Good afternoon, everyone, and thank you for joining the fifth session of the H.C. Wainwright 27th Annual Global Investment Conference 2025. My name is Daniel Smith, and I'm an H.C. Wainwright Equity Research Associate in Biotechnology. With that said, let me introduce our presenter for the session. I'd like to welcome Dr. Brent Pfeiffenberger , Chairman and CEO of Century Therapeutics. We're developing next-generation allogeneic cell therapies from programmable induced pluripotent stem cells for the treatment of autoimmune diseases and cancer. Century trades on the NASDAQ under the ticker IPSC. Brent, the floor is yours.
Thanks, Daniel, and a big thanks to the continued partnership with H.C. Wainwright and for this conference opportunity. Today, I'm looking forward to discussing with you the ongoing progress of Century Therapeutics as we continue to advance our pipeline of potentially transformative iPSC-derived cell therapies engineered with our Allo-Evasion™ technology. Before we begin, I'd like to remind everyone that today's presentation will include forward-looking statements. These are subject to risks and uncertainties, and actual results may differ materially from what we discuss. I encourage you to review the detailed risk factors in our SEC filings and on the slide you see here.
As we look at the state of Century Therapeutics today, I want to take a second to reinforce an important point: that we've been purposefully transforming the company over the last six months based on the unique insights and perspective we've gained on researching and developing a variety of different iPSC-derived cell types and targets, along with an increasing focus on relentless prioritization to ensure we're optimizing capital and resources to those programs that we believe have real transformation potential in the market. As we jump into our core programs, we are continuing to accelerate and advance a set of these core pipeline programs, all of them being engineered with our proprietary Allo-Evasion™ tech. First, starting with 308, we're advancing Century 308, which is our CD19 targeting CD4/CD8 alpha-beta CAR T- cell therapy, functionally comparable to primary T cells. That's currently in IND-enabling studies for B-cell-mediated diseases.
We're also accelerating our non-immune cell program in a high-impact disease area that's rapidly moving towards drug candidacy, and we're continuing to focus on clinical execution of Century 101 in our autoimmune disease trial Calypso 1. In addition to these, our team is continuing to leverage and progress a deep reservoir of novel iPSC-derived tunable CD4 and CD8 alpha-beta T cells. All these programs are really enabled by two core technology platforms here at Century Therapeutics, one our Cell Foundry and the second Allo-Evasion™. Our Cell Foundry is grounded in key developmental insights that allow directed differentiation of cells that function like primary cells, including both immune and non-immune cells, and our Allo-Evasion™ enables enhanced persistence and the potential for re-dosing of therapy.
We're continuing to focus on execution of multiple catalysts with a cash runway that's now estimated into the fourth quarter of 2027, which is beyond a number of key clinical milestones, including the initial clinical data of Century 101 in autoimmune disease at the end of this year, as well as our goal of Century 308 entering the clinic next year. Quick snapshot of our pipeline. The pipeline here at Century Therapeutics spans across iPSC-derived cell types and targets and a number of indications in autoimmune diseases and cancer. All of our pipeline programs are underpinned by our Allo-Evasion™ tech, which we believe is essential for successful and impactful allogeneic cell therapies moving forward. I wanted to take this opportunity to reinforce the steady progress and the phasing of our core programs.
With Century 101 currently in the clinic in autoimmune disease, Century 308 is nicely progressing through IND-enabling studies as we look to enter the clinic next year, and we're continuing to increase our focus on the continued acceleration of our non-immune cell program towards drug candidacy. A bit of time on Allo-Evasion™, and I'll just maybe start with a preface of, you know, immune evasion is essential to any allogeneic cell therapy. I think there's some good context we can provide on the work and the progress that Century Therapeutics has made on this front. As many of you probably know, allogeneic cells simply refer to the fact that the cells being provided to a person are not from that same person. Like any foreign organism in your body, those allogeneic cells would typically be rejected by the recipient's own immune system.
That rejection may come from T cells, that rejection may come from NK cells, or humoral immunity driven by antibody-mediated mechanisms. Allo-Evasion™ refers to Century 's technology, essentially a set of genetic edits that allows our cells to more healthily coexist with the endogenous immune cells of the patient, or the immune system of the patient. Here we're illustrating Allo-Evasion™ 1.0, which incorporates three distinct edits. I've got deletion of class I HLA molecules, deletion of class II HLA molecules, and the insertion of a non-polymorphic HLA, HLA-E. These three edits in effect allow us to protect the cells against T cell-mediated rejection, as well as a subset of NK cell-mediated rejection. We didn't stop there. Allo-Evasion™ 5.0 takes a step forward in providing more holistic protection from all the things the immune system can throw at it.
In addition to the deletion of those HLA class I and II molecules, we've also inserted a first-of-its-kind pan-NK inhibitory ligand CD300a. In addition to that, we've inserted an IgG-degrading protease, which allows the cells to be protected against antibody-mediated rejection mechanisms. We believe that this more holistic protection will allow our cells embedded with this technology to persist and perform their job. That includes the programs we have ongoing with immune effector cells, as well as our movement into non-immune cells. Here's some of the data that supports our belief in that holistic protection of our most advanced Allo-Evasion™. Specifically, what we're showing here is some of the science that's involved in the development of our CD300a taser.
