Well, welcome. Thank you, everyone. It's a pleasure here to host Steve Harr, CEO of Sana Biotechnology. Steve, thank you for being with us today.
Yeah, timely.
For those of you, yeah, are new to this, I'm sure you know we're not going to be making forward-looking statements a lot. So don't hesitate at all to take a look at our regulatory filings. We have all of this on-
Got it.
- Risk very tricky.
Want to check, are both mics working? Can you say something else?
Huh?
Can you say something just to check your mics?
You, you can't hear me? Should be good. Can you hear me now? There you go. There we go.
Okay, perfect. All right, great! Well, then maybe you can just start us off for those that are a little bit less familiar with Sana, and just giving maybe a two-minute high-level overview of the company, what you do, and what you're working towards.
Sure. Well, as I said, thank you, everybody, for joining us. I'm Steve. I'm making, you know, forward-looking statements. Take a look at our regulatory filings or Q for our risk factors. So the company was founded under a couple of ideas, and we had these aspirations that we'll never live up to. One was to be able to transplant more or less any cell into the body. Another was to be able to modify the genes of cells inside any cell in the body. The third was to really have access not decided by where you're born. We'll do none of those things, to be clear, but the more the closer we get, I think the more impact we can have for patients. It led us down a couple of different platforms that we've created.
Probably the most important and relevant for the near term for most investors is a platform that hopefully allows us to hide allogeneic cells from transplant rejection. And since the advent of transplant medicine, whether it's cells or organs, the major issue has been that when you put my cells into you or my organ to you, your immune system will recognize it and as foreign and reject it. And, you know, there have been two ways to get around that. One is immunosuppress the patient heavily. That comes with a lot of side effects and risks of infection. And the other has been to try to use autologous cells, which is both limited in the number or types of cells that you can do, and it's actually quite difficult to scale.
So our hope is that if, you know, we can overcome transplant rejection, which we can go through the data, I think, I think we're pretty confident we've solved the problem of transplant rejection for non-human primates. We've solved the problem of transplant rejection for mice. We've solved the problem of transplant rejection for humanized mice. And then, the real key is, does that translate into humans? And if it has, we think we have a number of really important medicines, right, on our cusp, and many of them will have some initial data over the next, you know, several months. One is the ability to make a host of different, allogeneic CAR T cells, for different blood cancers, targeting CD19, CD22, and BCMA.
In each of those, we have a validated CAR construct, which has worked quite well in the autologous setting. So, if we truly have overcome transplant rejection and our scaled allogeneic T cells live at least as long as autologous cells, we think we'll have, you know, a really important franchise in medicines across multiple cancers. The second is applying the same technology to autoimmune disorders, where, you know, we think it can be as big or bigger. You know, there are probably 70-75 diseases where it's been shown that depleting B cells has a positive effect for patients. It turns out that the best B-cell depleter humanity's ever made is the CAR T, CD19 CAR T cell.
There's been a lot of proof of concept now coming out of Europe that this works, and, you know, if manufacturing is a challenge for oncology, it will be a bigger challenge for the autologous setting in the autoimmune disorders, where there's a lot more patients. And so, this is something where if our allogeneic platform really works, we think we can be transformative. The third area we'll take this, hopefully, in the near term is in Type 1 diabetes, I'm sure we'll get into. So that's the Hypoimmune platform. We've got an in vivo delivery platform we can talk a little bit about, but that's a little bit about what we're up to. We're about 400 some people. We've got, you know, a host of different drugs in human testing.
We're kind of pretty well positioned to do 2-3 INDs per year for the next, you know, several years, resources allowing, right? You know, we have to make sure we have the capital and people to actually execute on that.
Yeah, great. Thank you for that overview.
Yeah.
You know, let's just start with the Hypoimmune platform and how it works. So you use CD47 overexpression as a way to evade NK cells. You know, how does that approach stack up versus some of the other approaches to making-
an allogeneic cell
... immune invasive?
So this problem of transplant rejection has been well-recognized for a long time, and a number of people started working, really with the advent of stem cells, about 15-18 years ago, around the idea of transplant rejection. There are two real important arms of the immune system to go after. One is the adaptive immune system of B and T cells. We hear a lot about that with vaccines and other things. It's actually relatively easy to deal with. I'll come back to that. And the other is the innate immune system. So the way that a bunch of these academics started out, and founders of Sana were scientific founders, so they studied the paradox of pregnancy.
