All right, good morning, everybody. Welcome to the Stephens Conference. I'm Jacob Johnson, the life science tools and pharma services analyst here at Stephens. Really pleased to be joined by Codexis. We have Kevin Norrett , the Chief Financial Officer, with us today. I'll be running the Q&A, but if anybody has any questions, feel free to chime in during the presentation. So with that preamble out of the way, Kevin, I'll turn it over to you for any introductory comments.
Sure. So, thanks, Jacob. Really excited to be here to tell you more about the Codexis evolving story. We've gone through quite a transformation over the last 12 months. I joined the company about a year ago or so with the new CEO, and we subsequently have turned over a few other pieces of the management team. And what we now think we have is really a compelling story, both in terms of an ongoing revenue-generating business, as well as a significant development option, almost a free option in many ways, in terms of potential upside, as we think we have a disruptive, game-changing technology for the manufacturing of RNAi Therapeutics.
Oh, okay. Thank you for that, Kevin. So maybe to kick things off, you used, I think, "evolving" and "transformation" in your comments, and you mentioned you're part of a new management team. Maybe discuss your background and what attracted you to Codexis, and what have you been focused on since you joined just over a year ago?
Sure. So my background is in finance, biochemistry, and commercial operations, and I think one of the things that really was important to me in my next opportunity, as I've been at five or so different emerging biotech companies over the last 10 years or 12 years, has been to, you know, build and reshape companies and get them ready for what could be significant commercial opportunities. And so, you know, when I was talking to Stephen Dilly, our CEO, we previously worked together at another company. What Codexis looked like to me was an organization that had a significant portfolio of assets and potential opportunities, but needed some additional insights into which ones were the ones we needed to be commercializing, where should we be placing our bets, and then how should we be entering those markets?
So it fit really nicely with my background. That gets to kind of the attractiveness of Codexis. You know, just to—from a broad overview standpoint around Codexis, this company has been around for about 20 years, and, you know, or two decades, and essentially has been applying its CodeEvolver Technology Platform , which is sort of directed evolution of enzymes, to a variety of different business segments and verticals. And that essentially has led to this massive portfolio, but really what hadn't been found was probably the killer app, as we like to say, for this technology. And so, as part of the last year, we've been streamlining this organization down to what we think its killer app is, as well as focusing down on our revenue-generating arm, which allows the funding of that potential killer app, which we call the ECO Synthesis Technology Platform.
Got it. So I promise we'll get to ECO Synthesis, but maybe before we get to where you're going, maybe get to what, what you've done over the last year. And so I think-
Mm-hmm.
When Stephen and the team came in, you guys moved very quickly to focus the portfolio, which you alluded to. I think that's been a big focus area for you. Can you just talk about what didn't make sense for Codexis and where you have pulled back on efforts?
So when I joined Codexis, we had three, maybe four business verticals. One was our pharma manufacturing, Biocatalysts business, supporting the development of small molecules and the active ingredients for those. We also had a life science tools, a portfolio of enzymes that were spread across genomics, in vitro transcription, PCR-based diagnostics, and we also had a Biotherapeutics arm that was spread across, you know, oral enzymes, for various types of inborn errors of metabolism, as well as gene therapy assets, and both of those were in partnership with key pharmaceutical customers, or key pharma partners. But essentially, my first task was to roll through the life science tools enzymes and look at which and where were ones we could exploit.
We had developed a suite of enzymes that, probably a smaller percentage of them were game-changing enzymes, which is where we needed to be focused. So streamlining that portfolio on those enzymes that we think were game changers, those for, you know, to name a few, the HiCap RNA Polymerase , which supports mRNA vaccine development, as well as our newly engineered DNA Ligase, which supports the genomics workflow. Those enzymes, in particular, were not just incrementally better, but game changers, at least according to our customer feedback. So the rest of the enzymes, we've been looking to, you know, leverage downstream partners, and we hope to be able to announce a few key out licensing types of deals in the next couple of months, as we've been in conversations to streamline that portion of the portfolio.
