Good day and welcome to Century Therapeutics Fireside Chat, Preclinical Cell Therapy Pipeline. At this time, all participants are in listen-only mode. Later, the speakers will conduct a question-and-answer session via the web. As a reminder, this call may be recorded. I would like to turn the call over to Morgan Conn, CFO. Please go ahead. Hello, and thank you all for joining us this morning. On the call with me today are Brent Pfeiffenberger, our Chief Executive Officer, Chad Cowan, our Chief Scientific Officer, and Greg Russotti, our Chief Technology and Manufacturing Officer. Before we get started, I'd like to remind everyone that we'll be making forward-looking statements today. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our disclosure documents as filed with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, and we disclaim any obligation to update these statements. Also, we invite you to submit questions for the Q&A portion of the call. To submit a question to the queue, please select the Ask a Question link in the upper right-hand corner of the webinar box. To kick off today's discussion, I'll pass it over to Brent. Thanks, Morgan. Good to be here today. I'd like to set the stage for today's discussion with a bit of a backdrop on some of our company fundamentals as it relates to the preclinical pipeline prioritization that we announced during year-end earnings last month. I want to start with an important point of reinforcement, and that is that cell therapy continues to be a significant commercial market with clear opportunity for further expansion. In 2024 alone, as seen on slide four, the small set of currently approved autologous CAR T products delivered over $4.5 billion in sales in hematology alone. Our belief is our iPSC platform and programs have the potential to significantly expand and enhance this market. Our belief stems from the key advantages which you see outlined on slide five. I think we're all aware of the advantages an allogeneic cell therapy can provide, such as immediate availability, manufacturing dependability. What sets Century apart amidst other allogeneic approaches are the unique aspects of our iPSC-derived therapies, specifically engineerability, reproducibility, and profitable scalability. Let me start with engineerability. We leverage the unlimited self-renewing capacity of iPSCs, which then enables potentially unlimited genomic precision editing. Our iPSC platform is truly unique in its ability to fully leverage multiple advances in synthetic biology in a single product. Second, around reproducibility, our ability to take single-cell clones of engineered iPSCs allows us to select a fully characterized clone for a master cell bank, which ensures safety and functional reproducibility of the final product. Finally, what we call profitable scalability. Based on initial scale-up work the team has done, and you'll hear a bit more detail from Greg today, we believe there's clear potential for antibody-like scale and costs, which provides the opportunity to create potential competitive advantages versus other cell therapies, as well as other non-cell therapy modalities in the disease areas we are focused on currently. What further sets Century apart is our ability to combine these benefits of iPSCs with our industry-leading proprietary Allo-Evasion technology, which is essentially a set of genetic edits that allows our cells to more healthily coexist with the endogenous immune cells of patients and enable the potential for persistence and redosing of our cell therapies. We've got a team that is deeply experienced in cell therapy development and truly recognizes the importance of integrating discovery through to manufacturing to incorporate the latest learnings as we move products forward. We're now going to dive into additional detail on the preclinical pipeline, including showcasing the transformational potential of our programs as we take the company forward in a new direction. Slide six shows the reprioritized pipeline that we disclosed in March of this year that we're going to discuss in a bit further detail today. Before we jump in, Morgan, maybe just a quick backdrop on how we arrived here. As we worked on this reprioritization over the past few months, we had the opportunity to run multiple preclinical programs in parallel across different cell types, some of which had overlapping targets and indications. This gave us a really unique insight with a focus on prioritizing those programs that we believe could clearly expand and enhance cell therapy value. We prioritized four potentially transformative programs, all of which are engineered with our industry-leading Allo-Evasion 5.0. Our leading programs focus on iPSC-derived CD4 and CD8 αβ T cells, in addition to a selective expansion to non-immune vector cells in high-impact diseases. We are excited to discuss these with you in more detail today. Thanks, Brent. Chad, can you start off by telling us a little bit more about the importance of immune evasion and our approach to it? Absolutely. Thank you, Morgan. As you know, allogeneic simply means not your cells. Like any foreign organism or foreign body, those cells would be rejected by the recipient's own immune system. Century has been a pioneer in Allo-Evasion from the beginning. In fact, they were the first to introduce genetically engineered Allo-Evasive technology into immune cells into a patient. Allo-Evasion 1.0 helps guard against the cells in the immune system that would reject any transplant. Those cells, just to remind you, are T cells, the innate cells, NK cells, and your humoral immunity driven by antibody-mediated mechanisms. In Allo-Evasion 1.0, there are three different types of edits that are included: deletion of the Class I HLA, deletion of the Class II HLA, and the insertion of a non-polymorphic HLA, HLA-E. This, in effect, allows us to protect the cells against T cell-mediated rejection, as well as a subset of NK cell-mediated rejection. As you know, Century has remained committed to Allo-Evasion and has continued to enhance and evolve this pathway until we've landed on what is Allo-Evasion 5.0, which is leading the field in its ability to protect cells in a holistic way from all of the things the immune system can throw at it. In addition to the complete ablation of the