everyone, or still good morning. It's 11:30 A.M. But welcome to the Citizens JMP Life Science Conference. It's my pleasure to introduce Sana. Presenting for the company is Nate Hardy, CFO of Sana. Welcome, Nate. I appreciate you being here. Thank you. I never know exactly who's in the audience or who's listening in on the webcast, and whether they know the Sana story, so I always like to start off these Q and A's with maybe a two to five minute overview of what, you know, Sana Biotech is about. Perfect. Sounds good, and thank you for inviting us, and JMP, we're happy to be here. Before I start, I will be making some forward-looking statements, so I do wanna point everybody to the risk factors. We've published our 10-Q last week for the first quarter. So for those not as familiar with the Sana story, just a little bit of background. You know, Sana was founded with the goal of using engineered cells to treat a broad set of very prevalent diseases, and to do that, there's a number of challenges. But the most fundamental challenge that we saw was overcoming allogeneic rejection of cells, and for those that are not familiar, if you take cells from one person and you try to use them as a therapy in another, that person's immune system is gonna recognize them as foreign, and it's going to kill them quite quickly. You really have to figure out how to make these cells persist long enough so that they can last and have kind of a therapeutic benefit. Where we are is we have a hypoimmune technology, and you know, with that hypoimmune technology, we've shown in all sorts of animal models, mice, humanized mice, non-human primates, that we can overcome this allogeneic kind of transplant rejection. And we do that by knocking out MHC class I and II, which people have known for a while will kind of take care of T cells and B cells, meaning they'll avoid those cells. But as soon as that happens, NK cells recognize them and come in and kill them quickly. And so in addition to the MHC class I and II knockouts, we overexpress CD47, and the combination of those has shown to be effective, and really, 2024 is the year where we're gonna see if our preclinical results really translate to the clinic and to people. And, you know, we've said we expect 40-60 patients worth of data. We shared earlier in the year in our first trial, ARDEN, which is a CD19 allogeneic CAR T, that the initial immune data looked exactly like it did in the preclinical trials. It was only four patients, so early, and more to come. And if you think about where we're taking this Hypoimmune technology, we have two platforms. One is allogeneic CAR T cells that use the Hypoimmune technology. There, we're going after blood cancers, as well as B-cell-mediated autoimmune disorders. And then we also have a stem cell-derived platform, and, you know, the first place we're taking that is type one diabetes. Excellent. So normally, when I, you know, talk about these things, I like to start off with the most advanced program and kind of work my way down, but investor interest is actually a little bit, you know, topsy-turvy with Sana. The earlier stage programs are what have got investors very, very keenly focused on Sana Biotech, and especially your diabetes program, and so maybe we'll start off there. What, you know, I guess, really excites you about this opportunity? I mean, we know the markets are large, but this is such a differentiated, you know, way of tackling diabetes. Would love to kind of hear more about that, and while we're thinking about that, what do you think are the kind of major hurdles as you set the stage with this program? Yeah, no, it's a good question. We do have a number of programs, but there is a lot of focus on type one diabetes, and I think for a good reason. If you just... I mean, one, the disease, I mean, it's. There's, you know, over eight million people worldwide that have type one diabetes, I think. Second, if you just kind of look at what's been done in the field, cadaveric islet transplants, where they take kind of a donor from an individual that's recently died and transplant those into a type one diabetic with a lot of immunosuppression, they've been able to show that the patients can achieve euglycemia for as long as the patient can withstand immunosuppression. Second, you've seen what Vertex has done with their stem cell-derived program, where, again, with immunosuppression, they've achieved euglycemia. The challenge is that, you know, for most type one diabetics, the thought of immunosuppression is not a good, good solution. I mean, they'd be better off with insulin. So to really create a scalable treatment, you have to have something that takes care of the immune system, and so what we're doing and what we plan to take forward in the clinic is a program called SC451, and it's a stem cell-derived program where we are taking beta islets, and we are making our hypoimmune edits, and the goal will be to, you know, treat type one diabetes. You know, that program is a bit further out there. We haven't said when we'll file the IND. So to start, what we wanted to do was to use a proof of concept where we were able to really establish that the concept works and the hypoimmune platform is performing as we think that it should. And so what we're doing is we're running an IST, an investigator-sponsored trial, with a university in Sweden, and there, we'll take the process they typically do, where they select a patient and a donor. And again, it's a cadaveric, so an individual that's recently died, we will make our hypoimmune edits to them, and then we will transplant them into a type one diabetic. And the goal is that, you know, we see really three things. One, we see the cells survive. Second, we see that there's no kind of immune reaction to the