I think we're good to go. I'm Tycho Peterson from the Life Science team. It's my pleasure to introduce Codexis. Happy to have Stephen Dilly with us again this year. Stephen, maybe just to kick it off, obviously a lot of focus on ECO Synthesis. Maybe let's go back 24 months since the platform was just getting started. Walk us through the journey there. Lots happened. How do we go from kind of technology and concept to execution and commercial product?
Great. Thanks for having me back, Tycho. Yeah, it is amazing that it's just 24 months since we rolled out the idea of the ECO Synthesis platform. At that stage, we were responding to a bunch of companies that we have worked with on biocatalysis for synthesis of small molecules, saying, you could really solve a problem if you could turn the enzymatic capability to making RNA constructs. We had some early success with mRNA that ended up with the partnership where we went with Aldebaran with our high-cap RNA polymerase. That's going extremely well. We've really been focused in-house on siRNA. That's become a really interesting sort of evolution of the landscape from enzymatic synthesis being a nice idea if you could do it to something that people thought, yeah, it's probably real, but not yet.
I came from the Tides meeting two weeks ago. Just about every other presentation somehow was involving enzymatic synthesis. Some of it was chemoenzymatic. A lot of it then talking about the advantages of actually enzymatic synthesis. We presented to a very packed, very large room. That's a room full of CMC people. Really, the acceptance that there is a need for this technology as we scale the siRNA modalities has really changed. Codexis is clearly out in front of the pack in terms of actually bringing that technology to fruition. Where we are right now is our GLP Eco Innovation Lab is up and running. We can make fragments or full-length molecules by sequential synthesis enzymatically. We've proven that our technology is quite flexible.
So far, we're batting at a very high percentage of being able to do all the constructs that people send us to do. Now it's all about scale. Now it's all about how do we get into processes for existing drugs, for drugs that are going to be important in the future. It's moved from the sort of whether we should do this to the how do we do this and how do we adopt the technology. The people we're talking to have changed often from the research people, the innovation people, to the CMC teams thinking about how they're going to build a process around this technology.
You said on the first quarter call, you've got your first revenue-generating contract. Talk a little bit more about that project timeline, scope.
That is the first revenue-generating contract associated with the ECO platform. We previously signed revenue-generating contracts with the ligase platform where we're putting together shortmers. This is actually manufacturing, initially at small scale, a novel construct for a third-party pharma innovator customer with our CDMO partner. From there, we are increasing scale to support the development of that molecule. Where we are with that right now is making the constructs in-house, transferring the technology, getting our friends at Bachem to then make the constructs themselves, replicating our process, and then to scale from there.
If you think about kind of what was presented at Tides, you had a number of the CDMOs, Bachem, ST Pharm, Nitto, Aviva, kind of all present. Talk a little bit about what they presented on. What were the takeaways there?
Right. What they were presenting on was the performance of Codexis ligase and often in comparison to other ligases. This was the focus of the presentation. It's the cornerstone of chemoenzymatic synthesis: you make your fragments using conventional phosphoramidite chemistry, and you can improve your yield and reduce your downstream purification costs by using a ligation step. Now, our ligases are highly engineered and made specific to the construct that you're trying to ligate. The alternative approach, which is already sort of widely adopted and somewhat entrenched, is using a generic wild type or very lightly engineered ligase, which is cheap to drive the same reaction.
What we're having to show is that even though our ligase might cost a bit more, it's well worth adopting because it reduces your overall production cost because of the improved efficiency of the reaction and therefore the impact that has on downstream purification, for instance. It's really getting to brass tacks from talking about how our ligase is a better ligase to saying that actually saves you money. That's what we're talking about with those people and what they were starting to present on.
I think you've talked about four customers purchasing ligase by the end of this year versus one last year. I think you've talked about a pretty good funnel. Can you maybe just talk a little bit about that pipeline, how it's progressed, and how you feel about is it more CDMOs? Is it more innovators? What's that mix like?
The three CDMOs that you mentioned, as in Bachem and Nitto and ST Pharm, already see it as advantageous to have access to our ligase to sell on to their customers. There is a sort of a multiplicative function there. We also have direct conversations with innovators. Sometimes we have three-way conversations with the CDMO and the innovator about how we use our ligase on the CDMO's platform to make the innovator's molecule, that kind of thing. Those conversations inevitably then lead to discussion of how we can facilitate adoption of the full ECO Synthesis platform.
Could you talk about the innovation lab, the ECO Synthesis innovation lab? I think you've said the goal is to fully allocate that capacity. It will be a few larger customers, a broader mix of smaller programs. How should we think about the mix there?