HLA Class I and Class II molecules, we have a first-of-its-kind pan-NK inhibitory ligand, CD300a, and we've inserted onto the surface of these cells an IgG degrading protease, which allows the cells to be protected against all of the antibody-mediated rejection mechanisms. Again, this allows these cells to persist and perform their job in an unprecedented way. We think it's going to enable this platform to not only make a transformative impact in immune effector cells, but also as we move into non-immune effector cells. Thanks, Chad. Touching also on Brent's mention of the αβ T cells, could you elaborate a little bit more about why that's important and how we're applying that? Before I get to that, I thought I'd take a couple of moments just to get into some of the deep biology on our Allo-Evasion. If you look at slide nine, we actually look at some of the science that's involved in the development of our CD300a TASR. As you may know, NK cells typically use their cytotoxic cargo to eliminate cells that they see as foreign. What shows them as foreign or infected cells is the fact that they're lacking HLA on the surface. They avoid killing dead or dying cells, which typically have flipped their phosphatidylcholine from their cell surface membrane. They use a molecule on their surface, CD300a, to actually identify those dead or dying cells. Our CD300a TASR actually mimics that same signal so that you are now skipping cells that are expressing the CD300a TASR, much like they would be dead or dying. In a paper that we recently published in Blood Advances, we actually look at this in sort of a mini in vitro trial where we look at a diverse set of PBMC donors, diverse across ages, as well as ethnicities, as well as previous infection histories, whether they've seen CMV, et cetera. What you can see in the data from that is that only the CD300a TASR was capable of protecting across all of the variety of NK cell types that are present in these donors. That is compared to things such as the HLA-Es or the ERs. CD300a is not only present, but it protects. In the bottom of that same slide, we actually look at that against one of the sort of leading competitors, which is CD47, which many people know is the don't-eat-me signal. CD47 does, in fact, protect against some subsets of NK cells that express the SIRPα, but it doesn't have the same effect across a large variety of NK cells that exist in many donors. We actually look at a variety of NK G2A donors, NK G2C donors, also 2A, 2C mixed. You'll see that across that diversity of donors, you really only see the protection by the CD300a TASR. On the next slide, slide 10, you actually see this unique and leading the field in a way, the only company that I know of that actually has the ability to protect against humoral immunity. Remember, antibodies can actually come after cells either mediating cell-based removal or on their own. When antibodies bind cells, they can actually recruit what is the complement system, which can eliminate cells on its own, but you can also have antibody-related cellular cytotoxicity. These IgG degrading proteases that we've tethered to the outside of the cell actually cleave the antibodies that your body would make and drive humoral immunity. They release the IgG or the fixed IgG chain from the variable domains so that the variable domains remain stuck to their target. The Fc domains, which would normally recruit all of the complement or antibody-derived cellular toxicity, can't be derived. You can see the data at the bottom. You can completely eliminate what is complement-dependent cytotoxicity with this protection. You can also completely remove the cellular cytotoxicity typically driven by NK cells, as well as the antibody-dependent cellular phagocytosis. Now, to skip to your next question, which you had just asked, Morgan, about our αβ T cell platform, why we're so excited about this is I think it's the first of its kind to truly recapitulate what we think are primary T cell characteristics. First and foremost, we make adaptive αβ T cells that are both CD4 and CD8+. Why that's important is we know that you need a mixture of these cells to have a very effective immunotherapy. The CD8 component is typically referred to as the cytotoxic component, and the CD4 component is often referred to as the helper T cell. It's the helper T cell because it typically responds to target by secreting the cytokines that help all of the cells persist for longer. You can see that the three key functions that we expect from an αβ T cell are actually preserved in our cells. That's that very key cytotoxic or ability to eliminate target cells. You will see that our cells perform on par with cells that are taken directly from the blood or primary CAR T cells. Perhaps more impressively, upon target engagement, our αβ T cells also secrete the main cytokine for the proliferation of αβ T cells, IL-2, at levels that are directly comparable to what you see from donors. What you see here is about 10 different donors that are looked at and their ability to produce IL-2. You will see some donors that are less good, some donors that are better, but on average, about the same as what we do. Lastly, perhaps the real superpower of an αβ T cell is its ability to, upon engagement of a target, logarithmically expand. In other words, you can make more of these cells to attack the invader. In this case, it would be tumor cells or those cells that are driving autoimmune disease. You will see that our cells, upon target engagement, are actually experiencing that tenfold expansion just 48 hours after that. That drives levels of persistence that, as of now, have not been seen. If you look at slide 13, we actually do a bit of a head-to-head comparison with our lead αβ product, the CNTY- 308 product, where we put it up against primary CAR T cells. You'll see that it's directly comparable. This is the first of its kind where you can actually see iPSC-derived T cells performing many of the functions that you would expect a primary T cell to perform. That's in total quantity of IL-2 secreted, the ability to expand without any exogenous cytokines as a result of that, the ability to in vitro, upon repeat challenge, expand and kill over 10 x. Perhaps most importantly, we see these things persist in circulation in the blood at