And the paradox of pregnancy is that each of us is half mom and half dad, and the only reason we're in this room together is that our mothers didn't reject us. But pretty much none of us would be viable organ transplant donors to our mom. So really, the question was, what's different about that maternal fetal border? ... and really it came down to a couple of, a host of things to test. And we think we've come up with what really works. So first off, the adaptive immune system of B and T cells is actually pretty easy to deal with. You knock out MHC class I class II. people have been doing this for 15 years.
The problem is that cancer and viruses figured this out a long time ago, and so we have evolved part of our immune system to deal with that. Natural killer cells will kill cells that don't have MHC class I and class II expression. So the way that we and people have been trying to deal with this for as long as I've been in the field. What we've done, as you said, is we overexpress CD47, and it turns out that the receptor for CD47 is SIRP alpha, and it's expressed on every single natural killer cell and macrophage, and so you are able to turn off that innate immune system. What's different about it is that it seems to actually work, right?
The challenge that the field has had is that people have found, you know, potentially receptors, use HLA-E as an example, or HLA-G or some of these things, and there are cognate receptors expressed in a minority of NK cells, might be 25%, 30%. Unfortunately, turning off 25%-30% of your immune system is effectively doing nothing, right? It's such a redundant system.
And you have to hit everything. So we've shown now, and I don't think this has ever been shown before, I know it hasn't been, that we can transplant allogeneic cells with no immunosuppression and see them live for months and months and months in normal non-human primates. We've done this in, you know, humanized mice. We've done this in mice. So I think that's what's different. I think the real question that stands in front of us is not, you know, is there something different about the human immune system that we haven't, that we don't understand, that is different from non-human primates? And I think if it turns out that this platform works in humans, a huge percentage of the risk of the company is out. And so we'll know that in the not-too-distant future, right?
I think that is what's different about what we do, is it actually has been shown to work. I will also give you one little, like, anecdote. There's only one cell that's ever been transplanted in human history successfully, and that's the red blood cell, right? And what's different about the red blood cell is that it's been done millions of times a year, right? And what's different about the red blood cell is that it has no MHC class I, it has no class II, and it overexpresses the CD47. And when CD47 is processed, the red blood cell is actually gotten rid of. It's just digested. So there is something about this system that's been shown to work in humans in certain settings.
So we're optimistic that it will show up and like we hope it does in humans.
Is anybody else in the field overexpressing CD47, or are you the only one taking that approach forward?
Not that I'm aware of.
Got it. Okay. So yeah, let's move into-
If it works, I'm sure others will try.
Of course. That's how it works, right? So let's move into the cell persistence data that you're referencing, that you're hoping to have by the end of the year. So that is from a phase I/II trial B-cell lymphoma for your lead asset, SC291. You know, what type of data are we looking to get, and what would you consider good data?
Yeah. So the drug. So what we do is we take the donor-derived T cell, let's say one of us, wouldn't be any of us, but, one of us donate. It would. I think we tend to pick younger people who have very robust immune systems. But you take the donor, you then gene modify it, grow this CAR T cell up, and we transplant those into a cancer patient. This is done with autologous CAR T cells, and we use. There's, and that's how we do. So when you give an autologous CAR T cell, a patient gets lymphodepletion. I think most people recognize that in the field. What that does is that knocks out the patient's T cells, and that's our killer cells.
They come back within a few weeks, and, and that's just kind of. That creates space. What we've seen in the allogeneic CAR T cell space is that when you knock out the immune system, cells can grow, but as the immune system comes back, to date, everybody's CAR T cells have died, right? So the real question is: Will our cells live in that setting? So I've given you all this background, so let's now peel back the onion of evidence that we'll have. The first and most important, I think, onion of evidence, piece of evidence or layer of evidence, is: Does the platform that's shown so much promise in preclinical settings really translate into humans?
The way to understand that is to actually, what we see, when we gene edit these cells, about 85% of them will have all the knockouts. So after the lymphodepletion wears off, at week 2 or 3, whatever, the immune system comes back. What we should see is 100% of the remaining cells will be our fully edited cells. So if that's true, then you know we have evaded the immune system in the setting or the context of an attacked immune system. If it's 85% or 90%, the immune system hasn't recovered, right?
Mm-hmm.