It's about the mix of programs. What we want to be doing is using it to facilitate market entry of existing products right now, working on things that are big now, but also to get our teeth into some very promising early phase molecules. We need to enroll, if you like, a few of the big innovators, the sort of household names everyone knows, but then also pepper it with some best athletes that we think that molecule is really interesting. It's early phase. If we can own a piece of that, it can be very, very important down the line.
Yeah, is it mostly phase one ready assets, or is it more interesting earlier stage?
In terms of the full ECO Synthesis, the majority of work being done is on early stage things that are getting ready for tox. It's that kind of level. That's why having a GLP capability in the Innovation Lab is great because we're now in a position to scale to 10 or 100 grams of an asset, which is enough to get you through those kind of studies.
What are the economics in the innovation lab? Is it shared cost? Is it R&D revenue stream? How do we think about how you actually get paid on that work?
It starts with a relatively modest upfront for access to the technology and access to the resource. Then there will be some shared cost as you move forward in the development work and a success milestone. We go from there in terms of scaling. We have to make that pay its way through those kind of R&D relationships because it's never going to be economically viable in terms of the quantity of siRNA it kicks out. If it's kicking out 100 grams and siRNA costs $1 million or $2 million a kilo, that's not enough to justify its existence.
Yeah. Maybe just thinking a little bit longer term on the commercial strategy then for ECO. Talk a little bit about how you scale that up, how we think about the go-to-market strategy. Again, will it be a broad-based base of customers? Will it be more focused? Are there a few big strategic partners you're targeting over the next couple of years?
We're absolutely targeting a few strategic partners over the next couple of years. The go-to-market strategy is to have the innovation lab as a magnet to build new processes, to have access then to a middle-scale GMP facility. We're right in the middle of working up exactly how long that's going to take us. We think that we can very cost-effectively build a 50 kg annual capacity kind of facility within our financial means. That'll mean we can take things on preclinically. We can do GLP up to 10-100 grams to get through tox. We can then scale them through kilo scale at GMP and then tech transfer an existing process with the critical process parameters all nailed down, the analytics nailed down, either to the innovator company or the CDMO.
It shifts from an R&D contract early in the innovation lab to increasingly about the product that we're selling as we scale.
When you say cost-efficiently, can you give us kind of a framework of what that looks like? Does that give you capacity for three years? What's kind of the roadmap on capacity?
We're looking at leveraging the real sort of volumetric productivity of the ECO process. One of the huge attractions, we showed slides of this at the Tides meeting, is you can do a lot more with a much smaller footprint and a lot less capital infrastructure. We're looking at a facility in the sort of range of 35,000 sq ft, which would give you an annual capacity of siRNA production of anywhere up to 50 kg. Those are remarkable numbers in the field of siRNA production. Really, it's about leveraging the fact there's a lot of vacant manufacturing infrastructure from cell and gene therapy days right now. We can use very simple equipment because the enzymes do all the work. We think we can stand up a facility in the range of $30 million spent over two years.
That's why I say it's not a scary number. I'm not talking 200. I'm talking a fairly accurate 30.
Kind of as we think about onshoring supply chains, kind of moving back into the U.S., how does that play into kind of your roadmap?
It actually enables us to have conversations with partners about putting enzymatic technology into existing facilities to bring important supply chains onshore. That is absolutely topical with companies that are looking at, "Oh my God, my supply chain is exposed to China and elsewhere. How do I bring it in without spending enormous amounts of capital?" The fact that we can reduce the CapEx and achieve comparable or even better run rates is really, really important. It also opens the door to conversations around government grant money as well because this is very topical. One of the attractions in both of those is that you can stand this up relatively fast.
The sort of gold standard for standing up a current sort of phosphoramidite chemistry facility, including building all the infrastructure you need for the highly flammable and sort of toxic solvents, is about four to five years to get it on stream. We're in the more like 18 months to two years because this is a water-based system in some very simple equipment. It takes you less than a year to build, and then you're doing your engineering runs. All of that is really attractive in terms of the onshoring. Where we also are going and need to go is the raw material supply and starting from very simple raw materials and using enzymatic processes to build the building blocks that you eventually make the RNA out of. Having a number of conversations with different flavors of partners for each of those steps along the way.
RNA ligase, I think you've delivered your first order to a large pharma customer. You've got a second initial order, a drug innovator. Maybe just walk through that process from securing the order to the delivery. Any feedback from the customer so far?
Yeah. Both of those cases were really interesting in that they initially told us they were going elsewhere. They tested the ligase and came back and said, "Yeah, actually, we've tested it. We believe it is important to use the best ligase. It makes sense economically." What we're looking at is scaling over time. As the drug moves through its phases of development, the amounts of ligase scale up. In both of those cases, they parallel processed initially and then moving increasingly towards ligation based on our product. We only just, I mean, a few weeks ago, rolled out our Machine Learning AI Platform for ligase selection. What this means is we can provide very, very rapidly a molecule optimized to the exact reaction people want to run.
