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

All right, 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.

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I want to if both mics working.

Can you hear me now? There we go.

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 2-minute high-level overview of the company, what you do, where you're working towards.

Sure. Well, I said, thank you, everybody, for joining us. And I'm Steve, making forward-looking statements. Take a look at our regulatory filings, our Q4 risk factors. So the company was founded under a couple of ideas. And we have these aspirations that will 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 the -- any cell in the body. The third was to really have access not decided by where you're born. And 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 let 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 myself into you or my organ into you, your immune system will recognize it as foreign and reject it. And 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 limiting the number or types of cells that you can do, and it's actually quite difficult to scale. So our hope is that we can overcome transplant rejection, which we can go through the data. I think we're pretty confident we've solved the problem with transplant rejection for nonhuman primates. We've solved the problem with transplant rejection for mice. We've solved the problem with 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 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. And in each of those, we have a validated CAR construct, which has worked quite well the autologous setting. And so if we truly have overcome transplant rejection in our scaled allogeneic T cells live at least as long as autologous cells, we think we'll have a really important franchise and medicines across multiple cancers. The second is applying the same technology on autoimmune disorders, where we think it can be as big or bigger. There are probably 70, 75 diseases, where it's been showing 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 CD19 CAR T cell. There's been a lot of proof-of-concept now coming out of Europe if this works. And if manufacturing is a challenge for oncology, it will be a bigger challenge for the autologous setting in the autoimmune disorders. So there's a lot more patients. And so this is something where if our allogeneic platform really works, we think we can be transformed. And 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 a host of different drugs in human testing. We're kind of pretty well positioned to do 2 to 3 INDs per year for the next several years, resources allowing, right? We have to make sure the capital and people to actually execute on that.

Great. Thank you for that overview. Let's just start with the hypoimmune platform and how it works. So you use CD47 over expression as a way to evade NK cells. How does that approach stack up versus some of the other approaches to making an allogeneic cell 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. And 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. 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 excited [indiscernible] they study the paradox of pregnancy. And the paradox of pregnancy is that each of us is half mom and half dad. And the only reason to run this room together is that our mothers didn't reject this. 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, it's actually pretty easy to deal with. You knock out MHC Class I and Class II. People have been doing this for 15 years. The problem is that cancer and virus has figured this out a long time ago. And so we have evolved part of our immune system to deal with that. And natural killer cells will kill cells that don't have MHC Class I and Class II expression. And so the way that we -- and people have been trying to deal with this for as long as I've been in the field. And 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 in an immune system. And what's different about it is that it seems to actually work, right? And so the challenge that the field has had is that people have found potentially receptors, using HLA-E as an example, or HLA-G or some of these things, and their cognitive receptors expressed in a minority of NK cells might be 25%, 30%. Unfortunately, trading off 25% to 30% of the 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 there's 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 nonhuman primates. We've done this in 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 -- does -- is there something different about the human immune system that we haven't -- that we don't understand that is different from nonhuman primates? I think 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? And I think that is what's different about what we do is it actually has been shown or 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, it's been done -- it's 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 MHC Class II and it overexpress CD47. And when CD47 is processed, the red blood cell is actually gotten rid of. It's [ disdigested ]. So there is something about the 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 over expressing CD47? Or are you the only one taking that approach forward?

Not that I am aware of.

Got it. Okay. So yes, let's move...

If it works, I am 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 at the end of the year. So that is from a Phase I/II trial B-cell lymphoma for your lead asset, SC291. What type of data are we looking to get? And what would you consider good data?

Yes. 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, 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 the -- and that's what you do. So when you give an autologous CAR T cell, the patient gets lymphodepletion, I think most people recognize out in the field. What that does is that knocks out the patient's T cells and natural killer cells. They come back within a few weeks. And that's just kind of what that creates space. What we've seen in the allogeneic CAR T cell space is that when you knock on to the immune system, cells can grow, but as the immune system comes back to date, everybody's CAR T cells die, right? So the real question is, will ourselves live in that setting? So I'm giving you all these [ backgrounds ] and it's a peel back the onion of evidence that we'll have. The first and most important, I think, ending of evidence, a piece of evidence or layer of evidence is, do we -- does the platform that's shown so much promise in preclinical settings really translate into humans. And the way to understand that is actually what we see. But when we gene edit these cells, about 85% of them will have all the knockouts. So when you -- after the lymphodepletion wears off at week 2 or 3 or whatever, the immune system comes back, what we should see is 100% of the remaining cells will be our fully edited cells. So that's true, then you know we have evaded the immune system in the setting for the context of an attacked immune system. If it's 85% or 90%, the immune system hasn't recovered, right? If it's 0, we haven't answered the question yet. So that's really -- to me, that's the most important thing we're going to learn. And if you've done that, most of the risk is out of the company, right? Because now you've translate the nonhuman -- all of the preclinical work in nonhuman primates and mice in the humans. And that isn't that complicated to figure out. That's part 1. Part 2 is then do these cells really grow and persist. That takes time to figure out, you want to see cells persist for 3 to 6 months. I think that's really where you see things. No, that may or -- we'll have that data over the next 3 to 6 months, I don't really know. Maybe we'll have it this year, maybe early next year. 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 well into next year. And CAR T cell trials are frustrating sometimes because when you're going through dose escalation, you're allowed to dose 1 patient per month right? And you use these [ studies 3 by 3 by 3 ]. So it can take up to a year to kind of get through the dose escalation phase of the study. And then you can hopefully go pretty quickly, particularly with allogeneic cells because we've made so many of them. So we'll have some data this year. We'll -- I'm optimistic, we'll be able to notice a platform work or not. I think if you want to see durable complete responses, you'll see it next year, not this year.