If it's zero, we haven't answered the question yet. So that's really, to me, that's the most important thing we're gonna learn. And if you've done that, most of the risk is out of the company, right? 'Cause now you've translated the non-human all of the preclinical work in non-human primates and mice into humans. And that isn't that complicated to figure out. That's part one. Part two is then, do these cells really grow and persist? You know, that takes time to figure out. You wanna see cells persist for 3-6 months. I think that's really where you see things. No, that may or may not, we'll have that data over the next 3-6 months. I don't really know. We might, maybe we'll have it this year, maybe early next year.
Okay.
Then there's the last layer of evidence: Do you have really high levels of durable, complete responses? We won't have enough time to get all that. That will take, you know, well into next year. CAR T cell trials are frustrating sometimes because when you're going through dose escalation, you're allowed to dose one patient per month, right? You use these studies three by three by, you know, three. So it can take, you know, up to a year to kinda get through the dose escalation phase of a study. Then you can hopefully go pretty quickly, particularly with allogeneic cells, 'cause we've made so many of them. So we'll have some data this year. I'm optimistic we'll be able to know does the platform work or not.
I think if you want to see durable, complete responses, you'll see it next year, not this year.
Okay. Okay. And so how long does it take for the lymphodepletion to wear off, like, in terms of, like, time on average?
So we have some-
Where you would actually start to see the attack of those non-fully edited cells?
It depends on what lymphodepletion regimen you use.
What do you prefer to use?
There are three things that have been used in the field, right? There's been really just crush the immune system, and we've seen that that can keep the immune system away for a couple of months. We're using regular lymphodepletion, like what's used. It's called low-dose lymphodepletion. It's what's used in the autologous CAR T cell setting. NK cells come back in about two weeks, and T cells come back with between week two and three.
Okay.
So it's very-
So by week three-
By week three-
-to four.
You see that in the field, right?
Yeah.
Generally, there's no detectable allogeneic CAR T cells in a month, or even with these enhanced lymphodepletion regimens. So you should be able to figure it out pretty quickly.
So, so we'll get hopefully a handful of patients with that data in terms of the number of edited cells, maybe get some data on persistence, and we'll wait for next year for a more robust persistence data in addition to potentially durable response data?
Yep.
Perfect. Okay. You know, what are your thoughts on how you're going to disclose the data? Should we expect something at ASH?
Sorry, say that again.
Thoughts on how you're going to disclose the data? Should we think maybe ASH? Should we think a webcast, or is that-
ASH is a good place.
ASH is a good place.
ASH at AACR, ASCO, EHA, that's kind of where everybody in hematology goes. Three of those meetings are within a month of each other, and the other one's in the winter, right? So ASH is a good place to start, and we'll work our way through next spring then.
Got it. Okay, so medical meetings are clearly-
Medical meetings.
Preferred for you.
I mean, there's always some chance... Let's, let's assume for a second we discover the platform doesn't work. We'll tell you, right? But, you know, the you know, so if it's something really material that we think we have to, we will. You know, a good example is something where it might not be a medical meeting, so I worry more about the disclosure, is this second place where we have a chance for... If you don't mind switching the deck?
Oh, yeah, we can jump ahead.
So there's a second proof-of-concept studies in humans this year, hopefully. So, so many people recognize, I think, that what we've seen in the field in Type 1 diabetes is the immune system killing a person's beta cells. They no longer make any insulin, right? And so for the last, call it 15 years, we've seen successful transplantation of cadaveric islet cells. So a person dies, they donate their pancreas, the islets are extracted, and they are put into a Type 1 diabetic. And that's been really, really successful for patients who can tolerate pretty profound immunosuppression. There aren't that many people, though, for whom lifelong immunosuppression is better than lifelong insulin, right?
What we've seen, you know, from others in the field now is we've started to see evidence that you can take a stem cell and make it into a beta cell, right? And you can transplant that, again, in the context of immunosuppression, and see a profound effect. So our goal is to have patients who have normal glucose with no immunosuppression and no insulin. So the way we're going to try to hopefully prove that we can do this in humans is an investigator-sponsored trial this year. What we're doing is we're taking cadaveric islets, and we're making our gene edits to them. We'll then transplant them, and I think you'll know within a couple of weeks, right? No, with no immunosuppression, if we've overcome allogeneic and autoimmune rejection.
