With any molecule, whether it's the DNA molecule or an RNA molecule, any nucleic acid, any gene delivery enzyme, whether it's a CRISPR, whether you're doing base editing or prime editing, where we work with therapeutic developers across the cell therapy space, using our artificial platform, it's called ExPERT Platform. It allows them to be able to bring in those molecules through the cell membrane on a very temporary basis.
We open the cell membrane with our electroporation technology. The molecules go in. We turn off the electroporation systems, working with the developers where we optimize the protocols depending on the cell type, depending on the molecule. We end up giving developers something that's unique, which is a highly transfected engineered cell with the highest efficiency of transfection, highest cell viability, and truly the highest cell health is what we call it.
What that has meant for us is we work across the development space. We have that has culminated in working in early research all the way through clinical development as well to commercialization. The first non-viral gene-edited cell therapy approved in the U.S., Casgevy, was used to use our systems to engineer the cells. We also have an additional 29 such licensees. We call them SPLs. These are key customers of ours that are using our system in the clinic to engineer the cell, exactly as I mentioned, to create gene-modified cell therapies. That is where MaxCyte is, and we can get into what those SPLs mean for us and what our overall economics mean as well.
Let's kind of dive into there. Maybe let's first start with the ExPERT non-viral cell engineering platform. Maybe give us what you view as kind of that most important point of differentiation versus competitors. I know it's a growing space. Where you kind of see the white space from where you guys are able to offer.
Yeah, absolutely. Where differentiation is, we focus heavily on the process development into the clinical side of cell therapy. Where we differentiate is the scale of transfection. We can provide that no competitor can provide. The transfection efficiency is what we focus on to ensure what you're transfecting is done at a much higher percentage than any other company can provide.
The cell viability we talked about, these are precious cells when you think about it. A developer is using oftentimes a person's own cells. That's called autologous therapies or allogeneic cells from a donor, ensuring that post-transfection you can have the highest cell viability and something that isn't oftentimes talked about, but higher cell health. These cells are precious.
We pride ourselves on ensuring that across the cell therapy workflow, whether it's T cells that developers are working on and NK cells, whether it's TILs, tumor infiltrating lymphocytes, we can do that with those three things always in mind: efficiency, cell viability, and really that cell health at scale. We can transfect cells up to 20 billion cells using our GTx and always meeting those three really criteria: health, viability, and efficiency.
I think kind of diving into some of your customer base, I mean, your core business model really includes sales to biopharma, biotech companies, researchers. Can you maybe just give us a sense to any trends that you've seen over the past few months in terms of instrument placements or recurring licensing revenues to just give us a little bit of orientation to where this market is today?
Yeah, I can add in that Doug, obviously, you know, weigh in here. The last few months is, you know, it's tough to give. We haven't given guidance just yet for the year. We're seeing the same trends we saw towards the end of last year. We said we're partially optimistic. We're seeing growth come back to the industry itself, to the cell therapy space, cell and gene therapy space.
What we're also seeing the trends are in terms of instrument placements and use of our system is the field itself is oftentimes going more towards allogeneic, not that autologous therapies are in any way diminishing, but you have more allogeneic use. You saw the recent signing with TG Therapeutics, our SPL with TG Therapeutics. That's for an allogeneic program where they're going after autoimmune diseases using our systems in the clinic in the future. You're seeing the space go more towards there, which really lends itself to our ExPERT GTx, which is that large-scale system as well. Doug, anything you want to add in terms of what we're seeing the past few months?
No, I mean, I think, and obviously we'll be reporting earnings in a couple of weeks, but in terms of the trends we saw, it was healthy uptick in PA sales in 2024. Those are processing assemblies or just single-use disposables. And we've always said that that was important. We thought that recovery would happen first with the disposables and then move to instruments.
All right. You talked a little bit about your SPLs. Let's talk about this a little bit more. Maybe how does the TG Therapeutics SPL and autoimmune disorders, how does that kind of symbolically reflect, first of all, where cell therapies are going and then maybe your actual SPL strategy as it stands today?
Yeah, no, great question. TG reflects something very similar to what we're seeing with other of our SPL customers and customers in general. The field itself is going more towards the cell gene therapy field, more towards the use of these therapies for the autoimmune space, which makes perfect sense when you think about it, right?
Because you're able to do it in a somewhat cost-effective way where you can use allogeneic therapies here where you're using healthy patients, donor cells, and be able to create a lot of doses and go into a space that, in essence, for the longest time, if you think of how autoimmune diseases have been treated, steroids, prednisone is one way. You have a lot of other small molecules and biologics also being used that have just treated the symptoms but never treated the underlying cause of these autoimmune diseases.
