Welcome everyone, to the 42nd annual JP Morgan Healthcare Conference. My name is Tessa Romero, and I'm one of the senior biotechnology analysts here at JP Morgan. Our next presenting company is Sana, and presenting on behalf of the company, we have CEO Steve Harr. Steve?
All right. Well, thank you, Tessa, and thank you, JP Morgan, for having us, and I appreciate everybody in the audience. So as I'm sure everybody recognizes, we'll make a few forward-looking statements, so please do refer to our 10-Q. We spent a bunch of time writing our risk factors. So 2024, I think, really promises to be an exciting and potentially transformative year for the company. We spent a lot of 2023 preparing ourselves for a bunch of clinical data, and we... At this time last year, we had no programs in clinical testing. Today, we have four across seven indications. We'll treat something, you know, like 40-60 patients in clinical studies this year. We'll have data available from every one of them.
During this talk, I'm gonna give you a little bit of information that we haven't shared before on why we're so optimistic about where this will take us. We've really focused the company's effort in the near term around a platform of overcoming allogeneic rejection of cells. Meaning, you put my cells in you, your body's gonna reject them. And hopefully, with the technology we have and the progress we've made, we can transplant cells more broadly. And we're doing this in three different broad therapeutic areas today in the clinic. One is in B-cell cancers like lymphoma and leukemia. The second is in B-cell-mediated autoimmune disorders, Lupus, Lupus nephritis, ankylosing spondylitis, and a whole host of others over time, and finally, in type 1 diabetes.
We have a number of drugs coming behind that, which we'll tell you about some other time, and hopefully, we have the balance sheet to allow us to really read out all that we're doing. So this is just a little bit more detail around our portfolio. The lead drug or the first drug into human testing is a drug called SC291. It's a hypoimmune modified allogeneic CAR T cell targeting CD19. And that trial has been up and going, and we'll show you a little bit of data from it. Just last week, we had a drug called SC262 allowed by the FDA. It targets CD22. It's a CAR T cell targeting CD22.
It's for patients who failed a CD19-directed therapy previously, a big unmet need and someplace we expect to move quickly. Over the course of the last 18 months, there's been a lot of excitement in the field, which we'll get into, around the potential to even have curative intent with autoimmune disorders. And we have a drug, SC291, that we're taking forward in a number of these disorders. The IND was allowed in the fourth quarter, and again, you can expect to see data later this year. And finally, we're moving forward in type 1 diabetes as we speak, and we'll get into that. So a little bit around the problem.
Since the advent of transplant medicine, the rejection of allogeneic cells has really been the big part of the limitation around broad implementation, and the same is true as you move into cellular therapy. Most have tried to get around it by substantial immunosuppression. That both limits the number of patients who can do this, but has a lot of long-term toxicities. The fields tried to move into autologous cells. They work in some cases. There are only a handful of cells where that's possible, and scaling it has been complicated. All of the efforts to really gene modify allogeneic cells haven't been complete and haven't worked to date. So what's our special sauce? If you take a step back, there are two big arms to the immune system.
There's the adaptive immune system of B and T cells. Dealing with that has been relatively straightforward and known for how to do for a while, and knocking out class I class II MHC. Unfortunately, or fortunately, tumors and viruses figured that out a long time ago, and so we've evolved the innate immune system and particularly natural killer cells. And so overcoming the rejection of natural killer cells has been the real challenge of the field. And what we've discovered, our team has discovered, is that expression... overexpression of CD47 in the context of knocking out class I class II gives you the potential to completely evade immune detection, transplant cells with no immunosuppression, and hopefully have them live as if they were the patient's own cells.
So we've done a lot of work in the preclinical setting, and I'd go so far as to say we've proven that we can overcome allogeneic rejection in mice, non-humanized mice, nonhuman primates, amongst others. And these data are published across multiple journals, including things like Science and Nature journals over the course of the last 12 months. So take a look if you wanna go more deeply. On the right-hand side, what you see actually is a transplantation into a nonhuman primate of a pancreatic islet cell. And the goal of doing transplants of pancreatic islet cells is to overcome type 1 diabetes. Our team wanted to do one more experiment as we were waiting for humans, and I wanna share that with you.
