Sana Biotechnology, Inc. (SANA) Earnings Call Transcript & Summary

Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Tess Romero, and I'm one of the senior biotech analysts here at JPMorgan. Our next presenting company is Sana. And presenting on behalf of the company, we have President and CEO, Steve Harr. Steve, over to you.

Thank you, Tessa, and thank you, JPMorgan, for having us here, and I appreciate everybody joining us here in the room and online. I think you probably know, we'll make some forward-looking statements. Take a look at our 10-Q for our risk factors. I really appreciate the chance to tell you a little bit about what we've been up to. And we started this company not that long ago with 2 main goals. And our real drivers were to be able to overcome allogeneic rejection in cell therapy, meaning if we really wanted to make this cell therapy a universal and widely available therapy, we had to figure out how to stop rejection of foreign cells. So if you put someone else's cells into your body, your body will see them as foreign and reject them. And so our first goal was to do that. The second goal was to figure out how do we deliver genetic payloads to cells. It's really easy to do everything in a petri dish now across the genome. And the hard part is getting the genetic material in the cell. And I'm thrilled to tell you we've made some real progress across both of those. And we brought focus. And so the focus of what we're trying to do with immune rejection is now around type 1 diabetes. And we'll get into this more, but this is a really large disease. It's a disease up until a little over 100 years ago, it was an immediate death sentence within a few months. With the advent of insulin, patients live, but it's still an area with a lot of unsatiated demand, and we need better alternatives. We made a lot of progress last year. We showed that we could transplant cells and evade the immune system. We made a master cell bank, which we'll talk about. We've made a lot of progress on manufacturing. And we had a chance to talk to regulators from many parts of the world and really align on what we are going to do going forward. We hope to file our IND this year and begin the Phase I study. And one of the things I want to outline for you is this is a therapy where the proof of concept and the -- is very quick. And we should know if what we saw -- if we're able to evade the immune system, if we're transplanting really functional cells. And if we're able to meet our goal, and our goal is very clear. It's a functional cure of type 1 diabetes. Moving over to the in vivo delivery side, and we've made a lot of progress there as well. And we're focusing on CAR T cells, and that's what we're going to talk about today. We actually could do other things. Even a few months ago, we published in Nature Biotech delivery to HSCs or hematopoietic stem cells, gene editing, base editing agents. But I think most of you know CAR T cells have been really transformative for many people with blood cancers. And it looks like they're going to have a big impact for people with a number of autoimmune diseases. Unfortunately, they're not for everybody right now. And only about 20% of people even in the most saturated markets who should get these drugs are getting them. And in vivo CAR T cells, where there's been some progress, really give us a chance to get rid of the conditioning chemotherapy that patients have to ease delivery, to have them available off the shelf and to hopefully democratize access. And I think what we can show you is that we've made really real progress here. And if you were a monkey, which I know none of us are, I would be very confident in telling you I think we have a best-in-class therapy. But what we -- we had the opportunity to do this year is to actually prove that in humans. And we do believe we'll be able to deliver you some data from this platform in 2026. So taking a step back, type 1 diabetes, I was -- like many of you, when I'm trying to figure out how a new problem or a new way to articulate something, I decided to have a little dialogue with my favorite chat box. And I asked some questions and how long does a patient who's diagnosed with type 1 diabetes, what's the impact on their expected life if they receive best therapy? And they said about a decade. So that's right. So I knew it was on to something. And I asked to compare it to what it was like if you were a 20-something year old and you were diagnosed with type 1 diabetes. It was shocking. You are better off being diagnosed with breast cancer or HIV than you are with type 1 