.com/in/michaelheltzen
https://www.linkedin.com/company/exozymes
https://exozymes.com/

In this episode:

🔹 Why "cell-free" systems outperform traditional cell fermentation.
🔹 How AI is used to "speed run" evolution for enzyme development
🔹 Insights into the 2024 exoZymes IPO and their commercial roadmap.

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🎧 Listen to more episodes: https://www.biopharmcatalyst.com/podcast
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Disclaimer: BioPharmCatalyst is not a registered investment advisory firm and the views on this podcast are not to intended to be financial advice. The stocks discussed in this podcast may be held in personal or other investment accounts. This content is for informational purposes only and should not be considered investment advice. Always do your own research before making any investment decisions.

Transcript

Sponsor Message (Scientist.com)

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Introduction: Michael Heltzen, CEO of exoZymes

SPEAKER_01 2:01

Good morning, good eat uh good good afternoon, good evening, depending on where you're joining us from. Uh welcome once again to another episode of Biotech Bulls and Breakthroughs. Today is um Wednesday, April 8th, 2026. We're really excited to have uh Michael Heltson on the line um from Exozymes, uh, which is actually a publicly traded company that trades on NASDAQ and specializes in uh biomanufacturing, um, actually without using cells. The enzymes operate outside the cells. And we're gonna get into uh a little bit on why that's important and sort of what the company does that that is unique um and why we think people should should care about this. So uh welcome, Michael. Thanks so much for joining us. Yeah, thank you for having me. I look forward to the conversation. Absolutely. Um so if you wouldn't mind, just for the the folks on the call, just kind of give a bit quick background on yourself. Um, I know that you're the CEO, but you know, what is your what is your background? You know, how did you um how did you come to um to uh to do what you're doing at Exoscience?

SPEAKER_03 3:04

Yeah,

Michael’s Origins: Coding and the Bioinformatics Spark

SPEAKER_03 3:05

absolutely. Uh born and raised back in Denmark, that's where the accent is from. Um I basically early on in life uh uh had a a personality of being like super curious. I needed to know how everything worked. I had to take everything apart and see if I could reassemble it. I uh just had a mind-blowing experience when my dad brought home a computer and the whole computational world opened up. So I was one of these kids that started coding relatively early on. And um, I was actually struggling a little bit uh between like I love biology, I love nature, and then at the same time, there's this whole computational world. So for a long time I thought I had to choose one or the other. And um it wasn't until I ran into to a guy that said uh that he and his brother wanted to start a bioinformatics startup. And I was literally like getting a shock. I was like, that's the two passion area in one word, and I had already started figuring out at that point, that was my really early 20s, that that I was probably on the entrepreneurial um uh spectrum uh of having kind of like a a want and a need for going and building uh new things and and and trying to overcome some of the big problems the world is facing. So all of that uh basically crystallized and and I became one of the first guys um in the startup uh CLC Bio that became uh that's a journey of its own, but basically became uh the largest bioinformatics platform for next race and sequencing. And um here 20 years later is is still in use and is is called uh Kyotian bioinformatics. Um that was where the exit ended up being. So my career had been basically teaming up with scientists that have had large technology breakthroughs and and capabilities and then commercializing those. And uh my journey uh in that those those last um 20 years had basically been by uh first uh genomics, then later on more multiomics, but always with an element of of machine learning, bioinformatics, and and and now AI. And uh that's basically why I was um uh invited in to uh to to our company here uh back some some years ago, because I'm I'm a strategist and and translator of technology breakthroughs uh to the commercial business. And I had a thesis on we could also apply AI to uh to that whole self-free world and basically make it even uh faster and better. And that's that's what we have done, and that's who we are today.

What exoZymes do?

