Welcome everyone to the 41st annual JP Morgan Healthcare Conference. My name is Tessa Romero. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by Taylor Hanley and Raj Shah from the team. Our next presenting company is Sana. Speaking on behalf of the company, we have CEO Steve Harr. Before I turn it over to Steve, I just wanted to highlight that for our Q&A after the formal presentation, there is an Ask a Question button in the portal, which should allow you to submit your questions, and I'm happy to ask the question on your behalf. We're also taking live questions here in the audience. Just wave your hand, and we'll get your question in. With that, I'm gonna hand it over to Steve.
Well, thank you, Tessa and thank you, JP Morgan. Thank you, everybody here in the audience as well as online for joining us. We're thrilled to have a chance to tell you a little bit about what we're up to, the progress we've made. You know, we're quite excited. Hopefully, you'll be as well. We have a lot of information, hopefully coming out that'll help you understand our company better in 2023 and beyond. Before we do that, though, of course, you know we will be making forward-looking statements, so please take a look and peruse our regulatory filings, Form 10-Q, and Form 10-K for risk factors. We spend a lot of time on them, and there's a lot of good information in them.
With that, you know, Sana's purpose is to change the possible for patients through the power of engineered cells. We went about trying to do this by really tackling two of the most fundamental challenges and actually making that vision a reality. First and foremost, every time we transplant a cell into another person, there have been challenges and problems with allogeneic rejection. Overcoming that, we think, can have a very significant impact. The other is it's pretty possible today to do anything you'd like to a cell in a petri dish. The real challenge in terms of modifying the genome and controlling the genome has been delivery in vivo.
We have a technology, our Fusogen technology for in vivo delivery, where we're able to really deliver the genomic modification reagents, gene editing, base editing, and others in a cell-specific manner. We've made a lot of progress there, we really wanna focus today, and we're gonna talk about that later on the hypoimmune platform. You know, overcoming immune rejection, as I said, has the potential to really change the way we approach and actually utilize cell therapy. I think most people recognize the opportunity and promise of autologous CAR T-cells and also some of their challenges. The field's been working on allogeneic CAR T-cells, but really struggling to overcome immune rejection.
We think if we have allogeneic CAR T-cells that perform like autologous cells, we can really transform the treatment of a whole host of blood cancers, lymphoma, leukemia, myeloma, and have the opportunity to treat tens of thousands of patients per year. You know, additionally, really, if you're gonna look at stem cell-derived therapies such as pancreatic islet cells, we have to overcome this allogeneic rejection issue, and then we think we're making real progress there. The beautiful thing is this year we have two opportunities for really clear clinical proof of concept of what we're doing. SC291, which is an allogeneic CAR T-cell targeting CD19, will have the IND's been filed. We anticipate having a substantial data as we move through the year.
Something we haven't talked about until today is we've been working on hypoimmune edited primary islet cells, which we can transplant into patients with type 1 diabetes and really understand, can we overcome allogeneic and autoimmune rejection in patients? We think these will not only provide insights for our portfolio broadly, but it also really will hopefully highlight that we have a number of drugs which can move forward towards the market. We have a lot of drugs we'll talk about in a second, and we have a balance sheet with over $500 million to hopefully see this through at least through the next phase of clinical development. This is just a little screenshot of our pipeline. You can see we've got an IND, we filed for SC291.
One was filed shortly for these hypoimmune primary islet cells, which I'll describe later. You begin to see data readouts this year from a couple of programs. With two to three INDs coming, you know, this year and next year, you can see that the data readouts begin to really pile up as we move through 2024 and 2025. We'll talk about the rest of this pipeline at another time. Today, we're gonna really focus on the allogeneic CAR T-cell portfolio as well as what we're doing in type 1 diabetes. Since the advent of cellular medicine and really transplant medicine, the problem of allogeneic bone marrow rejection has been at the forefront of challenges for the industry to or, and to really tackle. Cell-based medicines have the same problem as organ transplant.
The only real path to date to overcome this has been very significant immune suppression, and there are challenges with that. Patients end up with severe infections. They're at higher risk for cancer, and there are all kinds of other idiosyncratic problems with each drug. We've tried to overcome it with allogeneic cells. To date, you know, the genetic modifications have been incomplete. I mean, I think that's pretty transparent, and it hasn't really worked as well as we hoped. I think people recognize autologous cells have really had challenges with scalability, and they'd only work for a few types of cells that exist in suspension. In fact, there's only one and I remember this, there's only one allogeneic cell that's widely used today, and that's red blood cells, right?