cells. And third, we will see C-peptide. And, you know, for those less familiar, you know, C-peptide in a type one diabetic, they would naturally have none, because their immune system kills their islet cells, so they can't create it. And so if there is C-peptide present, it would be from these cells that we've transplanted. And so those are the three things that we hope to see, and, you know, we've indicated that we hope to share data in the first half of this year. And so, you know, given this is a really clear proof of concept, I think there's a lot of interest in it. So, you know, besides the fact that you answered all my questions, let me dig in a little bit, a little bit more there. With the... You know, call it the internal bar, right, for UP421. You mentioned that we're expecting data in the first half. Yep. You talked about the three, you know, kind of metrics that you're looking for, but when you're looking at cell survival, or you're looking for C-peptide, you know, what kind of number? You know, I guess, what kind of numbers are you looking for, right? Is just a little bit fine? Do you expect it to increase over time? How should we be thinking about it? What's your kind of metric that you look for, for kind of a go, no-go decision? Well, maybe if we start... I mean, I would break it down into kind of the cell survival, immune reaction, and then the C-peptide presence. And the first, I mean, if you talk to the individual behind this program, Sonja Schrepfer, she would tell you that, you know, if you look at kind of transplant medicine, there's really no kind of allogeneic cells that survive without immunosuppression for longer than, like, five-to-seven days or something like that. So if, you know, we start to get out two weeks, and these cells are around with no immune suppression, you know, it starts to feel like you have overcome that, because there's not a whole lot of known things in the immune system that would kill those cells. And so there, I think we're gonna know very quickly. C-peptide is, is the same concept, because again, naturally, these patients would have none. We get the question a lot around kind of the specific level of C-peptide, and I think the reality there is, you know, if they have any presence of C-peptide, we know it has to be from the cells. But defining a number, I think, will be really challenging in this study. There's just too many variables if you think about these transplants. One, you know, there's the donor, and kind of the quality, and kind of what happened to the individual, kind of as they passed away. And then pulling them out, how successful were you? And then you have to take our edits, and when you make the edits, it kind of beats up these cells anyway. Mm-hmm. And so how many we ultimately are able to transplant, I think there's just too many variables to try to set an expectation around, like, levels of C-peptide. Okay. You mentioned in the first half, so we're only, you know, a month or two away. You know, how do we think about this data? Well, I guess the first question is, I would think that we're gonna get data on, like, one patient. I mean, it, it's not, like, the easiest of trials to, you know, enroll. You have to be very, very specific on not just the donor, but the patient, right? You wanna make sure- Yeah ... everything is lining up as you, you know, evaluate this. Am I right? Is it, you know, just really gonna be about a patient's worth of data? And then secondly, as we think about moving UP-421, moving this data to augment SC451, right, or SC-451- Yep ... you know, how much data do you think we'll need, or is it just a brand-new IND, and you have to kind of start from scratch? Yeah, I think, I mean, if you start with that last point, they would be two very different INDs. One is a stem cell-derived product, which we have kind of much more control of, and the idea is to be able to scale it, to treat kind of thousands and thousands of patients. I mean, that will take us time, but, I mean, that's the goal. With Uppsala, I mean, it really is a proof of concept, UP-421. It is a proof of concept we're trying to test. You know, can we hide the cells, and can we see kind of C-peptide as proof of those cells surviving? You know, we've said before that if we see one successful patient, you know, we may not go further. In fact, I mean, I'm not sure how much shareholder money we want to invest in kind of a product that we're likely not going to commercialize, and so this is really about learning there. You know, I think you could argue that there are things we could learn about transplanting into the forearm, and so, you know, maybe we could make a case that we do two or three. But yeah, I think we've been clear that, you know, if you get one patient that sees those three things, the, you know, cell survival, immune evasion, C-peptide, out about 30 days, you know, given our focus on hypoimmune, it becomes material. And so we're likely gonna have to say something one way or another. Okay. Last question on this program, and we'll move to autoimmune. Who do you see as your biggest competitors? You know, we have injectables. You mentioned Vertex. I'm sure there are other players that you're, you know, kind of keeping an eye on. It is a pretty competitive space. I've seen players kind of fall behind and fall away as well. Yeah. Yeah. No, no, I mean, I think that honestly, I think this is a case where we can say that you know, the focus is on the disease. It's hard to worry about competitors in a space where I think the biggest challenge for anyone that's successful is going to be making enough to treat the patient population. I mean, if you just assume that everything works in this therapy, and it avoids the immune system, that kind of one treatment is enough