This is where we're seeing the trend. Imugene is one where they licensed azer-cel from Precision Bio. CRISPR as well is developing CTX112, another CD19 product, just like TG's azer-cel's CD19 as well, repurposing it from a CD19 malignancy development into an autoimmune development. We're seeing that path continue across the space as well as some other customers not yet in the clinic that are trying to also go after autoimmune diseases with repurposed CD19 therapies that in the past were just being used for CD19 malignancies.
Yeah. I mean, I think this is an important point too because I think when we think about things like CAR-T and just cell therapies in general, it's indication by indication basis, different tumor types that they're going after, but autoimmune disorders is really a pretty expansive collection of diseases. Can you maybe give us a sense how big the opportunity in autoimmune could be relative to what we've already seen from cell therapy? Are we talking about doubling the market opportunity? Are we talking about a 50% increase? Where does that stand?
It's more than doubling, right? It's enormous, actually. If you think about what you think of autoimmune disorders, lupus, MS, Sjögren's , Crohn's disease, myasthenia gravis, the patient population is enormous. I don't know how you even quantify it, to be honest with you.
It's as big as probably the entire cell gene therapy space in the past combined has been going after therapies. The field really is expanding there and the opportunity for us and the field itself, where in essence, you'll begin to have what we call those blockbuster therapies come about. That's what the autoimmune space gives the field itself when we're going after those indications, where I do believe you'll see those truly blockbuster therapies come about.
Because as I mentioned, as we've seen in the oncology space and some of the rare disease spaces such as sickle cell disease, you're seeing when these therapies work, they're not just treating symptoms. They're letting people live in essence disease-free, right? Even if they're not curing them sometimes, it's disease-free. In other instances, you're actually curing patients. That has never happened in the autoimmune space. The field is enormous as it goes into that and truly shows what I call curative or letting people live disease-free treatments. That's powerful.
I guess getting back to just your SPL strategy more broadly, can you just remind us of the economics of your SPL agreements and if you've seen any changes or variability in the downstream economics components of the given agreements?
Yeah. Doug, did you want to answer that? I feel like I'm taking up the.
Yeah, no, it's fine. These programs, they come in. First off, we don't sell the instrument for clinical and commercial use, right? That's under a lease. We're getting revenue from those leases on an annual basis. We also have milestones as they progress through the clinic and regulatory milestones as well if they're successful in being commercialized.
We have a royalty component. The royalty component, I'll just throw a number out there, some are a little different, but on average, looking for 1% of net sales. With respect to other benefits we get from the program, there's this recurring revenue that again comes from those leases. It comes from the processing assemblies. These are single-use disposables. In an autologous setting, you need one or more per patient.
In an allogeneic setting, you certainly don't need to do it on a patient-specific basis, but you need the tremendous scale that only our system offers. I think there's significant ability to participate in the downstream economic success of those programs that are eventually commercialized as well as achieve milestones along the way and see increased utilization of the system as things progress through the clinic.
Yeah. I mean, I think that's an important point too also, like this idea that you have the leases and the number and the length of these studies all continuously feedback to MaxCyte, right? I guess when you kind of look across your SPLs, I know we talked about autoimmune, you talked about Casgevy, but is it anywhere in particular that it's enriched from a therapeutic standpoint? It's not, right? I guess when you think about growth opportunities for SPLs specifically, what are the kinds of conversations you have as you're kind of trying to build out that portfolio for MaxCyte?
Yeah. The conversations you need with customers, so much, Brandon. What we have oftentimes, these therapies are also becoming more complex themselves. The number of edits that are being made to the cell itself, used for the longest time, you were making a single edit. Now you're making oftentimes four edits, six edits. I think we have one customer making eight edits to the cell.
Creating the application know-how on a cell-by-cell basis is really conversations we're having. The reason I say that that's the conversation we're having, if you take a step back and you think about what MaxCyte does in that transfection process, where we're genetically modifying the cell in the ex vivo workspace and the ex vivo manufacturing of these cell therapies, the one place where you actually are transfecting the cell and editing the cell itself is using our system.
Ensuring that you can have an optimized process and a workflow that works repeatedly across not just one CDMO where that manufacturing might happen, but across multiple CDMOs that are being used is critical. Ensuring that you are doing it across multiple cell lines is also important. As I mentioned, the majority of cell therapies right now are T cell-based, but you also have NK cells. You have TILs. You have TCRs, which are self-cell T cells as well. Ensuring that we can have that same reproducibility and high efficiency, high cell viability with multiple edits across different cell types are the conversations we're having with our customers.
