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

Welcome to the Bank of America Healthcare Conference, Virtual Vegas as it were. I'm Geoff Meacham. I'm the senior biopharma analyst here at BofA. I have Aspen from my team with me as well. And we're thrilled to have Sana with us and speaking on behalf of Sana and giving a presentation is CEO, Steve Harr. Steve?

Yes. Thanks, Jeff, and thanks for inviting us to Virtual Vegas. I don't think I've ever been to Vegas other than for the BofA conference. So I'm looking forward to being back again next year. And maybe to go once or twice without -- outside of this conference. So thank you, everybody. We go the first slide. I think most people will recognize that we'll make forward-looking statements, and we spend a bunch of time on the risk factors of our K and Q. So feel free to take a look at those. Is the slide up and available? I guess it is. I'll just assume that slides are available. So it's always found that under the belief that one of, if not the most important, advance in medicine over the coming decades will be the ability to modify genes and use cells as medicines. And our goal is to build one of the preeminent companies of that era. 3 aspirations really drive us. And if you take a step back and think about it, almost every disease known to man is caused by damage to or loss of cells. And we want to be able to repair and control the genes in any cell on the body basically to fix what's broken. Second is to replace any cell in the body to put back a cell after it's been damage. And third is to broadly improve access to cell and gene therapies. And it strikes us if you make a medicine and you can't deliver it for a patient. It's more like a science experiment than it is a therapeutic. We have a very clear strategy as we get into. The -- I would say a few years into this, the strategy is more right today than it was when we started the company. The technologies we brought in to prosecute that strategy are working. That's a ways from saying that they work, and now we have a good bit in front of us before. These are approved medicines. But we're happy with where we are. We're around 300 people today, more or less 70% of those people are -- about actually 75% to 80% are in R&D or in the manufacturing sciences. And if all goes well, we'll begin turning out multiple INDs per year beginning as early as next year. All right. So go to the next slide, 1 of the most important decisions we made at the beginning of the company was taking a view that we wanted to be an engineered cell company. And you hear a lot about gene therapy companies or cell therapy companies. And ultimately, you're trying to do the same thing. You're modifying and controlling genes and gene expression within the body. And there really isn't that much difference in the capabilities that you need to build, to do either of those, but there's a big difference in terms of at least intermediate term risk. And so when we thought about in vivo cell engineering or what's typically called cell therapy, ultimately, you're trying to deliver a payload and modify and/or control gene and gene expression. And it struck us that you can basically do almost anything you want to the genome in vitro or in a petri dish. But the real challenge is actually doing it inside the body. And so we started out really focused on delivery. And our goal is to deliver any payload to any cell in a specific and repeatable way. And every time you do 1 of those 4 attributes, you actually create a whole new category of medicine. And we brought in technology at the beginning of the company that allowed for cell-specific delivery, for example, just to AT cells. And with that, we actually got a lot of payload diversity. We can do integrating or non-integrating signals. We can do DNA or RNA or proteins. We can deliver gene editing machinery. And so we'll come back and talk a little bit about that. We are working to do all 4 at the same time on this page, but to be really clear, we don't yet. If you go to the other side of the page, which is ex vivo cell engineering or people call cell therapy, here, we get the opportunity to treat the diseases that most of our loved ones will die of. Unfortunately, it's also harder. And so if you distill it down to 4 attributes, again, we want to manufacture sell at scale that will engraft function and persist, you have to do all 4 in order to make a meaningful medicine. At the same time, it struck us that the biggest issue was cellular persistence. And in particular, overcoming immune rejection of foreign cells, and we really started out by focusing on that issue with the goal of then applying the technology where others had figured out how to get the cells to engraft and/or a function, something like T cells or pancreatic islet cells. So when you distill down all that we're doing, we really founded the company around 3 technologies. One was in vivo delivery, two was hiding cells from the immune system and three was stem cells. If we go to the next slide, we just see we built 5 capabilities more or less to do this and we actually built a lot more, but this simplifies. And the first is -- and each of