SPEAKER_01 5:51

Yeah, that that that's great. And obviously, you know, um certainly something that we're hearing quite a bit about and we'll get into a little bit um as far as as far as the machine learning and the AI piece, um, because that's definitely something that, you know, uh we've been talking about now, obviously, since the AI boom and continues to just, you know, evolve at an exponential rate. So I would love to hear a little bit more about that. But I guess just you know, um for you guys, just as uh from a company standpoint as a whole, could you just tell me a little bit more about specifically what it is that you guys do, what your general mission is?

SPEAKER_03 6:25

Yep, yep, absolutely. And hey, what why why does exercise matter? Basically, we can make uh natural product-inspired uh compounds and and things that the world otherwise doesn't have access to. So there's so many small molecules and and uh chemistries from from nature that we kind of have access to in trace amounts and we kind of therefore know of, and people have been playing around with it from a um either uh health benefit or other benefit uh product uh perspective. But it just comes down to like you can't isolate it enough of it in nature, you can't make it with petrochemistry and uh synthetic biology, uh, despite that, that was the big promise like five, ten years ago, have turned out to not really work at scale, and and a number of other things we can get into a little later. Um, but basically, we are a new generation of biomanufacturing methodology that allows us to be in that space in between all the possibilities of nature, but having basically engineering level control, and that's why we can apply AI to it, because it's like what one change leads to a feature change, and we can calculate our way through and plan our way through, and then learn from where we are right and where we are wrong, so we become better and better at it. But why does it matter? Um, let

Flagship Spotlight: NCT Molecule & Metabolic Health Revolution

SPEAKER_03 7:45

me give you our flagship product uh pits, really short here. Uh, we are able to make a small molecule called NCT. It boosts metabolism, that means turns fat into energy. That's really the short version of it. So it's a uh potential small molecule, the same way GLP1s have basically helped the world have a conversation about weight and weight uh loss and and metabolic health. Um the difference is that where GLP1s they basically they they mask or turn down your hunger signal and a number of other signals, kind of like uh bowel movement and muscle growth and other things, you end up with uh basically less of things where what our approach, the the drug receptor that NCT basically hits, uh is is the one that controls activity of mitochondria. That is your powerhouse of the cell, and therefore basically turns up the activity level of mitochondria. Hence burns more fat, creates more energy.

SPEAKER_01 8:49

Very interesting. So um, you know, hearing a lot of a lot of interesting things there. So would it be fair to say that, you know, within this space, you guys are almost competing with some of the the GLP1 drugs that are out there? Is that is that a fair assessment?

SPEAKER_03 9:05

So it's we we're still relatively young in that journey, but what is unique about uh NCT, because it's a natural product, is that we can take the natural product version, the exact same molecule as you find out in in nature. Um and and there is a pathway to make it a nutraceutical, that is over-the-counter supplement in instead of a um a drug and disease kind of conversation. So

Technical Breakdown: The engineering of an "Exozyme"

SPEAKER_03 9:30

that's that's the first uh route to a market for revenue and an impact on the world. In parallel to that, um, as you'll understand a little bit later in the conversation when I unpack how we actually do these things, we're in a very unique position to take natural products and make natural product-inspired molecules. That is still completely new chemistry from an IP point of view, but the reality is that we borrow evolution's worth of time up to this time point, and then we basically speedrun evolution forward and say what would the more optimal small molecule look like, and then we're in a unique position to build that because that is just optimizing on the enzyme step by step and giving it different building blocks, so it ends up with a slightly different end product that is uh more potent, more bioavailable, less less side effects, whatever it is we're engineering up against.

SPEAKER_01 10:24

Yeah, absolutely. No, that that sounds that sounds fantastic. And and my understanding was that there was um some you know pr preliminary results from the pilot. Um, I we I know we were talking about this a little before the call on that came out uh earlier this year. Did you did you want to touch on that at all? Um yeah.

