Good morning, welcome once again to TD Cowen's 46th Annual Healthcare Conference. I'm Phil Nadeau, one of the biotech analysts here at Cowen, and it's my pleasure to do a fireside chat with our newest company under coverage, Century Therapeutics. We have with us today Brent Pfeiffenberger, the CEO, and Chad Cowan, the CSO. Guys, maybe I'll kick it over to you to begin. Can you give a brief state-of-the-company overview? What does Century need to do to create value over the next 12 months to 24 months?
Yeah. First, thanks for the invite, Phil. It's great to be here, and I'm looking forward to telling the story. Just a quick note before we start, we may make some forward-looking statements which obviously are subject to change. Encourage anyone listening to take a look at our most recent public filings, and you can see the full list of risk factors and uncertainties. Look, I think what's important to reinforce for Century is there's really two foundational elements to what centers us as a company. One is the creation and development of iPSC-derived cell therapies, and second, that goes hand-in-hand with that, is our belief that you have to have the right technology, enabling technology to be able to evade the immune system to have successful impact clinically for these patients with those kind of products.
With that foundation, it really kind of drove us to what I'd say is our top two priority programs we think about the next 12-24 months. First is our Type 1 Diabetes program. It's called CNTY-813. It's an iPSC-derived beta islet cell replacement therapy. It's got our most advanced immune evasion engineering embedded in it, which we call Allo-Evasion 5.0. That is in IND-enabling studies currently, and we are on track to submit an IND towards the latter part of this year. I think why we're so excited about that program is we believe we've got a real chance to provide a functional cure for Type 1 diabetics, and I think that's just an incredible opportunity for us. The second priority program is called CNTY-308.
That is an iPSC-derived alpha beta T cell program. It's targeting CD19. It's also got our most advanced Allo-Evasion 5.0 engineered into it. The reason we're so bullish on that program is if you look at the landscape, and that's in B-cell-mediated autoimmune diseases, that we're trying to push that in the clinic this year, the reason we're excited is what's become really clear to us as you look at the clinical data being generated in autoimmune disease, autologous CAR T therapies work remarkably well in autoimmune disease. I think I'd argue the data is probably transformational based on what we've seen so far, and the list of indications that they work well in continues to grow.
Our belief is if you've got an iPSC-derived T cell that is functionally comparable to a primary CAR T cell, you can replace but also expand anywhere those products may potentially be going. With the more advanced Allo-Evasion engineered into it, we think we've got a reasonable shot at either reduced or eliminating lymphodepletion along with it. That's really our core focus execution-wise the next 12 months-24 months, is driving those two priority programs into the clinic, generating initial clinical data for us.
What's your longer-term vision, beyond the next one to two years for Century?
Yeah, it's a great question, 'cause there's obviously a lot of ways you can take iPSC-derived technology. I think there's maybe two helpful frames to think about this. One, if you think about in the context of our current programs we just talked about. Let's take CNTY-813, our Type 1 Diabetes program. If you think about the long-term goal for us in that space, we believe there's a real line of sight to going out and functionally curing the millions of patients who have Type 1 Diabetes, who are burdened by this disease, who are suffering from this disease. I'd argue that there's an obvious transformational impact for those patients if we're successful on that front.
I think there's a bigger impact on society and healthcare more generally if you can cure, functionally cure a disease of the magnitude of that size. That is a long-term ambition for us. We believe it's in the line of sight that we can accomplish, we're very excited about that as a company. The second is probably a more general one, if you think about those two foundational elements I talked about before of leveraging iPSCs as your technology base for your therapies and then ensuring you've got the right engineering and approach to evade the immune system, in theory, we can go after numerous different types of cells and disease states. I think what's exciting for us is we've now really built the capabilities internally around developmental biology, around genetic engineering, around clinical manufacturing, supply, and scale-up.
I think that vertical integration of capabilities and expertise and know-how is gonna enable us to figure out what's that next generation program, for example, after T1D, and the flexibility to decide what we wanna do in the space. I think there's a lot of exciting things out in front of us.
Maybe to dive into the foundational technology a bit more, can you discuss why allo cells are particularly attractive? Maybe weave into that why iPSCs in particular are the cell type that you wanna work with.