And if we have, I think it will be profound for the field. Because at that point, a cure for Type 1 diabetes becomes inevitable, right? You know that transplanting these cells can last for decades. We've seen you can make them from beta cells from others, and then we will have shown that you can get around the immunosuppression. And I think that even one patient becomes very, very material for the company, and that might be something where we have to disclose a bit earlier. You know, it could take us a while to generate that data. We have to make it. You have to have, you know, the right donor and the right recipient and those types of things.
But I'm optimistic we'll have data this year from that, and that that could be something that really transforms us, you know, our understanding of where we are with this platform at overcoming immune rejection.
Yeah. If you have the opportunity to show that in two disease settings-
Say that again.
If you have the opportunity to show that in two disease settings before the end of the year, how validating do you believe that is across the entire hypoimmune platform?
Works in two diseases, it probably works almost everything, right?
Okay.
I think if it works in one, it will probably work in most, right? So, you know, it's hard to imagine that there's a single set of changes you could make that work in every setting and every part of the body, and we already know we have one or two Achilles heels, right? Where there's certain diseases where this just won't work. So hopefully, we don't discover more. Sorry.... I got a lot of smoke this summer from the forest fires. I had a hard time recovering from it.
Yeah.
Really congested me.
It's been unfortunate. Okay. And so then, can you walk us through the design of the investigator-sponsored trial? How is that being run? I think it's a Europe-
Yeah
-based study, correct?
Yeah. So what we've shown. Just take a step back. We've shown that we can transplant cells into non-human primates, allogeneic cells. We've shown that we can transplant beta cells, pancreatic islets in a non-human primate, gene-edited pancreatic islets in non-human primates, and that they will live, you know, we've shown you data out 10 months. We've shown that we can make a non-human primate diabetic with STZ. We can then give them these gene-edited cells, and that they will completely reverse the diabetes, and that the monkey is euglycemic with no insulin and no immunosuppression.
Mm-hmm.
Right? We've also shown you in mice that we can make a humanized mouse with a diabetic's immune system, right? Make them diabetic by knocking out their pancreas, and then reprogram their cells back to stem cells, make them. Then reprogram them into beta cells, and make that and that we can transplant those cells with no rejection. We've shown this really, really, I think, concretely preclinically. So what this study is designed to say, this is translating to humans. So what we do is, we will take a cadaverically donated islet cell. We will make, we'll gene modify it. We will knock out MHC class I class II, and we will knock in CD47.
We will then transplant those cells in, hopefully into the arm of the patient, and if all goes well, we'll see cell survival and no immune response. If all goes really well, we'll see stable and detectable C-peptide over time, and if all goes perfectly, which I wouldn't expect in the early setting 'cause the dose probably isn't high enough, you will see euglycemia, right? So normal glucose with no insulin. I think that's. If that's your investment thesis, I'd probably hold off for a little bit. I think that we, we'll probably need to get a little bit higher in dose, but you know, we don't really know.
Okay.
That's the design. It's really simple. You do have to match. You know, we have to do some things to match the donor and the around just blood type. That's really it, and off we go.
How are you making sure that the donors are suitable donors? I know there's some, there's been some, historically, some cadaver-
Yeah
... cells that aren't as robust as others. So for this important first patient-
So-
in the study.
It's a really important point. So in the cadaveric transplant field, you know, about 30% of these cells just don't make it, and that could happen here, right? That won't be an immune response. We'll just have to do a second patient, right? You know, I think we'd have to watch out for that, so it's totally possible. That being said, the people who are running this have done hundreds of islet transplants. They have a really good understanding around what really good islets look like. And they also, just as an example, the amount of... You know, these are people who just died, right? The amount of ischemia or stress that the donor goes under prior to dying can have a pretty profound impact on the quality of cells.
You can actually see that in the product, and they want this to give it their best shot, and so they wouldn't, we won't be using poor quality cells. All right? It'll hopefully be cells that look a little bit better. This won't be the, "Ah, I'm not sure we should do this." This will be like, "These look really good, let's give it a shot." There's no question that when we gene edit these, I mean, you're knocking two genes out and knocking gene into non-dividing cells. We stress these cells out, right? So we will lose some, and we need to start with a pretty good set of cells.
Got it.
You know, there's... I, I worried a lot about a false negative.
Yeah.
You know, what we will ultimately do, if you have a few patients where it doesn't grow, we're transplanting these patients. I would have done—like, this is how investigators decide how they're gonna do this. There's no immunosuppression at all. Another way to do this is to transplant them with immunosuppression and see the cells be stable, and then pull away the immunosuppression. So if it... that, then that gets rid of some of that risk of a false negative. We will give that a shot if we need to.
