Programming Living Cells at Scale to Make Cell Therapies Available to More Patients: Dr. Thomas Eaton, Limula

Dr. Thomas Eaton: 0:00

Failure is not an option. We have the potential to do this. We cannot fail.

Alex, X-Health.show: 0:08

Hi, i'm Alex and welcome to the X-HELP show, where I talk to visionaries behind the latest innovations in Holke for the extra help of the future. We're at Biopolo Zan, two levels above, a lab where living human cells are trained to target cancer cells. Hosting me here is Dr Thomas Itten, a co-founder of Límila. With a background in chemistry and material sciences, he's embraced a change-makers' career from global corporates to startups, also swims in Lake Tudi year-round. Límila is a Swiss startup offering a modular platform for on-demand and at-scale manufacturing of personalized cell therapies. In essence, their hardware, the size of a cupboard, can replace a whole lab building. You'll hear today about cell therapies and CARTI cell therapy, how they are manufactured today and how to make them available to more patients, and about three elements that set the startup up for success. Tom, there are these new, as if miraculous therapies for liquid cancers. One injection cures patients like forever, but they cost now half a million to a million, and you at Límila, you want to bring that cost down to How much?

Dr. Thomas Eaton: 1:32

Well, I think the core essence is about access, and cost is a part of access. It's true today that these therapies are astronomically priced I mean these are the most expensive therapeutics that have ever come to market But actually the problem we see today is not even about the price People are willing and able to pay. That It's about access and the number of doses that can be manufactured even at the most expensive therapeutic price point. So our number one target is about the access. The price is going to be a consequence of increasing the access, And so we're on a mission to deploy our technology as quickly as possible to ensure that patients who are eligible from a medical standpoint have a chance at a manufacturer, And then the price will be a consequence of our ability to do that at a more reasonable cost.

Dr. Thomas Eaton: 2:32

So in terms of a target, I mean we certainly aim for order of magnitude, That's 10x down from where we are today. Oh, that's huge. But I think you know pricing in the drug market is itself a complicated topic And in essence, really the challenge here is about the payments model, because the premise of these cell therapies is one-time treatment, So one-time payment, which actually is not what our healthcare systems were designed for. So there's this mismatch between the design and history of our payments model looking at an annual basis, looking at reimbursements on an ongoing treatment, versus what is now a one-time treatment and you're done, But the effect of that treatment persists.

Alex, X-Health.show: 3:26

Yeah, so that's yeah. There are a lot of issues that you now mentioned. Let's start with this access. How many patients need this kind of treatment now?

Dr. Thomas Eaton: 3:40

Well, i'd say it's super exciting because the number of eligible patients, i mean, is just growing. As the clinical trials are coming to fruition, we start seeing the different modalities of these cell therapies, car-t being the primary one that's already come to market. Now six approved modalities. Also, looking at different indications, it almost feels like on a monthly basis we're increasing the eligible patient population of who could be receiving these therapies.

Alex, X-Health.show: 4:14

So the exciting part is that the treatment works right.

Dr. Thomas Eaton: 4:20

Yeah, i mean, if we step back a bit, this is what feels like a kind of science fiction. You have a cancer case, who presents, and nothing else has worked, and then we try this cell therapy treatment, and when it works is a one-time injection and they go from a terminal diagnosis to a state of complete remission when all of the stars have aligned. And so this is a new treatment modality in medicine in general.

Alex, X-Health.show: 4:56

Yeah, it is miraculous. You know, as I said at the beginning, Who can benefit from these therapies.

Dr. Thomas Eaton: 5:04

So today we should draw a distinction between the experimental use and the routine use And because these cell therapies are very new, access is in some extent certainly limited to those who are in a or access to a research environment.

Dr. Thomas Eaton: 5:26

But the exciting part is that that research has come to fruition. We're showing that these therapies, they really work, and so now we're shifting to approved therapies that have eligibility criteria linked to the way they're reimbursed, and this is what will be the future access problem is how can we align the reimbursements and the manufacturing of what are these very personalized medicines? So today you have two modes of access to a cell therapy. Either you're in a research setting, you've been referred there, you are at the cutting edge, but we don't know if that's going to work for you And on the other side we start to have these first approvals, first one in this oncology indication about five years ago, now six on the market for these different cancer indications. So it comes at a rapid pace and here is designated treatment centers that are able to refer your case and then your sample to a dedicated manufacturing site.

Alex, X-Health.show: 6:39

So any numbers we could speak about, like how many people already injected the cells they own, cells that cure them.

Dr. Thomas Eaton: 6:52

So the number of patients treated, i mean, is something that, fortunately, is changing every day. What we're focused on is this gap between the number of eligible patients who present and would qualify and those who actually get treatment. By some estimates, it's only 10% of eligible patient populations are currently getting referred for these treatments, in a large part due to the manufacturing slots and availability.

Alex, X-Health.show: 7:24

So how? yeah, let's speak about this manufacturing then, or maybe, no, let's go one step back. And what these cell therapies, what cancers we speaking here? they can be used for now.