Yeah, I'd love to. I've been working on those for, I guess, 25 years, or something like them, human embryonic stem cells. Induced pluripotent stem cells really provide you probably the best foundation for making a cell-based therapy, and that's sort of the twofold advantage they have. One, they literally have the ability to have unlimited scale. Undifferentiated iPSCs , I often tell people I could fill the room with those, right? You can essentially proliferate them forever. The other advantage the cells have is they naturally have the ability to become any adult cell type. While you've heard us choose alpha beta T cells, CD4 and CD8, and beta islets and a mix of endocrine cell types, we have the opportunity with that same starting cell to make any cell type in the adult human body.
It really is the sort of appropriate starting point today for anything that might want to replace or repair damaged human tissue in the future or make cells that can be therapeutically useful. Why you need to pair that with something around Allo-Evasion is you really, in a pharmaceutical sense, wanna start with a single source of this. In other words, you wanna make one big, you know, sort of massive batch of drug and then be able to deliver it to everyone. When you're using an iPSC cell or a cell that is not the patient's own cell, they're going to have an allo response and try to reject that upon transplantation. We've spent, Century from the very beginning has been committed to this idea that you can genetically modify these cells.
It's another thing that they lend themselves well to because of this unlimited proliferation to help evade that immune response, we've continued to progress that through Allo 1.0, Allo 3.0, to our most advanced Allo 5.0 suite of edits, which we feel really give you the most comprehensive protection from the patient's immune system, allowing the cells, whether those be beta islet cells or the alpha beta T cells, to peacefully coexist with the patient's own immune system. Once you've checked that box, you can start to imagine how much further you can go.
Specifically, what edits are you making in Allo-Evasion 5.0?
Yeah, that's a great question. What we really get informed by is the natural experiments of biology, and a lot of those come from transplantation biology, where people have done organ transplants over the years. Another area that's really informative is actually pregnancy, where most pregnant mothers should be rejecting the fetus, which is half the father. You sort of ask, what are those factors that allow for both tolerance and rejection, and what do you wanna avoid? What we know is there's gonna be a massive T cell response, you've got to avoid that, the easiest way to do that is to actually let this, you know, take away the factors that billboard the not self on the surface of the cells, and those are the so-called HLAs.
We take away Class I and Class II through a series of edits. Then we now have to contend with other parts of the immune system that we might have actually activated. For instance, taking away Class I and Class II activates another component in your immune system known as natural killer cells. We, in our Allo 5.0, insert the first of its kind universal pan-NK inhibitory ligand. It's called CD300a TASR. It takes advantage of an inhibitory receptor on all NK cells in humans. By putting that on the surface of the cells, we tell all NK cells, "This is fine." Now we've taken care of, in essence, the cellular medulla that will come after you and potentially reject you.
What we have actually taken another leap forward with is most long-term rejection occurs because of antibody-mediated rejection, and that's often IgGs that you create, just like you would if you were immunized to the COVID vaccine. You do this because you've been immunized to a different cell. We've built for the first time a protection against that IgG-mediated rejection through an IgG-degrading protease that's actually expressed on the surface of the cell. That gives us that ability to comprehensively protect against all of the main features of the immune system that are involved in graft removal, organ rejection, et cetera, which we've learned about.
What preclinical data have you generated?
We've, you know, I am almost ashamed to say it, we've generated a ton. We've done all of the various in vitro experiments that you can do, including one which I am particularly proud of because it was published just a little over a year ago, where we took 45 different patients', immune systems, essentially, their Peripheral blood mononuclear cells, and we exposed them to our Allo 5.0. What was really great about that is it's almost like a mini clinical trial, where you could ask in 45 different people with all of the variation in their immune system, how did they react to our cells protected with Allo 5.0? What we really deeply assessed was that NK cell protection, and we showed that we were superior to anything else out there right now.
We basically are the best in the business at protecting you against patients' immune cells and in particular NK cells across all of those patients. We've also done all the things you want to see in terms of IgG-mediated rejection, and we've built some relatively sophisticated animal models to allow us to sort of look at the human immune system and our cells at the same time in that sort of in vivo setting. So far, those have all checked the boxes as well, which has got me really confident about what we're trying to do now, which is push this technology into patients.