The goal here is to figure out, can you create type 1 diabetes in a nonhuman primate? We've never shared these data. Transplant allogeneic cells with no immunosuppression, and normalize the outcome for the nonhuman primate. So that's the goal. Can we survive and function? Will we get long-term glucose normalization? And actually, at the end of it all, can we eliminate these cells, which is both... We could do that to validate both our mechanism and a safety switch. So this is where the experiment work, and this is a look at the animals' glucose in their blood. And the green is normal, the white's a little abnormal for its meals, and red's abnormal.
So you give the drug, STZ, and that eliminates the pancreatic beta cell, and you can see the sugars in the animal are all over the map. Over the course of the next two months, we were able to stabilize the animal with insulin, and at that point, the veterinarians allowed us to try to transplant allogeneic cells with no immunosuppression. And what you see is for six months, the animal remained euglycemic, off insulin, with no immunosuppression. It's a spectacular outcome. The animal was able to, at that point, reinstitute itself in with the colony around it and was thriving. We decided, though, that there is some risk that, you know, maybe the pancreas had regenerated.
And so, our mechanism of overexpressing CD47, we can give an antibody to that and see what happens. So what you'll see is when we gave the antibody, the CD47, the beta cells were killed, and the animal became diabetic again. And on the right-hand side is what you see is the C-peptide, the measurement of insulin, which goes right along with that functional outcome. So a great outcome and about as all you can do now, non-clinically. So it's time for us to move into people. As I mentioned earlier, we're going after big markets, and large unmet needs. We're blood cancers, where over 100,000 people per year die in the U.S. and Europe alone.
B-cell mediated autoimmune diseases, where you have over 5 million patients suffering, and type I diabetes, which is, you know, a global, endemic and something where we think we can have a large impact. I'll start with blood cancers, and I think most people here recognize that with the advent of autologous CAR T cells, there's been the possibility of curative intent in treating patients. We've also seen a number of companies try to really scale the capability with allogeneic CAR T cells. The challenge with the autologous has been just patient access in many regards, and despite the fact that 100,000 people die per year, what you see here is this yellow circle is the number of people who get them per year, around 11,000. Unfortunately, the light blue is the number who benefit from them.
So there's still a very large unmet need. Allogeneic CAR T approaches to date have shown that you can get a pretty good early response, but unfortunately, as the patient's immune system recovers and reconstitutes, the cells are killed, and they're not around long enough to really lead to a durable, complete response. So we're moving forward with a drug called SC291. And what we've done here is we've gene-modified donor-derived CAR T cells using Cas12b. And you see. We knock out three genes, we disrupt MHC class I, class II, and then we stop TCR function. I can get into why in a minute. We then overexpress the CAR and overexpress, so we express the CAR, and we overexpress CD47. And so that's what we do.
The real goal is to figure out, do we have a drug here? And the first part of understanding, do you have a drug, is can we overcome allogeneic immune rejection? If we can do that, that's probably 80% of the risk of the program and 80% of the risk of the company, right? That is something that we've seen in non-human studies that we are, you know, really quite good at. We want to make sure that the animal data translate into people. If they do, can we make great CAR T cells? And that's measured by safety and efficacy of the program early. And then we want to see how does that translate over time into durable, complete responses. And finally, we need to make sure that we have a real scale manufacturing process.
These are the data for the first time we've shared. We've enrolled six patients. We enroll about one a month. That's just what you have to do during this time. On the right-hand side, what you see is that, importantly, the drug has been very well tolerated. It's a dose escalation study. We start at dose level one of 60 million cells or now at 120 million. Next will be 200. We've had no dose-limiting toxicities. In fact, we've also had not even any grade one CRS or ICANS. What you can see is that three of the four patients have had at least a partial response, even at these low doses, and two of the four patients are in an ongoing complete response.
So the drug is working as we hoped it would on the safety and efficacy side. Stay tuned. We'll have a lot more data as we get through dose escalation. We're able to enroll and treat patients very rapidly, and we'll have a lot more as the year goes on. But as we go through that, the real key question is, how does that early data that we've seen in animals translate into people? And one of the bugs of the drug is that when we take donor-derived T cells, and we gene edit them, we're really good at it, but we're not perfect. And so the drug is a little bit of a gemisch. You have all of the hit CAR T cells, which have every single gene edit we want to make.