Dr. Thomas Eaton: 7:38

So the initial cases for cancer treatment. cell therapies have had the most obvious success in blood cancers, anything related to blood cancers, and that's in part to do with the biology that, the way that they're affecting and is how the cells can get in contact the car cells can get in contact with the cancer cells. What's the mission and ongoing research is to break the paradigm into solid tumors, and here there needs to be some innovation, which we're seeing, but is a slightly different modality in the behavior of the engineered cells for them to be able to access the tumor.

Alex, X-Health.show: 8:26

In simple words. We'll come back to that later. How does this?

Dr. Thomas Eaton: 8:30

therapy work. So I mean, right from the basic principles, your body has an immune system and what we're doing with the cell therapies in these cancer approaches is to trigger, to use the innate immune system to target your cancer. And we do that by taking a sample from a patient who has cancer. But we're looking for a sample of their immune cells and then we engineer those immune cells, we train them outside the body to target the cancer.

Dr. Thomas Eaton: 9:06

It's something that you see in nature, i mean in your own body, in your own lifetime. You have cells that may be cancerous or pre-cancerous all the time, but your immune system is able to signal that the cell shouldn't be there. Well-known processes like apoptosis, where there's a signaling that causes a cell to self-destruct, and the cancer state is really when there's a persistence, where that normal immune function has not been affected. And so in a cell therapy treatment in cancer, in essence we're trying to mimic or find a way that we can piggyback what is already an observed phenomenon but engineer it to happen at either a much faster pace or to happen at all where there has been a way that the cells in your tumor have escaped the immune response.

Alex, X-Health.show: 10:05

So you train your own cells to kill the rock cells. In short, Yeah.

Dr. Thomas Eaton: 10:14

So what is a cancerous state? These are when cells have gone rogue, and so what we're trying in these cell therapy approaches is to use immune cells that are supposed to go after rogue cells either your own cells, foreign cells, bacterial cells or even, if there's a foreign body, this is your security system for the body. That got confused, in essence, yeah, and I mean, different cancers have different modalities for that, but they have tricks where they hide from the immune system.

Alex, X-Health.show: 11:10

Now how currently cell therapies are manufactured.

Dr. Thomas Eaton: 11:16

Yeah. So this is a great question And I think it's at the essence of what we're trying to do at Limula. So, if we start with the basic principles of cell therapy, manufacturing is you're taking a cell sample. You are often engineering the cells, either introducing new genetic material or you're giving them an environment where they express differently than they would do otherwise, but you're altering the state of these living natural cells And then you are culturing them to be prepared for reinjection to a patient, and so there's a series of management of cells that needs to be done currently outside the body, and that manufacturing process, initially in a research setting, has been completely manual, so we've been using lab techniques. If you have a classic image in mind of somebody in a white coat perpeting samples around handling plastic containers, that is exactly how these cell therapies were developed.

Alex, X-Health.show: 12:25

So is it the one person working on it?

Dr. Thomas Eaton: 12:28

I mean in a research setting, you'll have one person touching a sample at a time. We now get to the point that we've been able to take it out of the research lab and to the clinic So we actually can treat patients with that. But we're still using techniques that were applicable when it was purely in a research phase. And the rush to do that is this excitement that it's really working, And so we don't pause for thought, we rush these to the clinic, which is the right thing to do. But it's left a somewhat technical debt for the industry in being able to scale up the manufacturing.

Alex, X-Health.show: 13:07

How many doses, always speaking now, how many doses that can be manufactured now?

Dr. Thomas Eaton: 13:13

So the current approach is in a centralized facility where you have a dedicated site that you equip for one particular cell therapy. So a classic example is you set up a new building and you designate it only for manufacturing that one particular cell therapy. The whole building, yeah, i mean, what you want is manufacturing lines. And so we do start to see that there are economies of scale that if you have separate floors or separate rooms that you can designate for one therapy. But if you want to maximize the output of a facility, it would be a single facility.

Dr. Thomas Eaton: 13:59

But these are high grade clean rooms in order to do these processes, which have this manual component.

Dr. Thomas Eaton: 14:06

And so at some point we see these processes have an open step where those cells are exposed to the outside environment.

Dr. Thomas Eaton: 14:15

And because these cells end up getting injected back to a patient, we want to be absolutely certain we control that environment to prevent any risk of contamination, in particular things like bacteria, but also even particulates.

Dr. Thomas Eaton: 14:30

And so these high grade clean rooms, synonymous with what's used for making microelectronics, you have people in effectively full body suits to ensure that they cannot pass on any contamination to the sample, and so these are highly specialized facilities and highly trained staff who operate within them.

Dr. Thomas Eaton: 14:52

So to give you the numbers, about 250 million as a capital expense to commission such a building. You then have a positive atmosphere where you're ensuring that you have a positive flow of air through and you're controlling everything that enters that environment in terms of cleanliness, in terms of its behavior, that it cannot itself give off any particles. So there's a huge overhead even before you start And then in a manufacturing line where you've got a patient sample arriving, you then need to perform a series of steps on that sample And we see that typical on market processes use up to 30 people who at some point are making contact with that cell sample, either for doing directly manipulations adding reagents, media, fluids or doing the quality analysis, taking samples and checking that the cell product is what was designated and ready for injecting back to the patient.