The other piece was looking at the Biotherapeutics portfolio, and we had a lead asset there. Many of you might not know this, but we've recently decided to exit the Biotherapeutics segment, not because of the clinical data we saw. In fact, we had a very successful clinical data readout earlier this year for CDX-7108, which was an engineered lipase for increased fat absorption in pancreatic enzyme replacement therapy... definitely a billion-dollar opportunity, the two products that are currently in the market, you know, sell close to $2 billion annually. We were partnered with one of those folks, and that's the Nestlé Health Science. But what we quickly realized, and this is where my drug development background came into play, that there was a significant amount of runway needed to get to approval with that product.
We were in a partnership with Nestlé, a 50/50 co-commercialization, co-development agreement, and that product wasn't likely to get approved until 2029, and potentially be profitable by 2033. So we had to quickly pivot and look at what we could execute with our current resources and cash runway, and that really wasn't in our window. So we decided to exit that portion of the business and pivot towards where we think we make a huge difference, which is in engineering exquisite enzymes for various improvements in the manufacturing process, whether that's pharma manufacturing for API or whether that's improvements around the manufacturing of mRNA or RNAi.
Got it. Trying to think. There's a few follow-ups there. Maybe more explicitly on 7108, can you just talk about... Like you said, that's 50/50 with Nestlé, so presumably you're talking to them about how you can, you know, I guess, partner it off to them, for lack of a better word. Just what's the game plan there? When can we expect an announcement?
Mm-hmm.
How's that going?
It's going really well. Many of you might know-- not know, but I had worked with that company before when I was at Aimmune Therapeutics with Stephen, so we had a prior relationship. So we've been in concrete conversations with them around a potential out-licensing strategy for this, you know, phase one asset, so that they can continue development, 'cause this fits squarely in their portfolio with the Zenpep sales that they already have, and already being a key commercial player in that market. So we expect that go-forward agreement to probably be done here in the next couple of months, maybe weeks.
Okay.
And to give you a sense of what we're thinking about, really, you know, kind of a modest upfront milestones and associated royalties in order to allow them to continue to pursue the opportunity, but also to allow us to step back and reduce the burn, which is, it's an important part of the pivot we went through in July.
Yeah. So maybe on kind of reducing the burn there, so that obviously reduces it. Do they? You're not spending money, but also, as we think about partnering off some of these assets, what does that? How do those get structured? Like, do you wanna license them out to somebody? Could you get cash coming in the door from some of these arrangements? Any way to think about that?
Yeah, absolutely. We've been looking at potential ways to bring cash into the door. I mean, I think that's a big part of our streamlining the organization over the last year, was to rightsize the organization, provide the cash runway to develop—we'll talk about later, our ECO Synthesis platform. And a big part of that is being able to bring in some relative cash upfront for associated with some of these deals. That provides us the wiggle room we need to get to what we've said is our potential path to break even at the end of 2026. So we think... This is an important point.
We think we're really in a unique position where we have now a revenue-generating story associated with our manufacturing, a business growing at high single-digit, low double-digit CAGR, with an established customer base that overlaps nicely with our sort of killer app, as you might say, for the manufacturer of RNAi, and we have the cash to do it in a timeframe that is reasonable from getting to profitability within the next, you know, two to three years. So-
Got it. Sorry, on the life science tools side, so you have a couple of killer apps. I promise we're gonna get to the asset business.
Oh.
But just some of the other things you've exited, can you just talk about why you got it or why you're planning to partner those off?
Well, I think we want it. One of the things that Codexis has done as part of its history is do one-off customized projects for enzymes that fit in a portion of a workflow.
Yeah.
So when we look at the life science tools portfolio, we had, you know, a DNA polymerase, we had RNA polymerase, a reverse transcriptase. All of these are pieces of the workflows, as opposed to a more complete solution.
Yeah.
So in order to be able to move up the value chain, as you might say, for garnering a larger, you know, share of the economics, you need to provide more of a complete solution. So we just see some of those other enzymes, and we still have customized projects going on today. We can talk more about those.
Yeah.
And we don't expect to exit that business entirely as customers approach us with unique challenges, 'cause what we think we do really well is complex engineering, and can make a game-changing enzyme for somebody. But that doesn't mean we have to exploit that commercially ourselves. We can leverage partners to do that after we've completed the evolution, and let them extend that commercial reach as to how that fits in there. So I think that's where the out-licensing and sort of, you know, asset purchase component of being able to monetize some of these enzymes becomes really important. So we're not exiting doing engineering of novel enzymes for these different workflows. We're just not gonna make it a core focus of trying to provide a complete solution there.