levels that are directly comparable to what you see from primary T cells. That means in our preclinical models, we're actually seeing those cells circulating in the blood for more than 30 days. Up to 32 days, we can actually detect them. They are also able to do something that you expect from a T cell, that is that when they are given a rechallenge, and in this case, it's a tumor rechallenge, they can expand again and continue to control those cells. These are the fundamental characteristics that you expect out of an αβ T cell. It's something that we've been able to recapitulate in our iPSC-derived T cells, which is what gives us so much confidence about them as a tool for therapeutics. Thanks, Chad. I appreciate all that color. With that background, can we talk a little bit more detail about our first prioritized program, CNTY- 308? I'd love to. CNTY- 308 is again on our αβ T cell platform. It incorporates all of the genetic precision edits that are contained in our Allo-Evasion 5.0. That is the Class I, Class II knockouts, the CD300a TASR, as well as the IgG degrading protease. In addition to that, we also knock out the TCR gene through a TRAC- A knockout. That means that we have no graft versus host disease present in these cells, so no capacity to have that sort of off-target. We arm them with a CD19 targeted CAR. The CD19 targeted CAR, as many of you know, is the most broadly applicable target for all B cells. What we love about this is we have that the CD19 is capable of, again, engaging targets. It's highly proliferative. It secretes all of the cytotoxics. We think that this makes it ideally suited to not just replace existing primary T cells, but also expand the utility of this into places where you can't get autologous donor cells or even the allogeneic donor cells of today. We are super excited about this because it's based on an iPSC cell. You heard Brent already talk about this. You have a nearly unlimited proliferation potential. Now we can make these drugs at antibody-like scales so we can deliver them more easily to the patients in need, and we can expand the patient populations that are now getting access to CD19 CAR T-like material. I am extremely excited about the opportunity here. We think that it's not just good for, say, oncology, where it's started to really transform those diseases such as lymphoma, but also where we're starting to see a lot of inroads in B cell-mediated autoimmune diseases. It's where this same CD19 target will actually eliminate those B cells, allow for a healthy reset of the immune system, and allow those patients to now live symptomatically free in diseases such as lupus and myositis. Terrific. Can you talk a little bit about where this program is in terms of its stage? We are powering towards IND-enabling studies at the midpoint of this year. We are looking for ways in which we might be able to accelerate our path to the clinic so that we can get this important medicine to patients as quickly as possible. Excellent. As we think about that program moving towards IND-enabling studies, thinking practically about making it, Greg, could you talk a little bit about the manufacturing plans and what our capacity is to do that? Thanks, Morgan. Yeah, as you know, we have our own multi-suite, multi-product manufacturing facility in Branchburg, New Jersey, where we intend to produce CNTY- 308. We are currently producing CNTY- 101 there for our CALiPSO trial, both for the U.S. and EU portions of the trial. This facility has been commissioned, qualified, and operational for some time now. With the intention of this IND for CNTY-308, we've begun the tech transfer already of the technology into this facility. Terrific. What are some of the key learnings that you can share with us and the audience as we set that up? When we built this facility, we knew this would offer many advantages to us, and we're realizing those advantages now. The most important one is that when you have your own facility, the operational staff that runs it is on the same page as the development staff that's developing these programs and running the trials and the research team that conceptualized these processes and assays. Everyone has the same ambition, the same priorities, the same focus. When it comes to the finer details that you need to pay attention to, when you need to make process changes, when you need to troubleshoot problems, everybody's in lockstep to make this happen successfully, which means ultimately you're going to have the fastest possible path through your clinical trials. In addition to that, when you're working on these on your own, you're learning all of the details of how the process operates. You don't get that from a CDMO. They hide a lot of that from you. All those interesting learnings will then ultimately improve product quality as you make that product and as you iterate towards others. Lastly, when you're with a CDMO, you are going to be exposed to competitors indirectly. We feel we'll be able to better protect our very essential know-how with this facility. Terrific. We have referred to already in terms of manufacturing and cost of goods. Where do you think that's going with our allogeneic approach? I think we're doing very well. You've heard from Brent and Chad about how we have the unlimited proliferative potential of our iPSCs. We have massive cell banks, of course, laid down for CNTY-101 and already laid down for CNTY-308 that will last the lifetime of the product. Ultimately, what this means is we can make batch sizes as large as we want or as large as the cells and engineering allows. In order to do this, we've hired leaders who are from the biologics world where there's a precedent to scale these biological processes up to 20,000 L scale, for example, with CHO cells for antibodies and a couple of thousand liters for vaccines. We've taken those learnings, hired engineers with a strong fundamental understanding of the principles of scale-up, and we've begun to do experiments. As you see on this slide, we have data already. This is data from NK, the CNTY-101 program, but we also have data from our CNTY-308 and our T cell programs. The more advanced data, of course, is from NK. We've been doing it longer. You see here that we've shown that we can produce cells at a higher cell concentration and not shown