But we also have some cells that just express CAR. They don't have. They haven't knocked out class I class II. and we have some cells where we've knocked out the class I class II MHC, but we don't overexpress CD47. And what's been seen in the field to date is when patients get an allogeneic CAR T cell, they first get lymphodepletion chemotherapy, and as their immune system reconstitutes, the CAR T cell is killed, limiting efficacy. So what we want to see here is what we see on the right-hand side outlined, is that as the patient's immune system reconstitutes, our fully hypoimmune cells live. And we'll know the immune system is reconstituted because you will generate an immune response against the partially edited cells.
So this is the test of, does this really work in humans? So what we see is what we hope we would see. I'll start with that. On the left-hand side, what you see is in patients who don't knock out their class I class II MHC, or are not in patients, in cells that aren't knocked out. And this is real patient blood, right? They generate T cells over the course of several weeks that will recognize and kill the allogeneic CAR T cell, non-mod, gene modified. What you see in the middle panel is if they knock out class I class II, as you'd expect, T cells don't recognize these cells. And what you see is our fully gene-modified cells. Again, there's no T cell response, T cell recognition to them, and they can live.
So next question is antibodies. So how would B- cells do? Again, patients will generate an antibody response to cells where you have an intact class I class II MHC expressed. But they will not, if you've knocked it out, and they do not to the MHC to our fully gene-edited cells. The field has seen this broadly. So you've seen a number of companies that have knocked out class I class II, but the drugs haven't worked as hoped. Because the key has been, as we mentioned, natural killer cells. So this next slide is in my many regards my favorite slide in the whole presentation. And so it's the kind of the killer slide. It's the picture of what happens. So this is actual, these are NK cells from patients 28 days after being treated.
And what you see is when you have double knockout cells, this is what a lot of the field has done with class I class II. the green cell is the CAR T cell, and the rest is the NK cell, and very rapidly, the NK cells will recognize and eat and destroy the CAR T cell. We're often asked: Well, what happens if you knock out class I class II and overexpress HLA-E? We contrived that system for you. And again, the patient's NK cells will rapidly recognize and destroy those cells. And what you see here on the right-hand side is what happens to the NK cells and our fully modified CAR T cells. And they bump up against it, but there's absolutely no killing.
This is you know the most important slide in many regards because it tells you that with real patient blood, real patient samples, we've overcome the large challenge in the field, which is NK cell recognition of these cells. Just to be sure, we said, "Hey, what if there's something else in the blood that might kill these cells?" And what you see is against wild-type CAR T cells, as expected, they're dead. Again, that's just allogeneic cells, my cells into you. If you knock out class I class II, the blood from the patient will kill those cells. But what you see on the right-hand side is our fully gene-modified cells. They really do work.
So the drug is working exactly as we hoped it would, and the immune evasion that we saw in the preclinical setting seems to be translating into people. So stay tuned. The early data suggests that we have the safety, the desired immune evasion, and the clinical impact that we're hoping to see. We'll have a lot more data as the year go forward, and we'll share it across, you know, all these different parameters. So, you know, we're unlikely to do it at another investor conference. It will most likely be at medical meetings, so, so stay tuned. I wanna move next to autoimmune disorders. Over the course of the last 18 months or so, the field has really begin to begun to understand the potential of CAR T cells in this space.
That being said, if you go back over the last several decades, people have been targeting B-cells with autoimmune disorders with a number of different drugs, and there are around 70 different indications today, where at some level, there is a evidence that depleting B-cells or knocking down B-cells will have a clinical impact. Unfortunately, with the antibodies, what you see in the middle point is they're really pretty good at knocking them down in the blood, but they're unable to get to tissue-resident germinal centers. And, you know, that's where a lot of the problematic B-cells reside. And, you know, what we know is that the depth of B-cell depletion across multiple studies really does predict the efficacy in all these diseases.
So to date, the best B-cell depleter man has created is actually a CD19-targeted CAR T cell. And about 18 months ago, and I'm sure many of you are familiar with this, Dr. Georg Schett published data showing that you can see rapid improvement and actually just complete responses in patients with lupus. He's now, as of ASH, presented about 15 patients. You have follow-up over two years, and patients are living, you know, basically with a complete remission, and they are off of all drugs. So it looks to be a durable... For the first time, you have the audacity to talk about potentially curing autoimmune disorders. And so what we know is that the depth to which you deplete B-cells is the imperative factor in making these drugs work.