That is a very different approach from taking a generic ligase and just, if it does not work very well, putting in more. It is up to us to convince people that that is worth doing. It also increases the need for trusting relationships, so working with partners that increasingly trust us because in order to do that, they have to share the construct with us. Otherwise, we cannot select. All of that is toe in the water, and then people get increasingly confident. That is what makes me optimistic for the future because a ligase supplied for a big drug can be tens of millions of annual revenue to us. From our base, that is an important bridge to the full ECO platform.
Maybe just talk a little more on the AI module. I mean, what does that mean in terms of time saved? Is there a separate revenue opportunity for you there?
We believe so. It is orders of magnitude in terms of time saved. There has been a lot of buzz around AI and application to biology. This is actually a worked example where it worked, right? It worked because it is a very constrained problem that we are setting the AI tool. What we learned experimentally was that the function of the ligase is dictated by a finite number of nucleotides either side of the point that you are trying to stitch the molecule together. We also have generated many thousands of ligase variants in our library. It really limits the distance that the AI has to extrapolate, so it stays accurate. It is unlikely to be hallucinating. What we have had since we rolled this out is a few people throwing test cases at us, often when they think they know they have got the optimal ligase.
The cool thing is when we can say, "Actually, you're wrong. It's that one," right? There is enough sort of scientific traction. I'm really optimistic this is going to turn into something.
That's really interesting. Yeah. Anything you can say on the second customer you signed up there? It's a drug innovator. Anything about kind of the size, scale of the project? How does the pipeline look?
It is a drug innovator with multiple, many assets, very focused in the siRNA space. That has been what I have had my commercial team focus on. I do not particularly want the one-offs. I want companies that have a deep commitment to the area of siRNA, have a pipeline. It can be about platform adoption rather than having to start from ground zero every time with every asset. I kind of like to role-play the conversations within the big innovator of the CMC guy bowling into the executive committee saying, "I want to adopt this wacky new process to make your billion-dollar drug," right? How to avoid getting that guy fired, right? It has to be validated, and it has to be low risk. The second time is easier than the first time. Sometimes that comes from relying on really trusted partners.
What we've learned is we get a lot of joy by working with CDMOs who are already supplying the big innovators with their siRNA because then it's about the CDMO saying, "We want to tweak the process," right? "Trust us. We know what we're doing," as opposed to Codexis coming out of left field and doing this. It is really all this stuff about classic marketing, which is reducing the points of friction.
Not to be too myopic, but just thinking about the back half of the year here, effectively per guidance, doubling the revenues. Maybe just talk a little bit about how de-risked that is. Is it tied to potential ECO deals? How do you get there?
We get there partly through the natural sort of cadence of our business, which has always been lumpy. Orders moving from one quarter to another can significantly affect that. When we planned out the year, we're exactly where we should be in terms of the probability of orders, where we've got line of sight on what we'll deliver the second quarter and then the growth into the third and fourth without any sort of real Hail Mary's in there. We're quietly confident rather than totally ballistic about it. It's understanding the sort of patterns that people do their scaling in and how they order and the way the conversations go.
Some of that is based on work in the innovation lab and some ligase orders, but the majority is driven by pharma manufacturing, a heritage business where we have a lot of experience in what we're looking at.
Is any of that pharma manufacturing kind of being pulled forward? That's a common question we get just around tariffs and global supplies moving around the globe, but maybe some of it's being added to.
We haven't seen a huge amount of that, actually. It's been very much on track. The kind of drugs that we're working with, I'm probably not as exposed as some of the other modalities because of where we sit in the sort of CMC process, because we're one step in a long process and all the rest of it. We've not seen anyone sort of obviously stockpiling or anything like that.
How about competition? I mean, I assume kind of CDMOs are largely customers and complementary, right? Are any of them trying to compete with you more directly?
Oh, yeah. I mean, this was the thing that came up at Tides was we've always sort of had a notion that our competition is other people trying to do enzymatic synthesis. Yeah, but they're a long way behind us. That's not our principal challenge. Our principal challenge is people trying to do chemistry better, right? Two years ago, people thought we were mad saying there's going to be 30 metric tons of demand for siRNA by the end of the decade. That was received wisdom at this Tides Meeting. People were saying, "Yeah, 30 metric tons, and here's how we're going to get there." Ligation was a sort of new thing or very quiet topic. Everyone was talking about chemoenzymatic synthesis and ligation making it better.
There was a lot of work around how to use liquid phase and how to recycle solvents and how to do all this stuff to squeeze the pips and make chemistry as good as you possibly can. In that sense, that is the benchmark in one way for what we need to achieve with ECO. We are no longer having to justify our existence in terms of is there a demand for siRNA Medicines. We are past that now. Even the people trying to scale chemistry say, "We think we can meet the immediate demand or we can move to address it, but long term, it is going to move to enzymatic synthesis." We heard that out of the mouths of people like Hong Jin said that in words of one syllable, which is important.