Is it because if you have immunosuppression and the cells die, you know it was the donor?
So the reason they don't wanna do it is twofold. You're absolutely right. It's been shown that these immunosuppressive drugs are toxic to these, islet cells, and so they would prefer not to do it 'cause they think they'll end up with a more robust transplant without them. The other is that even a month of immunosuppression is actually, you know, not great for the patient. And so, kind of their thought is, if we're gonna justify putting a gene-edited product in, we feel much better if we also are taking something away, like the potential toxicity of an immunosuppressive drug.
Right.
Which is fair.
That is fair, yeah.
Um-
So then, you know, your product, SC451, will be derived from an iPSC master cell line, correct? How translatable would be some initial positive data from this IST into-
Yeah
you know, what eventually you would consider your actual product?
So immunologically, I cannot think of a way to have a false positive. Right? I really can't think of, I can think of false negatives, but I can't think of how you can have a false positive. So if we've overcome autoimmune allogeneic rejection in this setting, it is basically, I think, assured that we will overcome it. You know, nothing's ever assured in biology, but it's basically assured in the stem cell-derived product. The challenge will be making the right cells, right? I mean, the, you know, we will be, I don't think any of us know exactly what the perfect islet cell is, right?...
I don't think any of us, if you had the perfect islet cell, know exactly what the perfect cell composition is of a product, 'cause you need to have some support cells in there, and you need to make it at scale-
Mm-hmm.
and consistently over time. You know, our allogeneic CAR T platform is currently at a scale that is robust, will service the world. I think, you know, it with we can treat hundreds of thousands of patients if we have the opportunity, and we have a reasonable very reasonable cost of goods. Our stem cell process, we can make drug for phase I, right? We have work to do to have it at a commercial scale, and we have a lot of work. If you really think about this, if we treated 100,000 Type 1 diabetics per year for a decade, we will have treated around 20% of the patients in the US and Europe with Type 1 diabetes. So no matter what number you come up with...
I can't think of when I talk to patients in patient groups about this, there isn't a group that says, "Oh, I don't want this," right? They really, really want this. So, our challenge will end up being scale, much more so than competition or anything else. It is gonna be making this at scale, and we have a good bit of work to do to make that successful. There's no question.
Okay. But between now, let's say we do have positive data from the IST, you know, the cells survive. Between now and an IND, you're not gonna necessarily solve that scale problem. You know what, what-
You have to make sure you have a safe GLP Tox study.
Okay. Is that-
Right?
... is that what's left to do?
We have no desire. We're not gonna solve the scale problem for phase I. We kind of made just an intentional strategy choice. We have to do so much work between what we need to do for phase III. It's almost certainly gonna require at least preclinical bridging and maybe a little clinical bridging. So we were fine going in with a subscale process 'cause we have to make. It's gonna be different, the commercial process, to be really clear. 'Cause it has to be to get to the type of scale we need to really be able to even, you know, to treat the U.S., let alone the world.
Right. Okay. And so what's the minimum amount of duration of survival that you wanna see out of the IST to give you the confidence that you should move this-
Well-
forward for your own product?
When do you know or what do you want to see?
Yeah.
I-
Well, both maybe.
I mean, I think if you ask a transplant immunologist, they would tell you that 100% of cells will be rejected with no immunosuppression within 10 days.
Yeah.
So if you're starting to get out 2, 3, 4 weeks, you pretty much know there's nothing left to get you. Now, I would like to see them last a long time, right? You would love to follow this patient for 6, 12, 24, 36 months. You'll feel better and better about things. So after that, it's probably not immunology that's hurting you, though. It may just be cell quality.
Sure.
But-
Internally, what's your bar, though-
Yeah
-for the amount of survival to trigger, like, we should move forward with an IND for 451?
If you see the cell survive, you should just go. Like, it's just, just go. I mean, we're still just going anyway. I mean, we're not like, we're not, like, waiting for these results. We do have to, you know, do some work to make sure we've done all the preclinical work that needs to be done.
Okay. And you've sort of... You touched on this, but what would be the patient population that would be addressable with 451? Is it the more severe patients who are unable to control their hypoglycemia, or is it just everyone with Type 1 diabetes?
I mean-
Or how do you draw the line?