diabetes on the simple metric of how long will you live. We have a lot of work we need to do to make this a better outcome for patients. The second thing I asked you was if we were able to cure it, like what's the equivalent number of people? And if you could cure type 1 diabetes, it would be equivalent in the United States of curing both HIV and multiple sclerosis. So this is a very large unmet need. This is a place where patients still are not receiving adequate therapy. And even in that time, their burden is so much more than any other disease, every meal, every time you exercise, every time you get a little bit sick, you're having to modulate your insulin and your food intake and they have a daily burden around that. And in that time, they have risk of blindness, amputation, heart attacks, stroke, and we can do better -- and kidney failure. We can do better. So we know what the disease is. The disease is actually relatively straightforward. The patient's immune system attacks and kills the pancreatic beta cell. The pancreatic beta cell is the only cell in the body that makes insulin. I'm going to talk about both beta cells and islets and just think of islets as beta cells and their support infrastructure, right? So our goal is quite simple. We want to make a onetime treatment that leads to normal blood glucoses, where patients no longer take insulin and they receive no immunosuppression. And all of the component parts are here now. So about 25 years ago, James Shapiro in Canada began transplanting islets that were isolated from a recently deceased person, so cadaveric islets, and he would transplant them into people with type 1 diabetes. And these people, many of them have been able to stay off insulin for 10-plus years. The challenge is it's not a very good supply score. It doesn't scale, and there's a lot of variability in the types of islets that come from someone who recently died. And the second is patients have to remain on long-term immunosuppression, which leads to risk of cancer, infections, kidney failure, liver failure and other things. And there just aren't that many people for whom lifelong immunosuppression is better than lifelong insulin. But thousands of people have gotten this therapy. Over the last several years, several groups have shown that you can take pluripotent stem cells and make them into islets and transplant them. And you actually seem to have solved some of the challenges of product variability, very, very predictable and robust efficacy in doing that. Unfortunately, though, the patients still need to stay on lifelong immunosuppression. And what we've shown, and we'll show you a bit more data here in a couple of minutes, is that we can eliminate the immunosuppression. And therefore, now all of the component parts are together to make a cure. And they're big enough -- that each of these individually was a New England Journal of Medicine paper, the ultimate arbitrary of clinical data, ours came out over the summer, take a look at it. But these are -- this looks like now we can do this. So how did we do it? Allogeneic rejection is basically your immune system recognizing these cells as foreign and kicking them out. And so there are 2 parts of your immune system that we have to grapple with. The first is the adaptive immune system of B and T cells. And the way we deal with that is we knock out MHC Class I and Class II. That's relatively straightforward. Others have tried it. The challenge is once you do that, you have something called the innate immune system. And the innate immune system will immediately and particularly NK cells kill those cells. And so the company's insight, our scientists insight was that overexpressing CD47 in the context of knocking out Class I and Class II overcomes both the adaptive and innate immunity. So we've published a lot on this. We've shown this not just in our labs. We've done this in mice, in humanized mice, in nonhuman primates, and we've done this in oncology. And now we've done this in a patient in type 1 diabetes, and they've been published across a number of high-profile journals. So take a look if you really want to dig into our science. And I'll spend a little bit around this clinical study now because it is really important in showing how we can overcome immune rejection, both allogeneic, meaning someone else's cells and the autoimmune, meaning the type 1 diabetics, preexisting immune response to pancreatic beta cells. And what we did was in collaboration with a group in Sweden, there was a donor pancreas from a person who was recently deceased. It was a 62-year-old person, it