Others have said the same thing, that when you get to molecules needing multiple hundred kilos of supply annually, enzymatic has to be the way to go. The world's moving in our direction, but we have to move into that space as quickly as we can because otherwise the vacuum will get addressed through people brute forcing it.
Do you worry more about CDMOs or in-house pharma doing it?
More about CDMOs doing it and just crunching it. It's again where the political situation is interesting because some of the CDMOs with involvement in China or even Chinese-based are having to get out in front of that right now and moving quite aggressively. I'd rather be competing in a market where people are being aggressive about trying to get a share of it rather than having to tell people the market exists. It's a sort of healthier dynamic.
Away from CDMOs, are there any pure technology competitors that you're keeping an eye on?
Oh, we're keeping an eye on the group of technology innovators that can sort of evolve enzymes, all that kind of stuff, the ones that have been in the sort of DNA oligo space. There's only really one pure play enzymatic synthesis startup. That's N+1. Really nice science, really interesting. We're keeping an eye on them. We're at a significantly greater scale than those guys right now with more flexibility as well. In terms of putting forward the best technology, we're in great shape. Now we have the challenge in front of us to stop people talking about the technology and start talking about the implications and the product we can produce, right? What I want to be doing in a year or so's time is saying, "That's a kilo of siRNA. We've made it quicker. We've made it purer. We've made it cheaper.
You should go with this.
Can you maybe touch on the Aldebaran Partnership? How has that gone? I think they had some data at Tides as well. Yeah, maybe just give us an update there.
Yeah. I mean, that's been a delightful partnership. It's just over a year old since we out-licensed the high-cap RNA polymerase that's for making mRNA constructs. Aldebaran has developed a GMP process for that. They're really scaling it, and they're having really good traction commercially. We're super pleased with that. We think that's a very good model for some future enzyme supply partnerships as well. Aldebaran is exactly the type of company that we like to work with.
How has it been? I mean, Danaher, I guess you kind of got involved after they were acquired, right?
Yep. We absolutely are in conversations with Aldebaran and Danaher. Also, one of the other companies in their constellation is Cytiva. Our technology runs on the Cytiva Platform. That is, again, a great sort of room for conversations about how we can sort of have a symbiotic relationship because everyone that stands up an eco process is going to need Cytiva equipment.
Could we see, yeah, deals coming through the Cytiva channel in a year or two?
We think certainly through the Aldebaran channel, yeah, and the Danaher channel. Yeah, and so it's working with the innovators, the CDMOs, the technology enablers, and then having our tendrils out in sort of the sort of startup land in terms of the new stuff that's coming down the pike. We are a player in all those areas and doing that in a way where we can leverage scale, right?
Yeah. Maybe on capital, you've talked about reaching positive cash flow by the end of 2026. How do you think about the balance sheet and capital deployment with that in mind?
We need to move fast. We need to deploy capital to exploit this opportunity. When we look hard at the business, the traditional heritage pharma manufacturing business is profitable. It actually has a very decent margin. That is an engine that reduces our need for capital. What that means is we can always dial back how much we're spending on innovation. That is how we triangulate when we get to cash flow break-even and positive. We've guided to sort of crossing that threshold sometime around the end of next year, the end of 2026. That may or may not be the ideal strategy because it really is based on how concrete the opportunity is to invest to scale faster in the ECO Synthesis Platform. We're only going to do that when we know the deals are there. It's absolutely real. That is what we're looking at.
We're in nice shape at the moment.
I guess, how do you think about that trade-off? What is input from your board, feedback from investors? Do they want to kind of see you push off profitability to build a bigger book of business?
If we have a very high level of not just conviction, but certainty that those deals are real, right? Because think about it. If I have to scale to GMP through a GMP partner, they're going to want a share of the value of doing that. If I have to tech transfer a laboratory-based process into a CDMO, they are a CDMO. They're going to want a development partner share of that asset. If I'm transferring a baked process that's running at kilo scale, they're a CMO. They're simply scaling it, and they're operating as a scaling partner. That's the opportunity, but it needs to be based on real assets.
What we want to be able to do over the coming months and towards the back end of this year is announce some partnerships such that investors can sort of nod and say, "Yeah, okay, we see the trajectory now," right? That is what the commercial group is hard at work on right now. Just as a sort of index of that, we had five new customers come in after Tides with commissioning projects to do proof of concept of the ECO Platform on their RNA assets. We can see it. We know it is real. We have to have stuff we can show you, right?
Yep. Great. I think we'll leave it at that. Thank you.
Thanks so much, Tycho. Thank you.