Thank you so much for joining us for the Sana presentation. My name is Cha Cha. I'm a Biotech Equity Research Senior Associate based out of Boston. Really excited to introduce you to Sana and also, of course, to Steve Harr, our CEO. Steve, take it away. Is the presentation not working?
All right.
It's the wrong company you have up there. I'll start. First of all, thank you, Cha Cha, and thank you, Jefferies, for having us today. Thank you for everybody in the audience. Every conference has moved to a Q&A. We actually get to present the company presentation, so it'll be kind of fun. We will make some forward-looking statements, and you'll see that forward-looking statement slide. We spend a reasonable amount of time, actually a lot of time, writing our risk factors. Take a look at them. There's usually a good bit of information in them. We will make forward-looking statements. I'll just start, and we'll fill in with some slides as they come on. Sana was founded about six-plus years ago. The company really was focused upon two different platforms. One was something we call our hypoimmune platform.
The goal of that was to be able to hide cells from immune recognition and overcome allogeneic and autoimmune killing. The second is a platform for in vivo delivery of genetic material. I'm thrilled to tell you we've made a bunch of progress in both of them. Probably the most exciting data, or the most exciting data the company has had, is we ran the first study of testing our hypoimmune platform in gene-modified beta cells. We transplanted islet cells into a type 1 diabetic patient. We'll go through this in a minute. What we've seen is that those cells survive, and they function with no immunosuppression. It's the first example I'm aware of where anybody on the planet has been able to overcome allogeneic or autoimmune rejection without immunosuppression. We've done this.
This is a result that we think is really important for type 1 diabetes and delivering a cure for these patients. It is also something that we think is generalizable both across cell types and patient populations. It is the foundation for multiple drugs we have going forward, and many of them in large areas. The company's most important asset, and the one we are going to focus mostly on today and where I think the majority of our forward capital goes, is for type 1 diabetes. It is a drug called SC451. This is a gene-modified stem cell-derived pancreatic islet with the goal of transplanting it into the muscle of a patient, single injection. That patient will be rendered or will have normal blood glucoses or euglycemia for life with no more insulin and no immunosuppression. A functional cure for the disease.
We're also looking at utilizing the technology in allogeneic CAR T cells, where we have a program for autoimmune disorders as well as one for blood cancers. We have a separate technology. We'll talk on this very briefly at the end. That is for delivering genetic material in vivo. You probably recognize you can do more or less what you want to to a cell in a Petri dish. The challenge has been delivering that material in vivo. We set out with a goal of cell-specific delivery of basically any type of material, mRNA, DNA, protein. We've shown that we can do this at least in a preclinical setting in non-human primates.
We have the opportunity to make, in the first case, an in vivo CAR T cell with the goal of really a potent cell with no lymphodepleting chemotherapy and an opportunity to really transform the autoimmune and oncology landscape. We do have a balance sheet that allows us for multiple data readouts, but we will need more capital over time. I mean, that's no question about it. We are biotech, after all. I'm going to talk a little bit about now on this platform, the hypoimmune platform, the allogeneic rejection. Since the advent of transplant medicine, the largest challenge probably has been the challenge of immune rejection of someone else's cells. If you put someone else's cells into you, your immune system will recognize them as foreign and kill them. The standard of care today is lifelong immunosuppression.
There have been a number of efforts to grapple with this, whether that's with autologous cells, which are not that scalable, or different gene modification strategies. They haven't worked. There are two big arms of the immune system. There's the adaptive immune system of B cells and T cells. It's kind of what we learn about in immunology or with vaccines. That's actually relatively easy to deal with. You can disrupt class 1 and class 2 MHC, and these cells aren't seen by that part of the system. The problem is that the immune system has adapted a way to get around that. That is that natural killer cells will kill those cells very quickly. That's been the challenge of the field.
Our real insight has been that overexpression of CD47 in the context of class 1 and class 2 deletion renders these cells invisible to the immune system. We've shown this across multiple different animal models, non-human primates, mice, humanized mice, in many different cell types, in many different situations. What we really wanted to do is show you that this works in humans. The place that we decided, the easiest place or the most straightforward place to go would be type 1 diabetes. I'll talk about that, why. Type 1 diabetes is a giant unmet need.