What's the expected cadence now of additional SPL signings over the next 12 - 18 months?
Yeah. We have guided comfortably that we are comfortable signing three to five SPLs a year. We are comfortable with that for the foreseeable future as well. That is indicative of where the space is. It is probably more indicative of what we are and what we bring to that customer.
We are the only company that signs SPLs with therapy developers for use of a transfection system. It shows the breadth and really the deep scientific knowledge that we provide to these customers to work with them, to enable them to get to the clinic as fast as possible with the highest likelihood of success when you are in the clinic as well.
All right. Great. You often cite this Drug Master File, right? I do want to spend a little bit of time on this. Maybe just take a second to explain realistically what that is for your business and how that is kind of an important point of differentiation from MaxCyte.
Right. The Drug Master File is part of the platform that we talk about. We have the ExPERT line of systems. We also have the scientific support that we provide in our own application labs. The Drug Master File is something that is not novel to the industry, but it is novel to what we do in the electroporation process and transfection process.
The Drug Master File allows, in essence, de-risks the transfection process for therapy developers. They are able to go into the clinic, reference the Drug Master File under a letter of authorization to the FDA, or if it is not FDA, outside it is called a Technical File that we have as well, rather than Master File. They can reference our Master File that is used, referencing our system. It has been referenced, I believe, in over 60 clinical trials to date.
Each time it's been referenced, we've never had an issue in that reference because we were able to show that we can truly transfect cells and engineer the cells repeatedly and completely de-risk as much as possible. That is what it provides. It de-risks part of the manufacturing process and part of the manufacturing workflow for therapy developers.
Is this something that some other competitors are trying to develop themselves as well? Are there any particular areas where you're finding more competition versus others?
Yeah. I mean, obviously, are there other competitors that are trying to develop a Master File? I'm sure they can. I'm sure they are. At the same time, you need to have a Master File that's referencing a system and a platform that can give you the results that ours can give. Are there others trying to develop it? I'm sure there are. We don't focus too much on the competitors as much as we focus on what we do best, which is truly being that scientific arm as much as we can to those therapy developers when they're transfecting and editing cells.
I do want to touch on, I mean, you talked about some of the different approaches within cell therapy, T cells, TILs, NK cells. I guess, are there different transfection approaches that are better suited for some of these specific therapies? How does MaxCyte kind of take advantage of that?
Yeah. So in terms of transfection, depending on the therapies, for the ex vivo space, which is where we sit, where you're transfecting the cells outside the body, really transfection is the only way to do it. That's the modality, whether it's T cells or TILs or TCRs. Creating workflows around all of those is unique. What we have on our systems, on those ExPERT systems, we have over 100 + protocols that are based on the work that we do in the applications team internally, along with our FASs. FASs are called our field application scientists in the field, understanding what the need is, understanding what parameters we need to ensure that we're providing to our customers and our partners when we are transfecting the cells. All of those are unique.
Those different protocols, it depends on what is being edited, what cell is being edited, and what's going into the cell. Truly ex vivo, the way to do it is using MaxCyte and doing electroporation transfection.
These systems are getting much more, these programs are getting much more complex in terms of the number of edits on these cells. Therefore, even in scenarios where it is not solely electroporation or MaxCyte's system, there is a role we can play.
I mean, are there any important limitations to using electroporation in different cell types or therapy classes or even like gene editing modality?
None that we know of. None that we know of. In fact, we like to say we have more information on electroporation than any other company out there. 20+ years. None that we've seen, Brandon. In fact, what we're seeing now is complementary uses oftentimes of electroporation with other delivery modalities such as LNPs or even AAVs.
The example I give is we work with a company called Kamau Therapeutics that's developing a product to treat sickle cell disease, a little bit different than Casgevy. They're actually using electroporation to knock out the gene of interest then using an AAV6 cassette to knock in the gene of interest. We are seeing complementary technologies used with electroporation as well. We're not seeing a limitation for electroporation.
When you kind of look across the different programs that you're involved with, can you give us a little bit of a sense of kind of the proportion that you're involved with across just different modalities? Are you able to kind of disclose that?
In terms of our partners or just the overall space?
Your partners.
Yeah. The different ones. We have 18 programs in the clinic right now using our systems, which is more than last year. The programs themselves are a mix of allogeneic and autologous therapies, about 50-50, roughly. It is over a wide stream. Many of these programs are oncology related. Many of them are not autoimmune related. The example I give is, I might have mentioned it, is CRISPR Therapeutics' CTX112, as well as TG Therapeutics, which licenses azer-cel for autoimmune diseases as well. It is a good mix of modalities.
