Good morning, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. I'm pleased to have you all with us today. And before I begin, I'm required to point out certain disclosures regarding the relationship between Piper Sandler and our next presenting company, Century, which are located at the back of the room and also at the registration desk. So, as you probably know, Century is developing induced pluripotent stem cells, or iPSCs, both CAR T cells and also natural killer cells to treat autoimmune disease and cancer. The company is developing CNTY813, which is a really cool new program that's been announced, which are iPSC-derived beta islet cells for type 1 diabetes, and also a CD19 CAR-iT, pretty sophisticated cell therapy, CNTY308.
Additionally, Professor Schett's lab at the University of Erlangen-Nuremberg continues to conduct the phase one Carmel study of CD19 CAR-NK natural killer cells, CNTY-101, in multiple autoimmune diseases. And we're going to get the first update from data from that trial, I think maybe on Friday or coming up this weekend. So, really exciting. And again, can't imagine better hands to have that program in. So, joining us today from Century are Brent Pfeiffenberger, CEO, and also Chad Cowan, who's the CSO. So, thank you all for joining us, and thanks, guys, for being with us and making the trip up. So, as I mentioned in the opening remarks, Century is developing iPSC-derived cell therapies with multiple edits. I mean, these are really sophisticated cells.
Maybe you can start off by describing why these are the right cell types and also, to the extent possible, layering in some of the discussion on these Alloevasion edits that you guys have really pioneered.
Yeah, sounds good. Thanks for the invite, Ted. Let me start, and then I'll turn it over to Chad to maybe dive a little bit deeper on some of the edits and why we think there's some great advantages with what we've got. Century has been and still remains focused on iPSC-derived cell therapies, and I think there's enormous potential for these therapies. You know, I'd bucket the big advantages of the iPSC cell therapies versus other allogeneic approaches into three areas. One is engineerability. I think these are the cells that you can really fully harness all the powers of synthetic biology in a single cell type. I think the second revolves around our ability to fully characterize and reproduce these cells. It's amazing what we can control at every step along the way of the process, and that's a really powerful tool to have with cell therapy.
And the third is what we've termed profitable scalability. You know, I think we have a very clear pathway to antibody-like scale and costs, and I think those are really big inherent advantages versus other modalities. Now, what sits behind that, Ted, are really two fundamental capabilities. One is what we call our iPSC cell foundry, and that allows us to really do direct differentiation of different cell types. I mean, in theory, you can create any cell type you want from iPSCs. And so, we have the ability and have shown that we can do that and create cells that are really comparable functionally to primary cells, like beta islet cells, like alpha beta T cells. And so, we think that's an inherent advantage of what we have here at Century. The second is what you mentioned, which is alloevasion.
Essentially, you know, it's a set of genetic edits that allow our cells to more healthily coexist with the endogenous immune cells of patients. I'm going to let Chad speak to some of the deeper dive on that and why it's so critical for these cells.
Yeah, happy to. So, as Brent just mentioned, Alloevasion is probably one of the key differentiators for Century, and it's a journey scientifically I've been on for about 15 years, where the big question has been, how do you make a single cell that's now compatible with everyone, right? So, this is the equivalent of making cell therapies into antibody-like therapies. Obviously, the barrier is the individual's immune system, and we have, over those years, pioneered individual edits and sets of edits that now allow you to, you know, essentially live in harmony with the patient's immune system. In our Alloevasion 5.0, we have the league-leading or industry-leading set of edits and the ability to sort of defend against the immune system. That includes two edits that remove the HLAs from the surface of the cell, so you have no T cell engagement.
That's not particularly distinguishing because that's what a lot of the groups are doing, including companies I've worked with before. What is really special is we have two unique edits that are unlike anything else out there. First, we have a universal NK cell inhibitory ligand. It's the only one of its kind. If you look at CD47, which I've worked on, HLA-E, they hit subsets of NK cells. This is the first where the receptor is found on every single NK cell, and the synthetic ligand that we've built that activates that receptor provides protection that's the equivalent to these cells having intact HLAs. So, it's like having a normal cell being encountered by an NK cell. So, it's phenomenal.
The second thing that we've built in, which we think is completely different than the rest of the field, which is the first of its kind protection against antibody-mediated immunity. So, humoral immunity is a real thing where you'll develop antibodies that essentially either direct killing through complement-mediated pathways or through other cells. These are the ADCCs and ADCPs. And we've put, for the first time, an IgG degrading protease tethered to the outside of the cell so that those antibodies that are developed against the foreign cell or any foreign antigen are actually cleaved by the protease. That means that their Fc portion is released, and that's the business end for the antibody in recruiting either complement-mediated killing or ADCC.