actually had relatively high hemoglobin A1c of 6.2 and took those cells and gene modified them, knocked out Class I and Class II, and we knocked in CD47. And then we took those cells and put them into the arm of a person with type 1 diabetes. The patient received absolutely no immunosuppression. The patient had diabetes for over 40 years and made 0 insulin, had a documented negative C-peptide for many, many years. And we look to see what we would find. So it was a low dose first-in-human study. So the first thing we were looking for was safety. The second thing we're looking for is immune evasion. And the best way to figure out those cells are really still around and functioning is to look for something called C-peptide. So when a beta cell makes insulin, it actually makes pro-insulin. And as it's secreted out of the body, that is cleaved into insulin and C-peptide. So measuring C-peptide is a 1:1 molar ratio of how much insulin you have in your body. And so that's really the goal. The goal is safety and see if these cells would survive and function. So I'm happy to say the patient is now out over a year. He's doing well. He continues -- we haven't had any drug-related or potentially drug-related adverse events. The cells are surviving. The cells continue to function. We can see them on PET, MRI, and we continue to have immune evasion. So I'll show you the data here. So you have on the left is C-peptide. And you see at baseline, it's undetectable. And you can see on the right hand actually, even with a meal, the patient secretes no C-peptide at all. And then you see on the left-hand side that you continue to be able to detect C-peptide now out at a year, at 9 months in a year and that you continue to see some level of increase with a meal. Now it does look like the C-peptide levels are coming down a little bit over time, not unexpected as we talked about. The way we would -- we don't expect these cells to live forever. If their donors old, and this is someone who -- this is a low dose and these cells are stressed. They're working 100% of every day. And so what we were looking for is if they went down very quickly, we should think it might be an immune attack. If they go down gradually, it's probably just the cells petering out as they get older. And so we have no evidence here of immune response and a continued function of these cells. So we're thrilled of what we're doing. And you can see these cells on PET, MRI. This is a PET scan where the reagent that's given recognizes beta cells. This is a PET of the [ 4 arm ]. We don't have beta cells in our arm. They're in our pancreas. And so very clear pictorial evidence that these cells are continuing to survive and the function as normal beta cells in the arm of the patient. And then we did an immune analysis. So one of the lemons of what we did is that when you make these cadaveric islets, some cells are fully edited and some cells are only partially edited and some cells actually got no gene editing at all. And they were all transplanted in the patient. And making lemonade out of that lemon, we've been able to take the drug product and test it over time against the patient's blood and to see what really happens, we have any evidence of an immune response. And we've done B cells, T cells, NK cells. We can get into the details, but this is just looking at everything in the patient. And what you see on the left is if you transplant a cell, it takes -- actually, there's no reaction at very baseline because -- but -- and it takes time, really just like a week, and they develop an immune response that rapidly kills unedited cells, normal unedited cells from the donor. And that remains true even after 12 months. If you have partially edited cells, we've knocked out Class I and Class II. Now you have this -- we talked about this NK cell thing that's set up to kill those things. And there, you can see that they would kill that today, kill at baseline, it kills it at 12 months. And in the fully edited cells, what you see here is that they can completely evade immune detection and these cells survive and thrive in -- at least in this in vitro assay. So we're quite excited to say that we've now out over a year. The patient continues to do well. He continues to make his own insulin for the first time since the 1980s. And we have evidence of survival both by C-peptide and by MRI, PET scan and no evidence at all of any immune response to these cells. It's not really our goal, though. Our goal is to [ make ] a scalable therapy. I'm not touching anything, by the way. If that's going to happen. I apologize for the...