Alex, X-Health.show: 15:56

So each person responsible for a different step of manufacturing the dose.

Dr. Thomas Eaton: 16:01

Indeed, and even more than that. Currently, with the pending investment in automation, a lot of these steps have a manual component And so, in order to control that, we see pair processing Very familiar in a different space. When you do pair programming, you have somebody who's typing a line of code and someone else who is there just to watch And we implement the same inside a GMP facility. So this means there are two people now dressed in their suits. One is not active. He's ensuring that the other has performed the procedure as defined in the protocol for that manufacture. And this is where we see a big opportunity, as Lymula, to provide a tool where we can render those steps into a device And then you can control the behavior of the device. You take away the overhead of having this manual contact.

Alex, X-Health.show: 17:05

So I heard your co-founder look. So Dr Luc Henri, during the VGSTATUP award ceremony, and congratulations, i mean, you won the award. Lymula won the award. He actually compared the current state of cell therapy manufacturing to early watch industry, when a watch was manufactured manually And it was very, very expensive, and then the whole process was automated And suddenly you know, everyone can afford a watch. How do you want to make it happen? So what's yeah, what's limola device?

Dr. Thomas Eaton: 17:54

I think the watch is a great example, because it brings to mind a level of complexity, and that's what we're trying to address is how can you reduce that complexity or how can you manage the complexity In the case of these biological cell therapies, it's in managing the biochemistry, in the addition and removal of reagents over time and changing the environment that those cells are in, and so at Limula we have a unique technology. Where we do that in a closed system is a very elegant design that we actually have just a single chamber that hosts the cells and then we bring the reagents in and out of that chamber without moving the cells around, and so we maintain actually the same level of biological complexity. We're exposing the cells in the same way that they would be in other processes, but we have this design that allows us to manage that complexity.

Alex, X-Health.show: 19:01

Let's speak then first about the limola kit. Like, what is it? You brought it here right, So we've got the device here. Could you describe it? What does it consist of?

Dr. Thomas Eaton: 19:14

Yeah. So maybe to give you the imagery, as we're on the podcast, here is a piece of hardware that hosts a kit, and so I think the best is to go to analogies, as prosaic as may be. I think, being here in Switzerland, we're all very familiar with the Nespresso machine and a capsule. And so you have a piece of hardware, you add a single use component to it and you push a button and you get something out. So, in the case of making coffee is a very elegant way to personalize your own coffee. You can adjust how much of the liquid you want to pass through, even in some devices, right How hot you want your coffee to be. And we have the similar design concept that you have a piece of hardware that's used again and again, but you have a single use component that allows you to adapt for different cell therapy types.

Dr. Thomas Eaton: 20:22

So indeed, i have one here in front of me, and our core chamber is a vessel where we host the cells is made of plastic Maybe you can hear me hitting it on the mic.

Dr. Thomas Eaton: 20:36

It's not too thin. No, indeed, and in our proof of concept study, we actually were replicating some of the original protocols for CAR T therapy, where we host cells there for up to three weeks. So it needs a certain level of robustness, and with this core chamber we can make certain physical manipulations. We can move the chamber in space, and just under gravity means that we move fluids around, and because we can spin the chamber we can keep cells in position whilst moving fluids in and out of the same chamber. And it's this trick of in situ centrifugation. And then, coupled to that core chamber, we have rotor stators that allows us to spin but maintain a closed system, and so there's an engineering part to this that is in combination with that plastics component, and then beyond that, we set up a kit that includes the set reagents that are needed for a given protocol. That we can have all that in place before you start a manufacturing run.

Alex, X-Health.show: 22:02

So now, step by step. So cells arrive. What does? yeah, i don't know. There's scientists, a lab around you know someone who knows what to do. What do they do with their cells?

Dr. Thomas Eaton: 22:16

So we see differentiation here in different protocols and different cell types or even different indications, using the same cell type But for a different purpose, have slightly different procedures. And what we focused on is the commonality is that you are handling cells and you're putting them in contact with different reagents, media, different temperatures, different physical environments, at different points in time.

Dr. Thomas Eaton: 22:46

That's the training you described before part in part, yeah, so I mean the most specific parts, for a CAR T therapy is inserting a gene copy for expressing a car, and so here you actually are introducing new genetic material. There are different ways of doing that, but the approved therapies use a viral vector, and so in our reagent setup we want to be in a position where you could be adding such a viral vector in the right point in time for your process.

Alex, X-Health.show: 23:24

So we're speaking now CAR T cells. So that's just, you know. We're, all you know, on the same page.

Dr. Thomas Eaton: 23:30

Car means Yeah, very good. So a car stands for CAR T named because these are expressed on T cells, this part of the immune system, and the car stands CAR for chimeric antigen receptor, and so this is the component that we want these T cells to express that they can interact with the cancer site, specifically the cancer cells, and that's also why these modalities have had their early success in blood cancers, because you're in the same medium, once you've injected those cells, that they can actually make contact with the other cancer cells. And now there is a large body of research ongoing, also in the clinic patients getting treated, looking at ways of adapting that car expression to make it amenable that these T cells can access solid tumors, but as Lymula, and looking at the problem of manufacturing. We're interested in supporting all of these players right. So to your point on what's needed in the manufacturer it's really specific to the biology you're trying to do.

