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Going Boldly into Biomanufacturing and Bioeconomy with Inscripta

Final Transcript 

Harry Glorikian: Hello. I’m Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare. 

Today on the show we’re gonna talk about biomanufacturing and bioeconomy, where companies engineer microbes like yeast and bacteria that grow in big fermentation tanks. 

Thanks to their altered genes these microbes can pump out almost anything you can think of, from new medicines to agricultural products to cosmetics. 

Our two guests are helping that revolution along. 

But before I bring them on, I need to give you some of their backstory.  

So, a couple of years ago I was joined here on the show by a computational biologist named Richard Fox 

Richard had spent years at a company called Inscripta, helping to build a machine called Onyx that could take microbes like bacteria or yeast and make programmed edits at thousands of different points in their genomes, all in parallel and very quickly. 

When we talked in April of 2021, Richard had just left Inscripta to form a spinoff company called Infinome. 

The idea at Infinome was to use the Inscripta technology, along with the principles of directed evolution, to help customers rapidly engineer and optimize new microbes for biomanufacturing and bioeconomy. 

That platform was called GenoScaler

In one example, Infinome partnered with Kalsec, a company that makes spice and herb extracts for the food industry. 

Together, Infinome and Kalsec used GenoScaler come up with ways to use fermentation to make new flavoring ingredients.  

Well, now it’s two years later, and Richard is back inside Inscripta. 

And today he’s back on the podcast, along with his new boss, Inscripta’s CEO Sri Kosaraju, to explain why Infinome and Inscripta decided to reunite, and what they plan to do together. 

The very short version of the story is that Inscripta decided to pivot away from selling the Onyx machine and focus instead on becoming “power users” of their own technology and ultimately making their own biomanufactured products. 

So it made sense to bring Infinome and the GenoScaler technology back inside Inscripta. 

At the same time, Inscripta bought another startup called Sestina Bio that’s one of the first companies to show how the underlying technology can be used. 

Sestina plans to use biomanufacturing and bioeconomy to make synthetic form of Bakuchiol, which is normally derived from rare plants native to South Asia.  

The companies hopes to market its version of Bakuchiol as a replacement for Retinol, also known as Vitamin A1.  

A lot of people are familiar with Retinol. It’s used as an anti-aging ingredient in skin creams. 

The problem is that it causes photosensitivity in some people. 

Richard and Sri think there would be a big market for an alternative without that side effect, if there were an easier way to make it—which, now, there is, thanks to Sestina’s work and the GenoScaler platform. 

So, I just threw a lot of names and history at you. 

But the big picture here is that Sri and Richard think we’re just at the beginning of a biomanufacturing and bioeconomy revolution, and they want to be the ones that are  out there making some of its first big products. 

The three of us talked back in mid-February of 2023.  

Here’s our full conversation. 

Harry Glorikian: Sri, Richard, welcome to the show. 

Sri Kosaraju: Thank you, Harry. Thanks for having us. 

Richard Fox: Great to be here, Harry. 

Richard Fox and Sri Kosaraju on The Harry Glorikian Show

Harry Glorikian: Richard, I want to say welcome back, but we’re going to get into some of those details in a few minutes. But there’s been a lot of change at Inscripta since the last time I talked to you, Richard. Before we get there, I want to step back at a really high level and ask you two gentlemen to talk about the specific field of biotechnology you’re aiming to revolutionize. And that is biomanufacturing. I mean, we have a pretty broad audience on a global scale. So I think it’s maybe it’s important to start by explaining what biomanufacturing and bioeconomy is, why it’s so important today, the essence of biomanufacturing and bioeconomy. You know, if I’m characterizing it correctly, it’s the use of genetically customized microbes, like, let’s say a yeast cell, to produce complex biological molecules in big fermentation tanks. Right. And. That’s how the class of drugs known as biologicals has been made for decades now. But these days biomanufacturing and bioeconomy are also being used to make more kinds of, you know, different kinds of products, not just medicine. So if you could spend a, I don’t know, a few minutes talking about the biomanufacturing and bioeconomy space, why it’s so important to have better ways to design and engineer microbes that are actually doing all the work. And then we can go into deeper depth as we’re going forward. 

Sri Kosaraju: Yeah, Harry, it’s a big question. Maybe I’ll start super high level and let Richard maybe talk more specifically about what is biomanufacturing and some of the details under it, because I’ve always watched and admire the way he articulates it. It’s elegant. But the bigger picture, just for the layman, like me, I’m not a scientist. I don’t have a PhD. But what captured me about the the bio economy at large is the role that biology can play in so many different industries and themes that aren’t just therapeutics or life sciences. You know, we’re talking about the bio industry, which are everything from food, agriculture, personal care materials, you know, biology as a core underpinning ingredient or raw material or supply that goes into so many of the products around us, is quite large. And our appreciation of that opportunity and the themes that it can lead to. There are three in particular. Yes, we talk about health. There are obviously some health applications and improving health and wellness. There’s sustainability. That’s a major, massive focal area for consumers and now many industries and how they operate their companies and serve their constituents or customers more sustainably to protect our environment. And the last one is, is really also around economics: manufacturing productivity, right? And um, so much so that even our, our government, you know, the Biden administration, President Biden has put out an executive order on the bio economy talking about this. You know, that’s how imperative it is and that’s what’s at stake. And I say it that way because it adds a different sense of urgency. You know, it’s not an opportunity. It’s what’s at stake, you know, for our future and our competitiveness on the global stage. So that’s at a high level of like how we paint the picture now and what, what we’re organizing the company around. But, but maybe I’ll pass it to Richard to talk more specifically about, you know, what is biomanufacturing and bioeconomy. 