This data was published in Blood Advances, and we evaluate this in an in vitro experiment where we looked at a diverse set of PBMC donors, diverse across things like age, ethnicities, and previous infection history. What we saw in the data is that only the CD300a taser was capable of truly providing protection across all the variety of NK cell types that are present in these donors. Importantly, you can also see how the CD300a taser performed in context of another approach using CD47, where the taser clearly demonstrated protection across a diversity of donors. Here you can see some of the data supporting our ability to protect against humoral immunity. This is showing the ability of Century 's IgG-degrading enzyme to completely eliminate complement-dependent cytotoxicity, also remove the cellular toxicity, which is typically driven by NK cells, as well as the antibody-dependent cellular phagocytosis.
Hopefully, this gives you some proper context on the data that's supporting our confidence and belief in our Allo-Evasion™ technology to be a critical enabler of successful allogeneic cell therapies. If we move forward to our alpha-beta T cell differentiation, I wanted to start by emphasizing that creating iPSC-derived CD4 and CD8 positive cells that look and act like primary T cells has probably been one of the great challenges in the iPSC field. I am incredibly excited about the progress and work our team has done on creating what we believe is a first-of-its-kind iPSC-derived T cell program that is comparable to primary T cells. Why do you believe, why do we believe that creating alpha-beta T cells that look and act compared to the primary cells is so important? I think this is a good place to start.
This shows a high-level snapshot of the 2024 worldwide sales of all the currently approved CAR T therapies, essentially showing close to $5 billion in worldwide sales, and I'd argue a healthy market on face value. Although these autologous CAR T therapies have produced outstanding clinical benefits, the access to them continues to be a significant challenge, with some sources and references estimating fewer than 30% of patients who are eligible for these CAR T therapies are actually able to receive them. What's similar across all these products is that they're all alpha-beta T cells delivered as a mix of cells expressing CD4 or CD8.
The starting point for us here at Century in relation to T cells was to ensure that we could create an iPSC-derived alpha-beta T cell product that was providing that mix of CD4 and CD8 cells and was comparable in function to primary cells, but also provides inherent benefits as an iPSC-derived allogeneic therapy, including improved time of treatment, consistent and highly controllable manufacturing process, and reduced cost of goods. If successful, this would potentially allow us to not only replace current autologous CAR T cell products, but significantly expand the current market. Century 308 is our CD19 targeted CD4/CD8 alpha-beta CARiT therapy, as depicted here, engineered with AlloVision 5.0. It's clearly displaying those important characteristics of an autologous CAR T cell, which I'll dive into over the next few slides.
This is a nice summary of some of our key preclinical studies, and what it depicts is a lot of the critical functional elements of Century 308 as we put it up against primary CAR Ts, where you can actually see iPSC-derived T cells performing many of the functions you would expect a primary T cell to perform, including total quantity of IL-2 secreted, the ability to expand without any exogenous cytokines, and the ability to, in vitro, upon repeat challenge, expand and kill over 10 rounds. Perhaps most important, we see that Century 308 cells persist in the circulation and blood at levels that are comparable to what you see from primary T cells. They're also able to do something you would expect from a T cell, that is, when they're given a tumor re-challenge, they can expand again and continue to control those tumor cells.
These are fundamental characteristics that you would expect out of an alpha-beta T cell. It's something we're excited to be seeing in our iPSC-derived T cells, which increases our confidence in its ability to have the right impact therapeutically. The Century team has created a four-stage differentiation process shown here, and that allows us to generate a tunable mix of CD4 positive and CD8 positive alpha-beta T cells. We're making adaptive alpha-beta T cells that are both CD4 and CD8 positive, and it's this mixture of cells that we believe is essential for creating an effective immunotherapy. Stepping into a bit more detail on our supporting data on that functional profile of Century 308, here we're showing in vitro data from the three key functions that we would expect from an alpha-beta T cell that are actually preserved in our cells.
First, our cells perform on par with primary CAR T cells in cytotoxicity or the ability to eliminate target cells. Upon target engagement, our alpha-beta T cells also secrete the main cytokine responsible for proliferation of alpha-beta T cells, IL-2, and it's at levels that are comparable to what you see from donors. The third piece is perhaps the real superpower of an alpha-beta T cell, which is its ability to logarithmically expand upon engagement of a target. You're seeing that demonstrated by the Century 308 cells in the right-hand side of this slide. If we transition now to some of the key in vivo datasets for 308, we're very excited to see this data play through in comparison to primary CAR T cells.