It may be an initial trial that's done in a different population, but I challenge you to find the person with Type 1 diabetes who says they wouldn't want this. So many people ask us, "Can I be the first patient in this study? Can I be involved?" For those of you who have friends or family members who have, I mean, it is difficult. It takes over your life, and you know, it takes over the family's life in a lot of regards. And there are a lot of long-term health sequelae, and there are just daily life intervention sequelae. And this is something where it'd be just really great to be able to offer this to patients. I haven't found anybody yet. I'm sure there are some who'd say: "You know what?
It's probably not for me." And I'm, I doubt we'll go into little kids at the beginning, right? You'll wanna see some safety. It gets developed over time. But hopefully, over time, that safety is adequate, that allows us to go broad.
Got it. Okay. Wanna-
And-
Okay.
... just for the record, some people ask me often about, like, cures for Type 1 diabetes. Don't worry about that with us. It'd be wonderful. It won't really impact us, right? We the prevalence... But I would love that to happen. We're if you were able to prevent Type 1 diabetes from ever happening.
Mm-hmm.
The prevalence pool is so large, right, of patients who have no islets, that it's gonna take us a long, long time to be available to really treat that group of people.
Yeah. Good to know. So I wanna, I wanna switch gears, make sure we have some time to talk about autoimmune-
Mm-hmm
CD19 CAR T for 291. So, you know, we have a growing body of academic data showing that, you know, autologous CD19 CAR Ts are capable of inducing these durable remissions, at least out to the follow-up date that we have. You know, what does an allogeneic CAR T look like in that setting?
I would hope an allogeneic CAR T cell, if we've done our job, looks like an autologous CAR T cell. Like, I don't see any reason why it wouldn't. If you really look closely at the data, autologous CAR T cells actually often face an immune response to the CAR, a T cell response to the CAR. We shouldn't have that, right? So we should have again, if we have T cell responses to our drug, we've got bigger fish to fry than long-term persistence. It was to die really quickly. So, it should work as well or better. And the other thing we have is, we have two benefits that you don't have with autologous. There's autologous cells: one...
In autologous cells, patients will have gotten various degrees of T-cell suppressive therapy over time just to deal with their disease. We will be transplanting an allogeneic cell from a healthy volunteer. So we will have product consistency, right? And we will have vigor, like, hopefully a T-cell product quality that is high, you know, across time, across patients. The second is there's a risk with autologous CAR T-cells when you have an immune disease, that you have T-cell responses. And you can put a CAR into an autoreactive T-cell. And if you do that, you're gonna unleash a hurricane, right? It has not happened. It's a theoretical concern. That will not happen, though, with allogeneic cells, right? Because it just can't. So we have, 'cause we're gonna take it from healthy volunteers. We have a couple of theoretical benefits. It should work as well.
You know, optimistic that this is a pretty straightforward path. The other thing we have is, you know, the field has struggled to make enough CAR T cells to treat refractory cancer.
Mm-hmm.
Right? If we go forward with a dose that's similar to autologous CAR T cells, we're making somewhere between 500-1,000 patients from every manufacturing run. It's not hard to imagine somebody, a company, even an academic center, doing 100 CAR T cell runs a year. Yeah, that's not bad. So let's assume that's what we do. That's 50,000-100,000 patients a year, and that's at a cost of goods that will allow us to really go after a host of different diseases around the world as well. So, this is one where, and the last thing I would say is, our product sits ready to go. It won't be different across different diseases, right? You don't have to do a different process. We're, we have the vials sitting on our shelves from cancer, and it's ready to go.
We make it at plenty of scale to go forward with, just from the phase I cancer study, so we can go really quickly. CMC section's the same as the IND for oncology. Yeah, just reference it.
Got it. I wanna get your thoughts, actually, though, on the cell persistence part. How important is it to have cell persistence in the autoimmune setting versus oncology? I mean, we've seen the B-cell depletion happen so rapidly, within days. Do you really need 3-6 months persistent?
I don't think we know. I have no idea. I mean, if you look at the data carefully, in every single patient at every single time point that they've published on, they have detectable CAR T cells in the autologous setting. They also have seen some recovery of B cells.
Mm-hmm.
I don't know how to circle that square, right? And so I don't think we yet have a good idea of what is the optimal level. I do think you probably need a much shorter duration, and you probably need, you know, a lower dose, right-
Mm-hmm
... than you do in autoimmune than you do in cancer. Just 'cause you just need to wipe out the B-cells, not the B-cells plus the cancer.