Richard Fox: Yeah, I think that’s a great overview. I don’t think I could have said it any better. I mean, there’s lots of estimates out there about what’s the size of the market out there. It’s, you know, from hundreds of billions to trillions of dollars or more, depending on how you want to do the do the calculations. But this, you know, by all accounts, and many have written this, I’m not the first to say it certainly won’t be the last. This really is the century of biology, right? I mean, the last century was about the atom and the byte. You know, I think the byte will live on. Hopefully the atom and civilian uses will be the only use. But really, this is the century of biology. This is now we’re going to, you know, unlock the potential of the genome and our specific areas around biomanufacturing and bioeconomy. But there’s a larger, you know, bio economy as well, of course. But I think Sri painted a good picture about, you know, like the way he said it, not just the opportunity set, but, you know, what is the stakes because so much of our environment and social pressures and where you source material and having consistent, you know, stable manufacturing supplies for lots of, you know, compounds of value to society and of interest is going to be critical going forward. And so I think that’s that’s the area that we’re pretty excited to be playing in. 

Harry Glorikian: So one more sort of, I guess, science or engineering question before we get sort of to the interesting, you know, business backstory that brought you two together, maybe I should say, back together. Um, what are the basic ways, say, Inscripta can help its customers optimize these microbial strains they use for biomanufacturing and bioeconomy? I mean, maybe you guys can walk through the various products or platforms. I know there’s something called MAD7 nuclease for CRISPR-based gene editing. There’s GenoScaler, the computational platform that was brought back in from Infinome, where you were, Richard. And I don’t know if all of this is still a big part of your business, but also the Onyx instrument to automate the massive parallel genome-scale engineering. So can you guys paint a picture of how all these pieces play into how you’re servicing the customers that you’ve got or you’ve you’re going after? 

Richard Fox: Yeah, I think we can do that. Sri, maybe you want to start a little bit with perspective on that. 

Sri Kosaraju: Yeah, and I’m happy to. So Inscripta’s history goes back quite a quite a long ways, right? It’s not just the last few years. It’s, you know, back in 2015, the foundational technology was around genome engineering, right? How do we leverage CRISPR on a much larger scale and leveraging the philosophies of some well known scientists that came before us, and espousing their philosophies and advancing that, using the technology that was now available and afforded to us by CRISPR. Inscripta is very well known in the industry, by offering a lot of these technological and scientific components to the industry. MAD7, you mentioned, is a nuclease that many researchers have accessed for free, which is a very, very unique proposition. And it’s something that the company offered really to help advance people’s work in the lab. Right. Critical research and academia and industry. And we hear a lot about it today. Um, what’s built around that scientifically, the biochemistry, the engineering that all was put together on a platform called Onyx. And the idea was how do we basically build a bio-foundry on a that someone could put on a bench in their lab, right, and utilize. And a really exceptional piece of technology. The first bio-foundry on a bench that was ever launched, Inscripta created. And Richard and the team from Infinome were critical in the early stages of getting that off the ground. And so as much as we talk about these different pieces and the different technologies and organizations, it was always close. And the idea, and Richard can go into this more, of Infinome, and now where Inscripta is, is not just being on the side of creating and selling that technology, but on the side of continuing to evolve that technology and using it because the power of that technology and what it could produce. Leading back to our conversation on the bio economy, we’ve now seen as incredibly powerful and a huge opportunity. So, Richard, I don’t know if you want to take it from there, but that’s just explaining some of the components of historically where we were and where we are now. 

Richard Fox: Yeah, I think that’s really well put. And so to sort of frame why those components are important, I think we talked about this at length last time, Harry, but it’s worth, um, it’s worth repeating, which is, you know, the, the central challenge around engineering biology is it’s very difficult. It’s not amenable to the same kind of approaches that you see in lots of other engineering disciplines, whether it’s electrical engineering or computer science or building bridges or airplanes. We simply can’t look at even a single protein, let alone a pathway or a genome, and say these are the precise changes I want to make and have it work right out of the gate as, as you would wish. Um, so there’s a long history of people trying to, you know, bring as much as they can to the table in terms of computational design and literature and lots of really good first rate science. But historically and for the foreseeable future, we’re going to need methods that allow us to rapidly and efficiently explore the sequence space. We have a lot of experience in history of doing that at the protein level. And there was a there was a healthy competition over the last 10 or 20 years between empirical, directed-evolution type approaches to engineered proteins and rational approaches. It turns out they’re actually complementary. But at the end of the day, the Nobel Prize went to directed evolution. And the reason for that is because it works. And you actually don’t even really have to understand how the systems work. In many cases you can’t. And yet it works. And so it’s a very reliable method if you have the right tools supporting that strategy. And so the central thesis behind Inscripta, and what we were doing as a subsidiary for a couple of years at Infinome, using the core technology that Sri described, was to use those very efficient empirical approaches to be able to rapidly engineer very complex biological systems. 