They have been used broadly in millions and millions of patients really successfully. I'm gonna come back to that in a minute. We think overcoming this immune rejection has the potential to really unlock not just what we do at Sana, but really a host of drugs across the field. How do we approach this? One of my core learnings over time has been when you're faced with a complex scientific challenge, see if Mother Nature solved it, and if she has, exploit that system. It started really around the paradox of pregnancy. The paradox of pregnancy is that we're each half mom and half dad. The only reason that we're in this room together today is our mothers didn't reject us in utero.
Our DNA and proteins are different enough that really none of us would be good immune organ transplant donors to our moms. What we set out was to really understand what was different about that maternal fetal border. You have to overcome two aspects of immunology to really make this work. There is the adaptive immune system of B and T cells. It's actually relatively easy to deal with. People figured this out a long time ago. In some way, we need to disrupt class one and class two MHC. When you do that, the challenge is it's easy enough that cancer cells and viruses figured it out a while ago. We evolved the innate immune system of things like natural killer cells, and they will kill cells that are missing that, and that's been the challenge.
What we figured out is that with overexpression of CD47, we can both turn and knocking out class one and class two, we can both turn off the adaptive immune system and also turn off the innate immune system. Remember I told you this has only been that there's only one place that you really are successfully able to transplant allogeneic cells, and that's red blood cells. It turns out, and this was not why we went down this path, but it turns out sorry, red blood cells have no MHC class one and class two on their cell surface, and they markedly overexpress CD47. We have been able to successfully transplant them in humans over and over again, for decades now. When we started this is just a little bit of the in vitro data that we did.
You know, the first challenge is overcoming T cell killing. What we have is across the top, knocking out class one and class two MHC, HLA 1 and 2. Then there are various strategies that we and others have tested for trying to grapple with this innate immunity. Doing nothing, and you can see the T cells actually do fine. Knocking in some other things which may impact T cells. As you do this, on the bottom, what we plated are just regular cells, and we put on top of it regular natural killer cells. What you see is that for every example here, except for overexpressing CD47, the natural killer cells will rapidly chew up and eat these modified cells that overexpress some other protein, or just knockouts of class one and class two.
We know this, these other systems don't work. We believe that what we're doing is working. This is in vitro. We tested this in mice. We've tested this in human mice. The next real test was to figure out what happened when we put them into normal immune non-human primates. Here, these is an experiment of eight non-human primates, four in each arm. In four of these animals, we put in a hypoimmune cells. Hypoimmune, again, have these three gene modifications. The other, we just transplanted regular unmodified cells. On the bottom, what you see is with unmodified cells, they're killed within a matter of a couple of weeks. What you see across the top is that our cells thrive and survive for as long as we watched them in this study which is about four months.
That was exciting for us, and it was a real transformation in our understanding and our belief because no one that we're aware of has ever transplanted allogeneic cells into a normal immune non-human primate with no immunosuppression and seen them live. It was a big step. We wanted to see what happened when we went into other cell types. This is an example of transplanting pancreatic islet cells. What you see on the bottom is, again, that these cells are killed very rapidly, really within one week, If you have not made any genetic modifications. We transplant our gene-modified cells. What you see is cells are living. At this point, we're out to 10 months, and the cells are still doing quite well and thriving.
Not only can we transplant, you know, iPS cells, we can transplant real thriving cells like islet cells, and you're seeing them live for a prolonged period of time. We've now done this across multiple cell types. Here you see iPS cells, islet cells, retinal pigment epithelial cells, cardiomyocytes. Our general take is if you're a non-human primate, we've solved this problem. Unfortunately, none of us are, right? We're people. The most important step for us is to get this into humans and see really what happens. To do that, the first place we're going is into allogeneic CAR T cells. Just to set the pattern, the table a little here, I think sometimes this is a marketplace that can be very confusing for people.
It's lymphoma, leukemia, multiple myeloma, and it feels like there are so many drugs that are coming after them. It feels like with, you know, particular CAR T cells, maybe this problem's already solved. What you see here on the left is if you look at just the U.S. and E.U. five, there are 250,000 people annually who are diagnosed with these diseases. There are 100,000 people a year that are still dying from these diseases. There are only mid-single-digit thousands of people that are treated with CAR T cells, and of those, only 30%-40% benefit. That little blue dot is the only thing that the market is currently satiated and the rest of it is available for us to go out and hopefully transform the way these cancers are treated.