SPEAKER_03 10:41

So so so basically that that was NCT exactly. We have we've been basically building our biosolution here at the headquarters here in the lab and and shown to ourselves that we can uh make this uh very, very pure, highly efficient uh biosolution. But what one thing is that we can do it with all of our specialized people. Can we hand it over to someone that doesn't have insight to how the technology works uh in in detail, but just want to manufacture it? So we we basically did a tech transfer to to K-man chemicals that uh, with all fairness, are more sophisticated people uh in in regards to to manufacturing things than than most, but uh we handed it over to them and and basically gave them the ingredients and and what is needed, but then let them take it from there. And um what is pretty unique about self-free is that, as we also showed in in this pilot, is basically that it actually performs equally well or better at scale. That's the exact opposite of what Synbio basically died on, that you could make things work in a picture dish and it was all fantastic, and you could have big value propositions, and then come with a little astro chop in the corner saying like, okay, get it to scale. Yeah, yeah. So so it it it almost ended up as a tease sometimes where these very, very big value propositions were were born, but but the world never got the product, the world never got the opportunity. So with cell free, because it's much more like a chemical

AI in Action: How ML predicts high-performance mutations

SPEAKER_03 12:15

reaction, it's biochemistry, it's it's the enzymes from inside of the cells that we basically look at from a genetic point of view and say, okay, that's how nature does this. And let me give a very concrete example so you can kind of follow the journey here. Yeah, that'd be great. In in NCT, you've already had, because it's in, for example, black pepper. Challenge is just that you would have to eat a houseful worth of black pepper to get one dose of NCT. And so it's practically impossible to harvest from nature. It's it only exists in trace amounts in in um in a couple of different sources, and there's just not enough of it. And the the economics of like burning all of that black pepper to give you one dose of NCT just doesn't make any sense. Right. Um, you you you can't make it in the pure form via pitochemistry. So up until now, it's been a known compound, it's it's been played around with a lot of researchers, but people can't get it at scale, and they also have a problem with with purity. Um so basically we sat down and said, okay, in black pepper, there is basically uh these six enzymes, some some uh feedstock that is broken down by some breakdown enzymes and then the buildup enzymes that makes NCT. That's that's the biochemistry that works inside of a cell. So we study those genetic codes for those enzymes and say, okay, this is how evolution got us to this point where NCT is possible. What if we brute force the rest of evolution or the next couple of billion years worth of evolution by sitting down with uh basically the protein folding tools that have become available to the world over the last uh number of years and said, like, okay, this is the genetic code that leads to the enzyme. What if I want the superman version of the enzyme that we call exocyme? Enzyme is inside reaction, exo is outside reaction. So that's why we use that uh that word. And and basically we want these superman versions of the enzymes that can survive outside of the cell, that keeps functioning for a long time, and and are basically uh willing to work with the uh substitution that we do that otherwise the cell typically uh manages, thermodynamics, all kinds of things that is in place in a cell, why we have been using cell fermentation up until now uh as humankind to make biomanufacturing, but now we're moving it outside and we we provide those support systems and then we put these exosymes uh up. But to finish up, how we make an exozyme. So, okay, I have the genetic code, I know that leads to this enzyme. I have some theses on what an exosyme would look like, what I need to improve. Now I sit down and calculate backwards and saying, like, wonder if I made one genetic mutation here, would that lead to an improvement or something that is worse? And that then when we basically just think that through via uh last language models uh or large protein models, um and and come up with a thesis of, let's say, like a thousand mutations that we think will improve this enzyme getting towards the state of being an exozyme. And uh that's where a lot of people will then say, like, well, Michael, you have a problem now because now you have a thousand lab experiments to run. You need to put that DNA into a cell, grow up, and get enough enzyme that you can take it out and then performance test to see if you're right. So predictions are kind of cheap