to cure a patient of type one diabetes, and then you assume that, like, we could get up to treat about 100,000 patients a year, which from where we are now, you know, that's gonna take significant investment, and I would say time. If we do that, you know, after 10 years, we will have treated about 20% of the total population of type one diabetes patients. So from my perspective, there's room for kind of multiple players here. It's not really about kind of the competition, it's about just getting this to work. Okay. That sounds great. Let's switch gears to SC291 in autoimmune diseases. Sounds great. So, you know, autoimmune, for all of you in the audience, in the webcast, you know, this has been an area of significant investor interest. A lot of CAR T players are pivoting, right, to, to autoimmune, 'cause we've seen some pretty profound data. Maybe, you know, just to, to ask you, can you talk us through the rationale for evaluating SC291 in, I think it's, you know, several, right? It's lupus nephritis, it's extrarenal lupus- Mm-hmm ...... ANCA-associated vasculitis. Kind of, you know, why you're thinking about kind of all those. Yeah. Yeah. No, so maybe to even step back, you know, our SC291 product, which we're going into the indications that you mentioned, it's a allogeneic CAR T, where we make the same hypoimmune edits. And, you know, it's the same drug product that we actually use in the ARDEN trial, which is further, furthest along. And because of that, we were able to kind of leverage the same safety data and all of that, which allowed us to get kind of the three indications that you mentioned. And the two things I would say about kind of the rationale there is, you know, we lupus nephritis and extrarenal lupus, there's been a lot of data that's come out, you know, starting with the kind of German institution, Georg Schett, and then others have released data. So I think getting early data that's easily comparable to others is important. With kind of ANCA-associated vasculitis, you know, publicly at least, we're the first ones that have an indication going after that, and so I think it's a place where there's a little more clean space for us to kind of expand. And as you think about how we kind of go into autoimmune more broadly, I would assume we'll take a similar path, you know, going into some diseases where others have proven that it's working. But it's... There's so many diseases that are caused by B-cell mediated issues, that we could potentially look for other places that are more of kind of a clean space that we could operate. And in terms of what we want it to look like, you know, our perspective is autologous seem to be working. You know, our goal, similar to on the oncology side, is to make an allogeneic cell that works as well as an autologous cell. But where we believe we have one big advantage is, you know, when they treat a patient, they have to do a manufacturing run. When we do a manufacturing run, we make doses, you know, 400 doses, if you kind of assume the middle dose of our ARDEN trial, which is, like, 120. Got it. As we think about, you know, how many... That data is also expected in the second half. So you have a really, you know, impressive and exciting second half that's shaping up. If you can just kind of guide investors or talk to us, you mentioned 20-60 patients worth of data in this year. I don't think that's per, you know, trial- No ... that's just total. So how are you thinking about, you know, how many patients worth of data you might see, and what... You know, how you would guide investors to kind of look at this data? Yeah, what I would say is, the 40-60 number is... You know, the trial that started last year was ARDEN. And that, again, is treating kind of NHL and CLL patients, and kind of B-cell malignancies, and there, you should expect the most of that 40-60, just given it's going on. I do think on the autoimmune, kind of in those three diseases that you mentioned, you should expect data this year. And you know, I think our view is, given what others have shown, it doesn't take long to see if you're having an effect. So, you know, in a number of patients getting out 3 months, you start to understand if you have something. And so I think this year we will learn, you know, meaningful information about SC291 in autoimmune. What do you think are the key, kind of, you know, metrics there that you would like to, you know, kind of, kind of evaluate, right? When we were talking about UP-421, right, you mentioned cell survival and C-peptide, and the like. How about here? You know, what is kind of the metrics, if you will, for that go/no-go decision? Yeah, I think the expectation should be that we look a lot like what we've seen with autologous. So after three months, you know, the disease is gone in many of these patients. And, you know, our view, again, is that autologous work, and so our goal is to create an allogeneic that looks like it. Yeah, I think those are the big things. We have, you know, autologous to kind of compare it to. I think there are other modalities as well that are being explored. Am I right about that? Are bispecifics being explored or, you know, could they be explored? It seems like it's a, you know, it's becoming, again, a very heated, competitive space. Yeah. But the answer might be, much like with diabetes, it's such a large, you know, space, that there's gonna be multiple competitors. Or maybe there's a, maybe there's a different answer. I'm kind of curious how you- No ... how you accomplish it. No, I think it's. There's you're seeing a lot of a lot of different approaches right now. I mean, you do see numerous bispecifics, you see NK cells. There's, you know, a number of different approaches that I think we're gonna learn a lot about this year. I