Okay. And so how long does it take for the lymphodepletion to wear off, like in terms of like time an average where you would actually start to see the attack of those [indiscernible] cells?

It depends on what lymphodepletion regimen to use. And so there are three things that have been used in the field, right? There's been really just crushed 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 autologous CAR T cell setting. So NK cells come back in about 2 weeks and T cells come back between week 2 and 3.

Okay. So it's by week 3 to 4.

Week 3. And you see that in the field right? Generally, there's no detectable allogeneic CAR T cells in a month, even with these enhanced lymphodepletion regimen. So you should be able to figure it out pretty quickly.

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?

Yes.

Perfect. Okay. And what are your thoughts on how you're going to disclose the data? Should we expect something...

[indiscernible] again.

Thoughts on how you're going to disclose the data? Should we think maybe ASH, should we think of webcast...

ASH, 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 is 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...

Medical meetings, there's always some chance -- let's assume for a second, we discover the platform doesn't work. We'll tell you, right? So it's something really material that we think we have to, we will. 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...

Okay. We can jump ahead.

So there's a second proof-of-concept studies in humans this year, hopefully. I think -- so many people recognize, I think, that what we've seen in the field in type 1 diabetes. 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 lifelong insulin, right? What we've seen from others in the field now is we start to see evidence that you can take a stem cell and make it into beta cell. And you 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, is an investigator-sponsored trial this year. What we're doing is we're taking cadaveric highlights, and we're making our gene edits to them, now then transplant them. And I think you'll know is in a couple of weeks, right, with no immunosuppression if we've overcome with 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 material for the company. And that might be something where we have to disclose a bit earlier. It could take us a while to generate that data. You have to make it. You have to have 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 would be something that really transforms us our understanding of where we are with this platform and overcoming immune rejection.

And if you have the opportunity to show that in 2 disease settings before the end of the year, how validating do you believe that is across the entire hypoimmune platform?

Works in 2 diseases, it probably works almost everything, right? And I think if it works in one, it will probably work in most, right? So it's hard to imagine that there's a single set of changes you can make that work in every setting in every part of the body. And we already know we have 1 or 2 Achilles heels, right, where there are 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 a congestive...

It's a bit 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-based study, correct?

Yes. So what we've shown, just take a step back, we've shown that we can transplant cells into nonhuman primates, allogeneic cells. We've shown that we can transplant beta -- pancreatic islets in a nonhuman primates. And the thing will live, we've shown you data of 10 months. We've shown that we can make a nonhuman primate diabetic through with STZ. We can then give them these gene-edited cells and that they will completely reverse the diabetes and that the monkey euglycemic with no insulin and no immunosuppression, okay? We've also shown you in mice that we can make a humanized mouse with a diabetics immune system, right? Make them diabetic by knocking out the pancreas. And then reprogram their cells back to stem cells, make them -- reprogram them into beta cells and make that -- and then that we can transplant those cells with no rejection. We've shown is 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 will gene modify it. We will knock out MHC Class I and Class II, and we will knock in CD47. We will then transplant those cells and 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 because the dose probably isn't high enough, you will see euglycemia, right? So normal glucose [indiscernible]. I think that -- if that's your investment thesis, I'd probably hold off a little bit. I think we'll probably need to get a little bit higher in dose, but we don't really know. That's the design. It's really simple. You do have to match. We have to do some things to match the donor and 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 been some historically some cadaver cells that aren't as robust as others. So for this important first patient in the city...

It's a really important point. So -- in the cadaveric transplant field, about 30% of these cells just don't make it. And that could happen here, right? That won't be an immune response. We just have to do a second patient, right? I think we 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 -- these are people who just died, right? The amount of ischemia or stress that the donor goes under prior to dying could 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 the best shot. And so they wouldn't -- we won't be using poor quality cells, right? Hopefully B-cells look a little bit better. This won't be that -- I'm not sure we should do this. 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 nondividing 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.