In our studies, that has completely eliminated that humoral facet of the immune system, which is particularly important if you want to see really long-term persistent sort of life and viability in your cell therapy.
Yeah, really, really cool, really innovative. You know, just a question that kind of popped into my head on the second one. With that protease, if it's selected to IgG, does that interfere with any other activities that the cells are doing or anything else in the immune, in the tumor microenvironment, or in the immune milieu, if you will?
Yeah. So, we've tested it fairly extensively preclinically, both in animals and also in these sort of extensive whole blood assays where you'll take whole patient blood and sort of expose it. We see no activation. We just see IgG cleavage across all isotypes of IgG. And that's really important. I will say it doesn't even. We think there's a minimal risk that you'd even deplete IgGs. There's a similar protein in development by a company, Hansa, which is being infused to actually deplete IgGs. That's infused at a million-fold. In fact, it's 10 million-fold for their lowest dose. We're a million-fold lower than the lowest dose they've ever put in a human if you look at their biomass calculation on our cells. So, I think locally it definitely degrades IgG. It's unlikely to give you any systemic reduction.
Yeah, very cool. Really, really innovative developments there. And this is relevant too, for your newly unveiled preclinical beta islet cell program, CNTY813. Chad, I know we joked about this yesterday on the panel that this is sort of back to your roots. Please describe these cells and how they can be used to treat type 1 diabetes.
Oh, I'd be happy to, so you know, it is back to my roots. Back in 2001, I joined Doug Melton's lab because we had the vision that you might take a pluripotent cell and make it into an insulin-producing cell. What we were successful in over those years is making a really robust beta islet. Those beta islets are functionally equivalent to the cadaveric islets that are used in transplants for the last 25 years. There's two approved drugs where you can use those cadaveric islets, and many of you have seen the work in Doug's lab matured into Semma and then the trial in Vertex, and that is showing equal efficacy right now in humans. Now, the major drawback is that you have chronic immunosuppression in every one of those cases. These are not minor, but heavy-duty immunosuppression, tacrolimus, sirolimus.
The patients are always getting the infections, they're getting the kidney problems, and even cancer over time. That's the main limiting factor for adoption because the results are fantastic. 80%-90% of these individuals are typically insulin-free for up to a year. If you look at the Vertex study for more than two years, you have people who essentially are functionally cured from diabetes. What we've done by building in this Alloevasion is we've made a functionally equivalent beta islet to what you see from Vertex, but for the first time, we have the ability to try to administer this with certainly reduced, but hopefully free of that chronic immunosuppression.
Because of the Alloevasion.
Because of the Alloevasion.
Really, really cool. Where are you guys in development? And sort of this is obviously a big opportunity to pursue. I know there's some other companies like Sana working in the area too, but what's sort of the development path you guys?
Look, we've been moving at pace. I mean, we kicked this program off, you know, earlier this year, around March or April, and I think with the expertise, unique know-how of people like Chad on the team, we've been able to understand the most critical factors of moving this through both preclinical as well as clinical. So, the next steps, Ted, for this program are: one, we are still on track to move to IND-enabling stages by the end of this year. I think the critical elements of the program that we're working on are, one, is making sure we lock down the process for the larger scales of our clinical development, and we're already in, as Chad mentioned, bioreactors from a CMC and development standpoint, which is a critical element to this. The second is just a rate-limiting time dynamic of tumorigenicity studies.
We've kicked those off, and so those will be something that we'll follow for this year, which are critical for an IND submission. We still remain on track to submit an IND as early as next year.
Really exciting. So, we'll follow that program with a lot of interest. Now, you guys also recently emphasized your focus on CD19 CAR-iT, CNTY-308. Firstly, what are the unique properties of these alpha beta T cells? And maybe you can describe 308.
Oh, yeah, I'd be happy to. So, I think the thing that is becoming completely clear to the field is that autologous T cells work. Autologous CAR T cells are working not only in hematological malignancies, but I think what has been really eye-opening is the broad swath of autoimmune diseases where we're seeing this incredible efficacy. What we set out to do was to build from iPSC cells something that was functionally equivalent to the autologous T cell. That means that it's got CD8 and CD4 T cells so that you get the real durability of persistence in those cells, and perhaps most importantly, the ability upon antigen recognition to substantially proliferate. So, that's what makes T cells special, is this ability to, you know, upon antigen engagement, logarithmically expand until the antigen is depleted, but also persist for an extremely long amount of time.