Harry Glorikian: Okay, now that we’ve got that background, I want to sort of back up a little bit and talk about how did all these pieces sort of come together? Right. Because, Richard, you were on the show almost like just two years ago. When I went back and looked and I was like, oh, my God, like time is flying, it was back in April of 2021. And we talked about Infinome and the path you followed to the founding of that company. And you know, that path led through Inscripta, back then. And you were, I think, executive director of data sciences from like 2017 to 2020. And now that Inscripta has acquired Infinome, as Jack Nicholson would famously say, “Honey, I’m home,” right? You’re back at Inscripta, you have a new title which is SVP of Synthetic Biology Products, right? And so that sequence of events is a lot to keep track of. So I wanted to sort of, maybe do some of the history for everybody because we haven’t spoken to Inscripta before. Maybe Sri, you can [explain] when was it founded? To solve what precise problem? At the time of founding, you came to the company, I believe in 2020 from Penumbra, which makes medical devices, and I’d love to hear what got you excited about joining the company. And then, Richard, I’m going to jump back to you for a couple more questions. Yeah. 

Sri Kosaraju: Well, I’ll tell you the story. It’s a fun one. So I came on board, as you said, about two years ago, and I was introduced by our board to in-common investors from another company I’m involved with called 10x Genomics. 10x is an extremely successful company in single cell and now moving into spatial and in situ research tools. Public company. Great company. Great management. Great board. That same group of investors and board are behind Inscripta and that’s how I got introduced to it. And our chairman, John Stuelpnagel, an exceptional individual who initially had the conversation with me about Inscripta and the technology and the idea that we were about to launch Onyx, you know, this really forward thinking opportunity to really leverage CRISPR and offer a tool in people’s labs that could offer the opportunities that Richard talked about. Right? And if you think about an analogy like next gen sequencing of what that did, you know, to read genes and the leaps and bounds that it offered in research, you know, and what it did to for scientists and their discoveries. We thought about it in the same way of now writing genes, and a tool like Onyx could do, you know, for opening up this whole new opportunity set that that technology could afford. As we did that, as I came on board, Richard, Andrew Gerst and two other of the co-founders left to start Infinome. Fortunately, we connected at that time and I stayed really close. Richard and I stayed really close, talking about what they were doing. And it made a lot of sense, you know, leveraging our technology, but advancing into the application layer and the product layer, right? And really getting closer to the opportunities that we could impact, that made a lot of sense to us. 

Sri Kosaraju: It wasn’t part of the Inscripta business plan, because we were launching an instrument or a tool. So it was set up as its own independent subsidiary that Inscripta backed so that that team could move quickly against that different opportunity set, of not selling the technology like Inscripta was, but using it and advancing more into exploring bioproducts, biomanufacturing and bioeconomy. So what’s happened in the last two years since that? Two things. I think we’ve been encouraged by the opportunity of the bioeconomy. We gained a tremendous amount of confidence that that opportunity is real. It’s massive, it’s real, it’s out there like many transformational industries. Questions around what’s the timing or what’s the catalyst for that to go, that remains a big open item or a risk. But we became very convinced of the opportunity of the bioeconomy. We also became very convinced of the power of our technology. We even saw it through Onyx, through some of the customers that had it and were using it and what they were doing. We saw it through what Richard and team were doing through Infinome. We had a lot of confidence in the technology and so the conversation we had was how what do we do with that? How do we become a bigger, more prominent player, impactful player in this opportunity leveraging our technology? And the answer was to take a very bold, proactive step, which was to follow the Infinome model and really redirect our energies and our strategy behind it. 

Sri Kosaraju: And that was a big move. Harry, I’m not going to lie. There were a lot of people and a lot of investment in the Onyx product and that tool strategy and a pivot away from that was so incredibly hard to do. And so many people were heavily invested in that. But again, we wanted to be bold, to point ourselves against the opportunity and how to really leverage our technology the right way. So we did that. We announced it in January, just last month, that we were reorienting the strategy. We were folding in Infinome. Even though that seemed like a transaction it’s really not. They were already part of the family. We also folded in Sestina Bio, who was a customer, an Onyx customer, so very familiar with the technology and some incredibly talented folks who also complimented our platform and were successful in bringing a product forward called Bakuchiol that was driven from their approach in genome engineering and can we can share more about what that product is. But it’s a real live, tangible example of what we’re talking about that this technology can create. So that’s that all happened in the last few months. You know, we took those bold steps to reorient the strategy, fold in and begin the integration process with Infinome and Sestina Bio. And off we go. We’re running at this new strategy very aggressively. 