How does this technology compare to some of the other immune-evading edits or technologies out there?
I think it compares favorably. Part of that's because I am very knowledgeable about them. My history is, I was a founder at CRISPR and head of research there and a founder at Sana and their CSO. I've been a part of the story of the evolution of Allo-Evasion, cloaking, Hypoimmune, and each of those have been the right step in the right direction, much like Century's even Allo 1.0, where you could see what we were trying to do is sort of build the defense against the immune system. Initially, it started with the taking away the T cell responses with these HLA reductions, then it became, okay, what about the NK cells? You could see Century's first attempt at that was HLA-E, which is terrific. It's only effective against a subset of NK cells.
Similarly, the effort that we mounted at Sana works really, really well against a subset of NK cells. Why I think this is a game changer is it's the first time I've seen us have that type of effect across all the NK cells in the human body that we've tested it against. It really gives us that kind of comprehensive coverage. We took one step further than anyone else out there, which is to provide protection against the long-term rejection that occurs due to IgGs. I think that I'm really confident saying that it's definitely the best in the business today to give you that kind of protection.
Moving to Type 1 Diabetes, maybe could you set the table by discussing the unmet medical need in Type 1 Diabetes and exactly what is CNTY-813?
Absolutely. I think a lot of people take for granted that Type 1 Diabetes is something we don't need to worry that much about because we have insulin, for instance. That's been the mainstay of our clinical treatment for diabetes for 100 years now. The problem, of course, with diabetics who are on insulin is they often have to determine where their blood sugars are, and they're not particularly good at that. As a result, you can have these crises where you've had abnormally low or hypoglycemic events, and those crises can be so acute and so severe that it drives them into the hospital. It's not unusual. Their estimates are 10%-20% of diabetics are suffering from those types of acute hypoglycemic events that actually require hospitalization once a year.
There's patient populations that are smaller that have two or three such events every single year, and that's often because long term with diabetes, you start to acquire something known as hypoglycemia unawareness. You don't really know what your blood sugar, you know, the brain circuits that normally tell you, "I'm feeling, you know, hypoglycemic or low blood sugar," they don't work as well, so you don't actually have that sense of, "Gosh, I might be crashing." It's a feature of the disease. I think another important thing that people don't realize is even with all of the pumps and even with all of the insulin therapy, most of these patients still end up with some of the severe complications that we know about, whether that be cardiovascular disease, the retinopathies, the kidney damage.
It all occurs later in life, and it significantly foreshortens the life of Type 1 diabetic patients. That type of unmet need in a patient population worldwide that's on the order of 10 million really does speak to what could we do that could transform the care. As you heard from Brent, we think by transplanting what is in essence lost in those patients' functional islets, you can now functionally cure those patients of that disease.
What data have been produced using islet cells from cadavers that kind of form proof of principle for this approach?
I mean, I think that's where we start to build a lot of enthusiasm and excitement. We're now 25 years in on data from cadaveric islet transplants. Back in 2000, James Shapiro did the very first cadaveric islet transplant in patients. We've been able to accumulate a tremendous amount of data over those years about how effective it is. I think I always like to start with some of the success stories. There are patients that were transplanted in James Shapiro's clinic in Edmonton more than 20 years ago that are still free of exogenous insulin. They are walking around today like they don't have diabetes, right? They don't have to check their blood sugars. They're not injecting themselves with insulin. They have HbA1cs that look relatively normal. That's the sort of like proof of principle that it could work.
As you look more recently with larger patient populations across many different sites, you're seeing thousands of patients now getting free of injected insulin up to a year, and that same sort of outcome with normoglycemia and essentially what we would call, you know, free of the disease, the functional cure. The big downside to all of the cadaverics is that while we now know it works and it can work really well long term, it comes along with this side effect of having to use severe and long-term immunosuppression. Many of the patients can't tolerate the immunosuppression because of a lot of the factors it has associated with it, kidney damage. It has associated with it adventitious agent infections.