We think it's much better to be doing that around a segment that has relatively lower competitive intensity, could be hugely disruptive in the next several years, and we can provide a more complete solution with our platform.
Got it. So, kind of what you just mentioned, these kind of one-off projects. You know, I think historically, Codexis, you know, had all these.
Mm-hmm.
A lot of irons in the fire, I guess. And I think one thing Stephen was pretty clear on is, like, we need to figure out where we can win, and we need to focus on kind of lumpier—lumpy is the wrong word, larger opportunities. Right? So I guess as we think about that pharma manufacturing business, and maybe also kind of on the tools side, but, you know, how much effort are you putting into business development there? Or is it more just about what's already kind of in the pipeline, continuing to work on that, continuing to manufacture the commercial stuff? Like, how are you approaching that?
We feel... Well, we're putting a fair amount of resources. The way to break it down really is about two-thirds of our organization is focused on our development program, which is the ECO Synthesis Technology Platform, and the remaining third is focused on driving our pharma manufacturing business and any other customized or partnered enzymes projects that come in through the door. I mean, we still have goals of driving, you know, this high single digit, low double digit growth in this category. And while we're starting to see some materialization or some of the pipeline starting to come through there, that was put in place three to five years ago-
Yep
... from a customized enzyme project, so we have to continue to fill that pipeline. So from a business development standpoint, we continue to engage with our partners. We're continuing to try to target, and this is something Stephen and I said when I first started, which is this sort of, you know, medium-sized pharma and-
Yep
... large biotech to fill the pipeline, 'cause frankly, we hadn't spent a lot of time. We had been focused on large pharma, where we have established relationships, so we're expanding the pipeline in that regard, and also being more selective as we take on projects. Before, Codexis, you know, was taking on projects as much as possible to see, like you said, irons in the fire-
Yep
... to see what could work. I think we're at a point now we can be more selective. We've developed huge screening libraries and be able to customize and scale up enzymes to manufacture for phase II, phase III clinical trials in this segment much more quickly. And I think that sort of lens is what we need to do there. So it's, it's not a matter of reducing the focus there. It's more a matter of just being more streamlined and optimizing that business.
Got it. That's helpful. All right, so I think you were just at TIDES, discussing the ECO Synthesis Platform. You've alluded to it a few times. For those who are maybe newer to the Codexis story, what is ECO Synthesis? And we only have, I think, 40 minutes left, so keep it tight. I'm just kidding.
Fair enough. Yeah, so ECO Synthesis, what does that stand for? Well, it's the enzyme-catalyzed oligonucleotide synthesis platform, and what it is, is a suite of enzymes and reagents and raw materials that is designed to be a game-changing technology for the manufacturer of RNAi or RNA-based oligonucleotides. What are those? Well, those are short strands of RNA that are about 20-30 nucleotides in length, that have become a significant therapeutic modality in probably the last 10 years, primarily because of, you know, Alnylam launching four commercial products in the last, I may be a little off here, but in the last 10 years, mostly for small, orphan rare diseases. There's been an additional recent launch of this therapeutic modality in, Inclisiran from Novartis into a large in... the first large indication.
When we looked at the development pipeline of this particular therapeutic modality, there's about 400 products in development. About 40 of them are in phase II and phase III, most of which are for larger indications, because the dosing regimen is very attractive. It's twice yearly, a relatively small injectable dose. That becomes very convenient for people with conditions like hypertension, Alzheimer's, diabetes, oncology. So at the end of the day, like, this is a hugely growing area that is just emerging, and when we looked at the scale that was needed to manufacture the kilograms of RNA for these therapeutic assets as they reach commercial scale, it doesn't exist today.
So we can talk more about that, but it's really we're talking about going from, you know, about 1,000 kilograms of capacity today, upwards of 15-30 times that capacity by the end of the decade.
Got it. Maybe just first, as we think about the... Well, actually, let's start on kind of where the product is.
Mm-hmm.
So you were just at TIDES. You know, how did conversations go? How much interest was there? And I'm curious, too, when you're having those conversations, is that informing you on... You know, it's still, you're still kind of developing this product, right? So is that informing where you're going, or is it more like you have what you have, and you're selling it to people? Kind of how's that going? Yeah.