Is it possible to sit down? And continue on your presentation with that mic right there. And just go ahead and go with the...

You want me to sit down?

Yes.

I don't like sitting down. I'll step back. I have too much energy to sit down if you guys know me. So I'll try to step -- stay back from this and not touch anything on the stand. The -- our goal though is to take a single stem cell. And what we had -- we took is an o-negative stem cell, meaning it's a universal donor, gene modify it once and make a master cell bank. And that single stem cell then becomes the product that we make forever into islets for patients. And so you take a stem cell, you grow them out, you then differentiate them into islets, you store them and you deliver them hopefully as a single therapy into the muscle of a patient. And again, the goal is quite simple. treatment, no insulin, no immunotherapy, no more fingersticks or monitoring and no immunosuppression, right? And our goal is to file the IND, I'll show you and begin our Phase I study this year. The -- we made a lot of progress last year. I just told you a little -- if you take a step back, a few years ago, we outlined 4 scientific challenges to really making this work. The first one is to overcome allogeneic and autoimmune rejection. I think we've done that, and you can see -- the human data show you that. The second is to make a gene-modified master cell bank that doesn't -- that can continue to make pancreatic beta cells, but that doesn't create genomic mutations. And it's been a huge problem in the field. If you look just through the literature, you see BCOR, p53, these cancer-causing mutations showing up all of the time. And we've done that. And we've done it not only in a research setting, we've now done it and released it with our GMP, master cell bank. We've aligned with regulators from around the world around how we're going to test this and take this forward. It's a gigantic accomplishment for the company. We've begun the tech transfer our Phase I process into our CDMO. We're working really hard on -- sorry, the other 2 things we're making the product at a -- out of potency, purity and yield for Phase I. We can do that. And we've started to move that into a CDMO. The third is -- fourth is to make this at a purity, potency and yield to treating a disease of 10 million people. We have a lot of work to make that happen still, and we'll talk a little bit more about that. That's the scale-up work. But we started to do that and make some progress. We've had this great opportunity to have dialogues with regulators from many, many parts of the world. And we have alignment around the master cell bank, the preclinical testing plan, a lot of the manufacturing, and we're beginning to get the final alignment around what the clinical program looks like as well. We're in the middle of our -- the nonclinical testing that needs to be done to move this into humans. That will be done hopefully later this year. And we've actually started to really get the sites going to start our Phase I study. And so this is -- feels like it's been a ways off, but it's starting to turn really real. So what do we have to do next? We have to finish our nonclinical tox studies. We have to finish the tech transfer and make the material for Phase I. I really want to make progress in scaling for commercialization this year. We have to file the IND in the United States and the equivalent. We'll do this in more than one geography from the outset and start our Phase I study. And that's really what we're looking to do in the near term. And one last thing. So Phase I is going to actually be really, I think, straightforward to understand how well this works. Remember, we knew within a few weeks after transplanting the cadaveric islets if this had really -- this had evaded the immune system and these cells are functioning. Similarly, we hope to see very early immune evasion and endogenous immune insulin production through C-peptide. That should be pretty straightforward. We should be able to get insulin independence within a matter of months. And so it's not that far away before we're going to know the answer to whether or not what we have is actually going to be work, potentially be scalable and to really be transformative for patients with type 1 diabetes. So I want to move and talk a little bit about this in vivo capability. It's been a while since we really delved into it together. So taking a step back, we're always looking to leverage insights from Nature to figure out how we do this. And the way we've gone about making cell-specific delivery is to modify something called a paramyxovirus, one of the paramyxoviruses so that it's specific for the cells we're targeting. And think of a paramyxovirus, it's got 2 components, a logicated system to get into cells. There's a G or guide, and there's an F, which is fusion. So we mutate the G, so it recognizes nothing. We then put in a receptor or something that will recognize a cell surface protein. And when it binds, that G undergoes a confirmational change that tickles the F. And then the F will deliver payload on the right-hand side directly into the cytoplasm of the target cell. We don't go into the endosome, and that's really different than other mechanisms. And it leads to cell-specific delivery directly into the endosome for a patient. And so the way to turn this into a CAR T cell, I think many people understand this, that little fusosome, think of that as our medicine, and it will specifically target just a T cell. And it will deliver the genetic payload, which is in the middle panel is that little blue minus sign. And that will encode for a gene -- it's a gene that encodes for a protein that makes the chimeric antigen receptor, the yellow kind of wise on the cell surface. And that CAR, when it sees a target cell, whether that's a B cell or a tumor or a plasma cell, whatever we're trying to go after, we will do 2 things. It will kill its target and it will divide. And so then you get amplification and more and more drug available to take out all of the tumor. And then when you've cleaned out the body, they just kind of recede and go away. And so hopefully, this allows us to eliminate the conditioning chemotherapy. It simplifies manufacturing. And because we're not manipulating the cells out ex vivo like in a CAR T cell, we should make better T cells as well. So we made 2 really critical assumptions. It's a competitive field that we made 2 critical assumptions when we started this program. One, cell-specific delivery matters. You don't want to go into other cells. We think that lowers off-target toxicity risk. It definitely lowers immunogenicity