Good afternoon, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler, and I want to thank you all for hanging out for our last presenting company of the day. Before I begin, I am required to point out certain disclosures regarding the relationship between Piper Sandler and Century Therapeutics, which are posted in the back of the room and also at the registration desk, so Century is developing induced pluripotent stem cells, or iPSC, natural killer cell and T cell therapies to treat cancer and autoimmune disease. The company conducts multiplex genome edits to create really sophisticated cell therapies that are homogeneous and less expensive to produce. Joining us from the company are Brent Pfeiffenberger, CEO, and also Chad Cohen, Chief Scientific Officer. Guys, thanks for being with us.
Really, we had a great cell therapy conversation earlier, and I think we can dig a little bit more into what Century is doing specifically. I'm going to start off with a question kind of like I just asked downstairs. You guys are developing iPSC-derived therapies with multiple edits. Maybe you can kind of describe these cells and the edits that you're knocking in and using CNTY-101 as sort of a starting point. Tell us about some of these core edits that you're making, both on the allo-evasion side and safety switch and things like that.
Yeah, happy to start, Ted. And thanks for the invite. Maybe before we go specifically to those edits, I thought it'd be helpful just to set up a little bit of the advantages we see in the iPSC platform, because there's a tendency that all these allo therapies tend to get lumped together as allogeneic therapies. And I do think there's some really unique characteristics of what we're doing at Century in the iPSC-derived cell therapy space that are important to point out. I think I can synthesize it in three key areas. And one is engineerability, two is reproducibility, and three is profitable scalability. And I'll go through each one of those. So on the engineerability side, we are leveraging the unlimited self-renewing capacity of iPSC. And so with that, you have the ability to do potentially unlimited precision genetic editing. And that's a really powerful tool.
It's a unique platform in that it's probably the only one we can think of that can truly harness all the advances in power of synthetic biology in a single product. That's a really important component. It's helpful in areas that we're in today in the clinic, like autoimmune disease, B-cell malignancies. But I think it can become even more important as we think about solid tumors, where the complexity and the challenge in that space are even more inherent. So that's one big, I think, unique attribute of what we do. The second around reproducibility is the fact that we can take single-cell cloning of our engineered iPSC cells and allows us to select a fully characterized clone that we put into a master cell bank, and that ensures safety and ensures functional reproducibility of that final product, and that's a really important element in the cell therapy space.
And the last around profitable scalability is from that master cell bank of which we produce the product, it comes from a single donor and essentially, in theory, an unlimited supply of product from that. And so that allows really large batch sizes. It also allows a very clear path in our mind of a reduction in cost of goods that we believe is multiples, not just below autologous-based therapies, but also donor-derived allogeneic therapies. So those three areas are really important and unique, I think, to the Century iPSC platform. Maybe just one click down, I think this will help us transition to your question around edits and allo-evasion. When you think about a smaller set of companies working on iPSC-derived therapies, there's a couple of things that I believe set Century apart. One is the fact that we can create and are creating multiple immune effector cells.
We can create iPSC-derived NK cells, gamma delta T cells, and importantly, alpha beta CD4 and CD8 cells. The second aspect is allo-evasion. We've been a firm believer since the inception of the company and continue to be focused on it today. I'd argue that we are leaders in this space. It is the ability through a set of genetic edits to allow our cells to more healthily coexist with the endogenous immune cells of patients. That enables things like repeat dosing of our cell therapy in more drug-like fashion. Maybe I'll turn to Chad to speak to a little bit more detail about what edits are contained within allo-evasion and why they're so important in the space that we're in.
That's perfect, yeah.
Absolutely. So I think that it's important for people to know that allogeneic just means cells that aren't you. And one of the key features of allo-evasion is we're making changes to the cells that let them, as Brent said, peacefully coexist with the intact immune system or innate immune system. The edits that are in CNTY-101 are three specific edits: two that actually remove the HLAs, class I and class II, from the surface of the cell so that T cells can no longer identify these and kill them. And then the other edit is a non-polymorphic HLA, HLA-E, which is put on the surface, which specifically lets natural killer cells know this is not one of the cells you want to kill. So these three edits are the sort of front runners in the field in terms of allowing you to overcome cellular immunity.
For the first time, we're actually seeing real-world data from some of our products that it's, in fact, improving the pharmacokinetics of our product.
That's really helpful background. And it really shows the power of this platform going forward. And I think where you're going to be able to apply it's going to be really exciting. First project is CNTY-101, your lead CD19 NK cell therapy. Remind us of the phase 1 ELIPS-1 data. And this is your B-cell lymphoma study. Tell us what you reported. When would we get the next update?