Okay. Let's talk about the recent acquisition of SeQure Dx. Maybe first speak to the bigger picture of where MaxCyte could be in five years as a diversified cell therapy tools provider and really how SeQure Dx fits into that picture.
Yeah. Let me speak to where MaxCyte can be and really is working towards. We are a cell engineering company. That's what we are. We provide the insights to how to engineer a cell really from early discovery all the way into the clinic. If you look at where we're going to be in five years, we're going to have these offerings where I call, we're going to standardize the cell therapy, the cell engineering workflow, right?
We talk about oftentimes automation of these cells, automation of manufacturing of these cell therapies and cell gene therapies. That is needed. That is where this space needs to go. There is something more than that. We also have to standardize for these therapy developers how you actually engineer a cell from early discovery all the way into the clinic, right? That's what SeQure Dx gives us.
SeQure really is the foundation of us becoming that true cell engineering company that can standardize cell engineering. The excitement for SeQure is enormous in the company as well as SeQure. Let me talk a little bit about what SeQure does and what they are. SeQure was founded out of the labs of Dr. Keith Joung.
Keith Joung is a pioneer in this industry, the cell and gene therapy industry. He's the founder of Editas and Beam, Verve, Chroma, Nvelop, and SeQure Dx. SeQure Dx allows us to work with developers now early in the process to truly help them ensure that when you're making edits to the cell, ex vivo or in vivo, using viral or non-viral, using electroporation or non-electroporation, that the edits to the cell are as safe as possible.
If you think about it for a second, when you're using CRISPR or a base editor or a prime editor, you're making nicks to the DNA of a cell. That cell is going to go back into the body. SeQure Dx does something that every developer should be using. It allows you to understand, are there any off-target effects of those enzymes being used? Think about it for a second.
These therapies are going back into the body. Don't you want to make sure that you're ensuring you've de-risked the editing of those cells as much as possible? You have something to give the FDA, to give to EMA, and to give to other regulatory bodies, almost de-risking that there are no off-target effects. That's what SeQure does. They do it better than anyone else.
It's a group of highly specialized scientists right here in Waltham working on this. They really started commercializing their services in 2024. They came out of stealth in late 2022. We can't be more excited. They've become, it's part of MaxCyte. We're all one company. We want to help standardize the space to help developers get products into the clinic faster, safer, to get them to patients.
Realistically, how do you see the integration of SeQure kind of growing the commercial enterprise with MaxCyte maybe, again, five years from now? What's kind of the lowest hanging fruit for you guys with them?
The lowest hanging fruit really is just ensuring that we can leverage our commercial infrastructure that we've built out here to be able to get their services to the broader array of customers, both in vivo and ex vivo. That is where we started, Brandon. That is where we started. In fact, if you go to the SeQure Dx website, there is a new SeQure Dx website.
It is directed at the MaxCyte website. We did that from day one. From the time the acquisition was announced, that was launched. We also are integrating their scientific team with our commercial team to make sure that we have the leads and the customer funnel exactly where it needs to be. That has happened already. We are not going to guide just yet in terms of what the revenues are going to be. I'll leave that to Mr. Doug, when we get there in eight days or so, when we announce our earnings, the growth trajectory for them is as positive as it is for MaxCyte as well.
I guess when you think about additional BD or additional M&A, what other areas of white space do you feel are worth pursuing maybe up and downstream of electroporation for MaxCyte?
Yeah. That's a great question. I mean, obviously, there are two ways to think about it. SeQure Dx is one where it's upstream from us. It's upstream from us in a different way. There's what you consider unit operation upstream, potential growth opportunities, but then also what I call biological tool opportunities as well upstream. SeQure Dx is a biological tool. You're using assays to ensure that the edits that you're making are exactly where they need to be in the gene of interest and that there are no off-target effects.
It is ensuring that we're able to begin to standardize that process more from an upstream perspective, both from a unit operation potential, but even more so from a biological tool perspective, what is being used by these developers to engineer their cells. That's where we see the growth opportunities for us to be able to potentially grow our offerings.
Okay. I do want to kind of zoom out just a little bit and maybe speak a bit to MaxCyte's ability to scale. Really, in the context of azer-cel, for example, how does your new facility from a couple of years ago support your ability to scale? Maybe what are your plans for any additional investments in this respect?
Yep. I'll mention a bit, and then Doug, I'd love to add to this. The ability to scale for us, we can leverage everything we've done since 2021 when we went public, moved to a new facility in 2022. We did that in anticipation of two things, in anticipation of making sure the company can manufacture and engineer everything in-house. So all of our manufacturing of our systems, all of the manufacturing of our possible assemblies are done in-house in our facilities in Rockville, Maryland.