We know the problem with autologous CAR T cells. They're hard to make, right? They're hard to scale. Sometimes people fail in making them. Even when they get them, the majority of patients actually will relapse and will not have a durable, complete response or a cure. The allogeneic cells to date, they do work. People have made them. The challenge is that we have not overcome immunologic rejections. The cells die quickly, and the cancer recurs at a very high rate. We have to make these cells work, really overcome the limits of CAR T persistence. With that, we think we'll have really great efficacy. We know the opportunity, we know the targets, we know the efficacy and safety bar. Really, it's up to us to go forward and make this happen.
How do we do this? The first thing we do is we take just white blood cells from healthy donors. We choose them based on some immunologic criteria and other things. We then select out the T cells, and we modify the genome with our three gene edits we talked about. That will prevent something called host-versus-graft disease, your cells trying to kill my T cells. We also have to make one other modification to the TCR alpha gene. That will prevent my cells from trying to kill your body, something called graft-versus-host disease. That provides a construct from which we make all of these allogeneic CAR T cells. We then can insert in different CARs, CD19, CD22, BCMA, GPRC5D .
With the first three of those, what we have chosen to do is we're taking forward clinically validated best-in-class CAR T cells. I hope to convince you is if it works in one, it's gonna work in three, right? This is gonna be relatively straightforward. Then we make them at scale. We can make these cells in the hundreds of doses per batch. You know, you translate that's going to be relatively straightforward, we think, to be able to treat thousands or tens of thousands of patients annually. We make very high-quality CAR T cells, we are off to the races. The first question really when you're dealing with this is, you're making all these gene modifications of have I heard efficacy?
In some way, have I made it so these cells don't work as well? This is a mouse model that everybody uses in making these CD19 CAR T cells. It's called a Nalm-6 model. A little bit differently, we put in a human immune system into these mice to see what would happen. On the left-hand side, what you see is you put in the tumor, and it overwhelms the mouse, and that the red is just cancer everywhere. In the middle, you see the unmodified cells. On the right, you see our HIP-modified cells. Typically, people run these experiments for about four weeks. What you see in the short term is there's no real difference between our cells and regular CAR T cells.
What you see as you watch longer, and the unmodified cells are rejected, is the cancer recurs in the unmodified cells, and it doesn't in our cells. Then we did something that really has never been done before. We actually reinjected tumor cells to see what would happen. You see in the bottom is that that really does still they're still around, and they still kill the cancer cells. That was something that when we presented this just about a month ago at the ASH meeting really kind of caught the eye of scientists and investigators in the field 'cause we haven't seen it. We're optimistic that these cells will work quite well. We filed the IND. We expect to see clinical data this year. It's actually really straightforward, we think, to understand what we have.
There is a direct correlation between CAR T-cell persistence and the durable long-term complete responses, hopefully they'll turn into cures, that patients receive. We think you can figure this out really quickly with some data. If our cells last in a month, we're gonna look like a lot of the other allogeneic CAR T cells today. That's really what the field's showing. If our cells last two-three months, we probably have a best-in-class allogeneic program. If the cells last three-five months, three-six months, we'll be comparable to anything you've seen from the autologous CAR T cells. They last more than six months, there's really we're optimistic we can be better than what the field is seeing today. That's data we can generate in very short order. We're quite excited to really understand what we have.
If we do, we're ready to move forward with this drug really rapidly in lymphoma, and leukemia, chronic CLL and ALL. We won't be done. If you look today, you know, a number of patients who receive CD19 CAR T cells fail. You know, the market estimates are that, you know, in the next five years or so, about 12,000 people a year will be getting these CD19 CAR T cells. You know, 35% of them will have a durable complete response, and the others will relapse. You're looking very shortly at a market of around 7,500-8,000 patients per year. Here what we've chosen to do is move forward with a CD22 CAR to treat these patients. CD22 is another target that's overexpressed, that's expressed highly, I should say, on these on these B-cell malignancies of lymphoma and leukemia.