There's -- I worried a lot about a false negative. And 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. I think this is how investigators decide how they're going to 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 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, it was the...

So immunosuppression is the reason they don't want to 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 because they think they'll end up with a more robust transplant without them. The other is that even a month of immunosuppression is actually not great for the patient. And so the kind of their thought is we're going to justify putting a gene-edited product in. We feel much better if we're not -- if we also are taking something away like the potential toxicity of an immunosuppressive drug, which is fair.

So then 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 what eventually you would consider your actual product?

So immunologically, I cannot think of a way to have a false positive, right? I can think of false negatives. But I can't think 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 nothing's ever seen biology. It's basically a stem cell drive product. The challenge will be making the right cells, right? I mean 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 because you need to have some support cells in there. And you need to make it at scale and consistently over time. Our allogeneic CAR T platform is currently at a scale that is robust. We'll service the world. I think 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 U.S. and Europe type 1 diabetes. So no matter what number you come up with -- and I can't think of -- when I talk to patients and patient groups about this, there isn't a group that says, oh, I don't want this, right? They really, really want this. And so our challenge will end up being scale much more so than competition or anything else. It is going to be making this at scale. And we have a good bit of work to do to make that successful. There's no question.

Okay. And between now, let's say, we do have positive data from the IST, the cells survive. Between now and an IND, you're not going to necessarily solve that scale problem. What...

You have to make sure you have a safe GLP tox study.

Okay. Is that what's left to do?

We are not going -- we have no desire, we're not going to [indiscernible] the scale problem for Phase 1. 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 going to require at least preclinical bridging maybe a little clinical bridging. So we were fine going in with a subscale process because we have to make -- it's going to be different, the commercial process, to be really clear because it has to be to get to the type of scale we need to really be able to even -- to treat the U.S., a little along the world.

Right. Okay. And so what's the minimum amount of duration of survival that you want to see out of the IST to give you the confidence that you should move this forward for your own [ product ]?

When do you know or what do you want to see?

Well, both maybe.

I mean I think if you ask transplant immunologist, they would tell you that 100% of cells will be rejected with no immunosuppression within 10 days. 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 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.

Internally, what's your bar, though, 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 just go. I mean we're just going anyway. I mean we're not like waiting for these results. We do have to do some work to make sure we done all the preclinical work that needs to be done.

Okay. And you've sort of -- you touched on this, 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? 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 asked us, can I be the first patient in the study? Can I be involved? It's -- for those of you who have friends or family members have, I mean, it's a difficult -- it takes over your life, and it takes over the family's life in a lot of regards. And there are a lot of long-term health sequela and there are just daily life intervention, sequela. And this is something where it would be just really great to be offer this to patients. I haven't found any but yet. I'm sure there are some say, it's probably not for me. I doubt we'll go into little kids at the beginning, right? You want to see some safety that gets developed over time. But hopefully, over time, that safety is adequate that allows us to go broad.

Got it. Okay.

And just for the record, some people asked me off about like curious for type 1 diabetes. Don't worry about that with us. It would be wonderful. It won't really impact us, right? For prevalence, I would love that to happen, if you were able to prevent type 1 diabetes ever happening, the prevalence pool is so large, right, or patients who have no islets, it's going to take us a long, long time to be available to really treat that group of people.

Yes. Good to know. So I want to switch gears to make sure we have some time to talk about autoimmune CD19 CAR T for 291. So we have a lot growing body of academic data showing that autologous CD19 CAR Ts are capable of inducing these variable remissions at least out to the follow-up date that we have. What does an allogeneic CAR T look like in that setting?

I would hope that allogeneic CAR T cell, we've done our job looks like an autologous CAR T cell. Like I don't see any reason why it wouldn't. If we -- 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, is that 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 very quickly. So it should work as well or better. And the other thing we have is you have two benefits that you don't have with 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 in an allogeneic cell from a healthy volunteer. So we will have product consistency, right? And we will have hopefully a T cell quality that is high across patients. 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 auto reactive T cell. And if you do that, you're going to unleash a hurricane, right? It has not happened. It's a theoretical concern. That will not happen to allogeneic cells, right, because it just can't. So we have -- we're going to take it from healthy volunteers. So we have a couple of theoretic benefits. It should work as well, optimistic that this is a pretty straightforward path. The other thing we have is the field has struggled to make enough CAR T cells to treat refractory cancer. If we go forward with a dose that's similar to autologous CAR T cells, we're making somewhere between 500 to 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 [indiscernible]. So let's assume that's what we do. That's 50,000 to 100,000 patients a year. And that's cost of goods that will allow us to really go after a host of different diseases around the world as well. So this is 1 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 have the vials sitting on ourselves from cancer and is 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 is the same as the IND for oncology. I just referenced.