It's a very rare market opportunity when you think about something that affects almost 10 million people globally, where the patient population has, on average, a 10-15 year shorter life expectancy than without it, where there are so many challenges along the way, whether that is microvascular or macrovascular disease and leading to things like blindness, amputation, heart disease, stroke, or all of the challenges of day-to-day management of blood glucoses. There hasn't been a truly disruptive therapy invented in over 100 years. The last thing was really insulin. We think this is a very large unmet need and an area where patients are really, really begging for something new and different. You probably recognize that type 1 diabetes is a relatively straightforward disease. The immune system recognizes and kills the pancreatic beta cell.
The beta cell is the only cell in the body that has glucose-sensitive insulin secretion. The patient no longer makes insulin. Before the invention of exogenous insulin, the patient would die pretty quickly. About 100 years ago, they started doing injection shots, which is nice. About 25 years ago, and this is part one, a group led by James Shapiro in Canada discovered that you could take primary cadaveric islets, so isolate the pancreatic islet from someone who just was recently deceased, and transplant that into a patient with type 1 diabetes. These people are now out 10, 15-plus years, and they have normal blood glucoses, off insulin. The challenge is that is not a great supply source. It is very variable, very difficult to scale. There just are not that many people for whom lifelong immunosuppression is better than lifelong insulin.
There are thousands of people walking around with this, but it has not yet really hit the mass market. Over the last several years, several companies have shown that you can take stem cells and turn them into pancreatic islets and that patients with those treatments can, again, be off of insulin. It seems to be a less variable supply source. Basically, 100% of patients who have gotten this therapy have benefited. It probably is more scalable. Some work to do to prove that. You still have this challenge of long-term chronic immunosuppression. Our goal has been a single treatment with long-term normal blood glucose without any immunosuppression or insulin therapy. I think we can show you and show you that we have now proven that we can eliminate the need for the immunosuppression.
Now we can circle this goal and say that this is an achievable goal. In our lifetime, I am very confident that patients will have a functional cure for this disease. I think we're going to do it. If we don't, someone else will. Why we can say this. We've shown, as I mentioned earlier, in non-human primates and other models that we can transplant islet cells without immunosuppression and overcome diabetes. We wanted to show if this works in humans. The study that we came up with was a straightforward investigator-sponsored trial at the Sahlgrenska University in Sweden where a donor donated their pancreas at death. That pancreas was gene-modified. The beta cells were isolated, gene-modified, and transplanted into a patient with type 1 diabetes. It was done into the muscle of the forearm, and the patient received zero immunosuppression.
Our key outcome measures were safety, immune evasion, cell survival. The best way to measure cell survival is something called C-peptide. When a beta cell makes insulin, it actually makes proinsulin. When it's secreted, it secretes C-peptide and insulin. C-peptide is a one-to-one measurement of the amount of insulin that the body is making. I can tell you the six-month data from this will be presented at the American Diabetes Association meeting on June 23. It's a plenary session at 9:00 A.M. Come see that. I'm optimistic that you'll like the results. What we've shown here is the 4 and 12-week results. To date, all primary and secondary endpoints have been met. The patient is doing well. He is making his own insulin for the first time in over 30 years. There have been no safety events.
I'm going to go through the efficacy here in a second. The first measure, as we talked about, is C-peptide. C-peptide is secreted. What we're looking for is is it detectable. That means the patient is making his own insulin for the first time in 30 years. It's undetectable at baseline. It has been for decades. We wanted to see would that be stable at baseline. What you see on the left-hand slide here is that if you look out over the first 12 weeks, it is absolutely stable. My view is all of the immune risk went away after four weeks. I expect this to be stable for a long, long time. On the right-hand side, you have a functional read. This is something called a mixed meal tolerance test.
A patient is given a meal, and insulin should go up as sugars go up. What you see here is that the C-peptide rises with the meal, and the patient is basically responding to the sugars going up. You have functional cells, and you have cell survival. You can also see them by pictures. This is an MRI. This is at four weeks. What you see on the left-hand side is a cross-section of the left forearm of the patient or the recipient. What you see on the right-hand side are these little dots. Those little dots are aggregation of cells, of beta cells, or at least we knew at that point that they were cells. They are stable over time at one week, two weeks, four weeks, eight weeks, 12 weeks.