All we're doing is swapping out that CD19 CAR, and we're putting CD22 in here. Fortunately, we've licensed a CAR T cell, the CAR that has been really utilized across the field and generated best-in-class data. In the autologous setting, what you see is over 50% of patients who have failed a CD19 CAR T cell who have treated with a CD22 CAR are generating a long-term durable complete response or complete remission. We'll file that IND this year, likely have data next year for you, hopefully that corroborate that, you know, what we see in CD19 really pulls forward into CD22. We won't be done then either because I think what everybody recognizes the potential and power of targeting BCMA with autologous CAR T cells.
You know, when we were at ASH having our meetings with clinicians in the field today, it was really exciting to see the data that's being generated with these drugs and the CAR T cells are moving earlier and earlier into patient populations, which are bigger and bigger market opportunities. Unfortunately, even today, what clinicians say is that for every 25 patients in their practice for whom they have a real need to give a CAR T cell, they're getting a slot for one. Even as that as access improves, that market will not be satiated for a long time. What we have here is this is a CAR that, again, in the autologous setting has generated at least as good a data as anything in the field.
This is a 100-patient study, what you see is the best marker of long-term complete responses is MRD negativity, meaning you cannot find the cancer by the most sensitive genetic test. 95% of patients are reaching MRD negative, this is in patients both who have received prior CAR T cells and those who haven't. About 80% of them remain in MRD negative out a year. We're really excited about the opportunity for this drug in myeloma as well. We've done a lot of the preclinical work. We have, you know, we just have only so much bandwidth. This is an IND we'll file next year, hopefully with data coming not too distant after that. Really set up, we think, with CD19, CD22, BCMA, and beyond to build something.
What we have is we have validated targets, right? You've got validated CAR constructs. We're not building these things from scratch. We're taking things from the autologous setting. You have the opportunity to treat over 100,000 patients. You know exactly what you need to do. We have a HIP platform or hypoimmune platform that's very well understood and validated in preclinical models. Now what we need to do is show that it works in humans. Hopefully, we'll do that for you over the coming quarters. You unlock everything in that blue box on the right. We move past that, we have the potential to move into lupus, where we're really excited by some data that's been generated in the field, in particular in lupus nephritis and other.
You know, we can go into other autoimmune disease and then solid tumors. Stay tuned. This is something that we think can be very powerful and really excited about. I'm gonna switch tacks for a second and move to type 1 diabetes. Type 1 diabetes is a disease where the immune system attacks and destroys the pancreatic beta cells inside of a patient. The patient can no longer make insulin, and they are able now to be controlled with endogenous insulin. Even with the best care, a type 1 diabetic will live about 15 years less than a, than you and I will on average. It's a very large unmet need with about 4 million patients between the U.S. and Europe.
Their lives are really challenged, even within those when they do live with a number of issues like stroke, blindness, kidney failure. Our goal is really simple. It's with a single treatment to allow a patient to live in euglycemia, normal glucose, with no exogenous insulin or immunosuppression. That's the goal. We know that transplanting pancreatic islet cells can cure patients with type one diabetes. It's been done a couple times by others in the field from stem cells. People have been doing this with primary islet cells derived from cadavers, you know, now for thousands of patients. Unfortunately, because you have to overcome the allogeneic rejection, the autoimmune rejection, patients get a lot of immunosuppression. There aren't that many patients for whom lifelong, you know, substantial immunosuppression is better than lifelong insulin.
It does work. We know it works. Our goal on the right, what we will do is from a pluripotent stem cell, make the genetic the HIP modifications. We will then make those cells into pancreatic islet cells and transplant them in the patient with no immunosuppression and hopefully, protect them from both allogeneic and autoimmune rejection, as well as, you know, return them to normal glycemia. We showed you earlier in non-human primates that we can overcome the allogeneic rejection with these cells. We're out 10 months plus now in transplanting islets into non-human primates. That's the allo side. There hasn't been historically a great model of autoimmune rejection, but this is something where some of our capabilities came together to create a unique model.
We took a type 1 diabetic, got informed consent in their blood, took part of the blood and made it into, transplanted a humanized immune system into a mouse. Now you have a mouse who has a diabetic immune system that will attack its own, islet cells. We then took some of the other, blood cells and reprogrammed them back into, pluripotent stem cells. We then gene-modified half of them with our, hypoimmune edits, and we left the others alone. We then grew them into or differentiated them into islets and transplanted them into diabetic mice. What you see on the right-hand side is it worked. When you With this, these are mice where we give them diabetes, they have a diabetic immune system, and we put in their islets derived from their own cells.
