Good morning, everybody. Thank you for joining us today. Our next presentation will be from Century Therapeutics. I'm joined on stage by CEO Brent Pfeiffenberger and CSO Chad Cowan. Thank you for joining us. Of course. Nice to be here. Let's start off with a little bit of background to make sure everybody's on the same page. So Century is a pioneer, really, in the induced pluripotent stem cell therapy space. So talk to us about what differentiates your iPSC platform from other off-the-shelf cell therapies. Yeah, I'd be happy to start there. Maybe I'll reinforce the start that at Century, we're singularly focused on iPSC-derived cell therapies, and I think what's been important for us is to have a very tight set of integrated capabilities related to protein engineering, cell engineering, genetic engineering. We have our own in-house manufacturing facility. And I think having that integrated set of capabilities is really critical to advance an ambitious science like iPSC-derived therapies. There's probably, Brittany, three big buckets of differentiation in my mind of what we do versus other allogeneic approaches. I'd say one is engineerability, two is the reproducibility, and three is what I'd call profitable scalability. And to speak to engineerability first, we're leveraging essentially the unlimited self-replicating capacity of iPSCs. And that allows you to potentially create an unlimited amount of precision gene editing in these products. And it really gives you the opportunity to fully harness the power of synthetic biology in a single product. So that engineerability is really first and foremost from a differentiation standpoint. The second around reproducibility is that through single-cell cloning of our iPSC-engineered iPSC-derived cell therapies, we're then selecting a fully characterized clone for our master cell bank. And what that ensures is that we're very clear and comfortable in the safety of these products and the functional reproducibility of the products. And then finally, around profitable scalability, we can produce really large batch sizes from that master cell bank. And importantly, it gives us the opportunity to have a pathway to significantly lower COGS. And that's multiples, we believe, beneath autologous-based therapies, and we think also with the right scaling and investment, multiples beneath even donor-derived allogeneic cell therapies. So those three elements, engineerability, reproducibility, and profitable scalability, are really critical to what we do in differentiating. I'd say there's then two components that make Century really unique, even amongst the small set of companies that are looking and working on iPSC-derived therapies. And that is, one, our ability to generate and create multiple immune effector cell types. So we've got the opportunity to create NK cells, gamma delta T cells, CD4 and CD8 alpha beta T cells. That gives us really good insight preclinically as we look at these programs and what may have the most impact. And I think the second really important point is related to what we call Allo-Evasion, which essentially is a series of genetic edits that allows our cells to more healthily coexist with the endogenous immune cells of patients. What that also enables is the ability to do repeat dosing of our cell therapies in a more drug-like fashion, which we think potentially addresses some issues like durability in the B-cell malignancy space, but also tighter control of drug exposure, for example, in autoimmune disease. Hopefully I give you some context on the key differentiation components. Yeah, I feel like that's a great foundation for us to launch into some of your programs. So let's talk about CNTY-101. You developed a novel persistence mechanism for your iPSC-derived therapies, which you spoke about, the Allo-Evasion, which has now been through several iterations. So can you walk us through the rationale and the potential differentiation from these other approaches by competitors, as well as what improvements you've made through those iterations and the learnings from those thus far? I'd be happy to do that. As you mentioned, probably one of the foundational technologies that we've invested in is the ability to make sure that our cells can actually coexist with the patient's own immune system, which is critical for an allogeneic cell. So many other allogeneic products actually don't have this. So that's why they lymphodeplete so deeply, because as the patient's immune system comes back, they're eliminated. Ours actually has the ability to withstand or peacefully coexist with the patient's immune system. And that's because we've taken a very targeted approach to the things that normally would eliminate cells as the patient's immune system comes back. Many of these players are things you've already heard of, such as T cells, NK cells, and other immune cells. We do precision gene editing to our cell product, and in particular, Century 101 has six precision edits, three of which are actually specifically tailored for the Allo-Evasion. Two of those gene edits actually remove the HLAs, which are the mechanisms by which you billboard information to T cells without those HLAs on the surface of the cells. The T cells don't engage, so you don't have any T cell-mediated rejection. Then we actually add another edit that actually expresses something on the surface, HLA-E, which specifically engages NK