on this slide, those same phenotypic characteristics and functionality using both rocking dynamic systems as well as traditional stir tank dynamic systems compared to, in this case, a G-Rex, which is what we use for CNTY-101 phase I. The good news is we've taken these learnings and applied them to T cells and already have shown that we can grow our T cells in dynamic systems and stir tanks. We plan to implement that initially in phase I, not start with static. That'll make our life easier as we go forward. In addition to that, as we look at the scales we're currently at, we already are at lower cost of goods than autologous. With even moderate scale-up, we believe we'll be order of magnitude lower than autologous. Again, with the unlimited ability to scale these because of the large massive cell banks and the proliferative potential of these cells, we believe we will be at antibody-like scales and costs, which will not only improve the patient access overall, but will allow us to address very difficult market opportunities like autoimmune. Exciting. Thank you. Chad, having gone through the CNTY-308 arc, could we turn to CNTY-341 and talk a little bit about the targeting approach that we've listed there? Absolutely, Morgan. If we look at slide 18, we've actually got a cartoon that shows, again, the engineering profile of the cell that we plan to put forward for CNTY- 341. Again, that's built on our Allo-Evasion 5.0 platform. Again, it has a TCR knockout. What's unique about this is it's actually targeted with a dual targeting loop CAR that has a CD19 and a CD22 targeting point. You may know that that's incredibly important in that the more than a decade of experience we've now had with CD19-targeted CAR T cells in lymphoma, the main mechanism of resistance is actually through what's known as antigen loss, where a subfraction of the tumor actually loses the CD19 antigen so that the cells can no longer target or remove them. By incorporating a dual targeting CAR, one that targets both CD19 and CD22, we're capable of finding those lymphoma cells and eliminating them. It has been shown already in preclinical studies as well as in other clinical studies that there is a much reduced potential for resistance or removal of both antigens. It is much more likely to be effective across the more than 30% of lymphoma patients who have relapsed, as well as the BLL patients that have got CD19 loss, which can be upwards of 70%. Great. Thank you. Talking specifically about the CD22 targeting, can you say a little bit more about what's different with our approach? What I'm particularly excited about is this is a completely unique and proprietary CD22 target that we've developed in-house that is capable of uniquely targeting the CD22 molecule on the surface of either B cells or, in this case, B cell lymphomas. It doesn't have any of the liabilities that have been associated with other CD22 targeting points. It's a uniquely configured CAR so that you actually have both of these targets on a single mono CAR. I'm particularly happy with our synthetic biology group's ability to both de-risk its binding as well as improve its ability to eliminate both targets, both a CD19 and a CD22. Great. Thank you. As we stay in the oncology field, I'd love to hear you talk a little bit more about our solid tumor approach. I think solid tumors is where Century can really show its strengths of this platform. As Brent has already mentioned, one of the main advantages is our ability to make unlimited precision edits. This is something that you're likely to need when you start confronting solid tumors because, as we all know, solid tumors actually pose quite a problem for today's CAR T cells, whether it be through resistance mechanisms, whether it be through the tumor microenvironment, or whether it be through the ability to target appropriately. We've actually taken a very holistic approach to this by looking at all of those aspects and trying to target each of them in our solid tumor programs. Let's speak first about our lead program, which is using a verified Nectin-4 targeting CAR, which is entirely proprietary for Century, in combination with some additional edits that we think will give it a leg up. Those include cytokine engineering, which are going to be able to improve our cell resistance post-infusion, as well as engineering that we've included that allows us to enhance our trafficking as well as sustain our function within the tumor microenvironment. Those additional precision gene edits not only make our cells as good as primary CAR T cells, but can actually improve their performance over CAR T cells and give us a consistent product that targets those. What I'm equally excited about is that this lead program has several other programs directly behind it. We have several novel targets for targeting solid tumors. Those include GPC3, CD70, and mesothelin that are all proprietary, developed in-house, and have shown wonderful characteristics that we would like to see. We also have novel TCRs that we've developed as a result of the acquisition of Clade that provide additional functions as well as additional targets for us to explore in our solid tumor program. Fantastic. Thank you. I think we talked a little bit about, you talked a little bit more about Nectin-4 and where we think that could be applied. Absolutely. Nectin-4 is starting to show a lot of promise. It has been found in a number of tumors, is what I should say if I should step back. We're seeing that Nectin-4 is prominently expressed in a whole host of tumor types. We're specifically starting in urothelial tumors and the metastases that arise from them, but it is also found quite prominent in non-small cell lung cancers as well as triple-negative breast cancers. All three of those cancer types seem to express high levels of Nectin-4. You may have already seen some of the impressive results from the ADC-ligated Nectin-4 antibodies. We know that this is a well-validated target. If you can now improve that by providing cells that have the deeper persistence and deeper cytotoxicity of a T cell as well as the ability to sustain their function due to our cytokine engineering as well as overcome the tumor microenvironment because of the edits we've put there, we have high confidence that this Nectin-4 CAR-mediated