Harry Glorikian: Well, it’s funny because I think Richard, Richard remembers when I was talking to him the first time and I was scratching my head going, I don’t think you’re going to get very far. I think they’re going to suck you right back. Based on what you’re doing, I can’t imagine that you’re going to get very far without something pulling you back into the mothership. So it’s good to know that, you know, I wish I had published that prediction and we could go back and look at it. But, you know, so the model is now changed. I mean, you guys raised not an insignificant amount of money. There’s been, you know, the downsizing, the restructuring. If you had to summarize now this bringing Infinome back inside and, if it’s not the tool, what are you? What’s the real, the new offering that if you were pitching somebody, what would you say that we’re now bringing to the table for you as a customer or client? 

Sri Kosaraju: Well, I’ll bring a real life example of how we’re now talking externally to our commercial partners/customers. Um, I mentioned a product that Sestina Bio had developed called Bakuchiol. Bakuchiol is a replacement for retinol in the personal care industry. A lot of people use retinol, the over-the-counter retinol, on their skin. It’s an anti-aging treatment, but it has some side effects. It has irritation, sensitive to light sunlight, but people still use it. It’s a large product, right? Um, there have been studies on its replacement called Bakuchiol that have shown that it’s safer, it’s more efficacious, it doesn’t cause irritation, doesn’t have the photosensitivity. Um, but it hasn’t taken off. Why? And that’s because of the supply. It’s sourced from a rare plant that’s grown in Asia and the supply is not there. So Sestina Bio, leveraging their own platform, but parts of Inscripta and Onyx, developed bakuchiol through yeast, engineered a bio-based product that now we’re confident we can scale and we’re talking to partners about. So the opportunity for a more efficacious product, you know, to what’s already out there and that can be sourced naturally and not threaten the environment is a great story, right? And I’m raising it because it provides an example, but an entree to open a discussion of personal care companies of, hey, there may be other actives that we’re interested in that could be great consumer products that we’d like to explore GenoScaler to help us produce, develop and manufacture. Um, so that’s the personal care industry. But like I’m saying, the bio economy is much larger. Our opportunity set is much larger to create molecules that either can be replacements or open up new markets using, you know, effectively nature right through our engineering. So that’s now what we’re offering. We’re offering in this case ingredients, products and that that can be manufactured at scale to these companies. And in the case of what I just mentioned, personal care companies. 

Harry Glorikian: Yeah, it’s interesting. I mean, there’s so many life sciences companies. I know that when I see sometimes what their platform can do, I’m like, You can make a lot more money using it than selling it to them, right? Especially because you know how to use it better than they know how to use it most, you know, a lot of the times. But yeah. Richard When you left Inscripta to start Infinome, if I remember correctly, you were just starting to figure out how to turn your statistical modeling or machine learning work into a platform to sort of speed up the directed evolution experiments by predicting how changing multiple parts of a microbiome genome will change its phenotype. And I think that’s the platform that we’re talking about, which is GenoScaler. And now it’s part of the Inscripta lineup. I mean, can you talk a little bit about where you are with GenoScaler, maybe its capabilities. Maybe there’s an example that you can drive to like a, you know, a true customer that you can bring up. I think you guys have a partnership with a company called Kalsec, if I remember it correctly. So I don’t know if if. You can sort of tie those to that whole story together for everybody. Yeah. 

Richard Fox: Sure. So actually, we can step back a little bit. So I kind of alluded to this now and I think I spent a lot of time in the last time we talked is that a lot of our experiences and our vision have been informed by our experiences trying to engineer proteins for lots of different applications. And a lot of the things we learned over the years, engineering proteins we believe and are now seeing are equally applicable to engineering entire genomes. If you have that editing capability, that is the foundation for everything we’re doing in Inscripta. A piece of that is very well developed in proteins and in other larger sequence spaces, which is to learn from that data and inform next round designs, as it were. But actually the fuller, more important sort of view of GenoScaler is it’s it’s not just computational. That’s just one piece of it. It’s really the ultra high throughput, massively parallel way of empirically interrogating genomic space, as it were, that will generate lots of data in time that we can learn from. And there’s we could spend a whole hour on just that. But our platform isn’t necessarily in any way limited to that. And in fact, right now it’s just a piece of what we’re doing. It’s really more about bringing the foundational editing technology along with an integrated technology stack to run this whole engineering cycle efficiently. 

Richard Fox: And you just you had said something just a few minutes ago that was absolutely one of the founding principles that we had at Infinome, which was this idea of, it’s not enough just to have a powerful technology like what was embodied in the Onyx instrument. It’s knowing how to use it, right. And that was one of the lessons that we had in Inscripta and we certainly believed in our hearts at Infinome. We felt like power users of the technology. We knew the ins and outs of how to make it really successful. And so that integrated holistic view of engineering biology with this transformative piece that was missing now essentially is GenoScaler. And GenoScaler is the rapid engineering piece, the rapid design, build, test, learn of optimizing proteins, pathways and genomes, but it’s also the scale up. So going from high throughput, looking at lots of different, thousands, or tens of thousands of, you know, genomic variants in microtiter plates and then scaling that up robustly to, you know, five liters and then 5000 liters and then 50,000 liters. You know, that’s the whole picture from concept all the way to commercialization of GenoScaler at large. 