cells from the patient's immune system to essentially let them know everything's OK, is the easiest way to say that. And that combination of edits is as sophisticated as anything anyone has put into patients so far. And we're already seeing how it works. We're actually seeing that it can allow for the persistence of our drug product in the exact same fashion, whether it's under the cover of lymphodepletion or without lymphodepletion. And we've put some of that data out recently, which we're really excited about. So it shows that, in fact, Allo-Evasion is allowing us to do just what we said, which is allow our cells to persist in the face of the patient's own immune system. We haven't stayed still. We're not just relying on the first version of this. As you might imagine, it's an area of core emphasis at Century. And so Allo-Evasion 1.0 was built into Century 101. We also have an Allo-Evasion 3.0, which goes further to protect against the myriad of NK cells that are actually present in the immune system. Allo-Evasion 5.0, which we're really excited about, has not just the ability to have a universal protection against NK cells and T cells, but it's the first product that we know of that actually starts to go after the final stage of the patient's immune system, which is the humoral immune system or their antibody-derived immune system. As we start to build these features into our cells, we think you can drive even longer persistence and more redoability, which is the real important part of this, because these are drugs, and being able to control the doability of the drugs is one of the important features. Super. And so let's talk a little bit more about CNTY-101, which is a CD19-derived CAR NK cell therapy. So can you talk to us about the design of this asset and how it's well-suited for both oncology and autoimmune indications? I'll take that, Chad. Happy to do it. So I think I mentioned already this is an NK cell derived from induced pluripotent stem cells that has six precision gene edits. Three of those are devoted to the Allo-Evasion technology. One of them is actually devoted to its cytokine engineering. So as you know, NK cells, by their very nature, don't proliferate as much and aren't as long-lasting. We've actually built in an endogenous cytokine, which actually enhances the persistence of our NK cells, and that's the IL-15 edit that you see in them. Then there are two other edits. One is the targeting, which is absolutely necessary, which is the CAR, the CD19, which you mentioned. And then the last one is actually a safety feature in case we would need it. We can actually eliminate our cell specifically based on that edit. So those six edits make the cell. Those NK cells, we think, are really tailored for what they do. You've just got to remember that NK cell biology, these are some of the most cytotoxic cells that you'll find, so equally cytotoxic to a T cell, but as I've already mentioned, they have a shorter duration, which allows for a tighter control of sort of drug exposure, which we think is a real advantage in certain indications like autoimmune, where you won't see the lasting B-cell depletion and B-cell aplasia as a result of sort of cells proliferating like mad, and that, we think, is not just something that you could use in oncology, which you just talked about in B-cell lymphoma, where we're targeting it to CD19-positive cancer cells, but also into autoimmune diseases, where we think the removal of a CD19-positive B-cell and plasmablast is probably the source of much of those diseases. The sorts of deep depletion of those are really well-suited to these particular cells. Perhaps more importantly, that deep depletion along a timeline that makes sense. Rather than making them devoid of B-cells perhaps for months on a time, you can actually perfect or try to precisely make that amount match what the patient needs. It might be two months. It might be one month. As you know from the data that's emerging, it does look like it's somewhere in that range of about two months of B-cell depletion to get these healthy remissions and B-cell resets that people are seeing in autoimmune disease. Perfect. And you alluded to the data. So last week, with your third-quarter earnings, you released some updated interim data from the phase 1 ELiPSE trial. So can you remind us what data we've seen thus far and to what extent that data provides a proof of concept for the concept of the Allo-Evasion strategy? Yeah, I can take that one. Look, we're really encouraged by what we're seeing in that ELiPSE trial. And maybe just to reinforce for everyone, ELiPSE is a phase I trial evaluating CNTY-101 in relapsed and refractory non-Hodgkin's lymphoma. And at our third-quarter results, we put out some updated data sets. It was 20 patients that were valuable for safety and 19 patients for efficacy. I did want to reinforce these are very severe and refractory patients in this setting. Median of four lines of prior therapy. Most of these patients were refractory to their prior treatment. Approximately half of them had received a prior CAR-T. So it really didn't have a lot of options in these patients. A few important things that we saw in that updated data set, I think, once starting with safety, we continue to see a very favorable safety and tolerability profile, which you would probably expect for an NK cell type profile. But no instance of GVHD, no instance