Dr. Thomas Eaton: 24:47

The cell therapy that you're making And this is where we see our customer base is in the inventiveness, in being able to play with that biology, and what we're presenting is an automated tool that allows you both to do that research step but then also take that protocol and put it into an environment where you can scale the manufacturer And so you could actually use the same tool for your research and going to the clinic and receiving an approval that you could go to routine clinical care with the same device and the same protocol.

Alex, X-Health.show: 25:25

So meaning that there is a patient coming over to a clinic, a doctor prescribes car T cells and they manufacture them at the same hospital for the patient.

Dr. Thomas Eaton: 25:38

I mean as a vision. I think that that's where the industry is tending towards, is about, or, more correctly, is where we need to get to as an industry. If we want these to be routine, use Now question marks on how we get there. We see where we are today in the centralized manufacturer in terms of trying to scale, but the clinical studies are doing localized manufacture on a case by case basis.

Alex, X-Health.show: 26:10

And that's very interesting because I can imagine it also shortens the time for receiving the treatment to an extent.

Dr. Thomas Eaton: 26:19

I think the biggest hurdle we're certainly focused on is really on the number of manufacturing slots. I mean the time of the treatment. Yes, there's a component. If you have centralized manufacturing, you need to ship the sample. But there are ways and we can do that. You can play with the biology, adapting the modality of what cell therapy you're doing, and I think that's where you'll have more effect on the time, even even than adjusting for shipping. But what you don't adjust for is what are the number of slots that you have for such a manufacturer? And here we really want to engender the process into a device that, for every number of devices you have, you could be making the therapy.

Alex, X-Health.show: 27:11

And let's stick to the vision. then What do hospitals need to implement that? to implement Limla into their systems, workflows, into treatment for patients?

Dr. Thomas Eaton: 27:27

Very good question. So there's in pharma industry and value chain in general, a historic distinction between manufacturing and patient delivery. If we go back far enough, right, they were aligned. Your doctor or your pharmacist would actually be formulating the medicine that you receive, and we see big efficiency gains in separating the manufacturer from the dosing. I think with cell therapies, because this modality of the personalized nature questions how do we maintain that separation or do we need to?

Dr. Thomas Eaton: 28:09

I mean, if you look at again a totally different treatment modality, but in surgery, which is the ultimate personalized treatment, you have to be present and you're acting directly on only that one patient. The issue initially is when you come up with a new surgical procedure, how can you scale it? And you can't. You have one surgeon who knows how to do it. He was the first one to do that particular surgery And only after he trains other surgeons can you expand the scope of patients that can receive that treatment. And we see similarities in the cell therapy space with this personalized nature and the one time one manufacturer, meaning that your scaling is in your ability to scale up the manufacturing. And so what we want to do at LIMULA is render that process onto the device. These are effectively the surgeons on your cells. And then, for every number of devices we have, we're able to perform more personalized manufacturing.

Alex, X-Health.show: 29:20

So it means more therapies available for more patients.

Dr. Thomas Eaton: 29:26

Absolutely Yeah, no question.

Alex, X-Health.show: 29:29

So let's now go back a bit to like yeah, how did you come up with the idea? Right? So I heard there was a garage involved. Could you tell a bit more about that?

Dr. Thomas Eaton: 29:39

Yeah, i think our founder story.

Dr. Thomas Eaton: 29:42

I mean there's a couple of different avenues where we're three co-founders that came together to form LIMULA, but we didn't all start at the same time, so the initial seed was really from our tech lead, jan Pearson, who at the end of his PhD, was interested in sciences and looking for applying his learnings into a technology space, and he started what I think is the most effective way around for creating innovation, looking for hard problems to solve And this is where he was introduced to the cell therapy and the promise that they have in these one time treatments, coupled with the immediacy of, or urgency.

Dr. Thomas Eaton: 30:35

We can't treat patients unless we can manufacture these. And so, in his garage, came up with some prototypes, 3d printed initially, looking at ways to address exactly this problem of how do you manage cells in contact with media in an efficient way that you can scale the process by scaling the number of devices that you have. And so, yeah, his very first prototypes were all made in his garage. Now, the background as to where that comes from he had a side job, let's say, in open innovation space that he and Luke Henri, the other co-founder, were working on together with the premise local here to Colonel of opening up science, that it doesn't have to or should not be only done in academic or closed door inside companies, But science projects and science skills should be practiced by anyone anywhere, and so it was in that hacker mode that Jan was first working on this principle of open science and then using that facility that they set up for testing out his ideas in addressing this cell therapy manufacturing.

Alex, X-Health.show: 32:08

This episode is brought to you by The Ex-Hell Show and me. So if you like this podcast, be generous, hit, follow, leave a review. That'll help me invite more such amazing guests for you. Thank you, You went through you already told me that to do some proof of concept studies. How did they go?