The Scale Problem: Overcoming the traditional failures of SynBio

SPEAKER_03 15:40

or or at least um easy to get around versus actually knowing if your prediction was right. So this has been the huge bottleneck in in applying AI to well, a lot of drug discovery and drug development, but specifically for enzymes, where it's a specific feature. So it's not just the structure of the protein you're predicting, it's the feature we're talking about. So it's it's it's even harder. But um, our team basically sat down and took on the challenge, and we are now, because we're so good at cell-free, able to take DNA and express the enzyme without putting it into a cell. So we have cell-free protein synthesis uh platforms up and running so that when our computer program uh or platform predicts what an exoscyme would look like and which mutations will go there, we can then go and mass parallel build all of those enzymes, performance test the different versions, and feed that data back to the algorithm and say, on this first guess you were right, the second guess you were not right, now go and learn from why you were not right, and then we can run that circle, reinforcement training style. And that is basically what we call brute forcing evolution, because that is what nature has done until now. They're just taking one generation lifetime permutation to see if it's better. But if it was better, that would become the prevalent trait of whatever that is, and that way evolution over billions of years. So we run a couple of billion years worth of evolution in a matter of a week. Oh wow. That gives us exoszymes. And that's why we can now start building with biochemistry that exists in nature as if it is chemistry, because we control those exosymptes to that extreme degree, and we have these self-free um uh the the self-free core platform that we spent a decade all the way back to when we were an academic project, uh, a decade figuring out what is it actually an enzymatic pathway needs from a cell, and one what can we replace one-to-one with a non-living system? Because the whole living um uh perspective on biomanufacturing is the whole problem. Like cells, by definition, only want to produce chemicals they need, only in amounts that they need. So they will try to regulate down everything you ask it to build. So your chemical factory does not want to produce chemicals. Number two, uh, if you overcome that, you often end up kind of getting the titers, basically, the production up so high that it becomes toxic or deadly for the cells. So you're actually killing your own, you're burning down your own factory if it's a chemical factory we're talking about. And then in the last end, because if if we have this picture of it being a factory, your end product ends up inside of the walls and the floors and the ceiling. So you have to take the whole goddamn thing apart and isolate out um your um your end product. So the isolation cost is often higher than the value of the product you're producing. So you will never have a business case.

SPEAKER_01 18:40

That that makes a lot of sense, and it's that's extremely interesting. Um I guess one one question that that comes to mind is you know,

Cayman Chemical Case Study: Validating 100-fold scale-up success

SPEAKER_01 18:50

this kind of self-free approach that you guys are doing. I mean, it sounds fairly unique. Is there, you know, would you say you guys are um like a unique player in that, or like who else is kind of doing something similar to what you guys are doing, if anyone?

SPEAKER_03 19:05

Yep. So so so obviously, like uh you you you're right. At at the first level, everybody seems to be, you know, everybody is cell-based. Uh and and there are there are use cases where cells are better than cell-free. So obviously, I'm focusing on what what works, what unlocks uh markets, products, business opportunities with this new platform. So when when when I talk about it, talk about that uh perspective only. But all of these problems are real. It is why synthetic biology as a market had not done that well, and I'm being diplomatic right now. Um so um, so where where cell-free is unique, you can argue we we were not the first people to liberate the enzyme from the cells. That that goes back to at least the 80s, if not much, much earlier, where people started realizing some enzymes can actually be taken out of a cell and still function on the outside. So the enzymes you have in your washing powder from um uh novosymes, now novonesis, uh, that breaks down dirt and blood and the different breakdown enzymes that kind of can be produced and harvested and put into to detergent is is an example of something we had for a long time. We have had other enzymes we've basically been harvesting from cells. So you can argue one step at a time, it's not that unique anymore. It's been done for for generations, starting to talk about the pathways, so more than one chemical reaction. That's where most scientists will come and tell you that's not possible. Those those pathways will only run inside of a full functioning cell because there's so many support systems. Like you need to have something regulating uh the feedstock, regulating uh thermodynamics, regulating all the cofactors, regenerating the cofactors. So all of those things is what our uh scientific co-founder team basically took on as a challenge back a decade ago at UCLA. Basically, uh they they they tell the story as a uh basically Jimbawi, the professor, um, have these two uh great students that are now our co-founders here, uh Paul and Tyler, and they make a SILP-based um uh biofuels system, and they're getting a nice publication out of it, and everybody's celebrating them, but then afterwards they're saying, like, but let's be honest with ourselves, this is never gonna work at scale, and we would really like to build something that makes a positive impact on the world, not just uh publications. And and and Jim pushes back a little bit and says, like, well, in that case, just give me the system without the cell, because the cell is all the problems. And he basically slams the door on the way out of the lab and and and thinks he made a good joke. But but the guy sits down and goes like, huh, what would that actually take? And that becomes basically the research thesis of that uh lab. other great things but this is this is the big thing that came out of of of the Bowie uh lab basically sitting down and and unpacking what is it enzymatic cells