This next slide, oh, I thought we had somewhere we had it. I thought we had a slide as well that showed we've shown that by MRI, PET MRI, that those are definitively beta cells. You can look, and they will go with a beta cell marker. You have visualization of these cells. You now have function of those cells. What we want to look at is what was the immunology like in the patient. The way that this product is made is you actually take a donor cell, and we gene-modify it. We knock two genes out. We knock one in. We're not 100% in everything. Every product is a little bit of a gimmich.
Our team decided they could figure out they could make lemonade from this lemon by looking at the various patient populations and seeing what was their immune response. You have three major types of cells. We have the hypoimmune islet cells. Those are the cells where all three gene modifications have happened, overexpressing CD47 and knocking out class 1 and class 2. We have cells where you've knocked out class 1 and class 2, but you don't overexpress CD47. We would expect the natural killer cells would kill those cells. Then you have wild-type immune cells where you still have HLA class 1 and class 2 wild-type islet cells. In that setting, what you'd expect is that you would see a T-cell response, and the patient would generate antibodies against that. That's basically what we went and we tested.
Now, if you look at the wild-type islet cells, again, these are unmodified cells. What you see is within a week, a very robust, on the left-hand side, T-cell response. What you see below is when you pour those T-cells on the product, they kill the cells. They kill it over and over and over again over time. What you see on the right-hand side is that the patient has generated antibodies within a week, IgG antibodies to these cells. These antibodies recognize and will kill these cells. Immunology is playing out as we expected. It is enough cells that you're generating a very robust immune response to unedited cells. This is looking at the double knockout cells. They knock out class 1 and class 2, but they do not have the CD47.
What you see on the left-hand side is they generate no T-cell response, exactly as we'd expect. What you see in the middle is they generate no antibody response, again, exactly what we would expect. What you see on the right-hand side is that the natural killer cells just kill these cells. They kill them rapidly and immediately. They are dead very quickly. What you see here on the hypoimmune cells is that the patients generate no T-cells. They generate no antibodies. Natural killer cells do not recognize these cells, and they remain and thrive inside the patient. The last thing I wanted to show you is we just took all of the blood from the patient. We basically poured it onto the drug product to see what would happen, just in case we were missing something.
It's also a really nice visualization. On the left-hand side, it's against those wild-type islet cells, not gene-modified. In the middle, it's the double knockout cells that are overexpressing CD47. On the right-hand side, it is our hypoimmune islet cells. What you can see is that the wild-type cells are killed very rapidly. The knockout cells are killed rapidly. These cells survive and thrive over time. Exactly what we hope to see. I think what we've shown you here is that we've actually accomplished this, what we set out to do. We've overcome allogeneic and autoimmune rejection. Our goal, though, is not to make this in cadaveric islets. Our goal is to take a single cell, a stem cell, a pluripotent stem cell, gene-modify it with knocking out class 1 and class 2 and overexpressing CD47.
We also put in a safety switch, by the way. We grow those up, and then we differentiate them into pancreatic islets. Islets made of alpha, beta, and delta cells, the beta cell being the most important part. We manufacture that at scale and, with a single treatment into the arm, hopefully deliver a functional cure for the patient. We hope to have an I&D on this next year. There are four major scientific challenges in our mind to making this happen. The first is to overcome immune rejection without any immunosuppression. I think we just showed you we've done that. The second is to take these pluripotent stem cells and make them into islets at a purity, potency, and yield that enable us to run a clinical study. We've done that. So have others, by the way.
The third is to generate a gene-modified master cell bank that's GMP-compliant that has a stable genome over time. It's been super hard. As far as we're aware, no one in the world's done this. We think we've done that now. We have that one in the rearview mirror. The fourth one is to manufacture these at a scale that will end up being a commercially important level. I think we still have a lot of work to do to do that. I think you should feel good about our ability to get to an I&D. I think you should feel really good about our ability to get to a proof of concept. I think there's some work to do to kind of see if we get for commercialization.
I want to show you one more slide, which just gets at some of what we see on differentiation. This is basically looking at the left-hand side, which is just an RNA expression or DNA expression. Without getting into too much around with this, this is a very highly pure islet population, right? We have alpha cells, beta cells, and delta cells. In the middle panel, what you see is that you have glucose-sensitive insulin secretion. This is an in vivo test performed in an animal at one year. It happens, and it maintained over time. On the right-hand side, from the exact cell line, the sub-clone that we intend to take forward, this is a 15-month study in animals that shows, one, no histologic abnormalities. That is the biggest risk.