Dr. Thomas Eaton: 32:32

The results Yeah, so linked to that initial ideation creation phase from the garage having a promising concept and a demo, to then actually apply that to real human cells.

Alex, X-Health.show: 32:48

I mean, you know, because it sounds like a science fiction and basically also, you know, just looking at the device. You know, I'll be posting guys the picture on LinkedIn, if you allow that.

Dr. Thomas Eaton: 32:57

Of course, of course.

Alex, X-Health.show: 33:00

It looks impossible because, like the whole process you just described, you know, taking the whole building into, well, like a something of the size of a wardrobe, right, with a crucial part being like, well, how big it is? 20 centimeters tall, yeah.

Dr. Thomas Eaton: 33:21

I mean with up to a liter useful volume. I mean we tuned that for a particular cell therapy use case. We've looked at different sizes but actually from the design we can accommodate very small volumes to larger volumes.

Alex, X-Health.show: 33:38

So I can imagine like when young came up with the device, you know they were like you know I bros raised, at least you know like what is this really? how this can work right.

Dr. Thomas Eaton: 33:52

Yeah, and I think that's, you know, the key part in that process of innovation going from a problem definition It's clearly defined that you know when you've got something that is amenable is addressing the problem or not And from that problem definition to then have the ideation phase and these initial concepts, and this is what Jan worked on in his garage.

Dr. Thomas Eaton: 34:21

After this ideation stage you then go to a mode of needing to collect the real world evidence of really showing does the idea meet the requirements in the problem definition, and so for that we ran our proof of concept with support from a private foundation, the Gabriel truth, and the inno Suisse, as a government led funds to bring the project back to a university environment, which gave us access to clinical samples. And so we had a inno Suisse project that was led through EPFL in coordination with the University of Geneva and the technical school in. In even don't have a gvd, and it was through the data collection that we did there that we could really show this proof of concept. We can replicate all of the steps of the cell therapy manufacturing as would have been done in a manual research setting.

Alex, X-Health.show: 35:26

So you passed that. I can imagine, right, this works. And then you joined the team, or you joined it before.

Dr. Thomas Eaton: 35:36

So, coupled with that ideation and managing the match of this design to addressing the problem, is looking at how can you make impact with that. So, beyond a nice piece of research development is how can you bring that to the market? And this is where this, this transition from doing research to applied research and scaling, and that's best done in a company setting.

Alex, X-Health.show: 36:12

Now may I just add something that you already told me, that the three of you, the three co-founders, you are all chemists, but also chemists with completely different backgrounds. So there's this chemistry, literally chemistry that brings you together, and then you have also different skills and different other different backgrounds.

Dr. Thomas Eaton: 36:38

Yeah, so in our founding story we came together with different experiences looking at the issue at hand, which was we have a promising concept Which we want to bring forward and to take transfer into the market. And so my part of joining Jan and Luke in that journey was looking at the business case and the formalism of what it is to move from a research setting to a company, and I think the fact we're all chemists actually is useful in a different way And is that essence of the innovation we're bringing forward, which is a combination of hardware, electronics, plastics, with changing the approach in biology, and so these are all completely different disciplines that we bring together under one roof And that interdisciplinary is super exciting, but it's a real challenge because you have different ways of describing even the same problem before you. And so what's been useful with our individual formal training as chemists? We have the same background, way of addressing or looking at a problem, so we have a common basis, a common language, but then later in our development and careers, as they started, went in different directions, so we can bring very different angles, different experiences, but have a common way of talking about the problem.

Dr. Thomas Eaton: 38:21

So, speaking for myself, after my PhD moved into banking, finance and insurance, you know, as a way to learn what is business, always with a mind to address back and work on this tech transfer of bringing technologies to the market, and from Luke side, spent some time moving from chemistry to more immunology and biology side, and the on looking at the engineering approaches and had a lot of access to devices during his own research. So we have different technical backgrounds, but then also had different focuses, and Luke as well spent time in science communication. He was lead editor for for a journal for a time and then and chief scientific advisor to the technical school here in Los Angeles. And so we bring these what are effectively different careers together and now align on the common purpose of addressing this problem of manufacturing in cell therapies. And so the chemistry component is actually just the glue that allows us to bring these different experiences under one banner that we can all talk in the same way.

Alex, X-Health.show: 39:43

All right, and then your role was to make a business out of some wonderful research.

Dr. Thomas Eaton: 39:52

Well, i certainly put the emphasis the other way around, and that's at the essence of what is, or how do you make innovation? And classically, there's two approaches. one is you have a piece of technology and you try to find use cases for it.

Alex, X-Health.show: 40:10

Where do you know where?

Dr. Thomas Eaton: 40:12

Yeah, and the other is that you have a clearly identified problem and you look for technology engineering approaches that address that problem. And certainly that's our focus at Lymula is ensuring clear problem definitions and then looking for and developing in combination. How do we combine different engineering approaches to address the problems in cell therapy manufacturing?

Alex, X-Health.show: 40:42

So what were the challenges at the beginning, when you were funding a business?