Yeah, happy to go through that, Ted. I think the first is the reminder, as you mentioned. CNTY-101 is our iPSC-derived NK cell therapy. It's got six genetic edits on it: CD19-targeting CAR, it's got a safety switch, secreted IL-15, and then some three edits related to allo-evasion. That is in ELIPS-1, our phase 1 trial in B-cell malignancies. We read out some initial data back at ASH last year, some interim data at ASCO, and we put out a recent data update in our third quarter earnings. At a high level, what I'd say is, first of all, start with the patient population. We had 20 patients available for safety, 19 for efficacy in this latest update. These are a very severe patient population. I think it was median of four lines of therapy.
Most of these patients were refractory to the last line of therapy they were on. About half the patients had received a prior CAR-T. Some patients had received actually multiple prior CAR-Ts prior to our therapy. So a very severe patient population without a lot of options in this space. And if I start with safety as the first point, we're really encouraged by what we believe is a favorable safety and tolerability profile, as you would probably expect from an NK cell therapy. We saw no incidence of DLTs, no incidence of GVHD, small handful of patients with low-grade CRS, grade one, grade two, one grade one ICANS, but all resolved pretty quickly and transiently. So very encouraged by that.
We're able to treat the majority of these patients in the outpatient setting, which I think is really important not just for this space, but also other disease areas that we're entering into, and then from an efficacy standpoint, really encouraged by what we're seeing. We had started to see what we thought was a dose response and what we would have expected back at ASCO. I think we're clearly seeing that now as we get to the higher dose levels of the trial. What we thought was important at dose level 3B, which is a billion cells times three for each cycle that we give of CNTY-101. We essentially had the largest treated cohort there of six patients, and we had an 83% overall response rate, including 33% CR rate, and again, four or six of these patients had received the prior CAR-T.
So, I think very encouraged by that different inflection we're seeing in response rate to higher doses. We've now treated a patient at dose level 4B, which is actually three billion cells times three within each cycle. And we're excited to follow that up. And then the last piece of data I think is really important, and I'll let Chad speak to this in a bit more detail, relates to some of the translational data sets we had, both in regards to dose response as well as into some, I think, very encouraging data related to the allo-evasion technology that we have.
Yeah, I'd be happy to talk about it. So the dose response data is just what you'd expect. Often what you want to see is what we call a Cmax, the amount of cells or drug that you're able to put in. And as we were increasing the dose, you could see more and more cells present in circulation. And actually, for longer, with the regimen that we adopted, which is once a week for three weeks across that first cycle, we could actually see that the cells were present and detectable for the 28-day cycle itself. So the area under the curve of this was also expanded. And then one of the other very encouraging things is that while we do use lymphodepletion, it provides sort of an elimination of the immune system that lasts for only about 14 days. And then you see the immune system coming up.
Our dose schedule actually allows us to put a dose in after that immune system has returned, and we see an identical pharmacokinetic profile of the cells with the intact immune system or without, which to us is really encouraging because it means our allo-evasion is allowing these to peacefully coexist and do the same thing and give you that sort of expanded area under the curve. The result, of course, was deep B-cell depletion in the patients that we looked at, the 10 that were evaluable, and the other sort of encouraging data was we were seeing that sort of reset in B-cells from a memory phenotype to a non-memory phenotype.
To answer your second part of that question, Ted, as we have guided that we'll provide additional clinical update in mid-2025.
Yep. Awesome, well, looking forward to seeing that, and did you say it was three billion cells three times or four billion?
Or 4 billion. 3 billion.
Three billion. Yep. Awesome. And that'll be really interesting. How important is it? You started to kind of touch on this. How important is preconditioning? Is this something you would consider maybe reducing or finding ways not to use in cancer patients? And what is sort of the development path or the regulatory path? And what's it like in a crowded, but I think you've got a differentiated product in the B-cell lymphoma field?
Yeah, it's an interesting area. I know there's a lot of, obviously, products in that space. There's multiple CAR-T therapies currently available in that space. First, we're excited to get these patients treated with dose level 4B. I think the question that we want to be able to answer, well, two questions, actually. One is, can we increase the depth of response initially in these patients with that higher dose? And the second is the question around durability. And that just means a little bit of time to follow these patients out. So I think those are some critical questions that we have to answer as we continue on the trial.
My simple view of this space, Ted, and development opportunity is that if we've got a product that is essentially comparable or in the ballpark of autologous-based CAR-T therapy, and then specifically probably around durability, then there is clear value in both developing that product as well as commercializing that product. And that is because of the inherent benefits of this iPSC platform. And specifically, I think it's the profitable scalability that doesn't exist for many others that we have that really gives you that value. And I think the other context piece that's important is it's been a long number of years since the first autologous CAR-Ts were approved. There's multiple CAR-Ts approved in this space. And when you look at the amount of addressable patients they've been able to penetrate, I still think it's probably in the 30-ish% range, right?
