Hello, everyone, and welcome to the Annual Cell Therapy Day at H.C. Wainwright. My name is Mitchell Kapoor. I'm a Senior Biotech Analyst here at H.C. Wainwright. Today I have the pleasure of welcoming Century Therapeutics, and from the company I have Brent Pfeiffenberger, the CEO, and Hy Levitsky, the President of R&D. We're going to have a fireside chat and go through kind of the latest developments in the Century story. Thank you for joining us, gentlemen.
Good to be here.
Thank you. Pleasure to be here.
Great. Well, maybe you can start off by orienting investors to the Century story, those who may not be familiar with, you know, the history and what's gone on more recently. There's a lot that's changed in the pipeline, but also a lot that's been the same. So maybe you can just tell us, you know, a little bit about that and how Century is differentiated versus other cell therapy peers in the space.
Yeah. Sounds good. I'm happy to start and kick off with that overview. Look, let me start by saying Century is still very much singularly focused on building and developing the next generation allogeneic iPSC-derived cell therapies and cell therapy platform. And we are doing our best to leverage the unlimited self-renewing capacity of iPSCs, which we believe have some inherent benefits versus other allogeneic approaches, as well as leveraging cutting-edge cell and gene engineering capabilities, our own in-house manufacturing technology, which we think enable us to develop fit-for-purpose products with functionalities that are designed to overcome limitations of existing cell therapies. At the core of what we're doing, Mitch, is really what we call our proprietary Allo-Evasion technology. And it's essentially a series of genetic edits that allow our cells to more healthily coexist with the endogenous immune cells of patients.
And it's this technology, Allo-Evasion, that truly enables us to pursue repeat dosing of our cell therapies in a more drug-like fashion. That's without the need for continued lymphodepletion. That can give you the benefit of, for example, prolonged drug exposure in a setting like lymphoma, as well as potentially tighter drug exposure in a setting like autoimmune disease or SLE. We have our lead clinical asset, which is Century 101. This is an iPSC-derived NK cell therapy with six precision gene edits. We believe it's the only cell therapy out there with six gene edits that's in the clinic currently. That's currently in a phase I trial called ELiPSE-1 in B-cell malignancies. We read out some initial data at their lowest doses late last year, very encouraged by those initial results.
And then we also had clearance from the FDA of Century 101 in lupus and SLE. That's our phase I trial called CALiPSO-1. The team is working hard to get sites engaged and activated in the first half of this year. Maybe I'll ask Hyam to just touch on some of the more significant differentiators within an iPSC-derived platform and approach.
Thanks, Brent. I think, you know, broadly speaking, the major distinction relates to the starting cell type. We are able to reprogram normal cells of a given individual to create iPSCs that can be fully characterized. Those induced pluripotent stem cells, as the name infers, have the capacity to form virtually any cell in the body. We are working, of course, in making immune effector cells, T cells, and NK cells through an intermediate known as a hematopoietic progenitor cell.
The advantage of doing it this way is that the iPSCs, as Brent mentioned, have unlimited replicative capacity such that we can do serial genetic edits or modifications to the genome in a very controlled fashion using CRISPR-mediated homology-directed repair, such that we either insert a transgene or knock out an endogenous gene at a precise genetic locus and then are able to characterize that genetic event to make sure that we do not have any off-target integrations or other genomic perturbations. The cells can, at the end of the genetic editing, be serially, essentially down to the single cell level, can be cloned. And then expanded clones, fully characterized, including full genomic sequencing that allows us to be very confident of the alterations that have been made and then also to have a more uniform and robust functional assessment of the final cell product.
It also enables us to utilize specific steps during differentiation that drive the cells toward particular cell fate outcomes that have different applications that we seek to take advantage of. So broadly speaking, we'll get into some of the specific edits in a moment. But broadly speaking, this platform is really the only one, in my opinion, that allows us to really avail ourselves of all of the innovations that have taken place in synthetic biology and immunology to incorporate these technologies into a platform that can now generate a cell that has these varied attributes in a uniform manner.
Thank you both. That's a great overview. You know, talking about the ELiPSE-1 trial, the data just came out at the end of last year. Can we just get a little bit of a recap on that? Because it was such an important point for us as the investment community to understand, you know, what the potential of this is in the early days. And so if you could just talk to us about the efficacy and safety we've seen so far, how to contextualize that in anticipation of data coming up this year for this trial. Then can you also just point to this is really important about the Allo-Evasion signs that we've seen there because that translates to the entire pipeline. So I think that that's something important to highlight for investors.