these are built around people. I won't go through all the people here. But we -- if you look at the core capabilities of the company, it's around delivering genetic material, it's around modifying, editing and controlling the genome. It's -- we have to understand immunology, both hiding our medicines from the body's immune system as well as using the immune system as a therapeutic. Now one of the real challenges, I think that platform companies have is that we often forget that our platform is only important to the extent that it intercedes in relevant biology. And we've invested in really 1 of the world's leaders in every cell type that we go after, and then we surround them with people with significant drug development experience. And then the last area is manufacturing. And I'd start by saying that the beginning manufacturing is truly a science, and we've built a really significant process engineering and analytical capabilities. The second is that we're doing this across 3 different platforms. One is, which we'll talk about in a viral-based gene delivery system. The second is stem cell-derived cells. And then the third is a donor-derived or allogeneic T cells. And the last thing I'd say is we've been building the facilities. We have a pilot plant that's up and running in South San Francisco, and we are building a large plant to manufacture our drugs in clinical and early commercial as well. If we go to the next slide, this is just a brief flash of some of our pipeline. And you'll notice a few things about it. One is that it's pretty balanced between in vivo and ex vivo. Two is that you'll see we are going after a host of different cell types. And this has a lot to do with how we think about risk, which I can get into and maybe in one-on-one with people. And the third thing that may not be in here is, at least in our view, if we get one of these right, most of them represent more than just a therapeutic. They represent an entire pipeline. And an example, if we're able to deliver payload directly and efficiently to T cells, we won't just go after CD19 and BCMA as cancer targets, we'll go after a host of others as well. So these are medicines that could be in human testing as early as the next few years, and we have a number of others behind it. So how do we go about doing this? And one of the lessons that I've had is if you're faced with a complex biologic problem, see if mother nature solved it, and if she has exploited that system. In the cell-specific delivery, if you take a step back, viruses are able to target and deliver to very specific cells in the body. And actually the humans or mammals have exploited those systems for cellular communication. And even things as fundamental as human's sperm only goes to human egg to deliver its genetic material, doesn't stop anywhere along the way. And the viral system is called a fusogen. And if you look at the center of this page, it's like -- I think of it like nature's logic gate. There's a G protein, which I call guide, and there's an F protein called that drives the fusogen. And the G protein will look for a cell-specific receptor. A great example is COVID, where the coronavirus looks for the H2 receptor in a cell. And when it binds to it, it will undergo a confirmational change and tickle the F protein. And the F protein then is like a sphere, and it drives in the contralateral membrane and pulls it to cell membranes together and dumps the content of the virus into the cell. And so we can -- what we do is we take a viral fusogen, and if you look on the left-hand side, we then neuter its normal receptor binding way, so it won't recognize anything. And we then put on it in something like a cell-specific binding loyalty. So I guess scFv, which is an antibody like substance that we'll find something on a cell surface, such as say, CD8 on a CD8 T cell. And then we go through and we do some work to modify the protein so that we can naturalize the protein-protein interaction between the G and F. And we put that fusogen on something we call fusosome, and that could be a virus or a cell. And that fusosome will carry the payload that we want to take to a cell. So that's kind of how we go about doing this. And it works. If we go to the next slide. We are -- we've been successful now, I think in about -- going after about 44 different cell surface receptors on about 14 or 15 different cell types. And so we've chosen to target really 4 cells at the beginning, CD8 T cells, CD4 positive T cells, hepatocytes and hematopoietic stem cells. So I'll give you just a couple of examples here. One is targeting T cells. And blood cancers remain a very significant unmet need. And there has been a lot of promise delivered by CAR-T cells and the ability to really provide meaningful clinical benefit to a number of patients with lymphoma, leukemia and multiple myeloma. And if you look at the left-hand side of the page, which you see these CAR-T cells are made outside the body, and they're actually quite complex. And they -- both in the manufacturing process as well as before the patient receives their cells back, they undergo some conditioning chemotherapy. And Sana score on the right is