Commercial Verticals: Balancing supplements and clinical drugs

SPEAKER_03 22:10

uh in cells supporting enzymatic pathways does for the pathway and what would it take to make those enzymes to what we now call exosymes and exosyme pathways and it's it's taking a decade so it's not been something it's it's an overnight success that took uh a decade yeah well that that that that's fantastic um obviously really really exciting work i i guess you know one of the the the other questions that i have um you know a lot of the the listeners on our on our call are you know investors in the biotech space and so they're always eager for for new opportunities um that present themselves from an investment standpoint so kind of what are these how how do you feel about the future um you know what do you think about these in innovations from that you guys are doing just kind of from a sheer sheer investment standpoint yeah I'm I'm by nature uh very optimistic um so um full full disclosure on on that I'm I'm a biotech entrepreneur that likes building solutions to big problems so so my answer to your like what what what is the perspective well this is a new form of chemistry that can basically give us abundance in the future so it's pretty big from a long-term perspective yeah I'm also a Danish guy we are known to be very concrete and very to the point it it doesn't matter it had if it has a big future potential if we're not executing on it uh step by step in front of us. So this is why I when I came in I basically narrowed the strategy of the company down to this nutraceutical and pharmaceutical strategy. Let's build natural products we already know is really expensive or really valuable and and basically get to market with something that can start generating revenue relatively fast while never giving up on on the really big impact potential of taking natural products and enhancing them by this brute forced evolution and and other optimization tricks we have so we can start making a new generation of small molecules because that is really where I'm uh short to medium term super focused. There is a large demand for small molecules that is the drug type that farmer knows exactly how to take to market it's it's basically the the the the the favorite type of drugs we just ran out of white space in the small molecule space because there's only so much petrochemistry can do and there's only so much you can isolate from nature. Now we are reintroducing a new way that means we're expanding the white space of small molecules significantly and we are also not just expanding it from the perspective of kind of like more diversity, more different things they can do, but we're now living in an era where we can start talking about what is the small molecule exactly? What should it do? How should it function on its drug receptor and then that's reverse engineer that small molecule to kind of like then it should look like this to make this small molecule that doesn't exist anywhere and you can't make by normal chemistry which enzymes can get us there? Can we basically reverse calculate and say okay these are these are the buildup enzymes that need to build these building blocks together where could we get those building blocks? What feedstock and what is unique about this platform is that despite here in the beginning we are going often after natural