Many patients start to come off those immune suppressive drugs, and as a result, they'll lose their graft and they lose some of the benefit. Interestingly, and I always like to point this out, even in patients that have stopped immune suppression and have lost what we would call full glucose control, there's still enormous benefit even in those. You'll look at the five-year data where a lot of patients don't have surviving grafts, and yet they have fewer severe hypoglycemic events, fewer hospitalizations, et cetera. There's a real opportunity here to make an enormous benefit in patients through the transplant of something that recapitulates a lot of what you see from cadaveric islets, but without the immune suppression.
Can you describe the preclinical data that you have supporting 813? In particular, what's the evidence that you're actually inducing beta islet cells from the iPSCs?
In the good news, I think it was Isaac Newton who said, "I can see so far because I'm standing on the shoulders of the giants that came before me." This is a field that's been very well established, and I was lucky enough to train in one of the labs that was sort of one of the you know, progenitors of the whole thing. Douglas Melton, who started the whole field of let's try to make pluripotent cells into an insulin-producing beta cell, it has come a long way, and it's taught us a lot about what are the key steps to do that from a pluripotent cell.
Perhaps even more importantly, it's showed all of us what you need to measure and understand in that sort of final product to know it's going to be comparable to something that you would take out of a patient, such as a cadaveric islet. We have an enormous number of assays that we can do in vitro as well as in vivo to sort of assess that. I'll give you a quick sort of summary. You wanna know, gosh, at the very end, have I made these cells that have the sort of signatures on a gene level that make them endocrine cells? Checkbox. We've got that. They look just like the cells that you'd expect to take out of somebody's pancreas. Do those same cells function like the cells that you'd take out of somebody's pancreas?
In particular, for beta cells, the insulin-producing cells, that means do they respond to glucose and secrete insulin at the right levels? You can assess that very carefully, both at very low glucose and very high glucose levels. In other words, if I just drank an entire Gatorade or if I just had a little, you know, candy like an M&M's, and you can ask yourself how well can I secrete insulin to control glucose across those sort of wide ranges. Again, we can check the box, and they look just like cadaveric islets. Then perhaps the most important thing you can do is say, "Well, gosh, what if I had an animal model that looked a lot like a Type 1 diabetic?
Would these actually rescue it in the same way? As we've published and shown or you know, at least shown in some of our publicly available material, we've transplanted sort of the human equivalent into animals that have been made diabetic, those beta islets. Not only do they very rapidly return the animals to normoglycemia, typically in less than 15 days, they maintain that non-diabetic phenotype for now well over 4 months.
Where is centering the IND enabling process?
Yeah, look, we're progressing nicely. I think, you know, we're still on track to submit an IND this year. I think the key components that, you know, we need to pull together the final package on mostly relate to the tumorigenicity study and the GLP toxicity studies for the IND submission. You know, I think some recent good news that I can share here is, you know, we had a engagement with the FDA through a Type D meeting, and it was mostly centered around kind of the body of evidence we needed to make sure we had that package right. You know, I think overall we received very clear and positive feedback from the FDA, and based on that, we believe we're still on track based on the work we're doing.
That's probably the most critical kind of rate-limiting component that we're focused in on. I'd say the second piece of it is just finalizing the trial protocols with our sites and investigators to make sure that's all buttoned up and lined up, obviously towards the IND.
Can you give us some sense of what the trial could look like?
Yeah, look, I think there's a couple key things that we're looking to get out of this clinically early on, because of the profile that Chad just explained, and based on the, you know, our opportunity to help these patients. I think, you know, first and foremost, there's a few things. One, you wanna make sure you've got a safe product. I think second, you wanna make sure your cells are actually engrafting the way you want them to engraft. Then the other components are: Is that engraft durable and holding? Can you eventually see the removal of exogenous insulin? Can you start to reduce or eliminate that chronic immunosuppression? As we think about, you know, the trials that we're working on finalizing now, I think those are really gonna be the centerpieces of how we think about it.
I think it's gonna be making sure we've got a relatively early and clear way that we can show safety of the product, cells are engrafting properly. We're seeing the functionality of those cells relatively early, which you're gonna be able to see in weeks or months through things like human C-peptide. It's probably gonna take a little bit longer as you think about what we've seen elsewhere clinically with cadaveric and, you know, through the Vertex programs that somewhere between 6 months and 9 months, you tend to see the majority of patients be able to remove exogenous insulin. As far as the chronic immunosuppression, that's a piece we're still working through on the best way to either eliminate or reduce that.