of dose-limiting toxicities. We did, in a small handful of patients, see low-grade CRS, grade one and grade two, but those all easily resolved and were very transient. We saw a grade one case of ICANS, but that resolved in 24 hours. And I think importantly, we're also able to treat the vast majority of those patients receiving some of their treatments in an outpatient setting, which we believe is a great opportunity for us, not in this setting, but also in others. So safety and tolerability, I think, looks very favorable. From an efficacy standpoint, we had expected, I think, as we put out initial data, both at ASH initially at our lowest dose levels last year and then ASCO this year at some of the dose escalation levels, we were starting to see some signals of dose response. And you would expect that, I think, with a typical NK cell profile. And we believe that's what we're starting to see now. We've treated six patients at our dose level 3B cohort, which is essentially one billion cells times three for each cycle. And of those six patients, four of the six had received a prior CAR-T. And in that dose level, we had an 83% response rate, including two patients with CR. So I think we're very encouraged by what we're seeing on the efficacy standpoint at these higher dose levels. And then some really interesting data from our translational data sets. I'll let Chad speak to these in a bit more detail. But essentially, we had some interesting data related to the dose of CNTY-101 and the PK we're seeing both in circulation and in the whole body. We had some really interesting and intriguing data on proof of concept around Allo-Evasion starting to play out, especially at these dose levels. And then importantly, some B-cell depletion and profiles of the reemerging B-cells we're seeing in these patients that may have applicability related to the autoimmune disease setting. But maybe Chad can speak to some of those translational data sets. Yeah, happy to. So the first one was, as Brent already mentioned, this has been a dose escalation study. And as we gave a single dose of cells, it wasn't until we started to get to about a billion cells per dose that we could actually see the kinetics and profile that you might expect from this type of drug product, where you could now see the cells present in circulation at three days and at seven days. So it really confirmed that you needed to dose escalate to start to see what you wanted. As you might also know, in the 3B cycle, we're not just giving a single dose. We're actually giving three doses once a week across essentially a month. And when you look at that PK or the sort of exposure, you actually see consistent exposure for the entire 28-day period, which is really nice. You're now seeing that area under the curve extend for the month that they're being exposed to the drug product. As Brent mentioned as well, we're really encouraged by some of the first data from our translational data that indicates that our Allo-Evasion might be working. As everyone knows, lymphodepletion temporarily removes the immune system, and this includes those T cells and NK cells. That cover only really lasts for the first week to two weeks. We can see with our three different doses that even under the cover of that lymphodepletion, you have a certain kinetics, and it does not change at all in terms of the PK, even in the presence of the patient's immune system now several weeks out when we give our final dose. That's very encouraging because now we're seeing not just the persistence of our cells along the same time course, but we're seeing, like I said, that sort of full month of exposure to the drug as a result of the Allo-Evasion likely protecting them as they are injected under both the cover of lymphodepletion and without the cover of lymphodepletion. Then as Brent said as well, we're seeing a lot of encouraging data from the early data sets in NHL that we think translate well to the autoimmune disease context. In particular, many people are encouraged by B-cell depletion as one of the key features of what you're going to want to see in an autoimmune disease that has B-cells at the heart of it, like lupus. We saw in 10 patients complete B-cell depletion, and that persisted for up to a month in each of those patients. So that really deep B-cell depletion is one of the hallmarks of a drug that you think is going to perform well in autoimmune disease. And then the second part of that is there's been a lot of correlation between the changes in B-cells that occur after the B-cell depletion. So those B-cells that typically drive the autoimmune diseases are the ones that are class switched and matured and actually make the autoantibodies. What we're seeing and what others have seen is that after the B-cell depletion, the reemerging B-cell profiles don't have any more of those memory cells, but in fact, are preponderantly or mostly composed of naive cells that haven't class switched. So this is what people are often referring to as the B-cell reset. We also see those profiles emerging in our patients and think that those have been associated in the past with this long-term durable remission and are encouraged by that as well. Super. And so certainly, I think one of the learnings that you highlighted is about the multi-dose and higher dose regimens producing more efficacious results. And so based on your learnings and your proceeding