So we came above the radar with this particular platform at the May TIDES USA meeting. We had been working on this platform in the background, in amongst the other portfolio of assets-
Yep
... that we talked about over the last several years. When you mentioned Stephen was looking for, you know, thinking about where we can win, this is one of those that emerged. So we came above the radar in May and sort of laid out what we have as the overall process, which is an enzymatic process for single nucleotide additions to create these 20-30 nucleotide in length RNAi Therapeutics. When we presented data at the most recent European TIDES meeting, which was at the end of October, and the data at that time was about a month old, so we've made progress since then, I think people were really surprised that we had made so much progress. Previously, we were focused on what was engineering a core enzyme to this process, a TdT polymerase ... to make sure that it-...
can be promiscuous enough to add any type of nucleotide, and that is, you know, a significant feat from our enzyme engineering team that they have to take a lot of credit for. But we were able to demonstrate, not only had we made that engineering feat done, we now have made progress on the building blocks and raw materials that go into the process, and been able to demonstrate that we could synthesize a, you know, in this case, a 6- nucleotide length long RNA fragment that, you know, with 90% plus coupling efficiency. Our next steps here are to actually demonstrate that the full process is complete, you know, in sort of a mini scale, and get to a gram-level synthesis of an RNA fragment.
And we're on target for that between now and the end of the year from an announcement standpoint, if not very early next year. And that we see as... I think this is the second part of your question, as an important source of validation for customers-
Yep.
that we actually have a process and platform with the suite of enzymes all working in conjunction together, to be able to scale up from there. So that's where the customer conversations went with TIDES. Immediately, it was like: When can we get our hands on this? How can we get more information around your platform? 'Cause I think in May, it was a little bit of, "Okay, that sounds great." And then in October, it was like, "Oh, well, you've actually done it and made a lot of progress. So now when can we start testing it?
Yeah. So as we think about this product, like, who, who's the competition here, and-
Mm-hmm
... and how, you know, when you're talking to customers about your platform versus others, what are the key focus areas for them?
Yeah, the ECO competition is really comes Phosphoramidite chemistry, which is the approach that people use today, and it's been around 40 years, you know, for brute force chemistry to be able to synthesize these oligo strands. And I characterize it as competition only because it's the existing, you know, incumbent in terms of how it's done today. Now, we expect the ECO platform to be actually able to work in conjunction Phosphoramidite chemistry in some ways.
One of the things we haven't talked about is we have a double-stranded RNA ligase, and this is a key milestone we're looking to launch next year, and we already have several customized contracts going on with key pharma customers around developing their own double-stranded RNA ligase, which is a way of working in conjunction Phosphoramidite chemistry to stitch together short strands that were synthesized chemically, together with an enzyme. So that is a sort of our gateway into getting people familiar with the ECO Synthesis platform, 'cause we do see that as a key piece of the ECO Synthesis platform. The other key thing that was really enlightening from TIDES was to hit on your competition point.
Some of the, you know, quote, unquote, "competitors," in terms of medium-sized, larger-sized CDMOs, completely shifted their dynamic of wanting to talk to us around this enzymatic platform from May to October. So looking to potentially work with us collaboratively on the technical specifications and the analytical development, and then they could become scaling partners for us in the future. I think that was not necessarily a surprise, but we were surprised as to how fast that had shifted.
On that last point, I think it's an interesting one, like, 'Cause I think generally interesting in pharma manufacturing of, like, the role CDMOs play-
Mm-hmm
... and how things are manufactured, right? So as you think about this, you know, is this something you need to sell to the CDMOs, or do you really need to get to the end customer at some point? Like, are the CDMOs kind of an accelerant for some of this, but still you need to get to the end customer? Just how that works.
We're talking to all of them at this point. I would say, you know, when you look at the... Let's take the drug innovator for a moment. The drug innovator, our small drug innovator, is looking at more complex RNAi molecules, longer strands, potentially, and a huge scale-up cost associated with getting to, you know, phase I, phase II material, you know, on the order of, you know, $500,000-$1 million per kilogram of material to be able to run their studies.