I think conceptually we're very much focused on either a fairly rapid taper or complete elimination of the chronic immunosuppression once we've shown those early elements.
Can you give us some sense of the overall clinical development timelines? Like when could this move into a pivotal study? When ultimately could CNTY-813 be on the market?
Look, still some work to do, I think some pieces we have to clear up, but I think there's a reasonable external precedent out there that Vertex has helped set a path for with their adaptive phase I, II, III trial. They've got a total of 50 patients in that pivotal program, including the 10, 12, 14 that had the early part of that trial. You know, as we think about the general structure and timeline, if you follow that general precedent and path, you know, and we're on track to submit the IND submission this year, you'd be producing early clinical data in the second half of 2027.
I think if you generally hold the timelines around regulatory development and no unforeseen major delays, you're probably looking at commercialization sometime in the early 2030s, but a lot more work between now and then.
What do you think ultimately would be the minimum product profile that you'd need for CNTY-813 to be commercially viable? How long would the graft have to survive? How much of a reduction in hypoglycemic events or a need for insulin?
Well, I think there's really two simple components that are really critical. One is the removal of any exogenous insulin for these patients. I think in order to say you've functionally cured a Type 1 diabetic, you have to be able to produce that insulin endogenously, right? That's a really critical element of the profile that we're looking for. I think the second piece of it is the ability to at least reduce the most burdensome or eliminate the most burdensome aspects of the chronic immunosuppression. I think as we've talked to investigators, to KOLs in the space, both endocrinologists, transplant surgeons, I think those are the pieces that have become really clear to us. You know, one, you've gotta make sure you've got cells that are engrafting and that you're removing all exogenous insulin from these patients.
That typically takes six to nine months, but I'd say once you get out to a year and you're also showing your ability to do that with the removal of some of these more burdensome immunosuppressions, I think you're gonna be in a very strong position as far as clinical outcomes for these patients.
Can you discuss manufacturing? What are your manufacturing capabilities? How close are you to being at clinical scale, then commercial scale?
Well, we built this program from the beginning with the end in sight and, you know, I think for us, that meant making sure we had a bioreactor compatible system, that we were doing all our differentiation and early work in on the cell type. That's where we're at now. We're at a scale of those bioreactors that could be ready for the early phase of that clinical development. There's work that we wanna do to continue to scale that. You know, just as an example, you know, if you use a certain type of bioreactor like the PBS bioreactor, those go to an 80-liter scale. For phase I trials, you're looking at like 0.5 or 3 liters, right?
For us, that's the kinda critical realm that we're in right now, is making sure we've got the right supply and scale for that early development. Then in parallel, we'll start to do some work on the broader scale-up as you think about pivotal and early commercialization.
Could you go into a little bit more detail about the market? I think you mentioned 10 million people with Type 1 Diabetes. What proportion of patients would be eligible for cell therapy? Who would be the low-hanging fruit, the initial adopters?
It's a really good question. again, I think we need a little more feedback, obviously from our health authorities on this and, you know, final trial protocols and some initial clinical data. I'll give you conceptually how we're thinking about it. again, I think there's good external precedence we can rely on a bit as a, you know, a base for this. If you take, for example, the path that Vertex is on, where they're looking at probably a pretty severe Type 1 diabetic population, which essentially are patients who have two or more severe hypoglycemic events, and they're what you call hypoglycemic unaware, right? A pretty dangerous combination.
There's estimated probably around 60-plus thousand patients who fit that criteria just in the U.S. alone, which is a very reasonable, you know, commercial opportunity as far as that patient sizing. I think the reason that they're starting there is my sense is they still have, through that product, have to give these patients chronic immunosuppression. Patients and physicians have to have that risk-benefit discussion as is this worth that risk or benefit, what we're gonna give you, versus the alternatives, right? Long-term insulin use, chronic insulin use. I think for us, if you go back to the profile we discussed, and if we're successful, at least at minimum of reducing or eliminating the most burdensome aspects of that chronic immunosuppression, I think that starts to expand even your early segment of patients that you could go after.