Yeah. That sounds good. All very good questions. Let me start us off. So maybe before I jump into the results of the trial, let me just reinforce the trial design and dosing schedule, which I think provides some important context for everyone. First, we're speaking about ELiPSE-1, which is our phase I trial for patients with CD19-positive relapsed refractory non-Hodgkin's lymphoma. Essentially, the trial is seeking to assess whether Century 101 can be administered safely and then enabled by our Allo-Evasion approach repeatedly without the need for continued lymphodepletion without allo-rejection. There are two dose schedules. Schedule A is a single infusion per cycle at dose levels of 100 million cells, 300 million cells, and 1 billion cells. Then Schedule B is evaluating a three-dose schedule per cycle at 300 million and 1 billion cells.
So in other words, the first dose level in Schedule B, a patient would receive 300 million cells on day zero, 300 million cells on day 8, and then 300 million cells on day 15. So all patients receive an initial standard dose of Flu/Cy. And then they would be eligible to receive a second cycle if they don't have a DLT and have at least stable disease. And then any additional cycles given beyond that are done without any lymphodepletion. So I think that's just an important backdrop to reinforce for the ELiPSE-1 trial. As you mentioned, Mitch, in December of last year, we read out data from the first seven patients at the lowest dose levels. We were very encouraged by what we saw. As a reminder, these were pretty heavily pretreated patients. There was a median of four prior lines of therapy.
Most of the patients were refractory to their most recent prior line. Starting with safety, we saw a very favorable tolerability profile with no DLTs. The majority of patients were also able to be treated in the outpatient setting. In regards to efficacy, we were encouraged by the early signals of efficacy at the study's lowest doses. That included a six-month durable CR at the lowest dose level and an additional CR at the 300 million dose level. I think, very importantly, no initial evidence of allo-rejection, even in the absence of lymphodepletion in those patients who were able to get additional cycles. Let me just maybe turn it to Hy to give a little more detail and context around the second part of your question, Mitch, which is around that translational dataset for Allo-Evasion.
Yeah. And let me also, for those who may not have followed the story, just say a word about the strategy Century has taken with regard to Allo-Evasion. We know that T cells are the first and most potent contributors to allograft rejection. We've made our cells insensitive to T cell killing through the elimination of HLA Class I and Class II. And then we've introduced an inhibitory non-polymorphic form of HLA Class I known as HLA-E that contains a defined peptide to block natural killer cells from the patient rejecting the cell product. So with those three genetic edits as part of the suite that Brent alluded to, you know, we have a cell product that can healthily coexist with immune effectors of the patient. And the best test of this is not only the pharmacokinetic profile of the cells upon infusion post-lymphodepletion, but the ability to redose.
Because, in principle, if the patient, particularly one who has recovered from lymphodepletion and now has normal lymphocytes, is allosensitized, you would not expect a subsequent dose of the cells to achieve significant drug exposure. In the ELiPSE-1 trial, we're working our way through the dose escalation and evaluating those parameters in detail. And at a high level, what I can tell you to date is that we are able to detect the cells in the blood for a short period of time. But interestingly, through the investment in an additional technology known as cell-free DNA, we're able to detect evidence of the cell's presence in the body more generally for periods of time that extend uniformly for beyond three days and in some instances as far out as 28 days after the infusion.
Very importantly, that exposure looks comparable in individuals who've received the cells post-lymphodepletion and then also who have then subsequently gone on to receive the cells in the absence of lymphodepletion. And so this, in many respects, in our mind, is perhaps the most stringent test of the evasion of immunologic rejection. Of course, we're also doing work in the laboratory for translational assays looking, do we develop antidrug antibodies? To date, we've not seen antibody generation that's led to the common pathways of rejection. And our assays in vitro for cell-mediated immunity are currently ongoing. But the encouraging news, I think, is as we escalate the dose, we're going to get a better line of sight on the ability of these cells to be dosed and not be rejected in the absence of lymphodepletion.
That's great. And Allo-Evasion is such a crux to our thesis. And, you know, it will hopefully translate into better durability versus some of the peers, just being able to dose in a more effective way, you know, for longer periods of time. So it was really important to see that from our standpoint. So whenever we're thinking about the context of this dataset in terms of the upcoming data and what we could see in mid-2024, could you kind of help us to the degree that you can say, you know, how many patients we might be able to see at this dataset, what kind of follow-up would we have on these patients, and what dose levels would we see? And then, you know, thinking about the patients that we've already seen, the seven patients, you had the CR that was for six months.
