Good morning. Welcome to the third day of 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. Speaking on behalf of Sana and giving a presentation is CEO Steve Harr. Steve? Thanks, Geoff Meacham, and thanks for inviting us to Virtual Vegas. I don't think I've ever been to Vegas other than for the BofA conference. I'm looking forward to being back again next year, and maybe to go once or twice outside of this conference. Thank you, everybody. We can go to the first slide. I think most people will recognize it. We'll make forward-looking statements. We spend a bunch of time on the risk factors of our K and Q. 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. Sana Biotechnology was founded 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. Our goal is to build one of the preeminent companies of that era. Three 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. We want to be able to repair and control the genes in any cell in 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 damaged. Third is to broadly improve access to cell and gene therapies. 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, which we'll get into. 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 we have a good bit in front of us before these are approved medicines. We're happy with where we are. We're around 300 people today. More or less 70% of those people are, actually 75%-80% are in R&D or in the manufacturing sciences. If all goes well, we'll begin churning out multiple INDs per year, beginning as early as next year. All right. Go to the next slide. One 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. You hear a lot about gene therapy companies or cell therapy companies, ultimately, you're trying to do the same thing. You're modifying and controlling genes and gene expression within the body. 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 near and intermediate-term risk. When we thought about in vivo cell engineering, it was typically called cell therapy. Ultimately, you're trying to deliver a payload and modify and/or control gene and gene expression. 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. We started out really focused on delivery, and our goal is to deliver any payload to any cell in a specific and repeatable way. Every time you do one of those four attributes, you actually create a whole new category of medicine. We brought in technology at the beginning of the company that allowed for cell-specific delivery, for example, just to a T cell. 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 genetic machinery. We'll come back and talk a little bit about that. We are working to do all four 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. If you distill it down to four attributes again, we want to manufacture a cell at scale that will engraft, function, and persist. You have to do all four 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. We really started out by focusing on that issue and with a goal of then applying the technology where others had figured out how to get the cells to engraft and/or function, something like T cells or pancreatic islet cells. When you distill down all that we're doing, we really founded the company around three technologies. One was an in vivo delivery, two is hiding cells from the immune system, and three was stem cells. If we go to the next slide, what you'll see is we've built five capabilities, more or less, to do this. We actually built a lot more, but this simplifies. Each of these are built around people. I won't go through all the people here, but if you look at the core capabilities of the company, it's around delivering genetic material. It's around modifying or editing and controlling the genome. 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. 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. We've invested in really one 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. The last area is manufacturing. I'd start by saying that at the beginning, manufacturing is truly a science, and we've built really significant process engineering and analytical capabilities. The second is that we're doing this across three different platforms. One is, which we'll talk about, a viral-based gene delivery system. The second is stem cell-derived cells, and then the third is donor-derived or allogeneic T-cells. 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. 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 in maybe in one-on-ones with people. 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. 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. 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. How do we go about doing this? 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, exploit 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. Actually, humans or mammals have exploited those systems for cellular communication and even things as fundamental as human sperm only goes to human egg to deliver its genetic material. Doesn't stop anywhere along the way. The viral system is called a fusogen, and if you look at the center of this page, I think of it like nature's logic gate. There's a G protein, which I call guide, and there's an F protein that drives the fusogen. The G protein will look for a cell-specific receptor. A great example is COVID, where the coronavirus looks for the ACE2 receptor on a cell. When it binds to it will undergo a conformational change and tickle the F protein. The F protein then is like a sphere, and it drives in the contralateral membrane and pulls the two cell membranes together and dumps the content of the virus into the cell. 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 domain, so it won't recognize anything. We then put on it something like a cell-specific binding moiety, so like a scFv, which is an antibody-like substance, that will find something on a cell surface, let's just say CD8 on a CD8 T cell. 