So they're looking at our platform going, "We'd really like you to start working with us on providing, you know, gram and kilogram scale production via a cleaner, more sustainable process." Then you have the medium-sized CDMOs, who may or may not be Phosphoramidite chemistry, and when I say may or may not, they may be at a smaller scale Phosphoramidite chemistry, not the huge CDMO doing most of the commercial production, of which it really centers around one or two key players. They're ones that are looking for a solution that they can plug and play into their existing infrastructure. I mean, to give you a visual around that, we're talking about doing, you know, reactions in standard fermentation, 1,500-liter fermentation tanks in aqueous solution.
Phosphoramidite chemistry is talking about thousands of liters of acetonitrile in which they do the chemical reaction. So it's a completely different scale, so it allows them an entry point to get into the market with a new solution that doesn't mean they have to spend $500 million-$700 million in capital expenditure to put in tank farms of acetonitrile.
Yep.
So it's really, it's a push and a pull. We need to be talking to the pharma customers, of which there's a huge overlap with our existing pharma manufacturing base. I think they might be a little bit later on the adoption scale. I think the medium-sized and smaller CDMOs could be our early adopters, because they're looking for this new technology platform that can be disruptive and allow them to scale quickly into a market that they may not be in today.
Got it. And then maybe just a detour on a kind of a higher level question of, you know, a lot, a lot of the capabilities you have offer the ability to kind of do more efficient manufacturing-
Mm-hmm.
-for customers on the pharma manufacturing side. Is that something that resonates in the current environment?
Definitely. I think one of the reasons that biocatalysis has grown a lot, which is our original business for replacing chemistry with single-step enzyme reactions, is 'cause the pharma companies are looking for more sustainable ways of manufacturing their products. That's a core focus for them in today's environment. ECO Synthesis also does this on an even larger scale, right? Because we're now talking about the potential for a scalable solution. That's one thing we haven't talked about, Phosphoramidite chemistry is not as scalable potentially as our enzymatic solution.
Yep.
But also the heavy use of organic solvents, which are petrochemical based. Acetonitrile is a derivative of, you know, sort of oil-based processing. So when we think about sustainability and the lack of use of organic solvents in the ECO Synthesis Platform, it's super attractive to this customer group.
Got it. And then just going back to ECO Synthesis, I believe gram scale by the end of this year, you know, how important is that for customers? I'm guessing it is. And then, two, what are the key milestones?
Mm-hmm
... beyond that?
So the gram scale synthesis, why we've made a big deal about that milestone is it really came from customer feedback. "We really need to see you synthesizing a real strand of RNA, of reasonable length, yield, and purity, at a gram level, so we can start to compare that Phosphoramidite chemistry, you know, dynamics, like, in terms of those same characteristics." And that is why we've been focused on that. So that allows us to have credible conversations with these customers and start to put the tools in their hands, so that we could lead to early commercial licenses in the 2025 timeframe. So 2024 is a technical validation, getting it in the hands of customers from an early access standpoint, and ideally lead to some potential commercial licenses in early 2025.
There is a step before that, which I had mentioned earlier, which is the double-stranded RNA ligase, which is one of those core enzymes that we saw, that while it's a single step in the workflow, it's critical both to our ECO platform, because we still, we don't need to synthesize 20, 30 long, nucleotide length RNAs completely with the ECO Synthesis process. We can be synthesizing that with 10-mers and stitch two of them together. That's another efficiency play. That can exist Phosphoramidite chemistry, and we already are putting that in the hands of customers and expect to continue that through 2024, with the launch in the second half of 2024. So the key milestones really come down to the launch of our double-stranded RNA ligase in the second half of 2024, putting the ECO Synthesis full platform in customers' hands in 2024, and commercial licenses starting in 2025.
We are looking at a full commercialization in 2026, where we have completed the enzymatic synthesis of all the building blocks and raw materials as well. So that's on our product roadmap, too.
Got it. Maybe just, Sri's not here, but to maybe just get to the numbers on this, can we just talk about kind of what the, the RNA ligase revenue could, could look like next year? And then kind of longer term, you gave, like, the trial number, but how should we think about the TAM of this opportunity?
Yeah. I'll start with the RNA ligase first. So, you know, it is a really important piece in terms of driving efficiency. We think it could potentially reduce 20%-30% of the cost Phosphoramidite chemistry, because you can... The cost Phosphoramidite chemistry goes up quite a bit when you start doing longer oligos.
Mm-hmm.