Dr. Thomas Eaton: 40:46

basically, I think we had the classic challenges. You know, the very first one should we found a business? You know, is this the right positioning for what up until that point had been a project to prove There could be an approach to address a problem? and I think that's in every founder story. Taking that decision is a process in itself and for us, was evaluating the potential. Is this a problem that is worth solving? And I think if you can address that, then you're ready to move forward as a business.

Dr. Thomas Eaton: 41:27

The key bit I would want to emphasize in our space is deep tech right, health care more generally, but certainly anything with a deep tech component. You've actually compounded the risks you're trying to address. One is purely technical does your approach, does your technology do what it's supposed to do? And you compound it with the business risk. Is there a market? is there someone willing to pay sufficiently to cover the costs of that technology? And outside of deep tech space it becomes a much easier question to manage because you're just looking at is there a business case? But in a deep tech startup you're really managing both risks And I think the the effective way is you focus on one and then you can look at the other And this is back to what I was saying on these two approaches to innovation.

Dr. Thomas Eaton: 42:30

Either you manage the market risk first ensure that there is a problem that people are worth is worth solving because there are people willing to pay for it Or you manage first the technology risk. You show that something works and then try and find a market for it. In terms of my approach for tech transfer is certainly to mitigate for the market risk. You know this is the externality that you don't control, for you want to bring something into an environment And so you've got to make sure that environment exists for you to bring your technology into. And then you manage later on for this technical risk.

Alex, X-Health.show: 43:15

Are you meeting the requirements of your customer And then I have a feeling we'll slowly approaching the complexity you mentioned at the beginning, because you've got the environment. That may need this device, but the environment is not completely ready for it, is it?

Dr. Thomas Eaton: 43:33

So there's different levels to complexity. I think we talked a bit about the vision for cell therapies to move to the hospital and that this could be very localized manufacturer. So I think the current ecosystem in health care is not set up for providing localized, personalized cell therapy manufacturing.

Alex, X-Health.show: 43:58

So I can imagine you can start differently.

Dr. Thomas Eaton: 44:01

Well, we certainly are making a start by supporting the established ecosystem for developing these cell therapies, and so there is this own value chain in the development of a pharmaceutical, but also an emerging ecosystem for the support of cell therapies. A key player there is CDMOs, these organizations that work on the process side.

Alex, X-Health.show: 44:29

What does CDMOs stand for?

Dr. Thomas Eaton: 44:31

Is a contracted development manufacturing organization, and so these are players that don't have their own therapy, nor are they traditionally the place of manufacture, but provide this in between step of how do you make the process work, that you can scale manufacturing And here is is really the core place for addressing cell therapy manufacturing, because these are the hands on looking at how can we manufacture And what we see. The tendency is that those are becoming the site of manufacture, with all of the limitations of scaling because of the heavy infrastructure costs required. But for us at Limmula, this is a channel for us to demonstrate our technology. We already work with a couple privileged CDMOs who have a version of our device in house that they're testing And in that way we're in a relevant environment with the technology but also access through to their customer base.

Alex, X-Health.show: 45:42

Could you tell a bit like one such a collaboration as an example?

Dr. Thomas Eaton: 45:48

Yeah, so in the value chain of cell therapy you need to combine the where the patient is with the therapeutic approach. So what is it that you're doing to those cells? Classically would be introducing new genetic material. So this is the IP on the therapy with the manufacturing location. And in order to have those players set up, you go through this step of process development, and this is where the CDMOs are kind of the link between a patient And the therapy, by rendering a process that can be performed routinely.

Dr. Thomas Eaton: 46:29

And so we've aligned this value chain in some of the research grants that we've received. So, most particularly from the European side, at the level, we have a couple different formalized grant agreements in the horizon program That allows us to work with these players. We get funded for our work and they also get funded for theirs, and so it delays the need for us to formalize the business side when we haven't yet finalized what it is that we offer to a patient. And so it's under the regime of these grant financings that we're able to already work with these players in a pseudo commercial setup where they're paid for their time, we're paid for ours. In a run states, when we're on market, they would traditionally be paying for our service, but in this way we have a grant that is covering that.

Alex, X-Health.show: 47:30

Speaking of grants, could you tell a bit more about your strategy for funding? you know, finding funds basically, because I you know you mentioned several runs so far. What was your strategy here?

Dr. Thomas Eaton: 47:46

yeah, so I mean, in terms of financing a startup in general, you need to position your financing in sequence with your stage of development, and different stakeholders will want to finance different parts or at different times of a startup companies development, and so on our side we balance those two risks of this commercial side and the technology side, and there are different stakeholders that are interested in one or the other, and so we use those to really identify what is it we're trying to do next and who in the ecosystem as a stakeholder is interested in supporting that next step. So, for a very concrete example, with the gaybert truth foundation, they supported us on a market research study of ensuring that there was a business case for what we were trying to do, and so, as a foundation, they made a grant which we could use for doing that that study. On the other side, there is the technology development and here players like in osuisse, as a formal, established part of swiss government, looking at ensuring tech transfer from research ideas into the marketplace. And so here we designed projects that are looking specifically at a sub part of the technology that we think we need in order to support the cell therapy manufacturing. And then, if we look at the wider, more European level. Was it grants in linking between a therapeutic and the manufacturing side? so we bring in this CDMO component as a partner, and so it's more aligning in terms of financing strategy, being very clear on what you're trying to do and identifying who, as a stakeholder landscape, is also interested in doing that same thing. I think you certainly need to do it that way round, rather than seeing that a particular stakeholder wants to invest in something and then design yourself to look like you're investable. It has many dividends to doing that, most of which is that you're both aligned to the same objective.