Right.
All that being said, you have to get them in, like, these difficult-to-reach places, in germinal centers, right, and things like that. So you have to be around long enough to kind of go and find them in, you know, tissue that have these, like, little lymph nodules, right, basically germinal centers, 'cause that's your problem for long-term antibody production. That's the difference between a CAR T-cell and an antibody, as an example. You kill the germinal center B-cell.
Right.
So,
Right, and we've never-- we haven't seen that-
I don't know the answer.
... B-cell depleting antibodies to date.
I have no idea what your answer is.
Well, I guess we'll see with data, right?
Yeah, yeah.
So, you've talked about a basket study that you wanna run for autoimmune indications. What does that study look like in terms of design, and would you be using a similar lymphodepletion regimen as you are for oncology?
Stay tuned. We'll give you details. I think it's safe to say a couple things: one, pretty much everybody who's gone forward in this field has at least included in their initial cohort of patients lupus nephritis.
Mm-hmm.
The data are profound, and the unmet need's quite high, right? The second is, I think it's safe to assume that we intend to have data from multiple diseases next year, right? We'll give you an update in the not-too-distant future around kinda what that looks like. We're optimistic we can generate data, you know, pretty quickly.
Okay. On the lymphodepletion piece, is that something you'll talk-
What's that?
The lymphodepletion piece for that trial. Do you think you'll need lymphodepletion in the autoimmune setting, or?
To date, the lymphodepletion has been the same lymphodepletion as, you know, kind of a standard CAR T-cell. It's a Breyanzi lymphodepletion dose.
Mm-hmm.
I think that's reasonable to start. I actually think because if you look, go back in your CAR T data, like to 2015. You'll find data that show in the cancer setting there was a controversy at the time. Do you use cyclophosphamide alone or fludarabine plus cyclophosphamide? And what you saw with the lower doses of lymphodepletion is that there was a T-cell response to autologous CAR T cell. So I actually think that we might be able to use lower lymphodepletion in an autologous CAR T cell, 'cause we won't have a T-cell response to our drug. Like, that's just we knock out the ability to have that. That's pretty much guaranteed, right?
Mm-hmm.
So, that is actually a huge potential competitive advantage. I think what you've seen to date, what most of the field are more afraid of from a toxicity perspective, is the lymphodepletion than the CAR T-cell.
Right.
Right? So we will if it works, we will test lower lymphodepletion for sure.
Got it. Okay.
Another question?
Of course.
Not sure if this is working. There we go.
I can't hear you, Andrew.
I'll shout.
Okay.
It's the accent. So just on the question of whether allogeneic, as opposed to autologous, may be a much more attractive alternative within the autoimmune setting. Presumably, you have had some initial conversations with the multinationals. So Bristol and Novartis are both engaged already in autologous approaches, building out capacity, leveraging where they're at. But many players have yet to declare their hand, so I'm thinking of J&J and Gilead. To what extent, when you meet with large multinationals, are they ready to jump in or at least explore an allogeneic approach in your potential partnering discussions, or is it too early for you? I'm just curious as to what feedback you've had from the multinationals and where their head is at.
So we own 100% worldwide rights to everything in our portfolio, and that is completely untenable for the long term, right? That's the first part. The second is, I always think that if you just take a big step back, we should lose to big companies in everything we do. Why would a little guy win? We win because we make faster decisions, right? Faster and better decisions. So the challenge of early partnerships is you often end up with big company decision-making, but you still have, like, little company resources, 'cause it's being done as a little company. So we will partner everything at the right time.
And autoimmune is one where, you know, you could see doing it ourselves because you can just go after a few indications at a time, but it's also one of those where a big global reach across multiple, indications can expand the pie pretty quickly, right? And so, I would presume that, you know, most pharmaceutical companies that are involved in the immunology space are quite aware of these CAR-T data. I mean, they're just profound, right? I mean, the idea that you might have curative intent, right? They're profound. So I think most are paying attention. You know, we'll figure out if there's ever a time-- There will be a time where it will make sense for some of us to work together.
You know, if it works, like we think it will, the allogeneic approach, I think, here is even better than it is in cancer because it's cheaper, it's faster, it's scalable, and we can be in the lead, right? We can be there... Like, there's no-- We're not behind like we are in oncology, where you have an autolog-- You guys will always be comparing us to the autologous setting, as will clinicians.