You need more raw materials, you need more acetonitrile. It's just from a scaling standpoint, it becomes challenging. So that provides a significant advancement. We think, you know, reasonable low single-digit revenues in 2024, depending on when we launch.
Sure.
Total opportunity for that could be, you know, high double-digit revenues. On the order of—we've said somewhere between, you know, $10 million-$30 million per enzyme type of opportunity. I think we're still trying to characterize that piece, 'cause we obviously see that as a gateway to ECO Synthesis, which is a full process and platform for the entire enzymatic synthesis of siRNA. And some people may wanna stick Phosphoramidite chemistry, some people will wanna switch over to the enzymatic process.
When you think about the total addressable market for eco, if you just do simple math, and we've walked through this a couple of times, and you can certainly reference this in our corporate presentation, you know, 40 or so of those assets I mentioned are in phase II, phase III clinical trials for large indications, and we're talking millions of patients. If you assume about a third of those get approved between now and the end of the decade, if not early 2030, then we're talking about 15 of those getting approved. Each patient requires about a gram on a per year basis. So you're talking about for, you know, millions of patients, anywhere between 1,000 kilograms upwards of 2,000 kilograms per asset.
So that's how I get to the total market opportunity of about 30,000 kilograms required. When you look at the actual cost Phosphoramidite chemistry on a per kilogram basis, that translates into, you know, a $7.5 billion-$8 billion type of market at $250,000-$1 million per kilogram. So, we don't need to capture all of that. This won't be the only alternative—this won't be the only method as an alternative Phosphoramidite chemistry. so we think that, you know, capturing 10%-15% of the market gets us to a billion-dollar opportunity, and that's where I, you know, pull back to say: "Look, this is a. I don't think we're getting a lot of credit for this today. This is sort of a free option to bet on a billion-
Yep.
-dollar market opportunity, which you'll start to realize in the next couple of years.
Maybe as we think about realizing that opportunity, you mentioned all these trials going on, like, when can you get substituted into something that's in a trial?
Good question. We have been thinking hard about this, and this is where the drug development experience from Stephen and others, and myself included, come into play, in that we're looking at how we can provide an analytical bridge-
Okay
... for what would be an enzymatically developed RNA fragment versus a chemically derived RNA fragment. What's important to note about that is, one of the core value proposition items of our product could be an improved purity profile. Because when you are Phosphoramidite chemistry, you have an immobilized oligo. At the end of the day, you're adding phosphoramidites, which are the single nucleotide additions with chemical blocking groups, and you end up with a fair amount of side reactions. When you get into longer and longer oligos, you have a significant challenge with, you know, greater than 50 impurities that you have to characterize and analyze.
From an analytical bridge standpoint, from our product, we think because we've immobilized the enzyme, and because we have the oligo in solution, and we're doing single nucleotide additions with blocked phosphate group, you know, and it's a relatively simple process. We'll see some n+1 or n-1 additions, but the purity profile can be tested throughout that process as well, and we're only adding one at a time. And with the oligo in solution, you can be testing that from a QC standpoint. So we think the analytical bridge could be more straightforward.
Okay
... to be able to allow pharma customers to make a transition in phase two, which is never something anybody wants to do.
Yep.
But in this context, it might actually be easier.
Got it. That makes sense. And then just on licensing in 2025, obviously, you know, that's a little ways away. I'm sure you're having conversations. I'm just curious-
Mm-hmm
... how you think about your strategy around who you license the technology to and who you work with?
Yeah. I, I think this gets back to your earlier question around who we think the early adopters are. I think the technology providers, in this case, will be the earlier adopters.
Yep.
And that's your small to medium-sized CDMOs, because they're looking for a platform they can plug into a small molecule-
Okay
... API manufacturing facility. So the early commercial licenses I see are gonna be more with that category of customer, that wants to get into RNA manufacturing, but doesn't wanna build a $500 million-$700 million plant-
Yep
... where you could be building, don't hold me to these estimates, but somewhere on the order of $50-$100 million type of small molecule facility to be able to manufacture RNA enzymatically. So I think that would be those types of partners, 'cause they can also help us scale as an additional product offering, as new products are coming into the funnel and pharma is asking for solutions. The other piece is, working with probably smaller drug innovators and getting into discovery and preclinical phase, 'cause then to your point on the switching-
Yep
... there's no switching.
Yep.