Two, that it continues to function and overcome the diabetes, or I should say the insulin, the lack of insulin. We think we have what we need. I think this is a drug. I do not think there is much risk to this working. We still have some risks and some work to do. The three main risks are time and capital. We need money to do this. Two is you can still run into a safety issue. We are very, very thoughtful around what we are doing preclinically around that. Three is we still have some work to do to scale it. We are really optimistic about this and think this is a generational opportunity to give patients a cure for one of the largest unmet needs on the planet. Moving on, we have been working as well.
I think most of you recognize that B-cells drive a lot of autoimmune disorders. I think most of you recognize that there are over 75 that have been shown actually to benefit from B-cell depleting therapies. I'm sure most of you recognize that Dr. Schrepfer in Germany and others have shown with autologous CAR T-cells that you can potentially reset the immune system and give the patient what looks like a durable, long-term complete response and maybe a functional cure with a single treatment of a CAR T-cell. We've been pushing that forward with our allogeneic platform. What we do here is we manufacture. We take a donor-derived T-cell, and we make a series of edits. We knock out three genes, and we knock two in, to be clear. We knock out MHC.
The first thing you have to deal with is graft versus host disease. You knock out the T-cell alpha. Simple. Many have done that. The second thing you have to grapple with is host versus graft disease, which is what people have really struggled with. That is the patient's immune system killing the cells. To date, the only real way that people have overcome that is actually knocking out the patient's immune system. We do that by, again, knocking out MHC class 1 and class 2, and we overexpress CD47. We also knock in the CAR gene. That's basically the product. We've done this now many times in the manufacturing side. From a single manufacturing run, we can make enough drug to treat hundreds and hundreds of patients. To just give you a sense, let's make that 500 for a second.
That means if we do 500, if we do 50 manufacturing runs a year, which I think with autologous cells, most of you would say that's not too complicated, we get enough drug to treat 25,000 patients. This is a scalable process, and it's a technology that we've shown you can evade immune detection. We started out with a CD19 CAR T-cell with SC291, and we started an oncology study, actually. What we saw in that study was a dose-dependent deep B-cell depletion. That's what we want in this autoimmune study, right? It was well tolerated. There was no grade 2 or higher CRS. There was a little bit of grade 1 CRS, and we had no cases of ICANS or neurotoxicity. We started a trial called the Gleam study. That is looking at patients with lupus or ANCA-associated vasculitis.
It's a dose escalation study. We can go into other indications over time. The trial started enrolling patients last year, and we expect that we can show you data this year. I think from what you've seen in the oncology setting with this drug, you know that the drug works, right? You can safely deplete B-cells. We have to see that translate into the oncology setting. We have to figure out, is the drug OK, good, or great? OK. The way I think about that is how it both affects the patient as well as how it fits into a very competitive dynamic with both autologous CAR T-cells and TCEs. We're optimistic about this drug. We'll have data soon. It's a challenging place to develop a drug. There is a lot of competition.
It will be an area where I know investors are less excited about than type 1 diabetes. But it's something where we think that we can create a lot of value for patients, both because of the manufacturing scalability, the lack of necessity to do an apheresis, which is very complicated in a patient with an autoimmune disease, and also because of the efficacy that we think we can see. We've also been moving forward trying to make an in vivo CAR T-cell with our other platform. The way that the in vivo CAR T-cell works is that we make a drug called the Fusizome. That Fusizome has, and I'll show you in a second, an ability to deliver genetic payload in a cell-specific way. That little blue thing is our medicine. Inside the patient is this T-cell.
The Fusizome will recognize the T-cell, and it will deliver the CAR transgene. That CAR gene is that little minus sign in the middle panel. The CAR gene then makes a CAR, which is expressed on the cell surface. That CAR hopefully will recognize its target cell, in this case, a B-cell. When it recognizes that B-cell, what you see on the far right is it will activate the T-cell. When it activates the T-cell, it does two things. It kills the target, and it divides. Now you have two. You just keep going like that. Hopefully, what we get is amplification and a deep B-cell depletion in the case of autoimmune disorders or just eradication of the cancer in the case of leukemia or lymphoma. How does that technology work? We use something called the Fusigen.