Dr. Thomas Eaton: 50:14

Now, for us, we looked very early on for these non dilutive grants and to, to an extent, this public financing, in order to ensure that what we were doing can be taken forward on a technology risk, because we had already clarified that market need.

Dr. Thomas Eaton: 50:38

And so, in terms of being successful with grant applications, you need to ensure that you're meeting the requirements of the grant and their objectives are also being met, because you're achieving your objectives. And if you don't have that alignment, you might get lucky, but you're going to create a problem in the future, which is how do you justify what you've done? So we've avoided that situation by only looking for things that align with what we're trying to do anyway. Now, in terms of our development, we're at the stage where we're ready to go commercial, and so the key stakeholders for that is more investors, equity investment And so this is the next stage of our development is moving away from a publicly funded space, less on the technology research side and more on the scaling, manufacturing and readiness for clinical quality. So we're now shifting our focus to look for what is equity, so private financing.

Alex, X-Health.show: 51:44

What was the most difficult.

Dr. Thomas Eaton: 51:46

So far in the startup journey. I think the most difficult thing on reflection was the decision to do it at all. I mean I was in a stable job before the limula case came across. I think it helped a lot that I knew Luke already from our early research days. I mean we first met studying in the UK about 15 years ago, so a long history of trust that allowed us to look at potential businesses that we could get involved with together. But really that decision to give up a stable income, a certainty to an extent in what your day to day looks like, and to take on that onus of being the founder I mean it's a very different mindset from meeting requirements that somebody has given you, to you being the one who sets requirements on yourself. Obviously, in the broader sense, as an entrepreneur, you get those requirements placed on you market requirements, market demands or stakeholders that you've brought in to align your meeting investor expectations. But it is a big step to say that I'm going to take responsibility for me.

Alex, X-Health.show: 53:13

Did you ever think that you may actually fail? So yeah, you may not achieve what you set to achieve. And then what?

Dr. Thomas Eaton: 53:21

I think this is a super interesting question because, at essence, if I rephrase the question, not what did you think or when could you fail, but what does success look like? And it's a very personal question for everyone and the journey that I think everyone needs to go on What does success look like? or, to rephrase, what does failure look like? Right, these are the two sides of the same question, and so, in the setting of what we're doing at Limula, the problem definition is so clear. What does failing look like? Well, it means these patients aren't getting the treatments that we know could work. So, i mean, my core answer is in terms of addressing that problem. Failure is not an option. We have the potential to do this. We cannot fail. So the question is more what is the success look like? And there is a journey and can change over time.

Dr. Thomas Eaton: 54:37

My personal journey has been more looking more broadly at bringing technologies to market, and so the success criteria is seeing the impact of my involvement in a project that's brought a new innovation to market. That's huge, i mean, and it's certainly a journey, right, and is more a career rather than just one company. And my personal journey. I've been involved in different startup projects along the way And my key learning is that you need three key components in order to bring a market, innovation and a technology to market, and these three components are a team, a technology and a market, a willingness to pay.

Dr. Thomas Eaton: 55:23

And in different guys is in other projects I was involved with, i nailed. Two of the three had a great team. We were looking at a very cool market space, but the technology wasn't there. It wasn't our IP, so we had a great idea but weren't able to implement for it. Or, in a different project I was involved with, we had a promising technology, rights to to in license it, but not the alignment within the team as to what the mission should be, and so Lymula is now my fourth startup, and it's the first one where, from the beginning, we had a team in place The three of us that we talked about, sharing a common vision, common language and ability to work together With a technology that was already, to an extent, proven and a very, very clear market need, and so it's just been in resonance from the beginning.

Dr. Thomas Eaton: 56:29

We never spent a day mitigating for something that was missing, and my learning reflection is that, in my journey in trying to bring technologies, innovations to market to have an impact, you really need to ensure that you have those three components And if you start having to mitigate or or a missing one, you need to start questioning should this project continue? Certainly in Lymula's case, we're really just on this momentum. We've never spent a day trying to cover up or mitigate for something that was missing. It's just about getting the alignment that this momentum is steered in the right direction.

Alex, X-Health.show: 57:13

And the team is growing right.

Dr. Thomas Eaton: 57:15

Yeah, so from from founding we were three. Within the last two years we've grown to nine people And, as we speak here in July, of twenty twenty three. We've even got several open positions, so we look to be up to 15 people before the end of the year.

Alex, X-Health.show: 57:33

How do you celebrate? or do you celebrate at all? because you've got reasons to celebrate, right. I mean, you won startup pictures at a future lab puzzle. Look one the grant, the division grant, right, do you celebrate?