I don't think we'll see that patient because I think they're now complete. The short-term PR and then the ongoing CR, which will be interesting to see potentially some durability there. Could you help us understand, you know, what would be meaningful at the next update in the context of what we've seen so far?
Yeah. Let me jump in. I think, you know, related to what to expect at mid-year, as Hy mentioned earlier, we're still in the dose escalation phase of the trial. So at the mid-year data update, it's intended to provide one initial efficacy and safety data at the higher dose levels in Cohort A and then some initial efficacy and safety data for Cohort B, which is the three treatments per cycle. And then, importantly, a more robust translational dataset on proof of concept for Allo-Evasion, building on what Hy was just explaining and what we shared late last year coming out of ASH. As we're still moving through the dose escalation phase, as you can probably appreciate, we won't have the full picture of durability at the mid-year data time point. But I think those elements that I mentioned will be really important components of that update.
In regards to, I think, the second part of your question, Mitch, on what would be, you know, meaningful, you know, as we get to that data update, one, I will reinforce, we were encouraged by what we saw late last year. I think this mid-year data update will be an opportunity to continue to build off that as we move through dose escalation towards dose expansion. We'd like to continue to see very clearly a manageable safety profile as you get to those higher dose levels and the repeat dosing schedule. We want to make sure we're seeing continued signs of drug activity and response. And again, I think really importantly is increasing evidence around the lack of allo-rejection in relation to establishing proof of concept on Allo-Evasion. But, Hy, anything I missed there that you'd add?
No. Maybe I've just embellished a little bit the last point, which is, you know, as you go up in dose, the robustness of the signal that we can detect from assays like the cell-free DNA gives us even greater confidence and quantifiability of that change between the dose without lymphodepletion and subsequent. I'm sorry, with lymphodepletion and subsequent doses without. So I think that the dataset is going to continue to become increasingly convincing.
Great. Yeah. We're definitely looking forward to that. Just to pivot here on the second part of our conversation towards the use of this same asset in the autoimmune setting, could you just tell us a little bit about how you're exploring 101 for development in the autoimmune space with SLE and explain a little bit about how the mechanism can be useful for both settings?
Yeah. Hy, you want to take that one?
Yeah. Sure. So, I mean, let's start with the target. And I know there's been a fair amount of discussion in this space about what is the best target to go after if you're trying to achieve transient but deep B-cell depletion. We have an asset that targets CD19 that's well-characterized. And clearly, in our view, and I think that of many others, this is really the central target that spans the B-cell differentiation from an early progenitor all the way through to a plasma blast. So we're pretty confident in the target itself. A second differentiator, of course, is the fact that we have an off-the-shelf product that can be prescribed by treating physicians at the time they're needed. There's no need for an apheresis or drug manufacturing.
And importantly, in that context, there's no need to wean patients off of their existing immunosuppressives during that time that you would have to be creating a product after an apheresis. So there are big advantages, I think, at large around Allo. And then, of course, the other element of this is that this is an NK cell. And clearly, the benchmark to date in the academic studies that have been reported in SLE and other autoimmune diseases is autologous CAR-T. And while the safety profile to date has actually been quite favorable, we do know that CAR-T cells have the potential to expand very rapidly and lead to associated toxicities such as CRS or ICANS. In contrast, NK cells have a much more benign or gradual expansion profile. They don't peak to the same level or at the same rate as T cells.
And so they are more controllable, if you will. And that is associated with a more favorable safety profile and, importantly, greater control over the drug exposure that will correlate with the depth and duration of B-cell depletion. So for all these reasons, we think it's actually a great candidate for these diseases.
Okay. Great. And thinking about the different dose levels that you could think about for the autoimmune setting versus the oncology setting, could you help us understand what dose levels those are? And have we seen some of those dose levels already surpassed in the data we've seen in the oncology setting already?
Yeah. I mean, it's really a great opportunity to take an asset that we have begun to understand in the oncology setting and now use those learnings to accelerate the development activities in a new indication. A great example of this is, of course, when it was a first-in-human study in B-cell malignancies, we had to start off at 100 million cells once a month. We're able to now start, because of that experience, as we move toward what we're referring to as the CALiPSO trial of SLE, we can start at 300 million cells given weekly times three in a treatment cycle. So the paradigm that we're starting with is standard fludarabine cyclophosphamide followed by three weekly doses at 300 million cells and then followed by a second cycle without any lymphodepletion, again, three weekly doses. That's the totality of the treatment at its core.