Their immune system will very rapidly kill these cells. You see that within a matter of a few days, and the diabetes is not controlled. This is an autoimmune model that really shows you know, the how the immune system kills these cells. In our gene-modified cells, what you see is it also worked. Here, we transplant the cells, the cells live, survive, they thrive, and the animal's glucose comes under control, and they no longer have diabetes. This is a model that's never been utilized before. We think it's a, you know, about the best way we could preclinically test autoimmune rejection. Feel really excited about how we've done preclinically in testing allogeneic and autoimmune rejection. The next key is to get into humans.
We've never talked about this, but about a year ago, we started working on a way to do this. We talked a little bit about earlier that patients have been getting primary islet transplants for years. There have been thousands of patients who have gotten them. Our what we've devised is a way to gene modify these islets and hopefully transplant them into type 1 diabetics. We'll do this very soon. We'll file our for regulatory approval shortly. Our goal is to have data in 2023 that will allow us to understand can we overcome autoimmune and allogeneic rejection. It transforms a cure for type 1 diabetes as something that we think about as being possible to something that's absolutely inevitable.
It will be inevitable if this works. It's really straightforward too. You see that cells will die within a matter of days, if they're not gene-modified. If we can do this, transplant cells with no immunosuppression and see them live and thrive, we'll know within, you know, a month if this is really working like we hope we do. We're, we're excited that this will give us insight into our ability to make SC451, which is stem cell-derived, islets, as well as really help us understand how well our stem cell therapies broadly are going to work in overcoming immune rejection. That's where we are. You know, it talks a little bit about the hypoimmune platform today. We've got a couple of shots on goal this year to really understand exactly what we have in humans.
If it does work, we'll be, you know, moving forward very rapidly with an allogeneic CAR T franchise in oncology as well as in autoimmune disorders. Since we'll understand what we have with stem cell-derived therapies, hopefully this year through type 1 diabetes and push forward. We're gonna come back, and don't forget about the Fusogen platform. Because this is something that we think is gonna be really powerful over time. We absolutely aim for cell-specific delivery of the gene modification reagents, and we think we can do gene-specific modification in a cell-specific way, and that will unlock a whole host of treatments across the field for, in particular, genetic disorders. With that, we should take questions. I think some other people are joining me on stage.
Yes, yes. Thanks, Steve. I'd like to invite the rest of the Sana team up on stage with me and we'll take a couple questions.
We all stand. Do you want to stand?
No, no, I can stand. Don't worry about it. Okay. Okay. Just a reminder to just wave your hand at me if you have a question.
As you're doing this, it's kind of getting.
Thanks. The IND for SC291 was filed. What can you tell us about a potential phase I trial design there? Will the trial allow for investigating the potential for redosing?
I'll take the last question and then I'll turn it over to Terry 'cause the redosing question's easy. If we have to re-dose, it hasn't worked like we thought it will. Right? We think that these cells will persist, and they will be there to kill tumor until it is gone. I don't see any need to re-dose. You know, we'll cross the bridge of exactly what the design is. You should know as you think about it, if we're redosing, things haven't worked as we thought they do. Terry, you wanna take the kind of just what our phase I trial design looks like, but maybe break it into phase Ia, a little bit about phase Ib?
Yeah, sure. The phase Ia portion of the study is a fairly standard, you know, phase Ia design, you know, dose escalation, you know, with the goal of understanding safety. We certainly, you know, expect, you know, at the doses that we're using, including really the first dose level, that there's, you know, that we'll be able to look at biologic activity and certainly, you know, cell persistence. You know, the diseases we'll go after will be CAR naive patients. You know, we'll include lymphoma, we'll also include CLL as an additional indication in the phase Ia portion of the study. When we go beyond the phase Ia, once we establish the dose, we'll look at multiple expansion cohorts to be able to understand efficacy better in preparation for the pivotal study.
For those of you who don't know, Terry Fry runs our T-cell therapeutics group, formerly was the head of pediatric hematology at the NCI. The number of the CAR T-cells that are in development and even one that's approved came out of Terry's lab. He's been doing this for a long time and hopefully will be there to help us navigate it. We really do think that the key out of the phase I study is you're gonna wanna see complete responses. That's very clear, is you wanna see these cells work. You're gonna wanna see how long these cells persist 'cause that will directly tell you, we believe, how. What % of your patients are you really gonna get to a durable complete response which is the only thing that really matters, right?
We're really not looking to make patients better for weeks. We're looking to make them better for years and years.