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. We put that fusogen on something we call a 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. That's how we go about doing this. It works. If we go to the next slide. We've been successful now, I think, in going after about 44 different cell surface receptors on about 14 or 15 different cell types. We've chosen to target really four cells at the beginning, CD8 T-cells, CD4 positive T-cells, hepatocytes, and hematopoietic stem cells. I'll give you just a couple of examples here. One is targeting T cells, and blood cancers remain a very significant unmet need. 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, multiple myeloma. If you look at the left-hand side of the page, what you see is these CAR T-cells are made outside the body, and they're actually quite complex. They, both in the manufacturing process as well as before the patient receives the cells back, they undergo some conditioning chemotherapy. Sana's goal 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. Your body serves as the bioreactor. If we go to slide 10, we can just show you a little bit of what that looks like. On the left-hand side of the page, you see those orange blobs, and those are our medicines. The spikes on those are the fusogen. In this case, let's say they recognize CD8, maybe also recognize CD4 on the T cell, and they will then bind to that T cell, and deliver the genetic material. If in the middle column, that's that minus sign inside of the cell. 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. When you make a CAR T- cell, the goal is that the CAR will bind to a specific cell, in this case, a cancer cell. When it does, it will activate the T cell. An activated T cell will both kill its target cell as well as amplify. All of this is taking place inside the body. 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. That may lead to either better efficacy and/or better safety. Two, that we can do this without any conditioning chemotherapy for the patient. If we go to the next slide, what you see here is the definitive model that's utilized in studying B-cell malignancies. It's called the Nalm-6 mouse. These are mice where a tumor, a 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. 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. 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. What you see is, and this is when we activate these cells or we don't activate these cells, a little bit of a nuance. 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. The next thing that we wanted to do, and every one of these mouse models has limitations. One of the limitations here is that because we're putting human cells and human cancer cells into a mouse, the mouse's normal immune system is eliminated. We wanted to look and see what will be the effect when we put it into a normal immune animal. It turns out that our Well, we actually targeted a fusogen that would bind to both non-human primate and human CD8. 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. It turns out CD19 is on B- cells. It was quite toxic for the monkeys. They had both significant neurotoxicity as well as cardiovascular instability. We did see that they were able to deplete B- cells in the animals. We wanted to recapitulate that experiment. You go to the next slide 12. What you'll note here is that with a single intravenous infusion, we saw a profound B-cell depletion in four out of the six monkeys. A couple 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, this is our first time that we did this experiment, this was the first dose, to see this type of reaction is very encouraging. We constantly get the question, what happened to the other two monkeys? 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. 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. We just have to see where we end up. Stay tuned. We'll have more information around this as the year progresses. Where are we? We're in the IND-enabling phase and scaling up GMP manufacturing. 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 six months, and may be in human testing, kind of the latter parts of next year or early 2023. We are looking at targets beyond CD19 and BCMA. 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. Just for context, that's in the U.S. and Europe, around 100,000 people a year die of those diseases alone. 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. Here is some progress we've made in targeting hepatocytes, which are the active cells in the liver. We use lentivirus as a positive control here. Lentivirus is actually a modified HIV, where one of the things that has changed is actually the fusogen. 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 it's no different than LNPs. It also goes everywhere else in your body, because the LDL receptor is more or less on every cell. What you see here is an in vivo experiment of our liver-targeted or hepatocyte-targeted fusogen. What you can see is that lentivirus will get you into just over 1/3 of all liver cells. What we're seeing with our hepatocyte-targeted fusogen is the ability to do just as well or maybe a bit better and get into about half of these cells. A picture's worth a thousand words, and it looks quite nice on the right-hand side. What are we going to do with that? If we go to slide 15, and we're moving forward with a program in OTC deficiency, and that's a nice proof of concept around our ability to get into the liver. Probably more interesting and more importantly is what's on the bottom, and 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. 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. Stay tuned because I think you'll see some more progress along that front in the not-too-distant future. The next slide goes to this ex vivo part, and again, taking lessons from nature. Our goal here at Sana, as I mentioned earlier, was to figure out how do we hide cells from the immune destruction of foreign cells if we're going to transplant them. Really the insight here was just to look at the paradox of pregnancy. 