We use a paramyxovirus. The paramyxovirus, we modify it. It is a logic-gated cell recognition capability that sits on the surface of like an envelope virus. It has a G and an F component to it. The G you can think of as guide. The F is fusion. What we do is first we neuter the G so it recognizes nothing. Then we add some kind of a binding moiety to help it recognize a target cell. We then do some protein engineering to make this F protein, the GF protein function really work. When the G binds to its target, it unleashes that F. That F then is like a sphere, and it drives together our drug and the target cell. The genetic payload is delivered directly into the cytosome.
You both get cell-specific delivery, and endosomal escape. It works. This is a non-human primate GLP tox study with our drug SG299. This is a CD8-targeted Fusigen, which means the drug is targeting CD8-positive T-cells. It delivers a CD19-targeted CAR, which means its goal is to either eliminate cancer or eliminate B-cells. What you can see on the left-hand side is that we get very potent transduction of circulating CD8-positive T-cells. This CAR does not bind a non-human primate CD19. What you see is you get into about 10-20% of circulating T-cells, which is a great number. What you see on the right-hand side is that it is very specific. I would challenge you to see this from any of these other companies that have put forward an in vivo capability.
You have no capability to find this in the liver. You see this in zero gonadal tissues. It is quite specific delivery. When we did this, what we did not know was whether or not it actually worked, right? Because we did not know the pharmacodynamic effect because, as I mentioned, CD19 does not recognize the target. The next study we did is we used a surrogate. We actually put a CD20 CAR into it that recognized a non-human primate. We added an additional component. What you see here is, with injection, a really nice, robust generation of CAR T-cells, great expansion in the periphery to the extent that you have 30%-50% of the circulating T-cells are CAR T-cells. That is like thousands of T-cells per mL. It is great. You see on the right-hand side very deep B-cell depletion, right?
It is what we're looking for in the autoimmune setting. Ultimately, we think it will be important in the cancer setting. Beyond seeing this great pharmacodynamic effect and seeing the cell-specific delivery with this, we also have biopsies. What you see here, the brown is a stain for B-cells. In the control arm, you see B-cells all over the lymph node. This is a lymph node from the animal. In the first monkey, what you see by about 28 days is a little return of the CAR, and you can see just in the periphery a tiny bit. The second monkey is a completely clean lymph node.
This is something, and we can show you data that show that you get a complete B-cell reset as well, what you've been really looking for in the autoimmune setting with a single treatment, no lymphodepleting chemotherapy, generating in vivo CAR T-cell. This is something where we can file an IND next year. I'll say we got to unlock the capital to do that. Right now, it's not something that we've prioritized. Our goal is to get that capital unlocked this year and then get it into humans next year. We've got a lot going on. We mentioned we've got this hypoimmune platform seems to work. In type 1 diabetes, all of the components for curative therapy now in place.
I think if you look at what others have done in the field in transplanting cells with immunosuppression, I kind of think of that like they invented the electric car, and it works, but it has to be plugged in. So it's not that useful. We then showed through this investigator-sponsored trial that we can overcome immunosuppression, sorry, the allogeneic and autoimmune rejection and need no immunosuppression. I kind of think of that as making a lithium battery. Now you can put it together, and you have a functional car, right? An electric car. And our goal is to make this into humans next year and have proof of concept rapidly thereafter. You'll see six-month data from that investigator-sponsored trial at the American Diabetes Association meeting in three weeks. I think that we'll also publish the results of this in a very high-profile journal, I think, shortly.
Expect to see a good bit from that. We have data coming from our gene-modified CD19 targeted CAR T-cell in the autoimmune setting. We have data coming from a CD22, which I did not talk about, in CD19 failures with different types of lymphoma. We are making real progress in moving forward our Fusigen platform. I think I am excited by where we are. I think we have a generational opportunity, as I mentioned, in type 1 diabetes. It is a drug that should work. We have to make sure we can scale it and that it is safe. I really look forward to keeping you informed about our progress in turning this into a therapeutic for patients. I think I probably have time for one question, or we can just break it because we are kind of in the minute-left time zone. I think we will just go.
We'll call it a day and talk to them. Thank you.