In a fairly commonly used mouse model to test CD19 CAR T cell therapies, a single infusion of Century 308 cells can control tumor progression similarly to primary CAR T cell controls. Here, we're showing that tumor cells were controlled for the duration of the study, over 30 days. Importantly, there were no exogenous cytokines or small molecule support that was needed to provide long-term cell persistence after that single infusion of Century 308. In a separate study, when the peripheral blood was analyzed by flow cytometry at day 7 and then day 21 post-CAR T cell infusion, we did detect Century 308 cells. In order to confirm that those Century 308 cells are not only persistent but also maintain cytotoxic function, the animals were re-challenged with tumor cells at day 27. Century 308 cells continue to be present seven days post-tumor re-challenge when blood was analyzed.
Those Century 308 cells were able to control tumor progression post-tumor re-challenge, indicating that the cells not only persist, but they maintain the capacity to respond to tumor cells in vivo. We're really excited about the continued progress of Century 308 as we advance through IND-enabling studies, and we've got a goal of entering the clinic next year. I just want to transition to our current clinical asset, Century 101. Century 101, as a reminder, is our CAR INK therapy targeting CD19 with AlloVision. It's currently in the clinic in two Phase I trials across four different autoimmune disease indications: SLE, lupus nephritis, myositis, and systemic sclerosis. On the left-hand side of the slide, you can see our sponsored trial, Calypso 1. This is a trial assessing two cycles of Century 101. It's currently enrolling patients. We've got eight sites currently activated across the U.S.
and Europe, and we're anticipating additional sites before the end of this year. We're going to continue to focus on clinical execution and building momentum in patient enrollment across geographies. The CARMEL trial is an investigator-sponsored trial being run by Dr. Schett and Dr. Mackensen at the Erlangen Group in Germany. It's assessing one cycle of Century 101 in autoimmune disease across those same four indications. We're expecting patient enrollment to commence in the third quarter of 2025. I'm just super excited to have such a renowned and experienced group of clinicians and staff supporting and driving this important trial. Taking a step back and trying to understand why there's so much interest in the autoimmune disease market, specifically around B-cell-mediated disease, I thought it was important to highlight three key parameters here. First, the size and the extent of the unmet medical need.
Second, the fact that there's very compelling clinical evidence out there. Third, there's a real opportunity to deliver efficacy and impact that would be considered transformational over all currently approved standard of care in these indications. Starting with the size of the potential market, our estimates and references indicate there's tens of thousands of addressable patients in the U.S. alone in many of these core B-cell-mediated autoimmune disease indications. We've clearly seen the fantastic outcomes of the early autologous CAR T data in these patients, but we know that autologous products have some limitations, especially in regards to the product availability, logistics, and costs.
I'd argue that the vast majority of emerging data from those autologous-based therapies, some allogeneic data that's been emerging, and some related modalities, if that data continues to hold across more patients, it's being considered transformational by the majority of rheumatologists versus the current standard of care in many of these diseases. We've got a real opportunity to make a very meaningful difference in the lives of so many patients suffering with this crippling and oftentimes failed disease. As we think about the unmet need and the opportunity to make an impact, what gives us confidence on the clinical profile of Century 101 in these B-cell-mediated autoimmune diseases? First, we've established a safe and well-tolerated dose for Century 101 based on our clinical experience in B-cell malignancies.
In addition, at the higher dose levels we've clinically studied, we've seen rapid and effective B-cell depletion of circulating B cells out to 30 days and sometimes beyond in the vast majority of patients who had detectable B-cell counts at baseline. In addition, when the B cells re-emerged in these patients, they showed a naive non-class switch profile, which has also been associated with SLE responses to CD19-targeted cell therapies. Importantly, we've detected Century 101 cells in the lymph node of tumor biopsies post-treatment at the higher dose levels studied in B-cell malignancies, and we've generated strong data on proof of concept for AlloVision. What's shown here is data from our peak, essentially park pharmacokinetic data from our B-cell malignancy trial with Century 101 that shows similar exposure of Century 101 in the presence or in the absence of endogenous lymphocytes.
On the top right of this side of this graphic, you can see the endogenous T and NK cell levels, they drop after lymphodepletion initial treatment, and then they return to screening levels by day eight post-infusion. On the bottom, you can see the three distinct infusions of Century 101 given at days 1, 8, and 15, with similar PK profiles observed for each infusion within a cycle, despite the endogenous lymphocytes returning. These data in aggregate provide us with confidence in the profile and potential of Century 101 in autoimmune disease as an allogeneic INK cell therapy with AlloVision that we believe provides the potential for tighter drug control over drug exposure, and we think it may provide for driving B-cell depletion and reset without the risk of prolonged B-cell aplasia. I just wanted to end with thanking all of you for your time and attention today.
I've got a firm belief that Century's iPSC platform and core programs have the potential to create real impact for the patients who are out there waiting, patients with severe, debilitating, and sometimes fatal disease. We have tremendous expertise here at Century in creating iPSC-derived cells that function like primary cells, and that fact, combined with our leadership in immune evasion technology, creates a powerful and unique combination. We're looking forward to moving with urgency throughout the remainder of 2025 to deliver clinical data for Century 101 and bring our pipeline underpinned by AlloVision 5.0 technology closer to patients. Thanks again for your time.