what you see is our goal, which is to replace that with a single IV infusion of our medicine and then to have the CAR-T cells actually made inside the body. So your body serves as the bioreactor. So if we go to Slide 10, we can just kind of show you a little bit of what that looks like. So on the left-hand side of the page, you see those orange blobs. And those are our medicines. And the spikes on those are the fusogen. And in this case, let's say they recognize CD8, they can also recognize CD4 on the T cell. And they will then bind to that T cell and deliver the genetic material. And in the middle column, that's that kind of -- that minus sign inside of the cell. And in this case, the minus sign carries the genetic code to get the cell to create a CAR or a chimeric antigen receptor, which is the yellow on the cell surface. And when you make a CAR-T cell, the goal is that it will -- that the CAR will bind to a specific cell, in this case, a cancer cell. And when it does, they will activate the T cell. And an activated T cell will both kill its target cell as well as amplify. So all of this is taking place inside the body. And the benefit of it taking place inside the body is that we believe that we can, one, make better T cells because we won't have them outside of the body and manipulating them and growing them. And that may lead to either better efficacy and/or better safety; and two, that we can do this without any conditioning chemotherapy for the patients. So if we go to slide -- the next slide, what you see here is the definitive model that's utilized in studying B-cell malignancies, it's called the norm 6 mouse. And the left hand -- and so these are mice where a tumor leukemia is actually infused, and you see in the left-hand panel that over the course of several weeks, the tumor completely takes over the mouse. And a typical CD19 targeted ex vivo manufactured CAR-T cell, what you see in the second column is that it will eliminate that cancer in more or less every mouse. On the right-hand side, you see our medicine. And what we've done here is we've taken our medicine in a single intravenous infusion into the mouse. Transduced the T cells in the mouse. And what you see is -- and this is when we activate these cells or we don't activate the cells, it's a little bit of a nuance. But in either case, we are able to eliminate the cancer very comparably to what you see on the left-hand side, but in a much more simplified way where the CAR-T is actually manufactured inside of the mouse. So the next thing that we wanted to do, and these are kind of -- every 1 of these mouse -- mice models has limitations. And 1 of the limitations here is that because they're putting human cells and human cancer cells into a mouse, the mouse's normal immune system is eliminated. So we wanted to look and see what will be the effect when we put it into a normal immune animal. And it turns out that our well actually targeted a fusogen that would bind to both nonhuman primate and human CD8. And there is an experiment that has been done in the literature with autologous CAR-T cells, where monkey CAR-T cells were used to eliminate the B cells in a monkey turns out CD19 is on B cells. I mean it was quite toxic for the monkeys. They had both significant neurotoxicity as well as cardiovascular instability, but then we did see that they were able to deplete B cells in the animals. And so we wanted to recapitulate that experiment. It's the first time we did -- if you go to the next slide, Slide 12. And what you'll note here is that in -- with a single intravenous infusion, we saw a profound B-cell depletion with 4 out of -- in 4 out of the 6 monkeys. And a couple of things of note here. One, there was absolutely no sign of any toxicity, whether we were looking at the clinical state of the animals as well as their biochemical state. The second, so this is our first time that we did this experiment. And this was the first dose, and to see this type of reaction was very -- is encouraging. We constantly get the question of what happened to the other 2 monkeys. And I have to say we don't know yet. It may be that just a little bit higher dose will help. It may be that we need to do something like activate T cells to really get them in every animal to work. Then it may be that, like a lot of medicines, we don't understand why, but it doesn't work in every single human or animal. And we just have to see where we end up. So stay tuned, we'll have more information around this as the year progresses. So where are we? We're kind of in the IND-enabling phase and scaling up GMP manufacturing. And we will initially target non-Hodgkin's lymphoma with CD19. We expect that we can be in human testing next year, if all goes well. We have a CD8 targeted fusogen. We're also looking at targeting CD4 cells. We have a BCMA that's behind about 6 months, and may be in human testing, kind of the latter parts of next year or early 2023, and we are looking at targets beyond CD19 and BCMA. But this is, we think, a really exciting platform with the potential to really move CAR-T cells into a place where not only can we scale them and get them to patients in a differentiated