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'd been rejected by our mothers. At the same time, none of us would be really great working donors to our mothers. What's different about that fetal-maternal border? To make a long story short, some scientists at Harvard University and Stanford University figured this out. They then went about figuring out what the differences were, and they then went about applying it, and the system that we have is surprisingly simple. When you think through the immune rejection, there are two elements to contemplate. One is what's called the adaptive immune system, and that's relatively easy to deal with, and you'll see a number of parties doing this, and that is 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 figured that a long time ago, and our innate immune system will attack those cells. We needed to figure out how to turn off the innate immune system, and in particular, natural killer cells. I'd say surprisingly, overexpression of CD47 has proven to be just a tremendous tool. Our goal is to create a stem cell line, make these gene modifications, hide the cell from the immune system, and then be able to differentiate in the manufacturing suite into something like a beta cell or a heart cell and replace that in the body. How are we doing? If you go to the next slide, these are just, again, pictures are worth a thousand words, and I think these are the most compelling data the company's created to- date. What this is we took non-human primate iPS cells, and we made the gene modifications that we talked about on the last page to them. On the top panel, what you see is if you transplant into the monkey muscle unmodified iPS cells, you see within about a week, most of the cells are gone, and by two or three weeks, they're entirely eliminated by the immune system. What you see on the bottom panel is that when we transplant our hypoimmune cells into the same spot, you see not only do these cells survive, but they actually thrive. These are data out to five weeks, and stay tuned. We'll have data out a good bit longer coming forward. 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 and survive. Importantly, what we see here is that this is looking at the immune response. On the top panel, what you see is in unmodified cells, T cells are activated, antibodies are produced, and natural killer cells actually don't see these cells because they have the Class I and Class II. What you see in the bottom is that our cells are hidden from the T cells. You see no production of antibody, and what is I think remarkable is that natural killer cells also don't recognize these cells. We're quite excited about where we can take this. We're going to move this into a host of different cell types, including T cells for cancer, pancreatic islet cells for type 1 diabetes and maybe beyond, heart cells for patients with heart attack, and glial progenitor cells for host neurologic disease. I'm just going to tease you briefly. Allogeneic or donor-derived T cells, you have to deal with three things if you're going to put my cells into you. My cells will try to kill you. That's graft-versus-host disease. Pretty easy to deal with. Knock out the T cell receptor. Your cells will try to kill me. That's called host-versus-graft disease. There, I think we have a very unique insight. We're taking donor-derived T cells, making these gene modifications we talked about, adding the CAR, and hopefully going out and targeting cancer. Where are we? First off, we want to make sure that the system works in killing tumor cells. This is that same Nalm-6 tumor modification. What you see is, on the left-hand panel, cancer takes over. In the middle, normal CAR T cells, they do very well in eliminating the cancer in these mice. On the right-hand side, you see that our HIP-modified CAR T cells are also quite potent in taking down the tumor. 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 or macrophages. 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 cell, or one made by the current standards by companies like Gilead, Bristol Myers, and Novartis. We'll go again into the B cell malignancies and myeloma to start. There are other places that might be as or more exciting to put this, though. Type 1 diabetes remains a real problem, and type 1 diabetes is when the immune system of the patient destroys their insulin-producing beta cells in the pancreas. It affects the 4 million patients in the U.S. and Europe alone. 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 2. This is a disease that, while there have been a lot of advances, even in places like the United States, there is 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. Our goal is to create a hypoimmune cell that will evade the immune system and normalize glucose. Here you see this is a mouse model, and we take stem cells, and we mature them into pancreatic islet cells. What you see on the left-hand side is that our cells respond pretty much like a normal human islet to glucose challenges. 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. If you go back to the animal model or the monkey model that I showed you, one of the things that we've done is cross the monkeys over. We put our hypoimmune cells into monkeys that already have seen unmodified cells and have an immune response to them. What we find when we do that is that there's absolutely no T cell activation. The antibodies don't recognize these cells, and natural killer cells don't recognize these cells, which gives us optimism that we're able to hide our cells from the immune system, even in patients with pre-existing immunity, like type 1 diabetes. We're in the process of making a GMP hypoimmune iPS cell line. It's a long process, I won't kid you. We're working on scaling our GMP manufacturing process. Our goal is to start IND-enabling studies soon. This is one that takes a bit longer. It's just a lot of engineering challenges, and we'd expect this to be in human testing as early as 2023, but I don't think it will be there next year. 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 R&D sciences as well as manufacturing. 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. 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 it. Thanks. Thank you, Steve.