now from dose level 3B to 4B, what kind of data can we expect to come next, and how will that meaningfully build upon what we've seen thus far? Yeah, we've actually treated our first patient at dose level 4B. So excited to get a few more patients ramped up at that dose level. I think it goes back to some of the key data sets we've been focused on already. I think safety is going to be important at these higher dose levels, both for the B-cell malignancies, but also as we think about the right dosing for the autoimmune disease setting. I think obviously the impact on efficacy in these patients, I think the big questions we need to still answer in this trial is related to durability. So as we get to these now higher dose levels, what is the durability of the responses and CRs that we're seeing in these patient populations? That'll take a little bit of time as we move out and monitor these patients. And then I think as we move to the dose level 4B, we want to see if we can get even deeper responses and earlier CRs in some of these patients moving forward. So those will be the data sets, along with some of the translational data we continue to keep our eye on in ELiPSE as we go forward. Super. And before we dive fully into the autoimmune space, can you just remind us where the CNTY-101 opportunity is in terms of your vision in the long term in B-cell lymphomas? Yeah, I'm a big believer that with the inherent benefits of an iPSC platform that we discussed and highlighted, that if you have an iPSC-derived therapy that is essentially in the ballpark of durability versus autologous-based therapies in a setting like relapsed refractory, it's significant value based on those inherent opportunities. And you think about the context. You've got multiple cell therapies that are commercialized today and approved in this setting. They're resourced by fairly big companies with a lot of expertise. And they're still faced with a lot of the same challenges they were six, seven years ago as they first got commercialized related to scaling, profitability, the complexity of manufacturing. And so we think that profitable scalability we have with iPSC-derived therapies is going to be incredibly important. I think potential for significant value if you can show that you've got reasonably comparable durability in this type of setting with autologous-based therapies. Awesome. We look forward to that. Let's talk a little bit about the CNTY-101 opportunity in autoimmune, so you recently initiated the phase 1 ELiPSE trial in systemic lupus erythematosus and lupus nephritis, and also recently announced the expansion into a couple of other autoimmune indications, including idiopathic inflammatory myopathy and diffuse cutaneous systemic sclerosis or scleroderma, so walk us through your rationale for choosing NK cells in an autoimmune indication and also why you chose these indications to begin. Well, I mean, I think the main reason to choose them is there's an emerging consensus that many of these autoimmune diseases look like they're tied directly to B-cells and B-cells likely producing disease-causing autoantibodies. So these have now become linked as a grouping of diseases that have that as a core etiology. So we're excited about that. It's also important to note that in each of those diseases, there's now preliminary data from a variety of sources that, in fact, the B-cell depletion using even cell therapies looks like it might drive a remission or a reduction in disease manifestation. So we're extremely encouraged by that. I think why NK cells is the question that we get most excited about. We take a philosophy which is right cell for right indication. And I think autoimmune disease may lend itself almost perfectly to the NK cell. I've already told you some NK cell features. They are highly cytotoxic, but they also don't persist that long naturally, and they don't divide much. So it really allows you to use these almost much more like a small molecule drug where you can now administer them and have them sort of reach their peak efficacy and then go away just like you want them to. And because of our Allo-Evasion, we can readminister them. So you get much tighter control of drug exposure as a result of this. So if you want 28 days of drug exposure, if you want 60 days of drug exposure, that can be driven as a result of using these NK-type cells. I've also already mentioned that they drive a really deep B-cell depletion, which we think is at the heart of the remissions people are seeing in these B-cell-driven diseases. So for those reasons, we think that NK cells are very well matched to a disease like autoimmune disease. And last but not least, of course, is the fact that they're remarkably safe. We're seeing a safety profile that's unlike a lot of other cell therapies. You don't see the CRS that's typically driven by proliferative cells. You're not seeing the high-grade ICANS, et cetera. So if the safety profiles continue to bear out, I think NK cells could be extremely well matched for these areas where there is a desire to have more safety and the sort of tighter control of drug exposure. Fantastic. And so can you walk us through the study design for the CALIPSO-1 trial and kind of your enrollment goals? Yeah, happy to. We first started that trial, CALIPSO-1, in SLE. It was moderate to severe patients who had received two or more prior standard immunosuppressive