way, but the ease of administration and the overall toxicity profile may allow us to move into very early lines of therapy for both CD19 positive B-cell malignancies as well as myeloma. And just for context, that's in the U.S. and Europe, around 100,000 people a year die of those diseases alone. So if we go to the next slide, this is a platform that extends beyond just T cells. And this is just a little bit of a teaser. And here is some progress we've made in targeting hepatocytes, which are the active cells in the liver. And we use lentivirus as a positive control here. So lentivirus is actually a modified HIV where 1 of the things that has changed is actually the fusogen. And the fusogen is something called VSV-G. And VSV-G is just like an LNP. It targets the LDL receptor, and it's very efficient in getting into the liver, which makes it an attractive control. The downside is no different than LNPs, it also goes everywhere else in because the LDL receptor is more or less on every cell. So what you see here is an in vivo experiment of our liver-targeted or hepatocyte-targeted fusogen. And what you can see is that lentivirus will get you into just over 1/3 of all liver cells. And what we're seeing with our hepatocyte-targeted fusogen is the ability to adjust as well or maybe a bit better and get into about half of these cells. And picture is worth thousand words and looks quite nice on the right-hand side. So what are we going to do with that? If we go to Slide 15. We're moving forward with a program in OTC deficiency. And that's a nice proof-of-concept around our ability to get into liver. Probably more interesting and more importantly is what's on the bottom. And -- but we are able to deliver with this platform, simple gene editing machinery like CRISPR-Cas9 as well as more complex and large gene editing machinery. And we think the ability to target specific cells and make very specific modifications in the genome is kind of the killer app in being able to control and modify the genome. And stay tuned, I think you'll see some more progress along that front in the not-too-distant future. So the next slide goes to kind of this ex vivo part. And again, taking lessons from nature. And our goal here, as I mentioned earlier, was to figure out how do we hide cells from the immune destruction of foreign cells and for going to transplant them. And really the insight here was just to look at the paradox of pregnancy. And the paradox of pregnancy is each of us is half mom and half dad. And none of us would be on this zoom call, if we've been rejected by our mothers. But at the same time, none of us would be really great [indiscernible] donors to our mother. So it's different about that fetomaternal border. And to make a long story short, some scientists at Harvard and Stanford figured this out. They then went about -- they figured out what the differences were, and they then went about kind of applying it. And the system that we have is surprisingly simple. And when you think through the immune rejection, there are 2 elements to contemplate. One is called the adaptive immune system. And that's relatively easy to deal with. You see a number of parties doing this. And that is, do you knock out MHC Class I and Class II, and you can more or less hamstring your T cell response and the ability to make antibodies. The challenge is that both viruses and cancers viewed that a long time ago, and our innate immune system will attack those cells. So we needed to figure out how to turn off the innate immune system and in particular, natural killer cells. And I'd say, surprisingly, over-expression of CD47 has proven to be just a tremendous tool. So our goal is to create a stem cell line, make these gene modifications, hide the sell from the immune system and be able to differentiate before we -- in the manufacturing suite into something like a beta cell or a heart cell and replace that in the body. So how are we doing? If you go to the next slide, this is -- these are just again, pictures are worth a thousand words. And I think these are the most compelling data the company has created to date. And what this is we took nonhuman primate IPS cells. We made -- and we made the gene modifications that we talked about in the last page to them. And so on the top panel, what you see is we transplant under into the monkey muscle unmodified IPS cells. You see within about a week, most of the cells are gone by 2 or 3 weeks, they're entirely eliminated by the immune system. And what you see on the bottom panel is that when we translate our hyper-immune cells into the same spot, you see not only cells survive, but they actually thrive. And these are data out to 5 weeks. And stay tuned, we'll have data out a good bit longer coming forward. And so I'm not aware of anybody who's been able to show that you can transplant foreign or allogeneic cells into a host with no immunosuppression and see those cells thrive in survival. And importantly, what we see here is that this is looking at the immune response. And on the top panel, what you see is in non-modified cells, t cells are activated, antibodies are produced and natural killer cells are