Harry Glorikian: Yep. So but if I’m, I mean, if I’m sitting in envisioning this, you know, in my mind, I’m thinking you almost want a machine learning platform that’s learning from every experiment and every test that you’re doing to then feed back in. And I mean, at some level, you could do some of this in silico at some point when you, you know, when you’ve done enough of these in one particular organism to understand what changes give you the results that you’re looking for. If you’ve got a this feedback loop… 

Richard Fox: Spot on. That’s exactly right. In the fullness of time, these data sets will, we have every reason to believe, and are working towards accelerating the engineering process in exactly the way you described. But it starts with that ability to to generate data. So, I mean, everybody is familiar with ChatGPT at this point. And for good or for bad, these large language language models, there’s some really exciting applications of them in the protein space, protein design. So I mentioned earlier, you know, rational design and directed evolution just in the last few years, using these large language models to sift through hundreds of millions of natural protein sequences to try to predict essentially new sequences that have fold and function is now starting to show some promise. It was kind of unthinkable before, but the only reason you could do that was because you had enough data to drive it, right? And so with biology, other than a few data sets, like those protein data sets and genomic data sets, what’s missing usually is the data, especially labeled data. Like, does it have function? And so what’s the other interesting piece that you already kind of said, Harry, but I’ll just build on is that this technology, for the first time ever, because of the scale at which it can produce data, now we’re uniquely positioned to be able to generate enough of it to do the very kinds of exciting, you know, AI driven types of design that you’re talking about. 

Harry Glorikian: Yeah, I was just I spent, you know, an hour and a half talking to, you know, one of the companies in AI and, you know, pharma. They just got, you know, the first AI drug, orphan drug approval here in the US. So talking about the exact same thing. But, you know, one of the things that comes out is on the front end, you’re generating a lot of data, so your price is high until you can get to scale. And when you get enough data, then it starts to come down over time. So it’s something you’ve got to to manage, right? Because we can spend a lot of money on data in, in, in the initial stages and you almost want a completely robotic lab that human beings are not fussing around with that can just repeat, next experiment, keep going, feeding that data back into the system as you’re doing I guess what might be termed as sort of high-throughput screening. But I think at that these days, as multiple technologies that are interrogating a sample to feed back to the, let’s say, the master algorithm. 

Richard Fox: Yeah, I think that’s right. I think definitely reducing cost and that’s a big part of our what we think is our value proposition is, is even now today, even without this additional accelerant from AI, we’re reducing costs by essentially, and speed and outputs, by essentially an order of magnitude compared to where we were just a few years ago. I think what’s going to really be the biggest dimension, because cost is already actually relatively small in the scheme of things, is going to be the speed, you know, getting cycle times down to maybe even days at some point and then making the best use of the edits or the mutations that you introduce in the genome. Right. I talked a lot about we have empirical approaches because we don’t know what to do. So we have to try lots of things. Eventually we’d like to get to the point where our our our batting average increases. Right now it’s, you know, maybe 1 or 2%. But guess what? We get 10,000 swings at the bat. So we have a lot of home runs. But still, it’d be nice to get up with a, you know, Ted Williams batting average at .400. And, you know, most of the time get on base or get it over the wall, right? I mean, that’s something that right now is not feasible. But with data and more experience and learning from it, I think is going to be the biggest sort of knob to turn over time. 

Harry Glorikian: Well, data from you guys that you’re generating yourself, but also any data that might be available outside that you can absorb that might be able to complement what you guys are already doing? 

Richard Fox: Yeah, precisely. Yeah. Like these large language models for proteins, they’re amazing in what they can do today. And yet the proteins that they’re designing still are often very low activity compared to what nature’s done. So still, they’re requiring fine tuning and things like directed evolution to get to where they need to be commercially. Yeah. 

[musical interlude] 

Harry Glorikian: Let’s pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that’s leave a rating and a review for the show on Apple Podcasts. 

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It’ll only take a minute, but you’ll be doing a lot to help other listeners discover the show. 

And one more thing. If you like the interviews we do here on the show I know you’ll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.  

It’s a friendly and accessible tour of all the ways today’s information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place. 

The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian. 

And now, back to the show. 

[musical interlude] 

Harry Glorikian:   So you mentioned Sestina. As you know, one of the acquisitions that you guys made during this whole, you know, shift in the last month, if I got it, got the timeline correctly. I you know, I know that they created this product that from is, you know, the endangered plant. Is that something you guys are just holding up as an example? Are you guys looking at commercializing it or is it a sort of a twofer where you’re you know, this is what we can do and oh, by the way, we’ve already got the product, so we’re going to we’re going to do this for you. And then. I mean, just having some experience in this cosmetic world, that does require some extensive testing to have them take that product on and put it into their production. So can you walk through maybe some of those dynamics that you’re dealing with? 