I think, Steve, you had a slide on this in your presentation about kind of what the bars for success are on persistence. Maybe it makes sense, 'cause I know, you know, we get this question from time to time just to dig in a little bit there on what the bar for success is on persistence and then maybe on response rate.
Persistence we kind of laid out in the slide. Just a reminder. You can look at data across the field, and it's really transparent, I think, around what the expectations are and the implications. You know, if we have cellular persistence that's less than one month, we're gonna be like all the other allogeneic CAR T-cell players. They're important. I'm not saying these are worthless drugs. But there is a, we think, a too high of a rate of relapse. If we're able to beat that and be a couple of months, two-three months, we'll have a best-in-class allogeneic product. And if we're able to kind of get more towards three-five months, something like that, we'd really start to look like autologous CAR T-cells, 'cause that's how long they're lasting.
If we can do better than that, we'll do better than autologous. You know, the reason we could do better is autologous CAR T-cells do actually often generate an immune response. I don't know if people recognize this. As the T-cells recover and the immune system recovers, you will see that a number of patients develop a T-cell response to the mouse and the CAR, in particular CD19, and those CARs then disappear. You see that when you try to redose patients. When patients are redosed with autologous cells, they have a very blunted early expansion. It's just the immune system. If we are able to truly hide cells from the immune system, our goal is to be able to really take care of any CD19 positive tumor cell.
Again, we still have a problem or a potential problem that some cells may stop expressing CD19 and then we'll just add our CD22.
Just as a segue from the CAR T, duration and persistence. In the setting of an islet cell transplant, you would need potentially indefinite or lifelong?
Sorry. With what?
In the setting of islet cell transplantation, the duration there would need to be essentially indefinite or lifelong. You couldn't re-dose or re-treat. How do you think about that 10-month kind of the primary data?
Hopefully the 10-month will be longer. A couple things to know, right? One, you'll know if you've overcome this auto and allo rejection within a handful of days, right? A handful of weeks. Your question really gets at clinically how long will be really meaningful. A couple things that I'd say. First off, beta cells do die, right? There's natural beta cell turnover in our pancreases every, call it four years or so. You know, we may overcome that. That's kinda the idea of the whole islet coming in there, and we may have challenges. Our goal y ou know, I would say if you can treat patients once a year, it would be transformative assuming that we have a cost of goods and a price point that's consistent with that.
Our goal is not to do that. Our goal is to be able to give patients this once a decade, maybe once in life and really have them kind of not worry about needing to come to the physician and monitoring their glucoses and getting insulin injections. Our goal would be it lasts, you know, for decades. You know, transformative would be a decade. I would argue that a year or two. You know, if you had to take one injection every year or two, it becomes our problem. I think the patients would really like that. Sonja, you've been working on this for a long time.
How would, w hat would you say?
No, I agree. I mean, if I look from the solid organ transplantation field, for example, we do retransplant there as well. I think it's acceptable to think about re-transplantation if it's necessary from the islet biology perspective. From the immune perspective, that we are hiding the cells from the immune system, that should be stable. There shouldn't be anything that can break that because as long as we have the edits, we should be able to hide them. The islet biology we can't control.
Sorry, just one follow-up. You don't believe that islets will be desensitized such that the immune system in a subsequent transplant would reject them or you believe you have persistent follow-ups?
That's a nice thing about the hypo.
Can you please repeat the question because there are people who are listening. You wanna go ahead?
Yeah. Your question was if with our hypoimmune product we would sensitize the recipient and then couldn't re-transplant. The platform is based on an MHC class one, class two knockout, and therefore you're not sensitizing against those molecules anymore. That's the biggest issue in transplant medicine, that we sensitize against the MHC molecules. Our product is a knockout, so there is no sensitization.
Maybe just to give you just a little data. We took it out of this. We've done a couple of things in these non-human primates to really get at this question. One, we showed you, we transplanted, you know, hypoimmune cells and wild-type cells. We then follow them. In the other leg, in the wild-type side, and then we've seen that they have a robust B and T cell response to those cells. In the other leg, we then injected our hypoimmune cells, and they were not recognized at all, and they continued to live and thrive. In the monkeys non-human primates that had the hypoimmune cells, after a few weeks, we actually injected wild-type cells into their leg.
We saw, again, a very robust immune response that eliminated those cells.