So I think there's a lot of value. You're talking about a readily available, off-the-shelf, profitably scaling product in this space. And so we want to be able to answer those questions first, but generally, that's the way we think about the overall opportunity.
I remembered a question I wanted to ask you on the initial data set. Because if these patients are getting prior CAR-T, what's unique about CNTY-101? I mean, obviously, it's an NK cell. Why is it working when these patients had already had a CD19 CAR therapy?
It's a good question. I'll say that our data doesn't give us a direct mechanism of action, but there's a couple of things that you can think about that are unique to NK cells. So NK cells in our NK product, we actually do target with a CAR that's to CD19. So that's supposedly to drive it directly to these B-cell lymphomas. But as you know, cancerous cells actually often put other things on the surface of the cell that typically let you know that they're transformed and they're often called danger signals. Innate immune cells, like NK cells, can often interact with these danger signals and actually use innate killing machinery to actually target and eliminate them as well. So you often get that additional benefit from an innate immune cell.
It could be part of the answer to why we're seeing in a relapsed patient that didn't respond to a CAR-T, it might now be responding to an NK.
Yeah, it's really interesting that they have that preventive effect. So I'm going to switch gears a little bit into autoimmune disease, and there's been a lot of excitement about CD19 CAR therapies too, and T-cells in particular, but obviously, we're moving into NK as well. You guys recently modified the phase 1 CALYPSO-1 study of CNTY-101 to enroll a couple of other indications as well beyond just SLE. Tell us about some of those modifications, and when can we start to see some data emerge from that?
Yeah, we're excited. Team's done a great job. We've now got four indications and cohorts into our CALYPSO-1 trial, our phase 1 trial with CNTY-101. We started with SLE because at the time when we were working towards the IND enabling stage, that was the clearest proof of concept data that existed. I think as more data started to emerge and I think clarity on the impact that these CD19 targeting products can have across a broad range of autoimmune diseases gave us a lot of confidence, and as well as input and feedback from our investigators and our sites that we were engaged with. So we're happy and excited to get those four indications now in CALYPSO-1 trial. We've got multiple sites that are active in the U.S. We've got more coming online in the coming months.
We are planning to activate sites in some select countries in Europe as well. And I want to see the initial cadence we get of enrollment across these indications before I guide on specific data timing because I want to put out a meaningful data set. And I first want to see what that looks like across these indications.
Back in April, you guys acquired Clade for preclinical alpha beta CAR-T, including CLDE-308, which is CD19 for autoimmune and B-cell lymphoma, CLDE-361, BCMA for myasthenia gravis, maybe for multiple myeloma. We'll see. You guys are also kind of going through a strategic review right now of the preclinical pipeline. What's your expectation? What should we be looking for as you kind of guide us to where these next products are going to come from?
Yeah. So back in April, maybe it's a good time to take us back to we acquired Clade Therapeutics, a private biotech company that was very much focused on iPSC-derived alpha beta T cells. And we were really excited to pull that in. It gave us a very expansive preclinical pipeline that spanned across alpha beta T cells, gamma delta T cells, and NK cells. And the idea was never to take all those preclinical assets and drive them to clinic. But what we were excited about is we had the resources and the opportunity to drive them in parallel to start to see how they stack up against each other. And I think that's a really important insight that it gives us both from a cell type as well as some of the variations in engineering as well as the evolution in allo-evasion that we're doing in these products.
And so we're excited to be able to get to a point where we're getting close to the final stages of showing which of those programs we are most excited about that we believe has the most potential. I think we'll see some of the first and earliest data of this at ASH, where we're unveiling some of the preclinical data sets related to the alpha beta T cell programs. It appears that those are looking and acting like real primary T cells. And so we're excited to share that and think it has tremendous opportunities.
Awesome. Well, looking forward to that. What else should we expect from ASH? Because I know you guys have quite a few preclinical posters. Are there anything else we should be keeping our eye out for?
Absolutely. So we've got five posters at ASH. As Brent mentioned, it's the first time we're taking the wrapper off the alpha beta T cell program, CD4, CD8s perform, in essence, identically to a primary CAR-T in these preclinical models. This is sort of the first of its kind for the field to make both cell types and to show that sort of comparable activity. The other one that we're really proud of is we've got a new allo-evasion edit called the TASER, which is capable of providing universal protection against all of the NK cells that are circulating, not just subtypes of NK cells, which is quite powerful, and then there's three others.
One, which is actually profiling our NKs and gamma delta T cells and their activity in B cells from both normal and autoimmune patients to show that those are actually quite capable of depleting those cells in preclinical models, and then two others that highlight the engineerability of our cells and we think might be really important as we move into solid tumors. One around CAR endodomains, which is the internal signaling machine, which allows our cells to persist and perform better, and the second, which is specific to the ability to express things on the surface of our cells in what we call a stage-specific manner.