Just as an example, if you move to patients who are still severe but only have one or more severe hypoglycemic events a year, you're looking at now probably 200,000-250,000 patients in the U.S. alone. I think for us from a development standpoint based on the profile of the product, that's probably where we're gonna angle towards 'cause we think we can have more clinical impact earlier in that set of patients.
Great. Maybe in the last few minutes, a brief discussion of 308. I think the key question investors have is that there are a lot of CD19 CAR-Ts out there. Can you discuss how you think 308's gonna be differentiated?
Yeah. That I'd be thrilled to. CNTY-308 is really the first time an iPSC product has made what looks like autologous T cell products. Remember what makes autologous T cell products so effective is they're a mixture of both CD4 and CD8, so the CD4 helper cells and the CD8 cytotoxic cells. Why T cells have proven themselves so effective in cancer and autoimmune disease is when they see target, they exponentially divide on their own. They provide their own juice sort of to kick off the engine. We're the only cell type that has shown that through publications, through everything else that we've done, that we have that same innate quality. In other words, we've made the right type of cell at the end of the day that comparably looks like an autologous T cell.
We're really excited about it, and then it's built on the background of that same Allo 5.0 that I discussed, so that means that we know that it's gonna persist in the face of the patient's immune system without any sort of immunosuppression or potentially without even real lymphodepletion, which is the barrier now in autoimmune disease. Do you wanna get these treatments after having to do a really burdensome lymphodepletion regimen? Being able to put our cells in, have them mix nicely with the patient's own immune system, but have the bang of a autologous T cell gives us a lot of confidence that we can get that type of efficacy without a lot of the patient burden. Plus it's on demand. It's ready when you want it. Everything else you'd like to see out of a cell there.
What preclinical data have you generated to support the program?
There we have a tremendous amount of preclinical data that we've published, both in animal models with cells that are involved in autoimmune disease like B cells from autoimmune patients. We've also done this in tumor models where we've shown that you can very rapidly and capably eliminate those tumors and persist. It's the animal model data that gives me so much confidence. We're seeing both persistence, expansion, and efficacy that is on par with what patients or what people see with autologous T cells. That's where we know our cells, for instance, last up to 30 days in the animals in the presence of, say, tumor cells, just like an autologous CAR T.
Just to put that in context, other T cell products people have made look much more like innate cells, so that you get a very sort of rapid diminution in the cells, so often by 15 days you can no longer see them in circulation in the animals, whereas ours not only are in circulation, but one of the things we've shown people is that when you rechallenge them with tumor, they actually expand again. You have a resident T cell population that can essentially stand guard against what might be disease-causing cells, whether that be a B cell in autoimmune disease or a tumor cell in the sort of cancers that people have been using CD19 CAR-Ts in.
Where are you in the IND-enabling process for 308?
Yeah. We, similar, we're trying to move that program to the clinic this year. I think we're still on track to do that. We've got a lot of really good engagement and interest externally from sites and investigators around the world who like the profile of this product. You know, that's our goal is to push in the clinic this year.
Maybe briefly on 101, what's the current status and Century's desire to continue to invest in that program?
Yeah, it's in a IST with Dr. Andreas Mackensen there along in group in Germany. They did treat a handful of patients that they report some initial data on at the tail end of last year. I think they expect to put out some additional preliminary data as we move through 2026. You know, what I would simply say is, you know, NK cells have an attractive profile in autoimmune disease. They're probably a bit more of an experimental cell type. There's just less data out there clinically to show the long-term impact of it. We think moving through the IST with some of the more renowned experts in the space is probably the most efficient way to get there. The other thing I'd say is we'll set a relatively high benchmark.
This is a highly competitive space. I think we've got another program with T cells that we're also advancing. You know, internally we'll probably set a fairly high benchmark on competition.
Can you remind us of your cash balance and cash runway?
Yeah. With the most recent, capital raise we did in January, we're estimating our cash runway gets us out to Q1 2029. Obviously past a number of key clinical inflection points for us.
That's great. You've answered all my questions. Anything else I should have asked you that would be important for investors to know?
Look, I think we've covered a lot of the critical elements today, and I just wanted to reinforce, you know, we're incredibly excited about the opportunity in front of us and looking forward to getting some initial clinical data to show what it really looks like in patients.
That's great. Thanks for coming by the conference.
Thanks, Phil. Appreciate it.