What would the appropriate partner look like, across your pipeline? Like, when you get to that stage, what are you looking for in a partner?
I think the most appropriate partner is the one that shares your strategic vision over time. 'Cause at the end of the day, these are a bunch of really, you know... They're really good companies. All of them, most of them can develop the drug. Most of them can commercialize it around the world. It really comes down to do they have a shared strategic vision? And if you have that, it's probably gonna go pretty well, and if you don't, it's not gonna work well. I think the other is, you know, the idea. My general philosophy is that decisions should be made by the person most likely to make a great decision. And so a pharmaceutical company that wants too early control probably shrinks the size of the pie because they're ruining your PTS.
Later, they're gonna be better than we are, right? They just are from a commercial perspective globally, so we have to find a way to kind of dance around decision-making. But those are really the two things, just strategy and decision-making. If you get that right, the money will take care of itself. And again, I think there are multiple companies that could do this.
Got it. Okay. So, you know, recently in the news, there was some chatter about some layoffs at Sana. I just wonder if you could-
Say it again.
Some layoffs at Sana. Recently, there were-
Oh!
-some news articles about that. I wonder if you could just comment briefly on that and the extent across the company?
So in any business, in any growth business, you have... So there was a press report last week that said we undergone some layoffs because somebody—two people had posted on LinkedIn that they'd been let go in a corporate restructuring. In any business, you're gonna have a few areas where you think you'd run them more efficiently and some areas where you need to invest. This was normal course. We've made no portfolio prioritization decisions. We will. Right? This was not a large change in the company. It was a small group there, people, and then the press picked it up.
But to be really clear, the company has a lot on its plate, and we have a big burn rate, and we are going to be moving hopefully into a lot more studies across a lot of patients, and that's expensive. So we will do three things, right? We will have to prioritize parts of our portfolio. We have to slow some things down, maybe even not do some things that look promising, right? We will partner things. We will go down what Andrew was talking about. We have to. There's no choice. And over time, we will raise equity capital. All three of those things have to happen. It's just the nature of the beast.
Got it.
Right? If we're not successful, we'll stop doing the things that aren't working. If we are successful, we're gonna invest more in the things that do work, right? And so, you know, so that, that's where we are. As an example, right now, we sit there ready to go forward with— We have a BCMA CAR. We've done all the preclinical work that needs to be done. It's got a validation in autologous setting with a, you know, over a 90%, you know, MRD negativity rate out at, you know, at, at, 28 days and over 80% at a year. It's a beautiful drug. We just, we just need the money to be able to... and, and, and the people, to be able to go forward.
And to do that, we wanna make sure we have some proof of concept, a little bit more money in the bank. So we, we'll be ready to go forward with that. It's ready to go. We hope it's an IND next year. It just needs a manufacturing campaign, and off we go.
Yeah. Got it. Thank you for clarifying that. I've gotten a couple questions on it.
Yeah.
I know we're out of time, but I'd love to give you the opportunity to just recap the next catalysts that are upcoming for Sana over the next, you know, 6-12 months.
Yeah. So the next, call it 3-5 months, we should be learning a lot about. There's a platform we've seen that has, you know, a lot of early promise, really translate into humans, and that will be two proof-of-concept studies: CD19 CAR T cell in oncology and this investigator-sponsored study in Type 1 diabetes. If you take a 12-month view, you can add at least 2 and maybe 3 more drugs to that. You will obviously have more data from those studies, but you should also have a CD22 CAR T cell and CD19 failures. That's one where the CAR construct has been validated in humans, and it has over a 50% durable complete response rate in CD19 failures.
We ideally will have some data in multiple studies and multiple indications from our CAR T cell in the autoimmune setting. And we also will hopefully file an IND later this year with an in vivo CAR T cell, which my guess is will go more slowly, right? But again, that could see data emerge as we move through next year. But the first four are pretty good bets, right? We're gonna have a CD19 in oncology, CD19 in autoimmune. We're gonna have this investigator-sponsored trial, and we're gonna have CD22 data. So, you know, it feels like we've been at this for a little while. The company's four or five years old, and we're really starting to, you know, get into where we're generating a lot of human data across multiple product candidates.
Stay tuned. It'll be fun.
Yeah, looking forward to it. Well, thank you so much for being here. It's been a pleasure.
Thank you, Sam.