solid tumor T cell is actually going to be something that we can now see drive even deeper remissions or deeper efficacy in these patients. Terrific. That sounds like an exciting target for us. As we look more broadly down the line for solid tumors, what are other targets that we think are interesting? As I'd already mentioned, we have proprietary targeted CARs to GPC3, CD70, and mesothelin. These targets appear in a variety of solid tumor cell types. We're excited about each of them in their own turn. What I would say as a researcher is I'm excited about the ability to develop simultaneously these to see which ones are going to pull ahead based on their both unique profile, unique tumor targets versus what might be their on-target, off-tissue liability. GPC3, for instance, is extremely exciting when we look at liver cancer, and CD70 has now been used in a variety of kidney cancers. As many people know, mesothelin is the main antigen on almost all mesotheliomas. It's become extremely exciting in a variety of either lung cancers as far as even intestinal cancers. The target range is broad. As most people understand, solid tumors represent an opportunity that dwarfs in scale what we're already doing with CAR T cells and lymphoma, and it even dwarfs in scale what the opportunity looks like in autoimmune disease. Terrific. Thanks very much. I think that completes our overview of the pipeline, and we have a number of questions in the queue. I think we'll turn to those. Let me go through the list. The first question up, I think, was a question asking a little bit for some more detail around our non-immune effector cell program. I wonder if we could elaborate on that. I'd love to step in here. We haven't yet disclosed what our non-immune effector cell type is, but I think that everyone who's been paying attention realizes that we're on the cusp of a new era with iPSC cells. There are now over 115 clinical trials that are currently running with iPSC cells, mostly phase one and phase two. Many of you that have paid attention in this field realize that these are the cells that provide the best hope for replacing cells that have been lost or damaged as a result of disease. We are seeing some impressive results come out of trials that are targeted towards Parkinson's disease, trials for people with longstanding epilepsy, as well as in dry AMD with the retinal pigmented epithelial transplants. Perhaps most exciting, many of you probably paid attention last June when Vertex had actually released their findings on 12 patients suffering from diabetes where they had transplanted insulin-producing beta cells, and 11 of those 12 patients were completely free of exogenous insulin injection. I think that the world is on the verge of a transformation in cell therapy where we can now not only use these for devastating diseases like diabetes, but possibly also in regenerative medicine. Terrific. Okay. We have a variety of both technical and strategic questions. Going to the next question is a revisit on the TCR in the αβ T cells and how we prevent graft versus host. That's a great question. The way we do it is we delete the TCR α gene, which allows you to remove the alpha chain of what would be an αβ TCR. You have no T cell receptor made and put onto the surface of the cell. The cells don't make a TCR. That means that without that TCR, they can't engage any HLA and give any sort of rejection. They have no targeting mechanism except the one we build in, which is the CD19 CAR, or if it's CNTY-341, the CD19, CD22 CAR, or in the case of our solid tumor targets, the solid tumor target we build. We remove the risk of graft versus host disease. You'll find that other companies that talk about using allogeneic cells typically try to do this in a similar fashion from host-derived or patient-derived T cells where they'll try to edit out or remove that risk, but they often still experience graft versus host because it's not a complete removal of the TCRs. Our cells are entirely free of any TCR expression. Thank you. We have a question on CNTY-308 and timing to clinic. We've mentioned the DC or IND enabling studies mid-year. Brent. Yeah. Happy to take that, Morgan. Yeah. We are still, as we disclosed back in March, still on track to progress CNTY- 308 to IND enabling stage in the middle of this year. I think the team has done a really nice job of working on the potential to accelerate that. In addition, I think what we think is important is looking to any and all ways to accelerate clinical proof of concept. There is a lot of work ongoing here at Century as we move towards that stage of understanding what our best options are to deliver the fastest amount of viable clinical data that we can use as proof of concept for CNTY- 308. Terrific. Thanks. A question coming in regarding autoimmune disease and prioritization or comparability between CNTY- 101 and CNTY- 308. Yeah. It's a really good question. Maybe if we take one step back, I think it's important to reinforce amidst a lot of the news flow out there that autoimmune disease, especially the B cell-related autoimmune disease space, is a very large potential market. I think as we've continued to talk to rheumatologists around the world, I think it's very clear that the data that has come out and is still emerging, if it holds, is truly transformational versus current standard of care. That not only across these indications, but within some of these indications, there's going to be room for multiple modalities to treat patients. I think what physicians and rheumatologists are telling us is there may be very specific patient characteristics or patient subtypes that warrant different types of therapy. For example, when you think about the profile of NK cells with CNTY- 101, I think one of the unique attributes of that is its ability to have a very tolerable, safe profile. And we've shown that in our CNTY- 101, ELiPSE-1 trial, as well as the fact that it is more short-lived and doesn't persist a long time. You have more ability to control the amount of drug exposure to these patients, but potentially prevent long-term B cell ablation. There may be certain patients across indications where that is a much more important attribute or benefit that physicians look to. There may be also in patients certain indications where you want