I think that with this approach, we'll have a great opportunity to look at both the depth and the duration of B cell depletion and changes in pathogenic antibodies as well. There is an opportunity to dose escalate in the SLE trial, and we'll certainly have that chance to look at going up to 1 billion cells in the same schedule. So I think within those brackets, we're going to hit a sweet spot that we'll be able to take forward for larger numbers of patients.
Okay. Great. And then, obviously, the tolerability profiles are quite different from oncology to autoimmune, and hence the discussion on the dose level. Thinking about also the dosing frequency of, you know, depending on what kind of duration you see, that will obviously guide how you move forward. But thinking about what's acceptable from the patient standpoint, could this, you know, be could you envision it as something like a yearly therapy? And if so, would you imagine that at some point you would transition away from lymphodepletion as being something that was a regular occurrence with autoimmune patients?
Yeah. Let's start with what you might call the induction, which may be the whole thing. But I think that currently, it's in line with what patients who are treated for these diseases experience in the context of other therapies in terms of the period of time where they would have weekly infusions times three. And the opportunity to do this without lymphodepletion in the second cycle, I think, is going to give us a great line of sight as to whether we can begin to back off on that element of the therapy. That ultimately becomes, I think, where the real differentiation of this approach may reside. More to your comment about, you know, the tolerability of additional treatment cycles if that were to prove to be necessary, I think we're going to have to wait and see about whether it will be necessary.
But if I think I understood your question correctly, you know, some form of maintenance is needed at some later stage in the course of the disease, and we can do that without lymphodepletion, I think that's huge and would be readily accepted. I do want to emphasize, although we've said it before, the early experience in ELiPSE-1 suggests that even in the oncology setting, we're able to give these cells as outpatient in the outpatient setting. And we hope that and have every reason to expect that that will be true, maybe even at a higher rate in autoimmune diseases.
Great. No, it's really exciting to see this being used in this setting as well. From an efficacy and safety standpoint in SLE, what do you think would be differentiated from competitors in terms of, like, a depth of response and some sort of duration?
So, you know, I think right now where we are in terms of our understanding of how cell therapies behave in this set of diseases is very much on the learning curve. We're encouraged by, you know, the data that Schett and others, you know, have presented in terms of the durability of the responses. And ultimately, I think the goal is going to be to, you know, liberate patients from the need for, you know, running immunosuppression. And so to my mind, that's the benchmark, is getting the patients into a remission that is ultimately durable. It's a little difficult to know at this stage what parameters such as B-cell depletion or normalization of immunoglobulins are going to best correlate with those clinical remissions. That will be some of the learnings that I think will happen as we're advancing the program.
But as Brent alluded to earlier, having control over the drug exposure really provides a lever for us to react to those kinds of biological learnings as they emerge in the field.
Great. Awesome. The last thing on this topic, can you remind us when we could see some initial data from the SLE program emerge and when we can get a look at how this is performing in the autoimmune setting?
Yeah. Look, I don't think it's any secret that there's, you know, a fair bit of competition and kind of entrance in this space more generally. I think one of the important aspects from our standpoint is that there's only a small handful of NK cell therapies that are actually in early-phase trials. And, you know, I believe that Century 101 is the only allogeneic iPSC-driven NK product that has IND clearance in autoimmune disease. So I think that's helpful because in this space, I think what is the challenge is you've got increased coordination between rheumatology and cell therapy, and then you've got, obviously, a number of competing products for a certain set of patients. So having differentiation amongst this set is really important. Having said all that, we have guided towards an initial set of preliminary clinical data at the tail end of this year, Mitch.
Great. Thank you so much. To close us out, if you could just recap the next 12 months ahead for Century, you have a lot going on, or touch on anything that, you know, that we didn't get to speak about that you feel is important for investors to know at this juncture.
Yeah. Thanks for the opportunity. Look, I think the next 12 months at Century, we've got a very high level of focus on continued execution of our clinical programs in both B- cell malignancies and the autoimmune space. We're continuing to make really strong progress on our pipeline programs, including, you know, an important collaboration with Bristol Myers Squibb. And we've got a number of near-term catalysts, including the mid-year update that we talked about for ELiPSE-1, the preliminary clinical data. We've got it too for CALiPSO-1 in SLE at the year-end. And then just a quick point on cash, we ended 2023 with $262 million in cash, which comfortably gets us into 2026. And as you mentioned, Mitch, we've got a lot moving forward and looking forward to an exciting year ahead of us at Century.
That's great. Well, thank you so much for your time, Brent. Thank you, Hy. A special thank you to all of the investors who dialed in today. We really appreciate your time, and we're looking forward to the next update. Thanks a lot, guys.
Thanks a lot. Thanks, Mitch.
Take care.
Take care.