That's what our cells do, and that's one of the reasons we're extremely excited. Pair that with our Alloevasion 5.0, and I think you remove the major barrier, especially in autoimmune disease, which is lymphodepletion. So, a lot of the patients are a little bit hesitant to go into a lymphodepletive procedure to see a cell therapy. We're very excited about the opportunity to deliver this product, CNTY-308, which is an alpha beta T cell without the lymphodepletion treatment.
Another thing, I know we've talked about this, but the ability for you guys to manufacture at scale and really address just these massive numbers of patients that will be required in autoimmune diseases beyond lupus. You know, I made the comparison yesterday. If there's 200,000 hematologic cancers, that's one-tenth of all cancers in America. There's 50 million autoimmune disease patients and growing in the United States. So, to ever be able to address those patients, we're going to need a different approach from the manufacturing side. Tell us about what your development plans are for 308?
For 308, we are planning to initiate clinical trials next year. And so, we've got a number of investigators and sites around the world who are very interested in pursuing clinical development of Century 308 and B-cell-mediated diseases. We haven't disclosed the specific details yet as we work through all those discussions, but we're excited to get that in the clinic next year and start to produce clinical data with it.
Do you envision this would be autoimmune disease and oncology, or is the primary focus autoimmune?
I think our plan is to start primarily with autoimmune disease. And I think just because there's such scale and breadth of the data that we're seeing in that space, as Chad mentioned, I think it's very, very clear that autologous primary CAR T cells work extremely well. And I think every few months that pass, we see another indication with that data being generated looks to expand that opportunity. And so, we think it's a phenomenal place to start. As Chad mentioned, we think it'll give us good line of sight on potentially reduced or no lymphodepletion with 308. And then beyond that, you know, we'll discuss as we get to that point.
Yeah, and there's really, it is almost like a purpose built for that indication. So, now you guys recently discontinued the Calypso study, and I would say this is maybe more, you know, put the focus with Dr. Andreas Mackensen at University of Erlangen-Nuremberg, who are conducting the phase 1/2 Carmel study, as I mentioned. And this is an investigator-sponsored study of your CD19 CAR-NK CNTY-101. Tell us about sort of that relationship, if you will. Maybe lay out the plans for that study. And I know we could even be getting data soon. Is there any, you know, any sense of what we should be expecting?
Yeah, well, look, we're very excited to have Dr. Andreas Mackensen and the team at Erlangen behind this. They continue to be big supporters of, you know, the partnership and the IST. They're extremely efficient, obviously, at what they do. And so, you know, the trial, just to remind everyone what it is, it's called Carmel. It's an IST. I'm essentially looking at Century 101 in autoimmune diseases. Right now, it's across four indications: SLE, lupus nephritis, myositis, and systemic sclerosis. They are giving one cycle of Century 101. And so, we've treated as of mid-November when we released Q3 results, they've treated three patients. And like I said, I think they've been right on track with what they expected in the trial so far. We felt that trial was the most efficient way to get to a real clinical proof of concept across these initial indications.
And then obviously, we will evaluate and have the potential to expand at that point. But as you mentioned, they are. We expect them to present some initial data of those early patients in a couple of days, December 5th, at the 14th Annual BMT and Cell Therapy Workshop. I think it's in San Diego. And what they've explained to us is they plan to present on safety, initial safety profile, and then some of the deeper translational work they've done. I think it's a little bit too early based on the timing of patient treatments to really get into some of the clinical outcomes for these patients at this point.
You know, I think this is the only NK cell they're working on. Is that accurate?
It is. And it was the first actual IST they sponsored. And so, you know, I think the interesting thing about Dr. Andreas Mackensen, they're involved obviously in a lot of different modalities as a site in the work that they've done themselves, but I think that gives them really unique insight into these different modalities. And like I said, they've been very big supporters of continuing to pursue this clinically, and we're excited to have them alongside our partners.
Yeah, I mean, again, they're the pioneers. Now, one thing I remember from my conversations with Dr. Schett or with Professor Schett is that he still is a big believer in lymphodepletion even for autoimmune disease. Is that part of the protocol for Carmel?
Yeah, so they are lymphodepleting patients in these early stages. I think there could be an option where we reduce or modify lymphodepletion going forward. I think our goal all along was to make sure that we're giving, as you're putting this in the humans for the first time, you're giving these patients who are very refractory and severe patients the best chance at clinical outcomes. I think once you've established that, I think you've got a better idea of the risk-benefit and then the ability to potentially modify as you go forward.