risk, we can go through some time, and it improves manufacturability. If you're delivering a lot of your product to the liver, you have to make a lot just to get it to the T cell. The second is we think that integration of the DNA into the T cell is super important. And the reason being that you're super optimistic and you think about making 100 million CAR T cells, you have -- we each have hundreds of billions of B cells, let alone tumor cells in our body. And so to really take a drug where you're only delivering a small number of the actual active pharmaceutical ingredient and eliminate many, many, many target cells, you're going to have to get some level of expansion. If it turns out those 2 things are wrong, others will have simpler solutions like mRNA and LNP. But this is the assumption that we made to move forward. So a few years ago, we were moving forward a drug called SG299. We ran a GLP tox study. It was 8 monkeys in the treatment arm, different doses, and we had a control arm. And we -- our fusogen, the way we target the cell has cross-reactivity between humans and this nonhuman primate, but our CAR didn't. So it makes it a really great model to see pharmacokinetics or what is -- where does your drug go? It doesn't make a great model for efficacy and how does it really work. And what you see here is we've got very potent dose-dependent transduction of the target cell in the animals, let's call it, 15%, 20% -- we then looked -- and this is something that's very unique to our platform. It was a very specific delivery. And you see no off-target cells, I should say, delivery to the liver. You see nothing in the testes. We can show other cells like HSCs and things. This is a cell-specific delivery, which is very, very important for safety. But we then worried that we didn't have a really good way to test efficacy. And as we did test efficacy by changing the CAR, it works, but it probably didn't work well enough. And so we really went back and spent the last couple of years figuring out why. And a lot of this has to do with restriction. Our T cells don't like to have these viruses transduce or infect them. And what we learned is that you can overcome that restriction in several different ways. One of them is a novel fusogen that we use. The second is that we'll show you, we did some other work to it. And finally, we wanted to minimize -- so it turns out when you make these virus-like particles, not only do you have the fusogen on the cell surface, the CARs on the cell surface, right? And that can lead to immunogenicity risk and delivery of your payload to the wrong cells, maybe the cancer cells. You don't want to do that. So we got rid of that, and that's our new drug. That's where we are today, and I'll show you a little bit of that. So what that looks like is, number one, we changed the fusogen. Number two, we add a little bit of CD3 at very low doses. At higher doses, if it's kind of -- you'll overstimulate the T cell. And you see that sometimes with very rapid fever and cytokine storms and things like that within a few hours of transduction with other therapies. And the third thing we did is we got rid of the CAR on the cell surface. So this is just a little bit about the novel fusogen. On the right-hand side is a way that I think many people do this. They use a fusogen called DSPG, which is what's our normal lentivirus. They blind it and they put a target agent on it. And you can see on the top row, it gets into T cells, but you see in all the other rows, it gets in a lot of other cells as well. The second is the middle column is our old drug, SG299. And you can see it gets into T cells like we hope. It's a lot better specificity, but it still gets into -- the PHH stands for primary human hepatocytes. So it still can get a little bit in the liver. And what you see on the left-hand side is an exquisitely specific delivery and doesn't get into other cell types. So then we went to do this in monkeys. And again, here, we used a surrogate because the CAR doesn't cross-react with the monkey B cell. So what we were looking for is this -- we use a CD20 CAR instead, is can we deliver this safely, right? Look for -- do you have fevers, other things? Do you have -- can you get CAR T cells to show up in circulation? Can you get rid of B cells and then we did biopsies and necroscopy just to see what else we can see. And the results were exactly what we would hope they would be. This is just a high dose, but what we do get is a dose-dependent. You see these CAR T cells expand just like they do if you put them in and make them in a manufacturing facility. The second thing is you look in the blood and we get rid of all of the circulating B cells. That's the target of the CAR that we have. We then looked at the lymph nodes, and you can see that they're clean and that's a real measure of deep B cell depletion. And finally, on the right, you have this B cell reset. And one of the things that happened over the last couple of years is as CAR T cells have moved in the autoimmune setting, Georg Schett and others have displayed -- have shown us that if you can get this B cell reset, that predicts maybe a long-term care for a person with these diseases. So this is a great result for us. We did the necroscopy as well, and we didn't see any cells and other tissues. And so we're ready to move forward. We think there's a potential here. We have a best-in-class in vivo CAR-T platform. It works in CD19, but it also works in a whole bunch of other areas. It's pretty modular. It takes a few months' work to add BCMA, CD22 and others. We hope to have our first trial going this year. We'll probably start in cancer and move very rapidly into autoimmune diseases. And we think we'll be in a position to report out clinical data sometime this year. So we think the next 12 to 18 months can be really exciting and important for the company. There's a lot of validation that a functional cure of type 1 diabetes is possible. It's a real unmet need. What SC451 does, that's the name of our drug product. It assembles all of the component parts into a single therapy that we hope can -- it is scalable, and we're going to file our IND and start our Phase I study, and we hope to have very rapid proof of concept. We think it can happen pretty quickly. And with the fusogen, as we said, we're going to be moving forward with what we think a drug that has a best-in-class profile. We have to show that in people. And our goal is to begin to show you human data as the year progresses, and really to help you understand how this translates into people. So with that, I think we're going to have a little conversation, aren't we, Tessa?