Dr. Thomas Eaton: 57:53

I think it's super important The the bit that we always have this dilemma between having set objectives for ourselves and knowing there's so much more still to do, and as you start to tick off to build this momentum and you have one small win and then another one, maybe slightly bigger, your perspective starts to shift.

Dr. Thomas Eaton: 58:17

But it's super important to take the time out to reflect on where we've got to and what it was when we were viewing the next hurdle that we hadn't yet achieved was still ahead of us, because it felt like a big mountain, and the the issue in the startup journey is that as you build momentum right The mountain that you're trying to climb, your, your ambitions grow, and so you always see what's ahead of you, and it's always bigger and further away, and you need to take the time to recognize that you are building that momentum, and so we try and take time out identifying, in particular, members of the team that have contributed to something, or where it's stakeholders or a network who have maybe made a key introduction that led to an agreement to work with a new partner. It's super important to celebrate even even these small objectives.

Alex, X-Health.show: 59:16

So how do you celebrate?

Dr. Thomas Eaton: 59:18

Well, most recently was taking the team out for a team dinner and extended that to work with our advisors as well, and so the reflection I have is it's doing it together. I mean, celebrating is something you should do in public. It's something that you feed off each other's energy. Celebrating in private is you don't get the same energy or or emotional bounce. So it's something that we do, taking the team out.

Alex, X-Health.show: 59:55

All right, i think you already mentioned that a bit. but just to wrap up, what do you need to bring Limula to the market, like your current needs, something that would help you move forward, or something that you actually work on now?

Dr. Thomas Eaton: 1:00:16

Yeah, So we're at this super critical juncture of we've shown our approach can work. We've frozen on the design and we've demonstrated with potential customers meaning physicians and manufacturers of self therapies that our approach could help and improve their current process. And our final hurdle to really get this in the market is having patients treated with that device. And here is more of a regulatory or systemic hurdle in health care, which is around quality. We need to be sure ourselves and then assure others that the quality of our device is at a sufficient level that Anything that's gone through that device should be injected into a patient. And so we're now on this process of bringing the clinical grade quality to the components that we use in the device, that we're confident and can show to others that they have the confidence to then inject into patients what has passed through our device.

Dr. Thomas Eaton: 1:01:34

So this is an engineering journey that we're on. The good news is we're not the first ones that have brought forward something to a clinical quality to treat patients with. So it's a well trodden path. I think that the number one thing we need is the time to do that, and the secondary is having the right people to support it, and this is why, in part, we're growing the team. We're also engaging with external parties who have expertise, have already done this step, and so there is also a financial component in terms of remunerating them for their expertise, and so this is where we're fundraising.

Alex, X-Health.show: 1:02:14

You mentioned time, so you need money to basically pay for that time, right?

Dr. Thomas Eaton: 1:02:20

I mean in engineering, in terms of the stage we're at, we've got to a point where the problems we have from a technical perspective are engineering problems, and this in terms of technology, space. This is a super good place to be, because engineering problems are solvable. It's a question of time and effort, money spent to overcome the engineering hurdle. This is a much different place than if there's some biological or some physical constant that may prevent you from moving forward. It may just not be possible to engineer cells in a certain way.

Dr. Thomas Eaton: 1:03:02

We're in the fortunate position We've already de-risked that, and so it's just bringing the engineering to the right level, and here we can spend money to accelerate the time. And the other part is just putting the effort in and securing the plan that we have. And so, as a wrap up, i mean at LIMULA we're really on the mission to do just that, and it's trying to do it as quickly as possible. And that mission that we have it's just compounded by the fact that the domain we work in right back to where we started is it's so amazing that these therapies exist, that you can, in one dose, treat a patient for what was a terminal disease. So, as humanity right, we know how to do that now, and then we have an engineering hurdle as to why we can't do it for more people, and so this is a super powerful mission, and we're just building the momentum just getting started.

Alex, X-Health.show: 1:04:12

Lovely Tom. Thank you very much, then, for this conversation. Good luck on your mission. I mean, the world is waiting. So I mean, take your time right And you guys, if you want to, you know, check what LIMULA does. Please go to limulach, which is L-I-M-U-L-Ach. Thanks very much again. I'm totally impressed by the odosity of researchers and startup founders, doctors and entrepreneurs or ordinary parents turned healthcare innovators, people battling the battles that no one fought before for the extra health of the future. So if you see a startup posting on LinkedIn, show them some love. Hit like comment. That's fabulous. If you have a couple of drops more of that altruism, follow the X-Hall show, leave a review here. I'll be able to bring more of these visionaries to you. So a big thank you. You're awesome. See you next week.

SPEAKER: 1:05:12

The information in this podcast is for informational purposes only and should not be considered medical advice. If you have any medical questions, please consult your healthcare practitioner. The opinions on the show are Alex's or her guests. The podcast does not make any responsibility or warranties about guests' statements or credibility. While the podcast makes every effort to ensure that the information shared is accurate, please let us know if you have any comments, suggestions or corrections.