Makes a ton of sense. Switching gears, you guys have been very successful at partnerships from the beginning. When I did the IPO for Century four years back, you guys partnered with Bristol in the past. You guys really have a lot that you're developing in this Gen 2, Gen 2.5, Gen 3, Century, however you want to kind of classify it. What are your partnering plans going forward?
First I'll start with, I've always been a big believer in just having a continuous open-door dialogue with pharma companies. You know, you never know when strategic partnership or assistance could be highly beneficial to you as a company. And even though we're super excited, for example, about our Type 1 diabetes program and the position we're in, you know, if you think about, maybe if I take a step back and think about some of those areas that we're pursuing, look at Type 1 diabetes. You know, we think we're in a really unique spot, you know, very limited competition, massive medical unmet need, very clear clinical proof of concept, and now a product that we think is uniquely positioned. But you're talking about 2 million patients in the U.S., 9 million worldwide.
That's a scale that probably lends itself to at least interesting conversations with pharma about how do you really get to those patients at an access and a scale that you want. I think same thing for 308, our alpha beta T cell program. I mean, I think you just mentioned how big and growing that autoimmune disease market is. I think to be able to get to these patients at the pace and scale you want, you probably need and want to have that type of scale sitting behind it. So, those are two areas that we'll continue to have conversations around. I think the third, which is interesting, you know, is around alloevasion. I think it's grown in prominence about the importance of it for allogeneic cell therapies, particularly. As Chad mentioned, you can take an iPSC and convert it, differentiate it into any cell type you want.
So, we're starting to really think through and be thoughtful about how we could potentially leverage Alloevasion with partners in areas that wouldn't create more competition to ourselves, but use that technology in some other field. So, I think there's a bunch of different areas that we're interested in pursuing, and you know, that door is constantly open for us.
Yeah, and I mean, you mentioned on the panel yesterday about the future potential role of regenerative medicine. So, are you guys looking even beyond? I think I was the only guy who was surprised that it was Type 1 diabetes, and I looked back. I was like, how did I not recognize that was what you were talking about when you said non-immune cell types? I should have picked up that clue. Are there other cell types that you guys are looking at as well right now, or is that a little bit more in the future?
Well, maybe I'll start more generally. I'll let Chad speak to some of the details around cell types that have really grown in prominence. I think, yes, the answer is we will continue to look at opportunities that we feel similar to type 1 diabetes that we can move very quickly in. We've got differentiated know-how and technology and have very clear clinical unmet need. I think that's going to be something we are always looking at, and we are looking at it right now. But maybe Chad can speak to just some of the cell types that have a bit more evidence and, you know, are clearer of where you can move on those pathways.
Yeah, it's, I mean, I think it's a super exciting time. Once you've unlocked the Alloevasion problem, you now have a few areas where you do see really mature early data. One of the ones that everyone's probably paying attention and tracking is Parkinson's disease and the ability to put in dopaminergic neurons and really transform the lives of patients there. That's, again, a really open space. There's really only one company that's significantly developing there. And you've probably heard the promise in cardiac disease, right? So, after heart attacks, you need to significantly change the heart muscle, and really the only way to do that is add back heart muscle cells. So, those are two really enormous opportunities with almost no competition where the barrier has been Alloevasion.
I'll just remind you, even with the BlueRock data, they're doing significant immune suppression because if you lose your graft, you get back to the Parkinsonian symptoms.
Yeah. But I look, we remain focused on execution, and we've got, you know, a lot of urgency and acceleration of the T1D program and getting 308 to the clinic. But yes, as a company, I think we're always evaluating those opportunities to move forward.
I really do admire how you guys have been flexible at looking at the data and looking at the opportunities and investing where it makes the most sense. You guys ended the third quarter with cash, I think, of $133 million, give or take. How long does this fund the company, and what's it enabled you to accomplish?
Our current estimates of this cash runway gets us into Q4 2027, so approximately two years. You know, I think these next 12 months are going to be really important for us. I think we've got a number of different catalysts, potential catalysts that are sitting out over the next 12 months. You've got clinical data generation, right? Both 101 with the Andreas Mackensen IST moving forward. You've got 308, you know, planned to be moved to the clinic and generating clinical data at some point next year. And then you've got the movement of type 1 diabetes into the, you know, an IND submission in 2026. So, you know, across those three priorities, I think we've got a lot of really important stuff, you know, coming in the next 12 months. But I think we're in a good position, and we'll continue to execute.
Great. I'm excited to continue to follow the progress. Thank you guys for being with us.
Awesome. Thanks, Ted. Appreciate it.