I want to 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 to 6 months persistence?

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 as they published on they have detectable CAR T cells in the autologous setting. They also have seen some recovery of B cells. I don't know how to circle a square, right? And so I don't think we have a good idea of what is the optimal level. I do think you probably need a much shorter duration and you probably need a lower dose, right? And then in autoimmune than you do in cancer. You just need a wipeout the B cells, not the B cells plus the cancer. All that being said, you have to get them in the 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 tissue that have these like little lymph nodules, right, basically germinal centers because that's your problem for long-term antibody production. That's a difference between a CAR T cell and an antibody, as an example, you kill the germinal center B cell.

We haven't seen the cell depleting antibodies, I think.

No idea your answer is.

I guess we'll see you data, right? So you've talked about a basket study that you want to 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 of things. One, pretty much everybody has gone forward in this field has at least included in their initial cohort of patients, lupus nephritis. The data are profound and the unmet need is quite high, right? The second, 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 kind of what that looks like. We're optimistic we can generate data pretty quickly.

Okay. And on the lymphodepletion piece? Is that something you'll -- 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 kind of a standard CAR T cell, it's a Breyanzi lymphodepletion dose. I think that's reasonable to start. I actually think because if you look -- go back in your CAR T data like 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 cyclophosphide? 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 because we won't have a T cell response to a drug. I think that's just we knock out the ability to have that. That's pretty much guaranteed, right? So that is actually a huge potential competitive advantage. I think what you've seen to date on most of the field are more afraid from a toxicity perspective, is the lymphodepletion and the CAR T cell, right? So we will, if we -- if it works, we will test lower lymphodepletion for sure.

Got it. Okay.

Any other question.

Not sure if this working.

I can't hear you Andrew.

I'll shout. 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 supposed to be engaged already in autologous approaches building out capacity, leveraging where they're at. But many players have yet to declare their hands. So I think you have 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 they 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 to everything we do. Why 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 because it's being done as a little company. So we will partner everything at the right time. And autoimmune is 1 where you can see do 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 you can -- I would presume that 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. 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. And 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's no -- we're not behind like we are in oncology where you have a -- you guys will always be comparing us to the autologous setting as well 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?

Actually the most appropriate partner is the one that shares your strategic vision over time because at the end of the day, these are a bunch of really -- 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 and they have a shared strategic vision. And if you have that, it's probably going to go pretty well. And if you don't, it's not going to work well. I think the other is the idea -- my general philosophy is a decision should be made by the person most likely 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 going to 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 2 things, just strategy and decision-making. If you get that right, the money will take care of itself. And then again, I think there are multiple companies that can do this.

Got it. Okay. So recently in the news, there was some chatter about some layoffs at Sana. I just wonder if you could -- some layoffs at Sana recently, there are 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 -- there was a press report last week that said we undergone some lag because somebody -- 2 people had posted on LinkedIn that they've been like in a corporate restructuring. In any business, you're going to 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 just depend the press picked it up. We -- 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. You would go down to 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, right? If we're not successful, we'll stop doing the things that aren't working. If we are successful, we're going to invest more in the things that do work, right? And so that's where we are. As an example, right now, we sit there ready to go forward with it. 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 over 90% MRD negativity rate out at 28 days and over 80% of the year. It's a beautiful drug. We just need the money to be able to -- and the people to be able to go forward. And to do that, we want to make sure we have some proof-of-concept a little bit more money in the bank. So 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.

Yes. Got it. Thank you for clarifying that. I've gotten a couple of questions on it. So I know we're out of time, but I'd love to give you the opportunity to just recap the next catalyst that are upcoming for Sana over the next 6, 12 months?

Yes. So the next, call it, 3 to 5 months. We should be learning a lot about. There's a platform we've seen that has a lot of early promise really translate into humans. And that will be two proof-of-concept studying, 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. 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 50% durable complete response rate and CD19 failures. We should -- we ideally will have some data in auto -- 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 we'll go more slowly, right? But again, that could see data emerge as you move through next year. But the first four are pretty good bets, right? We're going to have a CD19 oncology, CD19 in autoimmune. We're going to have this investigator-sponsored trial, and we're going to have CD22 data. So it feels like we've been at this for a little while at companies, 4 or 5 years old, and we're really starting to get into where we're generating a lot of human data across multiple product candidates. So stay tuned. It will be fun.

Yes. Looking forward to it. Well, thank you so much for being here. It's been a pleasure.

Thank you, Sam. Appreciate it.