Yes. Thank you so much, Steve. Always a loaded and robust presentation from you every year. So it seems like, Steve, you feel comfortable enough with the pushes and pulls that you need to complete before you can be in the clinic with SC451 to provide that fine-tuned and definitive guidance today of 2026. Can you just clarify how much work do you need to be manufacturing ready for Phase I versus commercial? Can you help us just understand the distinctions between those 2?

There's a lot to be done. So Phase I think the question is -- can you hear me?

Yes.

Okay. I think just -- I'm going to interpret the question is how much work -- how much difference is there between Phase I process and kind of a commercial. There's a lot of difference, right? And so a Phase I is pretty simple. It's kind of like let's just say it's going to be 10, 15 patients, right? And this is a disease of 10 million people. And so that's a completely different scale. And the challenge in moving to that scale is several fold. But the biggest, as you think about just regular biologic manufacturing, the way I kind of simplify this, is that what you're trying to do is you have a cell line and you want to just pump out a protein, right? And so to do that, you want a very consistent and constant environment to maintain that producer cell health. Here, what we have to do is you have to take these stem cells and you have to drive them or differentiate them from -- you start a stem cell, you go to endoderm, you then go down the path of like making it foregut and all the way to pancreas, endocrine pancreas and then is it. And the challenge in that is that you have to continually change the environment that the cell lives in. And so if you change it super quickly, you end up with a lot of sheer stress, and that leads to genomic mutations. And we do not want to transplant cells with cancer mutations in them. If you do it slowly, the cells can kind of wander off and you end up with a little bit of GI tract, maybe a little bit of stomach. And those cells aren't terminally differentiating. They might just keep dividing post transplant. That's not truly cancer. But if we want this to last in a patient for decades, having a stomach growing in your muscle for 20, 30 years is more than a nuisance, right? And so -- we really have to work hard to maintain that purity and that genomic stability as we go across scale. And I think it's very doable. I don't think it's hard to make a lot of beta cells. I think we have to make sure we don't make other cells we don't want.

Yes. Okay. And just to be clear, is your manufacturing process, are you ready for Phase I today?

Yes, we're ready to go. We're in the process of tech transfer in the Phase I.

Okay. And what is the work...