therapies. The way the trial is designed is essentially they'll get two cycles of CNTY-101. The first cycle consists of three infusions at day one, day eight, day 15. That is preceded by standard lymphodepletion, so Cy/Flu. Following that first cycle, they'll be eligible for a second cycle, which again is three infusions at day one, eight, and 15 in that cycle. That's given without lymphodepletion. The reason we chose that two cycles, which spans approximately 60 days, was based on the data we were seeing from autologous CAR-Ts in the autoimmune setting, which was the minimum amount of B-cell aplasia in those trials that was still leading to healthy B-cell reset. And so we thought that was a really good place for us to start in this trial. There are actually two cohorts that will start in parallel, one with IL-2 in combination with CNTY-101, and then one without IL-2. That'll give us good insight very early on of whether or not you need that additional combination or the impact of it in the autoimmune disease setting. And then I think importantly for Century, our team's done a wonderful job of creating a very flexible trial design and that after we establish early efficacy and safety in a handful of patients, we've built into the trial the opportunity to modify or reduce that initial lymphodepletion and potentially get an early read on that in very early development of CNTY-101. So that's the trial design. And then your second question, I think, was around status. Enrollment goal. Yes. So look, we're excited. We've got four indications that we've now got open in that trial. We've got multiple sites that are active in the U.S. We've got a number of sites that we're planning to activate in the coming months. And we've also had plans to activate sites in select countries in Europe. So a lot happening, and we're excited to continue to push that trial forward. Awesome. And I know we're looking forward to seeing that data. And the timing of the data is going to obviously depend on the cadence of your enrollment. But can you talk to us about when we get that first data preview? What will we be seeing in terms of sample size, duration of follow-up, and clinical outcome measures? Yeah, look, I think we want to make sure we've got meaningful data that we can present. There's a few things that'll be important, I think fairly straightforward. One is going to be the safety profile. You've heard from Chad and myself on the encouraging data we've seen from ELiPSE and B-cell malignancies. We continue to hear from rheumatologists that there's going to be a much higher benchmark for safety based on the patient demographics and a lot of these indications. So that'll be a key area for us to continue to pay attention to. There's obviously some really critical and interesting early translational data sets you can get in these trials related to B-cell impact. So B-cell counts, B-cell depletion, the reemergence of B-cells in their profile, autoantibody titers. So those will be typical things that we'll look at fairly early on in that trial. And then I think importantly, it comes down to disease modification and clinical outcomes. And based on the data we've seen so far in this space with cell therapy and non-cell therapy modalities, I think you are seeing some signs of disease modification at month one, two, post-treatment. I think more of these therapies are showing more complete impact as you get to month two, month three. So for us, that's going to be a really critical part of kind of our evaluation of data is what is that disease modification and the clinical outcome impact that you're having. And that's likely going to be seen probably that month two, month three based on data we've seen so far. Makes sense. And with the time that we have left, is there anything else from your pipeline that you'd like to highlight for the crowd? Yeah, maybe quickly, I'll just mention. I'll turn it to Chad to highlight one or two things. Look, we're going through right now. We've got a very expansive preclinical pipeline. The intent was never to take all of those to the clinic, but we've got multiple cell types across some overlapping indications and targets. And it gives us a real opportunity to get insight preclinically on how they stack up against each other. And we plan to present the results of that pipeline prioritization in Q1. But maybe I'll have Chad just highlight a couple of things we're excited about from a pipeline standpoint. Yeah, I'd be delighted to. So we're actually pulling the wrapper off, so to speak, of one of the programs that hasn't seen the light of day yet at ASH, which is our ability to make alpha beta CD4 and CD8 T cells. So that's a one-of-a-kind program. It's unique in that no one else has really made a CD4 positive alpha beta T cell. And just to remind you, those are the cells that when people talk about autologous CAR-T cells and what they do, that's the cells they're talking about. That mixture of cells that has the ability to engage, target, and essentially explode in terms of a proliferation as well as persist. So we're very excited to have made an iPSC-derived cell with very similar characteristics. We think it really allows us to not just unlock what CAR-T cells are doing today, but actually push into areas where you're not seeing disease therapeutics work as well, such as solid tumors. That's one of the areas that we're most excited about. Awesome.