a one-and-done therapy and a therapy that can proliferate and persist a bit longer in these patients. That's where CNTY- 308 could come into play in autoimmune disease specifically. Our firm belief is there's a tremendous amount of room for opportunity for multiple modalities and cell types within cell therapy. I think our cells also give us a lot of competitive advantage across non-cell therapy modalities as well. Terrific. Thank you. Technical question for Chad around the Allo-Evasion, which is around the drive for changing from the HLA-E, HLA-G edits to CD300a TASR. Namely, is it about the same result with one less edit, or are there functional improvements? I think you touched on this, but I think a little bit more. I'm happy to get into more detail and review it. One of the strategies that Century has employed and others have validated is to use what are known as non-polymorphic HLAs to actually provide protection against NK cells. Each of these HLAs, call it HLA-E or HLA-G, has a cognate receptor on NK cells or a specific subset of NK cells. One of the most broad classes of NK cells is an NKG2A+ NK cell that typically makes up about 50% of the circulating NK cells in most people, sometimes as many as 80%. That is what HLA-E targets, which is in our Allo-Evasion 1.0, which is why it's been so effective. In many patients and in many people, you'll see more than 50% of their cells are not 2A+. In fact, they will be positive for a variety of what we call inhibitory receptors. Even if you're using HLA-G, which actually selectively targets a KIR, you won't actually see much more but additive protection. What's really unique about CD300a is, as I showed on slide 8, you see pan-NK protection. In other words, we find it's expressed on all NK cells across a wide range of patients, and that each of those NK cells, no matter what their subset, are actually inhibited from attacking and killing the Century product. Terrific. A follow-up question there was around the timelines, whether the use of 5.0 has any difference in the R&D timelines relative to the 1.0 in terms of the Allo-Evasion engineering. I mean, the 1.0 simply incorporates an HLA-E molecule, and this now incorporates the CD300. So it's essentially the same number of edits for the same amount of Allo-Evasion protection, except that with Allo-Evasion 5.0, we take yet another step forward, providing for the first time of any product on the market a protection from humoral immunity. One of the great advantages of Century is not just the ability to create precision edits and almost unlimited number; it's actually the speed and scale with which we can do it. So we're not really limited by the number of edits we're introducing to the cells. We're able to take these cells and deeply characterize them and understand exactly which edits we've made and why we've made them. We are careful about making genetic changes that we know why we're making them, and they provide a benefit to the cells and to the patients. Otherwise, we don't find that there's a limit in terms of speed to the clinic. Yeah. I mean, I'll just also add, I mean, as I mentioned, we had a chance to, I think, a very unique position to start to run some of these programs in parallel against each other internally that incorporated overlapping targets, overlapping indications, but also looking at various versions of Allo-Evasion. I mean, we were very specific as we got to our prioritization of wanting to ensure we had preclinical programs that we felt had the potential to be truly transformational in the marketplace. Allo-Evasion 1.0 and CNTY- 101 has clearly shown proof of concept in our ELiPSE-1 B cell malignancy trial. We're excited to continue to show that in our autoimmune disease setting. Based on data we're seeing preclinically, we felt that Allo-Evasion 5.0 was a really nice step forward for us, and we want to make sure we had the most enhanced version of technology across our pipeline as we go forward, and that's what we're doing. Terrific. Thank you. I think as we go through, we've got a robust queue of questions here. On CD4 to CD8 cells, we have a question about the ratio that we plan to use and what the meaning of that might be, especially in oncology versus autoimmune settings. That's a great question. The truth is we have the ability to directly control the numbers of CD4 or CD8. What's great about our system of differentiation is it's entirely tunable. We can make a population that's almost entirely CD4+, or we can make a population that's almost entirely CD8 +. As I've already mentioned, there are distinct characteristics between the two. The CD8s are mostly the dedicated effector cells that are referred to as cytotoxic. They don't typically seem to have on their own the same proliferative or persistent capacity versus the CD4 cells, which seem to persist longer and typically make up a fraction of the mixture. In our own hands, what we're putting forward in CNTY- 308 is a mixture of CD4s and CD8s with about 60% of the cells comprising a CD8 component and about 40% providing about a CD4. It is about a 50/50 mix because in those cases, we want the combination of highly cytotoxic balanced with the persistence that we are seeing in our preclinical models. Terrific. We have a scale-up question. I think this will be for Greg. Can we talk about the master cell bank strategy mitigating genomic drift or genomic instability as we scale up? Right. Yeah. We chose clones for CNTY-101 and are doing the same for CNTY-308 in our future programs that have a genomic profile that's desirable. We look for variants that may cause deleterious effects and do not choose clones that might have those. We track our growth for master cell bank both to final candidate as well as something called end-of-production type cells where you do not differentiate them, and you look at genomic stability in those. Once you ensure that you have stability in the cell bank itself and also the growth of the master cell bank, you know you have a clone that works. Of course, we continue to track that through production to be sure that we are going to maintain a safe product. Terrific. Thank you. Another question on Allo-Evasion. As we characterize the advantage, how relevant is IgG-mediated allo rejection? That is, what% of rejection of humoral versus innate