Sri Kosaraju: I think the the product opportunity is is real and it has an ability to help. I think a lot of people, a lot of people want to use the product and don’t want the side effects they currently have. So I think there’s an impact that the product can have. But you’re right, it does offer a very real, tangible demonstration of what the platform can do. And Sestina had their platform before, you know, being integrated into Inscripta, but they did it in less than 12 months, you know, from discovery of the key enzyme to, you know, now producing it in lab scale, a production level that we’re comfortable that we can scale up. You know, that’s pretty remarkable and a great demonstration of what a platform like the one we have and that we’re creating can do. So that’s, you know, how we’re demonstrating this. And I think so many companies have created great technologies that are going to be doing the same thing that we’re doing, which is, hey, how do we point this towards, you know, the real opportunity in a more effective way and pivoting to try to create products and, you know, create a biomanufacturing and bioeconomy strategy like we are. But what makes it different is having success, right? Having a real product. You can demonstrate and having the repeatable success that says, like Richard mentioned, we can do this at a high hit rate, right? And a good success rate, which means we’re doing it faster and cheaper than anyone else. And ultimately that’s what it’s going to come down to. You know, we’re building this great technology, which I think everyone wants to hear about, but, you know, the demonstration of that and how it translates is going to be the ultimate measure. Right? And so that’s what we’re focused on.  

Harry Glorikian: Oh, yeah, Especially these days. You know, everybody’s like, show me, like, get me that product, get me that, you know? And then they start believing when when it gets farther down the line. But yeah, I was reading that you guys have this philosophy in Inscripta where it’s described as lean bioengineering, right? What does that phrase mean to you guys? 

Richard Fox: Yeah, so I’m partly responsible for that. When we were at Infinome, we we coined a couple of terms. One was GenoScaler, the other was lean bioengineering. And maybe the easiest way to say it succinctly, but I’ll, I’ll unpack it, is GenoScaler, what I talked about earlier, enables lean bioengineering. So lean bioengineering is these metrics that I talked about, you know, the speed with which you can do things, the resources that are the inputs. And then what’s your outputs essentially, you know, what’s your performance improvement, especially as measured in terms of your engineering, you know, the jumps per engineering cycle, that together these constitute, you know, what are your inputs and outputs and being able to do things in a way that doesn’t require huge amounts of capital infrastructure and operational burden because there’s a lot you can do with lots of people and lots of automation and lots of infrastructure, and there’s some really nice work that’s being done and has been done and will continue to be done because that’s the best way to do it with the tools that are available. But what this technology affords us is the ability to, as I kind of said earlier, essentially by several factors or orders of magnitude or more, change each one of those key dimensions: speed, resources and output. So together you now have what we now say is lean bioengineering. And and part of our confidence with this is, again, you know, apologies to go back to protein engineering, but we saw the same evolution that we saw in protein engineering over 10 or 20 years, and that is going from large teams of, you know, 10 or 20 people down to just a few people per team cycle times of months, down to weeks, and performance gains of, you know, percentages up to, you know, many orders of magnitude. 

Richard Fox: And so we know it’s possible to accelerate complex biological optimization if you have the right strategies and tools. And so now taken all together, we believe we’re there now with with GenoScaler doing lean bioengineering. And so this, and we already talked about it, but the importance of this is now even as a small company you see a lot of synbio companies have great ideas for really transformational products and they go out and they get, you know, well-deserved investment to go after one product. Hopefully they pick the right product. Hopefully they have the right engineering teams and science and technology to deliver on them. And we have an abundance mentality in Inscripta. We hope there’s there’s lots of room for lots of winners in bio space and we hope and wish all of those, you know, entities out there to be successful. But the thing a lot of folks are laboring under is they’re typically one product, one company, because that’s what the technology is. You know, they don’t enable you to do more than that for the most part, unless you’re very well resourced. And so even as a small company, Inscripta is trying to break that model, we have multiple products even with this, you know, relatively small number of people because of what the technology platform enables us to do in terms of our efficiency. 

Harry Glorikian: Yeah, typically, I mean, what you see is, you know, everything, you get a lot of them and then there’s a shake out and, you know, the space evolves. I mean, the good thing about having a lot of them is everybody’s, all the investors are paying for everybody to get educated and then learn how to do it better in the the next turn. And it it happens over and over and over again. I can’t tell you how many times I’ve seen it happen so far. 

Sri Kosaraju: We’re in a different environment, too, right? Like, we were in a beautiful environment where capital was readily available and cheap. And so it could fund being very risky and building out innovation. And the environment is different now. So whatever money you raise, it not only has to do the job, but it has to be economical and sustaining a real business and real model. So I think there’s three challenges with synthetic biology companies. One, can they create the molecules that we’re looking to create? Two, can they scale those at a scale with fermentation and manufacturing where it can be available to mass markets? And three, can they get through one and two in an economical way so that they can support their business, you know, and do it again? And I think those are the three major gates, you know, which means all of this, all the great technology, everything we’re talking about, it has to work in a model that allows us to scale as a company. 

Harry Glorikian: Yeah, I don’t know. Maybe I’ve just been around and doing this too long, but because I keep watching this cycle and I can see things and I try to tell people and they’re like, No, of course not. Like I’m like, that’s impossible. It just look at history. It’s going to repeat itself. Like we just don’t know what we don’t know and we learn as we go along. Yeah, but okay, now that you guys have dne this restructuring you’ve brought Infinome and Sestina technologies in, what markets and customers are you most excited about going after? 