think it's a bit too early to say kind of if they're working or not. I think that the two things that, you know, we know are, one, you know, that autologous works, so you wanna look as close to that as you can, and two, the other thing that, you know, most of the KOLs seem to be saying is you need really deep B-cell depletion- Mm-hmm ... kind of all the way down into the germinal centers. You know, I think the one thing that CAR Ts have shown, or CD19 CAR Ts have shown over the last kind of five, six years is, you know, there's not a better B-cell depleter out there. And they do get deep. So... Yeah. So let's switch gears to SC291, but in- Mm ... oncology indications. Mm-hmm. Right? You've talked about ARDEN. You mentioned, you know, we've had four patients' worth of data. You know, clearly the lion's share of the enrollment of patients will likely be in this study. You know, what kind of... What do you expect, if you will, when this next data update in the second half, you know, comes up? What do you want investors to kind of focus on here? Is it an improving efficacy profile and sort of the same safety profile? Is it even, you know, longer duration of the cells? Like, what's the key things, you know, that you want people to focus on? And do you think we'll be able to get to an RP2D by the second half of this year? Yeah, we haven't commented on the last question, so I'm not gonna answer that one. Okay. But what I will say is, you know, I mean, one, you know, from our perspective internally, and I think externally, when you're kind of looking at NHL in specific, you know, people wanna see data in a number of patients that's out kind of six months to start to see those complete response rates. And, you know, I think that people should expect, kind of as we get towards the end of the year, we're gonna be able to share data on kind of a number of patients that are out that far, and I think that helps us start to understand, you know, are we... You know, do our hypoimmune edits help us turn this into a viable therapy? You know, from a safety perspective, you know, we'd want it to be consistent, similar to efficacy with kind of autologous and what you're seeing there. You know, our early safety, you know, in the four patients that we talked about, there was no safety, no CRS, nothing. You know, I would say that was at our kind of lowest dose level, 60, and then a few patients at 120. We've since said that we've moved on to kind of our third kind of dose level, which is 200. So again, I would expect data across all of those as we get towards the end of the year. You know, when I think about the allogeneic space, right, as a whole, trying to compete with autologous, in cancer, it's been a tough nut to crack. Mm-hmm. You know, and I think, you know, the messaging has shifted to, well, you know, if we can perform almost as well, but we have enough product, right, that's out there, we can, you know, kind of, overcome the manufacturing- Mm ... kind of hurdle that's there. Do you think that's still the key hurdle that's out there? Do you think we can actually beat, you know, in efficacy as well? I think, you know, I think we've been clear that we hope to be as good as autologous in efficacy, and I think, you know, they've proven that these work. And so I think that should be the expectation, is that we are as good, and I think even then, I mean, they're entrenched, so it takes time to get there. But I think eventually the manufacturing is, it's helpful. Yep. But again, I think you need to see multiple patients out six months. I mean, allogeneic, as you said, I mean, there's been a lot of players that have kind of tried. I mean, from our perspective, we could have predicted a lot of this. I mean, ultimately, the cells have to survive long enough to have the benefit that you want, and, you know, I think a lot of the other allogeneics get killed quite early, before they can have a benefit. Yeah. So, that's what I asked you, actually liked, and we pointed out to investors, the data that came out at ARDEN- Yes ... right, I thought spoke volumes as to, you know, how these edits are, you know, ultimately looking in a very, very tough- Yeah ... you know, patient population and disease indication, and you know, ones with different immune signatures. I think it gives a great prelude as to how, you know, it may look in maybe, quote, "less severe" type of patients, right? Am I thinking about that correctly? Or, you know, or do you think that each disease indication is different enough, that we need to really see the signal from each? I think we need more patients in each to really start to see. I will say, we also were really encouraged. I mean, it was only four patients, but, you know, in those four patients at lower doses, to see three partial responses and two complete responses, we were certainly encouraged by that. Combined with the fact that the immune assays that were run also showed that we avoided the T cells, B cells, antibodies, and NK cells. Excellent. So in the last kind of, you know, I think we're done, but 15 seconds, let's say, just can you remind us of the cash position of the company and just kind of sum up in, for the remaining, you know, months, what to expect? Yeah ... what investors should expect? No, absolutely. So we finished the first quarter with just over $310 million on hand. We've said we'll burn less than $200 million on an operating basis. I would say it's not significantly less than $200 million. And, yeah, so we're in a place where we're gonna need capital again, but, you know, with these 40-60 patients across the four programs and seven indications, I think we're gonna learn a lot before we have to raise that money. Excellent. Nate, thank you very much. Really appreciate the time. Great. Thank you.