Well, again, we -- that doesn't mean tech transfer sometimes has complications, right? And so it doesn't mean everything is guaranteed. Things can still happen and slow us down, and that's kind of it's -- inevitably is if we're trying to do something this complicated and this novel, I'm pretty sure we should all align on this. There will be a few speed bumps along the way. And we don't know what they are. We don't know when they are. And we just need to make sure we have the organizational, cultural, financial resiliency that those are just little speed bumps, and they're not determinative in the company's outcome.

Okay. Great. And can you just clarify what the nonclinical aspects you're still working on for 451?

Well, you always have 2 things that you have to -- multiple things you have to do. One is you have an efficacy model, you get the FDA, two is you have your toxicology, your GLP tox, which is kind of think of it as an animal or other safety study. And those things have to wrap up before we're ready to file.

Okay. And of course, presuming once you file the IND, you'll definitely have conversations with the FDA. But can you just give us a little bit of a snapshot of what the kind of engagement has been with the FDA on this program?

What the -- what has been?

With the FDA.

What has been?

Around the program. What the dialogue has been like?

Just what the dialogue has been about? Yes. I think a few things are true, and this is true of the FDA and other regulators. I think they have a very significant understanding of the unmet need in type 1 diabetes. And they're very, very engaged. I think the second is particularly with the human data that we have in the cadaveric islet setting, they understand the transformative potential of what we're trying to do. The third thing is they understand the complexity of what we're doing. This is a combination of novel immunology gene editing and stem cell biology. And so I don't want you to walk away thinking that this is super simple from a regulatory perspective. They're very engaged. I think they have -- they're not easy, but they're very helpful in helping us navigate through all of this and very clear in their expectations. The other thing I would say just compared to some other experiences I've had is because of the level of unmet need and maybe the proof of concept in what we've done, we have very easy -- not easy, is that right -- very ready access to people. And that's not always true as you're moving through the regulatory process. I think many people recognize you may have one pre-IND meeting or something like that or you may have an interactive a pre-IND meeting. We've had the good fortune to have a number of dialogues to help us navigate the complexity of this novel area.

Okay. And can you talk a little bit about from a Phase I trial standpoint, like you had a nice slide somewhere in your deck around your kind of potential clinical trial design. From an enrollment standpoint, like what are the types of patients that you would enroll?

We'll enroll -- it's a very broad population. Just to start with, we're not going to enroll a little kids on the outset, and we're probably not going to -- so it will be adults with type 1 diabetes. We probably don't want someone who had a heart attack yesterday just because that could complicate your safety analysis. But it's a pretty broad population without many exclusion criteria. Our hope is that we will have nice Phase I data, and then we can move into younger patients pretty quickly, whether that's 16 and then down to 12 and then lower. And we'll then start to target and add some of the higher-risk populations that have had recent cardiovascular events or something like that. But the goal here is all comers, more or less. This is -- if you -- for example, and this is a dialogue we've had with the sites. If you said, well, there's a hemoglobin A1c, they have to be poorly controlled. They have to be, let's just say, they're over 7. Patients will just let it float up over 7 and enroll in the study. And that's not doing them a service or anybody else. So I think it will be a pretty broad population of patients.

Okay. And will it be a U.S. study only?

No, we will expand beyond the United States. The U.S. and other geographies. It may be that someone says we can't do it in their geography and it might even include the U.S., but our -- every intention is that it's U.S. and other geographies.

Okay. And to me, it seems like the Phase I trial that you laid out, like it seems pretty straightforward. There's no real nuances that we should be thinking about, correct?

Well, I mean, there's complexity, right, delivering the drug, ensuring that at different sites, we've really helped them understand how we can predictably and safely put -- administer the drug into the intravascular site. But from a trial design perspective, I don't mean to insult our clinical -- our Chief Medical Officer and clinical trial team, but this should be relatively straightforward. Yes. The complexities on other parts of the development.