It's like, if they're working with our process from the start, they get to the IND. So we're talking to folks that are doing benchtop synthesizers and so forth, so that when they're doing their early research and getting to IND and preclinical tox work, you can actually do that with benchtop synthesizer, 'cause you're talking about small amounts. If we're able to partner with one of those technical collaborators, that's another extension of getting us embedded in the process early.
Got it. Just on y- you know, you demonstrate gram manufacturing by the end of this year-ish, how difficult is it to get... You know, that's probably a feat in itself, and then the next question is... well, how difficult is it to go from that to commercial scale?
Yeah, anyone who's worked in sort of a CMC or a manufacturing environment knows that there are challenges when you go from, you know, gram level to kilogram scales, but they're—it's not rocket science, is the way we looked at it. That's why customers approached us and said the gram scale synthesis was incredibly important, because seeing the process work in its entirety becomes now a matter of—and getting to the higher level scales becomes a matter of capital investment and time. Which is why, again, we think extension into sort of these medium-sized CDMOs and small CDMOs, as a potential partner or early collaborator, could extend our ability to scale more quickly and accelerate that, as opposed to us necessarily building it all internally.
That being said, we do hope to move to a full service offering in our lifecycle product roadmap, but we need to see the full commercialization of the platform be successful and get embedded in the process first. So we're taking a stepwise approach there.
Got it. And then I think you've got a strategic advisory board around this offering, and a KOL event coming up. Can you just talk about what that board will help you with?
Yep.
If you wanna preview the KOL event, that'd be great, too.
Thanks. Yeah, so we recently announced in our last earnings, John Maraganore, the former founder and CEO of Alnylam, has joined our Strategic Advisory Board. He will be talking at our December 8th KOL event. He and also David Butler, the Chief Technology Officer at Hongene, who is probably the largest provider of modified nucleosides for RNA manufacturing today, will be talking at our event. Each one will be talking about different topics. John, you know, will be talking about the need for alternative approaches, the market size, the opportunity, because a lot of our hypothesis around that, you know, should be validated by someone who actually built that whole, you know, area.
And then secondly, David Butler will be bringing more of the sort of, you know, CDMO manufacturing perspective as to why an alternative solution can help overcome some of the barriers they see in the Phosphoramidite chemistry approaches. So we think it's gonna be a really exciting event. And to back to your point on the whole advisory board itself is, you know, this is where having an advisory board mix of people that have done it from a business standpoint, the CDMO expertise, some small drug innovators, potentially some academia, to help make sure that we're building and enabling the technology in the right way from all the way from research, into development, through commercialization. That's how we see the value of that strategic advisory board.
Got it. Maybe I'll pause and see if there's any questions. I should have done that earlier. But I had too much to talk about on ECO Synthesis. Maybe Kevin, just the last one for me, just going back to the legacy business-
Mm-hmm.
... just sustainable manufacturing. I think there's been some headwinds there this year, and look, there's plenty of headwinds in life science tools right now. But can you just talk about any kind of headwinds you faced there this year? And then, you know, I heard growth a couple times as you were you talked about the platform, and certainly it seems like you guys expect growth next year. What, what gives you confidence in that?
Yeah, to be specific, we also are looking at product revenue growth as our core-
Yeah
... metric there. And we recently reiterated our revenue guidance here for 2023. Why we see a return to growth there is threefold. One is, we have pretty good visibility of the ordering patterns at this point, to kind of have a sense that some of those dips that we saw earlier this year are returning to more of a stable ordering pattern from particularly our large customers. So for example, we sell probably 60%-70% of our revenues come from three enzymes that get sold to four customers.
Yeah.
Stabilization of those ordering patterns is critical to be able to make that comment.
Right.
The second piece is, we've talked a lot about this pipeline of products that we have in development, 18 or so, up to 20, it varies, is actually coming online and starting to grow. And that takes some time, which is why we have to keep filling the pipeline over time. So the maturity of the pipeline is coming at the right time as well, to allow for a picture of getting to 2026 with a cash flow break even or even profitability with those two factors. And then there was the third one, which is slipping my mind right now, but at the end of the day, it comes from our pipeline and it comes from our realization of the existing enzymes and returning to normal growth.
Got it. Well, on that note, Kevin, thanks so much for the time. Great to have you here.
Thanks so much. Appreciate it.