Very interesting. Looking forward to those posters for the conference. So CNTY-102 is a dual CD19, CD22 CAR gamma delta T cell. Tell us a little bit more about these gamma delta T cells and what makes them unique and maybe just what adding CD22 does to CD19.
Yeah, I'd be happy to. So I think as many people know, one of the reasons that people will relapse off of a CD19 CAR is that you can get removal of that antigen by the cells. And so by having two antigens, you can drive a deeper response because it's very biologically unlikely for you to downregulate two different critical antigens on a B-cell lymphoma. So we think that the CD19, CD22 CAR provides that opportunity to now target not just any B-cell lymphoma, but even those that have failed with a CD19 or even seen as CD19 negative. So that's very encouraging. And then the fact that we're using that on a gamma delta or now have the alpha beta platform means that we've got T cells with sort of different performances that you can look at.
And one of the advantages of both of those is that they might be able to drive deeper responses.
Excellent. And CNTY-107 is a solid tumor program that you guys announced maybe at an R&D day earlier this year or last year. I can't even remember at this point. And I thought this was kind of cool because it targets Nectin-4. Tell us why that's a good target for an iPSC cell therapy.
Yeah, I'd be happy to. I mean, first, when it comes to targeting solid tumors, it's all about specificity. And what's great about Nectin-4 is it seems to be present selectively and quite specifically in a few different solid tumors: urothelial cancers, cancers of the lung, also some cancers of the skin, etc. If you look at urothelial cancer in particular, you see that it's not just present in those cancers when they're in the bladder, but also when they metastasize. So you can actually find all of the cancer cells using this one target. And what's even more encouraging is there's now one approved antibody conjugated drug as well as a few more in development that are showing real efficacy. And although there's some safety concerns because of the conjugation, you're starting to see for the first time that this is a real viable target.
Now, pair that with what we can see from engineered CAR-T therapies, and we think there's a real opportunity here to not just get the contained tumors in the bladder, but also the metastases and drive this solid tumor into a place that you're seeing for prostate cancer.
Yeah. I can understand why you're so excited about that. That just makes a ton of sense. That program's always been really cool in my book. You guys are partnered with Bristol Myers, I think two programs, CNTY-104 for AML, CNTY-106 for multiple myeloma, maybe two additional programs. So remind us of the deal terms and how is the partnership going?
It's going great. I mean, really good progress. I mean, just as a backdrop, we entered into collaboration with BMS with a very sizable upfront payment along with typical milestones and royalties that are associated with potential future elements. The way it works is that Century is responsible for discovery and preclinical work of these programs, and then BMS will be responsible for the ongoing clinical development and commercialization. I think it's a really nice partnership because you've got the expertise and depth in the iPSC world with Century, and you've got the scale and commercialization power of BMS in two areas that they've been in for a very long time and have a lot of expertise. I think that there's been a really healthy dynamic on that front as we've been engaged in the partnership, and that's really progressing really nicely.
I can't share a ton more information just because of the confidential nature of the collaboration, but really healthy and continuing to make good progress.
That's great, and obviously we've got a lot going on at the company. Would you entertain future partnerships kind of like the BMS deal? Is the goal more to sort of drive your programs forward yourselves right now? Sort of what's your outlook for partnering in the future?
Look, I've always taken the general philosophy of having a proactive open-door engagement with potential pharma partners. I mean, first of all, we've got, as we talked about, a plethora of preclinical assets, and we think a lot of them have a lot of potential. We may not push all those to the clinic, so there's some clear opportunities to potentially develop and continue to push those forward. I think there's very clear interest in both programs and interesting technology that we're building. If it makes the most sense for us to have a partner who can have the same ambition, the same understanding of the high science that we're doing, but give us the scale and opportunity to do it, then it's something we should definitely look at. And we'll continue to have an open-door engagement on that.
Makes a lot of sense. You guys entered the third quarter with a strong cash position, $245 million. How long does this fund the company? And what's it really enable you guys to accomplish?
Yeah, our cash runway currently, we're estimating gets us into the second half of 2026. I think we've got some really important milestones in front of us over the next 12 months. We'll produce the outcome of that pipeline prioritization work that we've been finalizing now in the first quarter. So I think that'll give a lot of insight into how we're thinking about these cell types and the right cell type for the right indications, a little more color and context around some additional details of those preclinical programs. We've got an updated clinical data set from ELIPS-1, the B-cell malignancy trial of CNTY-101 in mid-2025. And then we're going to stay very close on the cadence of enrollment across those autoimmune disease indications. But that'll obviously be an important area for us to work closely with along with the BMS collaboration.
Yep. Awesome. Guys, thank you so much. Really appreciate it. Excited for the update early next year and more data next year. Thanks for being with us.
Thanks. I appreciate it.
Thank you, everybody, for joining us for day two.