That B and T cell response that was eliminating the wild-type cell left our cells alone, and they continued to live and thrive. We've tried to test that notion in non-human primates and feel good that we are not sensitizing these patients and that we can redose them. That's where we come back to your question. We can redose them if we need to. That we can also. It was the first time we started to get very excited about overcoming autoimmune disorders because with a preexisting immune response to that cell, we did not see any evidence of immune rejection.
François Vigneault from Shape Therapeutics. Great presentation. The in vivo data is really good. I don't know if people appreciate how good that data is, for the field. Two-part question. Do you think you've found everything that needs to go in these hypoimmune cells, or are you looking for the marker to push them beyond? If you could comment on manufacturing ability of these cells as well.
Sorry, for primary islet cells?
Both the HIP cells and manufacturability of the islet cells as well.
Do you wanna touch this?
I mean, I think in terms of the manufacturing, you're asking about what the current manufacturing status is for the phase I trial?
Yes.
Oh, for the Allogeneic T?
How hard is it?
The manufacturing for the Allogeneic T-cell product, you know, is, you know, a relatively standard manufacturing process that's used for autologous. The difference is that, you know, we can generate, you know, enough products to treat hundreds of patients instead of a single patient. It's a larger scale, but the process is very similar. We're currently doing that a CDMO.
With that, you know, what we see, because they're healthy volunteers, is that markers that we thought were important to activity in autologous cells, they're just better with these. We have a consistent, and hopefully, we don't know everything about what really makes these cells work better with the allogeneic CAR T-cell. With the primary islet cells, we will manufacture them as they become available, right? Because they come directly from a cadaver. They are harvested, gene modified and transplanted very rapidly, you know, post-harvest. You know, for our True program with the iPSC-derived islet cells. You know, we're. You know, we can manufacture this at a scale that's fine for our clinical development. We'll have work to do really to get to a scale that we can deal with the millions of patients that have this, you know, commercially.
There's work to do there. I think if we did nothing else to our allogeneic CAR T-cell process, we're at a scale that will allow us to go forward. The process could be locked and move forward from a process perspective. We don't need any more scale. We can service the market globally with what we already have.
Okay.
I think the follow-up question was. Sorry. It was about other additional hypoimmune edits beyond what we're currently incorporating, maybe for Sonja.
I'm gonna answer this 'cause she's gonna tell you too much. She's got like 30 or 40 of them. We've been working on them for a long time, and, you know, we are optimistic that we've solved the problem. We're realistic that it's highly unlikely we've solved the problem for every cell type and every immune setting in every part of the body. Trust that that is how Sonja spends her mornings and nights is thinking about. Where are the Achilles' heel in our process and how do we really grapple with it?
Yeah, these are multiple cuts that you're doing, the knockouts. Are you monitoring for translocations for the cells?
So the answer is yes. The question was about, you know, monitoring for genotoxicity translocations associated with multiple edits in the cells. You know, for the T-cell program, you know, First off, we performed, you know, extensive, you know, non-clinical studies to understand the gene editing cleanliness, so to speak, and then there'll also be product release that will be based upon, you know, degree of translocations.
Yeah. I would say, by the way, when you're getting into the genomics of the stem cell-derived products, I'm just gonna say that it's way more complicated than I thought it would be when we started the company. I think the field's been really emerging, you know, all of the work that we need to do to understand the genomic stability and integrity as well as the epigenomic stability and integrity of these cells. That's really what we spent a lot of the last 12 to 18 months doing. You know, we originally had a goal of the stem cell-derived islet cells entering human testing this year. It's gonna happen next year. Well, again, that was time spent really making sure that we understood and hopefully can control that genome going forward.
You know, anytime you're grappling with something like this, the most important step is characterizing and having a high-quality product. Maybe the second thing to do is make sure we put together diagnostics, so we can figure out if something goes awry. The third is, in everything we're doing, we're also engineering in safety switches or suicide switches, so we can grapple with the problem if something does arise. Maybe these last things. This is a great proof of the, l ike we told you then about red blood cells. I think it's a great proof of the biology in humans. Another proof of biology that we have is that when we knock out class one and class two and overexpress CD47, if you give an animal a CD47 antibody, the natural killer cells will come in and kill that cell.
Not a problem. That is a safety switch to eliminate these cells if something does go awry. It's also proof of the biology.
Great. Well, I think we're actually out of time here. I wanna thank the Sana team for joining us today, and thank you for the audience for the great questions.