Sri Kosaraju: Um, so I think it’s a great question and it’s a it’s a question of, you know, where do we point our ship and our priorities? And I think there’s a there’s a careful analysis about that opportunity set. Um, you know, there’s so many markets available, but a careful understanding of the dynamics of those markets, not just the magnitude of the dollars, but are those markets that are really truly a good fit for our technology and what we can do right? And so this will be a little bit of the secret sauce, Harry, of I think, how the next generation of synbio companies will be successful or not. It’s tackling those gates that I mentioned. It’s about the innovation and the platform. But it’s also going to be about how do we select and prioritize the markets that we approach. And I think that is going to be a competitive differentiation for a lot of companies. It’s very easy to get distracted in this market because everyone, every partner will come to you and say, Hey, can you do this for us? And we’ll say, Yeah, we’ll do that and we’ll dedicate a bunch of resources to go do that. But I think a careful understanding and analysis of the markets, their viability, the ability for us to execute on those and the timelines that are involved is is really, really critical. So I’m not going to perhaps on this call share exactly what they are, but I’ll confirm that it is a I think, a very big part of our success and we’re trying to build a competency to differentiate ourselves there. 

Harry Glorikian: So if you had to frame the company. I mean, are you going to be a services company helping biomanufacturing and bioeconomy companies create better strains or are you going to be, imagine yourself being developing your own strains in-house and becoming a manufacturer yourself? So, you know, because I’m thinking of it like a great question. A drug development company, right, they wrestle with the exact same question. Do I make my own drugs or do I help someone, you know, make a drug for themselves? And so so where are you guys on that? 

Sri Kosaraju: Our view is our best way to help and to have an impact is more along the latter of what you just said. Our ability eventually to bring our own products that we develop in in-house and we will need to work with commercial partners who are leaders in their fields to bring these products to market, a commercial partner, eventually to help us. We’ll supply the product, manufacture it. They’ll be the front face of it in their markets that they know well and have long established relationships with. That will be the eventual model. Our path there could mean that we partner with people earlier, you know, earlier in the development cycle to to develop something together that we know there is an established commercial market in that party, you know, waiting for it, you know, to to to have it. That could be part of the initial model to get us going and the relationships going. But again, we think we’re going to have the biggest impact and we think the most opportunity will be in eventually doing, developing and commercializing ourselves. 

Harry Glorikian: Well, I couldn’t agree more. I mean, you know, when you’re a venture guy like I am and you’re looking at what the dollars, helping people do stuff. It’s all you’re always getting squeezed and it’s always small dollars compared to having the product yourself. Yeah. 

Sri Kosaraju: Totally agree.  

Harry Glorikian: Yeah. So. Let’s move a little into maybe sci-fi mode. Speculate about the future of Biomanufacturing and bioeconomy. It seems to me like this can go in a lot of different directions. I mean, I know that there’s a company in Europe called I think it’s called BioPhero that uses an engineered yeast to produce synthetic insect pheromones that can be used for disrupting mating. Right. It’s a natural way for farmers to reduce pest populations instead of spraying the fields with large volumes of toxic pesticides. And it seems like the question with those kinds of ventures is whether the company has created the right microbe to scale up the biomanufacturing and bioeconomy process economically. Et cetera. But do you think that if we have a better way to design custom microbes, biomanufacturing will spread to more parts of the economy> I mean, help us, you know, potentially solve problems in agriculture or food production, climate change, I mean, some of these areas. So I’m going to let you, you guys spin it up a bit to to tell me where this is going, if everything goes right. 

Richard Fox: Well, you’d be surprised if we said no, right? 

Harry Glorikian: I’m giving you a platform, Richard. 

Richard Fox: Speaking of batting average, it’s a softball. Yeah, clearly, that’s one great example. And it’s a really interesting one. All of these natural products, this is a huge space and it’s not limited to just agricultural chemicals. It’s so many of the things that are being produced today are done either inefficiently through extraction based methods like, like the bakuchiol that we mentioned, or for nutraceuticals. There’s just almost a limitless number of examples of things that nature doesn’t either, plants or strange microorganisms, just don’t produce enough. But if you can identify what those pathways are and then move them into more tractable hosts and then not just that, but then be able to engineer them rapidly, the ways we’ve talked about here that just it it opens up just a universe of opportunities to replace things or supplement, depending on the case. You know, what’s the traditional bio-based route to those things. And then there’s a whole class of molecules that are natural products that really can’t be made at all. Maybe they’re just in trace amounts and there’s no way to engineer that bug at all. But it’s maybe some powerful anti-cancer drug or antimicrobial or it’s a new nutraceutical or something. And so there’s these large segments that I think this is why I think it’s the century of biology. There are people who, you can’t do certain things today because even if your imagination can go there, we just don’t have the tools and the capabilities to get there. 