Okay. And can you give us a little bit of a framework for like what kind of investment is ultimately required to get this to approvability for Sana?

Through what?

From now to being an approvable product. Like what is the level of investment here really look like and as people trying to think about it, right, and the path forward for the asset?

So the clinical development pathway, as you said, is pretty straightforward. I don't expect that to be really complicated either in Phase I or kind of the registration study. The investment in manufacturing is -- could be very -- could be more meaningful. And I kind of think of scale manufacturing on 2 different vectors. One is the number of doses per manufacturing run, and that's a science problem, right? The second is number of manufacturing runs. That's generally a capital problem, right? We're still in the science problem, right? I think we have to really increase the number of doses per manufacturing run. That's people. It's not tons of people. It's tons of -- it's a good group of really smart people who understand what they're doing with different experiences. And then we'll be in the capital problem. So the amount of money we put in somewhat has to do with how much -- how big you want your launch to be, right? With 10 million people, if you just go to the United States, I'll just give you -- this kind of always gets me. If we treat 100,000 people a year, and there were no new patients diagnosed with type 1 diabetes. It would take us 100 years to treat everybody with this disease. A cell therapy with 100,000 patients per year is an extraordinary number. So we will have a lot of scale work to do. And my guess is it will be an ongoing investment, a little bit like you see in some other areas where there will be some of it that's pre-approval. There will be a lot of it that's post approval, though as well.

Yes. So it's kind of like a little bit -- little by little as you go kind of...

Hopefully more than little by little, but, yes.

But like steady through the process. Steady for the process.

Yes, steady. Yes. Agreed. Right.

Okay. What has you excited? Well, you talked a little bit about your nonclinical work with SG293. What do you ultimately want to come away with having learned about the product as we exit the year as you talked a little bit about first-in-human data.

I want to see that we can deliver this safely. And there are 2 elements of delivering this in vivo CAR T cell safely. There is an initial kind of per infusion reaction that's been seen in the field. And that can be pretty severe insulin. I want to see what we've seen in nonhuman primates, and that is that we don't have that, right? The second is we want to see that we get this -- make a medicine that makes a best-in-class CAR T cell, right? And so if this is in lymphoma, you'd like to start seeing complete responses, right. And moving in the autoimmune setting, you'd like to see patients off of therapy in a complete remission, right? So that's what we're looking for. If it's an ALL, those are all things we'll go through. You want to see patients who are in a complete response. You want to see like that -- again, safety, that normal CAR T function that you see in a really well-made autologous CAR T cell. And then you want to see that the target, whether that's a cancer cell or a B cell is gone and the patient gets to go back to the life they had before they are diagnosed with this disease.

Okay. And is it your plan to move this forward, whether it's in B cell cancers or B cell-mediated autoimmune diseases yourself? Or is this something you'd rather have a partner for?

It's a great question. Like one of the things that's so different about type 1 diabetes, I think it's not that it's not a competitive field, but it's so big and there aren't that many people who are trying to do this. If you go into kind of strategies to deplete B cells, plasma cells and track these cancers, you're pretty hard-pressed to find a large company in the world that doesn't have some strategy to go after them. And therefore, speed and breadth of the clinical program is really important. So this is an asset that should be partnered over time because we're not going to be able to move likely as a single company where we have relatively -- we're relatively capital starved with a lot of our money going and a lot of our focus going to type 1 diabetes. We're not going to be able to move as fast alone as we could with somebody else. So you're right. And we can also move that into other targets more rapidly, CD19, BCMA, oncology, autoimmune diseases. And so it will benefit from a partner over time. When? I think often partnerships are best once you have a little bit of human data. And that -- so we'd like to kind of get that taken care of here in the not-too-distant future.

Okay. Great. With less than a minute to go on the clock here, I think that might be a good place to leave it. Thank you so much, Steve, for being here.

Thank you, Tessa, and thank you, everybody, in the room. Appreciate it.

Bye. Thank you.