That leverage for ExPERT, which became Casgevy that we built out, can be used for the foreseeable future. In fact, we can leverage everything we've done now for every product that we have currently in the clinic and future SPLs that we're going three to five each year. All those programs, we can manufacture all the instruments, all the processing assemblies in-house.
What we have now, we can leverage for the foreseeable future. What we can also leverage is the commercial and the scientific that we built out. For the other offerings that we brought in, such as SeQure Dx, we can leverage our commercial infrastructure as well, not just our manufacturing engineering infrastructure, to be able to scale out those growth opportunities as well. Yeah.
I guess, how much visibility do you have? I know we've spoken a little bit previously about, I think it's like $2+ billion for commercial milestones down the road. I mean, how much of that do you have any kind of visibility or insight into? Is there any particular near-term opportunities within that broader number?
Let's talk about what that $2 billion number represents. That represents the number of milestones that could be achieved under every potential program underlying all the SPLs that are in effect. That extends to current programs as well as the number of slots that they've negotiated in terms of being able to utilize our program for additional, utilize our program or our platform for additional programs.
Let's talk about what's actually in the clinic. We have 18 folks in the clinic, programs that are in the clinic. This does not include Casgevy, obviously. We can tell you that, at least to give you a tangible number, those programs alone, approximately $200 million of unrealized milestones can be achieved from those programs currently in the clinic.
Okay. I guess in just a sense of cadence over the next couple of years, realistically, how should we start to think about some of that coming through?
I don't think we can break that down, but again, because that approximate $200 million number includes programs that are actually in the clinic, and we can get the sense for what the timelines are for clinical development, particularly that is somewhat accelerated in our space.
For instance, we achieved a milestone last year where a program that was initially a Phase I program was deemed to be a pivotal trial, and we achieved a pivotal milestone for that. I can't give you an exact breakdown, but again, because these are programs already in the clinic, not all of them are going to be successful, but this is not something that we're looking out an endless number of years for. For that number, I'd be looking at or looking at the $2 billion number and see which additional programs are going to emerge from our current SPL relationships as well as future ones.
Okay. Maybe the last one here is really, how do you view the company's path to profitability today, and particularly in terms of timing, how you're thinking about that?
We're not a position or not willing right now to draw a line in the sand and say what it is. However, we've taken steps to move to work towards it, right? We've undertaken a significant amount of reprioritization of where the spending is. We've reduced costs. We talked a little bit about whether or not what's the leverageability of the investments we've already made.
There's tremendous leverageability. Our founder and former CEO would talk about, "We need to be ready." We are ready. We can support a multitude of commercial programs from the current facility we have. We have the resources in hand to reach profitability. That is important. I can't tell you what year. Maybe I could tell you what month. I can't tell you what year.
I think that we're in a position with the resources we have, inclusive of doing some corporate development in a disciplined manner, as evidenced by the SeQure Dx transaction we just completed, that we can reach profitability with the resources we have. Again, at some point, we're probably going to have to put a line in the sand and say when that is. We haven't been prepared to do it yet.
Can I add also we ended the year with $190 million in cash. As Doug mentioned, even inclusive of SeQure Dx and other potential growth opportunities, the path to profitability should not be a concern.
Yeah. I know we're out of time, but just let's bring it home. Kind of lay out the next year for us and most important inflection points and things for us to watch for over the next 12 months for MaxCyte.
Absolutely. One is our continued growth in the space. You want to see that from us, and we'll continue to deliver on that. You also should see some of the programs in the clinic as well. I mentioned it. You want to look at CRISPR, CTX112. These are programs potentially that can go pivotal this year. You want to look at Imugene with azer-cel, whether it's a CD19 for oncology malignancies that potentially could go into the pivotal this year as well. You want to look at KSQ. KSQ is an interesting company where they're developing a TIL program to graft for solid tumors. We work very closely with them. You can never forecast what's going to happen in the clinic, but highly exciting company.
A little smaller company that we recently signed, but really is something unique, is Kamau Therapeutics, where again, they're going after a different way of treating sickle cell disease. It is in the clinic, hopefully starting this year. I think we're going to keep an eye on these programs. If you look at the growth that we've done as an organization and the way we have looked for new ways to grow our company, look for more of that in the future as well. Having a healthy M&A outlook and doing it in a way that we were doing with SeQure Dx, where we find opportunities that fit hand in glove with what we do, that allow us to really become that cell engineering expert company that works with therapy developers.