versus T cell? For CNTY- 308, so that's the whole question. For CNTY- 308, are there potential clinical consequences of introducing IDP in relation to sequential therapeutic antibodies? I'll start with the first part, like why protect against humoral immunity? The simple answer is that humoral immunity is the ultimate cause of almost all transplant rejection loss. Anyone who receives a transplanted organ, that organ is ultimately rejected through humoral immunity. In fact, most transplanted cells and, as many people know, infectious diseases are typically protected through humoral immunity. It is actually a sequence of events. You aren't going to see humoral immunity rear its ugly head in terms of rejection early because it's the last line of defense. Early on, what you're going to see are T cell-mediated and NK cell-mediated events, which will typically happen within the first sort of 24-48 hours. By about two weeks, though, you're starting to now get educated about that new antigen, and you're starting to form a humoral response. By about six to eight weeks, you can start to see the impact of humoral immunity. In those patients, especially in oncology, where you want to see a long-term persistent remission, you'll want to be able to protect cells for an extremely long time. I'm particularly excited about this when we're thinking about our non-immune effector cell programs where you may want to be able to transplant a cell that may need to last for up to a year or more. Providing protection from humoral immunity will be key. Now, what about the side effects of the IgG degrading protease? The first thing I will say is that that protease is on the surface of the cells. A very similar protease has actually been used in clinical trials to actually remove humoral immunity that is preventing transplants, so organ transplants from existing. The lowest dose level that's been used at in patients is actually a million-fold higher than what we're seeing on the cell levels in the dose that we would consider putting into humans today. We find that safety has already been achieved in clinical studies with the circulating enzyme. We're not seeing any safety effect of that. More importantly, it's at a very low level, but a very localized level to provide protection just uniquely to our cells. Terrific. Thanks. Now turning to CNTY- 341, the question about your thoughts on the CD19, CD22 loop CAR approach rather than a separate bicistronic format. There are multiple ways. I think the thing to say is if you step back, there are multiple ways in which you might think about putting in targets or targeted CARs. One is that you could have one CAR with both targets or individual CARs for each target. We've actually explored each of these. We've put in what are often called dual mono CARs. You have one CAR moiety that's targeting CD19 and one CAR moiety that's targeting CD22. We've also looked at the CAR signaling domains that are downstream of that. What we found is that the dual-targeted loop CAR has been able to provide the highest efficacy in our preclinical tests, and thus that's the one that was selected and moved forward. Terrific. Thank you. Making a jump over to clinical development and landscape question, how do we see CNTY- 308 fitting into the current LBCL treatment paradigm? Do we plan on developing it for relapse-remitting patients in this community setting who can't access the autologous CAR, or do we plan to evaluate second line or first- line setting? I mean, I'd start by saying I think all the above are a potential opportunity for us. I mean, the way we broadly think about the DLBCL setting is the current approved and commercialized autologous-based products have shown very good efficacy and have really impacted positively so many patients. There is a clear opportunity based on the approach that we're taking with iPSCs and an allogeneic approach that you have an immediate available off-the-shelf product that is well-characterized, very consistent, and I think that in and of itself could be a significant benefit as far as potential replacement of those current approved products. I think in order to do that, you have to make sure that your efficacy and safety is at least as comparable to those products as you're doing it. As we mentioned earlier in this discussion today, I think there's a vast number of patients who potentially would be eligible for a cell therapy-based product but are not able to get it for various reasons. I look at it simply as there's a chance to replace the current autologous-based products based on active comparable efficacy safety, potentially better, as well as the inherent benefits of an allogeneic approach. There's also, I think, a dramatic opportunity to expand that market and tap into the addressable patients that aren't getting cell therapy that could be getting cell therapy. That's clearly applicable in the current indicated states, which are more later lines at this point for cell therapies, but as cell therapy continues to move up the line of treatment, that same opportunity exists for a therapy like ours as well. Terrific. Thank you. A question on our slide 17 around our scalable dynamic systems, which was color on how this translates to doses per patient. Is this similar benefit seen for iT cells too, scalable? Right. What you'll get is the ability to make larger batches because there's only so many G-Rexs, for example, or any static system used, only so many you can use in parallel. With scalability, you can go to tens, hundreds of liters, maybe even thousands of liters. The number of doses you get from a batch would go up greatly. Also, the productivity of the NK system is higher as far as cell concentration compared to static T cells, more similar, which is great. It doesn't have to be higher as long as the scale can be higher. We'll get a lot more doses per batch with the dynamic systems. I mean, I also just reinforce that I think it's been in the news more recently that some of the larger pharma companies are spending billions of dollars to create manufacturing facilities to treat tens of thousands of patients. I think, as Greg mentioned, we clearly have a product in the clinic today with CNTY- 101. We've got a master cell bank locked in for CNTY- 308. From those master cell banks, we essentially have