Sri Kosaraju: Yeah. Just to add on to what Richard said, which I couldn’t agree with more, that back to what we said at the beginning, it’s what’s at stake. Like this is going to happen globally where you’re going to move in this direction of where biology is more the underpinning of of the products around us, because we have to do it from an environment or sustainability perspective or because they’re just better products, you know, that consumers pull for, that we are manufacturing more effectively, that don’t stress our supply chains. I think industries are going to transform based on this. And the great analogy that I used a few times internally, like if you think about our our auto industry, the combustion, you know, well before the combustion engine, there was a huge transformation in combustion engines. But think about what we’re going through now. You go to a dealership, you look at a car, it looks exactly the same. You open the hood and it’s got an electric motor. And there was a huge investment required to do that, which we got through. It’s economical now. Consumers want it and see the value of it. And what are we globally? Only 10 or 15% of market share is electric vehicles. And that’s going to become probably half, you know, in the not so distant future, like we’re heading the same direction and industries will transform with this technology as soon as you know, there’s some skepticism on the science, which I hope we’ll get through quickly. We’ll demonstrate products, we’ll demonstrate the economics and the benefits and impact it has on the environment as well as the economy and consumers. It’s going to happen. This is going to be real. The question is how long is it going to take? 

Harry Glorikian: Well, look, I mean, whenever you’re changing industries, you’ve got to have, I always believe and nobody says like, oh, you can’t just have one person, but you need at least one person with a big, hairy, audacious goal that can raise the money and just doesn’t care about everybody else, that does what they’re doing and just plows it forward. And I totally agree. I mean, I think we’re getting to a point in certain technologies and certain areas where if your country doesn’t have it, you’re toast. And I’m not sure that most people understand this. You know, a law of change that’s happening here when you’re coming to data and how it’s going to have implications in biology and what it’s going to do to change the world. But, you know, I think if we don’t have it here we’re going to have problems later, later on down the road, if we’re not careful. So I wish you guys incredible luck in in what you’re doing and success. And I can hardly wait to see how this unfolds now that everything is is come together back under one roof. 

Sri Kosaraju: Well, we appreciate this is a fun conversation and yeah, we’re really excited to to share it and excited we’re part of one company and with this strategy now. And look forward to coming back in the not so distant future to tell you the progress we’ve made. 

Harry Glorikian: Awesome. Great to have you guys on. 

Sri Kosaraju: Thanks, Harry. 

Richard Fox: Thanks, Harry. 

Harry Glorikian: That’s it for this week’s episode.  

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FAQs about biomanufacturing and bioeconomy

What is biomanufacturing?

Biomanufacturing is the process of using living cells or organisms, such as bacteria, yeast, or mammalian cells, to produce commercially useful products. These products can include a wide range of biological molecules, including proteins, enzymes, and antibodies, as well as complex biopharmaceuticals such as vaccines, gene therapies, and cell therapies.

The biomanufacturing and bioeconomy process involves multiple steps, including cell line development, fermentation or cell culture, purification, and formulation. The cells or organisms are cultured in a controlled environment, such as a bioreactor, and then harvested and processed to extract the desired product. The purified product is then formulated and packaged for use in various applications.

Biomanufacturing and bioeconomy have numerous advantages over traditional chemical manufacturing processes, including lower energy consumption, reduced waste generation, and the ability to produce complex biomolecules with high specificity and purity. It is an increasingly important field in the biotechnology and biomanufacturing pharmaceutical industries, with a growing demand for biomanufactured products in areas such as personalized medicine and regenerative medicine.

What is biomeconomy?

The bioeconomy refers to the production, use, and conservation of biological resources and their conversion into a range of value-added products, including food, fuel, materials, and chemicals. It encompasses all economic activities that involve the use of living organisms, their parts, or their derivatives.

The bioeconomy is based on the principles of sustainability, efficiency, and innovation. It seeks to promote the transition from a fossil fuel-based economy to a more sustainable, biobased economy that relies on renewable biological resources. This transition is driven by the need to address global challenges such as climate change, food security, and the depletion of natural resources.

Biomanufacturing and bioeconomy includes a diverse range of sectors, such as agriculture, forestry, fisheries, biotechnology, and waste management. It also involves the development of new technologies and processes that enable the efficient and sustainable use of biological resources, such as biofuels, bioplastics, and bioremediation.

Overall, the bioeconomy is seen as a key driver of economic growth and job creation, particularly in rural areas, while also addressing environmental and social challenges.

What is special about resilience biomanufacturing?

Resilience biomanufacturing is a term used to describe the development and implementation of biomanufacturing processes that are designed to be robust, flexible, and adaptable in the face of disruptions, uncertainties, and changing conditions.

One of the key characteristics of resilience biomanufacturing is its ability to respond quickly to unexpected events, such as supply chain disruptions, equipment failures, or changes in demand. This is achieved through the use of advanced technologies, data analytics, and process control strategies that enable real-time monitoring, analysis, and optimization of biomanufacturing and bioeconomy processes.

Resilience biomanufacturing also emphasizes the use of sustainable and renewable resources, such as renewable energy and biomass feedstocks, as well as the development of closed-loop systems that minimize waste and reduce the environmental impact of biomanufacturing and bioeconomy processes.

Another important aspect of resilience biomanufacturing and bioeconomy is the development of flexible manufacturing platforms that can produce a range of products, from small molecules to complex biologics, using a common set of equipment and processes. This enables manufacturers to respond quickly to changing market conditions and produce a diverse range of products using the same infrastructure.

Overall, resilience biomanufacturing and bioeconomy represents a shift towards a more agile and sustainable approach to biomanufacturing and bioeconomy, which is better able to cope with disruptions and uncertainties while also delivering high-quality, cost-effective products.