IPO & Market Strategy: Navigating the 2026 investment landscape

SPEAKER_03 25:35

products so we can basically say okay this is how the pathway looks like in nature this is the genetic code behind it this is this is not a living system. So we can start taking enzymes from different organisms and plug and play them up against each other. This is chemistry. It's biochemistry synthetic biochemistry so so we can start saying and and we do that sometimes when we have a a pathway where there's one of the enzymes that we have a hard time evolving into something strong fast good enough then then we take a step back and say like does that chemical reaction happen anywhere else in nature oh over here in this completely different kingdom there is there's that reaction let's take that enzyme and and and optimize from that genetic code so so it's a um it's it's it's the physical manifestation of AI biochemistry that we're talking about here yeah absolutely um that that is extremely exciting um you know I guess one kind of final question from my end I mean are what's what's next for you guys in terms of I mean anything that you want to talk about that's upcoming as far as milestones or what you guys are working on that you know to the extent that you're able to discuss it what what should what should folks be aware of in terms of what's coming up next for you? Yeah so so we we a little uniquely IPO'd in November 2024. That was basically a time where everybody kept telling us like there's no way of IPOing right now as a biotech that does haven't even like you we couldn't even have the conversation about when revenue would happen because we hadn't picked a strategy and and a product guy yet. So so uh we we were uh very blessed and lucky that there was a lot of people with scientific insight and and insight to to to IP that that understood how big this tech breakthrough is and and how fundamental it is and therefore there to take a bet on us. So that's why it was possible for us to make a positive biotech IPO in a year where we were probably the only positive biotech IPO that year. So that's a year and some months ago so from a platform and a lot of potential we had now narrowed down to what our strategy is we have now basically built our first biosolution for the flagship product we are bringing that to market. So we're bringing NCT to market and in in these two verticals that we we talked about. So the value inflection points that I think people should keep an eye out for is when we continue that commercial journey of of partnering up with the manufacturing partners and the marketing partners around NCT and then over on the clinical side with the biotech pharma company that

Future Pipeline: Beyond NCT, What’s next for the platform?

SPEAKER_03 28:15

we're going to end up either joint venturing or licensing out the the the the the pharmaceutical use case of NCT. And this is product number one we have product number two being built already and we have product number three being built already and we have an idea management setup where we basically screen for what we call extraordinary business opportunities that lives up to basically top shelf kind of scoring of biggest markets, most value release, uh no competing products all of these things, us uniquely being able to to service those markets. So so we want to make a uh a series of natural product inspired nutraceuticals and pharmaceuticals over the coming years. And I welcome people to follow us we we try to be open and communicative in in regards to our shareholders and and potential investors and we have a lot of videos on our webpage that dives into everything from the science to how we go to market with NCT.

SPEAKER_01 29:20

Very very cool that's that that type of transparency is great. And um you know this has been extremely insightful. I really appreciate the time on this um it's certainly unique and um something that I definitely think folks should um should take a look into and pay attention to um uh Michael is there anything any final anything final that you wanted you want to discuss before we um before we wrap up any any last kind of words um if not that's fine but just wanted to give you the the opportunity I just want to remind people that the future is going to be bright we will have an abundance of resources like our our dream for the future is that we live in a future where there's enough for everybody.

SPEAKER_03 30:03

That is why we go to work and do the the the long days and and and the the the tough problem solving is because there are new generations of technology coming up now that really have the potential to do that. And sometimes when I open the newspapers it sounds like everything is going down the drain and nothing good will come from from AI. And I'm I'm not saying that there's not problems coming up and that there's not things we should navigate but I want to remind people that there's also good things. Like we are an example of how we can do a new generation of chemistry medicinal chemistry. There'll be new medicines that that are unthinkable today coming from from these kind of efforts and

Final Thoughts: Why the future of chemistry is nature-inspired

SPEAKER_03 30:45

that makes me happy and uh positive about the future.

SPEAKER_01 30:49

Yeah I I really I think that's a really important point. And we we see that on our end as well. I mean the the negativity sort of the the AI apocalypse right but I mean to the same point embracing the technology we you can just tell how powerful it is and if used appropriately particularly in things like drug discovery and medicine I mean we are talking about solving problems at you know possibly a more much more exponential rate than we ever have before um which obviously is is a great thing for humanity. So I I I would concur on that and I think it's definitely important to remind folks of um so thank you for for mentioning that. For everyone on the call um you know really appreciate you guys listening in again. Really think this is some exciting stuff um and something that everyone should take a look into. And uh Michael once again um you know I really appreciate the time here um this has been awesome and um thank you for for walking us through everything you guys are doing.

SPEAKER_03 31:48

Thank you so much for the opportunity.

SPEAKER_01 31:50

Yep absolutely have a good one everyone