actually -- don't see these cells because they have the Class I and Class II. And what you see on the bottom is that our cells are hidden from the T cells. We've seen no production of antibody. And what is, I think, remarkable is that natural killer cells also don't recognize T cells. And so we're quite excited about where we can take this. So we're going to move this into a host of different cell types, including T cells for cancer, pancreatic islet cells for type point diabetes and maybe beyond heart cells for patients with heart attack and [indiscernible] cells for host of neurologic diseases. I'm going to tease you briefly. So the allogeneic or donor-derived T cells, you have to deal with 3 things if you're going to put my cells into you. I'll try it -- my cells will try to kill you, that's graft-versus-host disease, pretty easy to deal with, knockout the T cell receptor. Your cells will try to kill me, that's called host versus graft disease. And there, I think we have a very unique insight. And so we're taking donor-derived T cells, making these gene modifications we talked about, adding the CAR and hopefully going out and targeting cancer. So where are we? First off, we want to make sure that the system works in killing tumor cells. And this is that same norm 6 tumor modification. And what you see is on the left-hand panel, cancer takes over, in the middle normal CAR-T cells, they do very well and eliminating the cancer in these mice. And on the right-hand side, you see that our hip modified CAR-T cells are also quite potent in taking down the tumor. And importantly, when we put these cells into mouse models, you see that both T cells and B cells are not activated. We don't make antibodies and natural killer cells, again, don't get activated more macrophages. So we're moving forward with an allogeneic T-cell program. We think this can be very, very important. Our goal is to utilize no conditioning chemotherapy above and beyond what's used for an autologous by the current standards by companies like Gilead, Bristol-Myers and Novartis. And we'll go again into the B-cell malignancies and myeloma to start. There are other places that might be as are more exciting to put this to. So Type 1 diabetes remains a real problem. And Type 1 diabetes is when you're immune -- that the immune system of the patient destroys the insulin producing beta cells in the pancreas. And it affects 4 million patients in the U.S. and Europe alone. And if we're so fortunate as to get Type 1 diabetes, I think we'll be able to apply this technology into the epidemic of Type II. And this is a disease that -- while there have been a lot of advances, even in places like the United States, there's still about a 15-year shorter life expectancy for patients. And that life is filled with not only challenges around hypo and hyperglycemia but also a number of long-term complications. And so our goal is to create a hypo-immune cell that will evade the immune system and normalized glucose. So here, you see we're able -- this is a mouse model, and we take stem cells, and we mature them into pancreatic islet cells. And what you see on the left-hand side is that our cells respond pretty much like a normal human islet to glucose challenges. And what you see on the right-hand side is a mouse model, Type 1 diabetes, where over the course of several weeks, we are able to normalize glucose and it remains that way. And if you go back to the animal model or a monkey model they showed you, 1 of the things that we've done is cross the monkeys over. So we put our hypo-immune cells into monkeys that already have seen unmodified cells and have an immune response to them. And what we find when we do that is that there's absolutely no T cell activation. The antibodies don't recognize these cells and that the killer cells don't recognize these cells, which gives us optimism that we're able to hide ourselves from the immune system even in patients with preexisting immunity like type 1 diabetes. So we're in the process of making a GMP hypo-immune IPS cell line. It's a long process. I won't kid you. And we're working on scale on our GMP manufacturing process. And we -- our goal is to start IND-enabling studies soon. This is 1 that takes a bit longer. It's just a lot of engineering challenges. And don't -- we'd expect this to be in human testing as early as 2023, but I don't think it will be there next year. So that's a little bit of a run-through of who we are. We've got a number of different capabilities that we're building. I'm thrilled with the people that have come on board to join us in this mission. As I mentioned earlier, we're around 300 people, most of whom are in our science -- our R&D sciences as well as manufacturing. And we have a broad and diverse pipeline that we're optimistic has the potential to not only generate medicines with meaningful opportunities to help patients, but they also can be proof of concepts for broader pipelines coming behind it. So with that, I will wrap it up, and thank you for your time and attention and look forward to an opportunity to interact in a more intimate setting throughout the rest of the year. Thanks.

Thank you, Steve.