an unlimited supply of these products that we can produce from. I think that is an incredible advantage as we think about the future ecosystem and landscape of cell therapies and the broad potential of indication diseases they can potentially treat. That's in color to that. In our current facility, as it's currently built, we can already treat thousands of patients per year, which we wouldn't do clinical trials, obviously. The point is, if we had to do a launch from that facility now, we could. There is potential to build it out further and do a much larger launch if we had to. This platform just enables so much. Thank you. More questions on Allo-Evasion. One is, and I think you've alluded to this a little bit, perhaps a little bit more in terms of what we could say, Chad, about the competitive landscape in immune cell edits and where we see our edits differentiating themselves. Yeah, it's a terrific question. I think there is a lot of activity here now after the first wave of allogeneic products. People have realized that you can't just have a cell that's not protected from the host's own immune system. I think Century really led the way with Allo-Evasion 1.0, and we're again leading with Allo-Evasion 5.0. If you look at what most of the competitors are doing, it's variations on the same theme. Basically, protect from T cell-mediated attacks, typically through the reduction of Class I and Class II or matching of Class I and Class II. It's often the incorporation of something that's supposed to provide protection from the innate immune system, typically NK cells. Each of those edits actually are all compromised by the fact that they are only targeting subsets of cells. If we thought about HLA-E, it's in KG2A+ cells. If it's CD47, it's only SIRPα cells that actually respond to CD47, and not all NK cells express that in particular, only NK cells that have actually been stimulated by cytokines. If you look through the varieties of flavors of immune protection, they typically come in those. There is one other flavor, which is the idea of sort of having the cell directly attack what might be an attacking cell. People have sort of called this more like a sword or a cloak and dagger. You might hide a little bit but also go after it. The one disadvantage with many of those systems is that they may not be as specific as you want them to. Typically, the thing that the dagger is targeting is not just on attacking or cytotoxic immune cells. It can also be on antigen-presenting cells and other facets of the immune system. You have an indirect targeting of what might be otherwise beneficial cells. It is not entirely contained within the protection of the cells. Those are all in one category. That is innate and immune cells. As I have already mentioned, there is not a single company that has even sort of crossed the threshold into humoral protection. Century is unique in that fact. I think it will not only bear fruit in the immune cell arena where we are going to see persistence being important, but in particular in the non-immune effector cells where when you want to replace a cell, whether it be Parkinson's or type 1 diabetes, you would like that cell to persist for as long as possible to give you relief from those symptoms. Thank you. I think we have a related question, which was about the combinability of, say, an HLA-E dock-in and the CD300a TASR. Have we done that? Is there benefit of any synergy there? It's a terrific question. I just refer anyone who is interested in that. We did publish all of this in a Blood Advances paper just this last year. In that paper, we actually did a direct head-to-head comparison with all seven known NK cell-mediating targeted sort of targets, including HLA-E, HLA-G, CD47, CD47 antibody, many of the other ones that have been explored, and our CD300a TASR. We also showed CD300a TASR in combination with HLA-E, and we saw no additional benefit. That is because the inhibition that was provided by CD300a was as strong as having intact HLAs in the cell. I'll just repeat that. One of the main ways in which NK cells are sort of told to go away is when you don't have any deletion of your Class I or Class II HLAs. Having CD300a TASR expressed on the surface is the equivalent of having intact HLAs. Thank you. More generally, questions have come in whether we've engaged with FDA around our Allo-Evasion strategy. I'm happy to take that. Look, I think as we look at CNTY- 101, our current NK cell product in the clinic today, Allo-Evasion 1.0 is clearly part of that product. We've had very good and successful dialogue with the FDA as we moved that from preclinical setting into the clinical setting, both in B cell malignancies, in autoimmune disease. We've discussed with regulators both in the U.S. as well now in Europe. I think we've got a really good feel and experience on what they're looking for and the types of data that is needed to support that. We feel really good about now taking the enhanced version of that to those same regulatory bodies for CNTY- 308 and our other preclinical pipeline programs. Terrific. We have come to our last question. I would like to take a moment to thank everyone on the line for robust Q&A and your interest in today's webinar. We will close out with this final question for you, Brent, I guess. Have we engaged in strategic partnership discussions with either our platform or specific targets? Look, I've always had a general open-door philosophy related to potential collaborations and partnerships in the general biotech and big pharma arena. I think no matter what stage of company, there's a lot of benefit that both parties can have depending on the technology, the programs, and the platform. We've continued to have those dialogues and conversations with a number of different companies. I think what I could generally say is I think what we're aware of is there's clear interest in both technology, platform, and programs at Century, and we'll continue to have those conversations. If it's something that makes sense for us and for those companies, we'll continue to pursue. Fantastic. Thank you. That is the end of our program this morning. Thank you all for your interest and attendance. Thank you for your participation. This does conclude the program, and you may now disconnect. Everyone, have a great day.