We've actually used this exact same drug, SC291, in cancer patients, and so we can look at the B-cells in the cancer patients. And what you see here is that very rapidly, we can completely deplete the B-cells. It's a reason why we're so optimistic about what we're going to be able to do in the autoimmune setting as we go forward. So the trial is gonna be across three different indications to start. You can see that between lupus nephritis, extrarenal lupus, and ANCA-associated vasculitis, there's over 500,000 patients in the U.S. and Europe. This SC291 is an allogeneic CAR T cells, the first one in human testing in autoimmune disorders. And it has a number of benefits versus autologous therapies.
Probably the most important one when we talk to clinicians is when a patient has an autologous, gets an autologous therapy, all of them are on some kind of immunosuppression. They have to taper off of that before they can get an apheresis. They're gonna have to get put back on their immunosuppression while they make the drug, then has to be tapered back off. That's very complicated to manage in a clinical setting. Here, the drug's available. We've got a scaled manufacturing process, where in every batch, we can generate hundreds and hundreds of doses for patients, and we can have consistent T cell quality across the program. So, this trial's ongoing. The first dose is actually at 90 million CAR T cells. That's higher than where we started in oncology.
That was something where I think the safety data really allows us to accelerate. That, that dose is consistent with the dose in the autologous setting, where Dr. Schett saw data in his studies, which is at 1 million cells per kg. We have the potential to go beyond in these indications rapidly over time. It's a flexible protocol where we can add multiple indications and expect to see some data across multiple of these, where we'll hopefully see early safety and tolerability, as well as, you know, what the early response rate looks like. And, and what we're looking for is not partial response. We're looking for complete responses and, and really seeing the disease go away for these people. So optimistic about where we can go.
I mentioned at the beginning, this drug SC262, where the IND was allowed last week. This is a you know, as CD19-targeted CAR T cells and CD19 bispecifics are becoming a bigger and bigger part of the treatment paradigm, unfortunately, the number of patients who have failed these CD19-based therapies is growing. And if you look out in a few years and just look at reasonable estimate for CAR T cells, you can see, you know, 7,000-8,000 patients per year, which would be a addressable market. When a patient's failed a CD19 CAR T cell, they have about a five to six months expected survival. So this is a, this is a bad place to be. Our drug, SC262, targets CD22. And it's a platform. What you can see here is the little blue part.
The only difference between this and SC291 is that little blue, blue part changed. It's. And so we make one change in our DNA plasmid and one change in the release assays, and we're able to really kind of move forward rapidly across multiple drugs, we hope. The CD22 we use has actually been studied in a number of different academic studies at both Stanford and the NCI, in the autologous CAR T cell setting. And what it's shown is, in CD19 failures, about a 50% durable complete response rate across lymphoma and leukemia. So we're starting the VIVID study, is what we call it. You know, it was. The IND was just allowed last week, so give us a little bit of time for site activation.
The dose, again, will be a bit higher than where we started with CD19 at 90 million cells. That is actually consistent with the efficacious dose used in the autologous setting. The primary endpoint, you know, with the dose escalation, will always be safety and efficacy, sorry, safety and tolerability. But we do expect to be, you know, able to share data on early patient responses as we move through this year. So, that's the next study. I wanna just switch tasks for a second and go to type 1 diabetes. type 1 diabetes is a disease caused when the patient's own immune system knocks out their beta cells.
It's a big unmet need, with over 8 million people around the world suffering from it, and they have really difficult lives, both in terms of managing the short-term hypo and hyperglycemic episodes, but also the long-term complications of the disease. Our goal is really simple: a single treatment with no future insulin, no immunosuppression, and normal blood glucose for life. Simple to say, hard to do. But it's actually something we believe where the field's teaching us it's possible. We know people have been doing this for about 10, 15 years, that somebody can transplant primary cadaveric islets from a donor into a type 1 diabetic, and in the context of immunosuppression, that patient can remain off of insulin with normal glycemia for years and years.
Patients have been out over a decade with this. Unfortunately, product quality is very variable. It's not a very scalable source, and there aren't that many patients for whom lifelong immunosuppression is better than lifelong insulin. The field is beginning to teach us from others that there may be a better source for these cells, and that is, you can take pluripotent stem cells, make them into pancreatic islet cells, in the context of immunosuppression, and again, see normalization of blood glucose off of insulin. But again, the problem is, there aren't that many patients for whom lifelong immunosuppression is better than lifelong insulin. So the key to really understanding, Can we cure patients? We think is, Can you eliminate the need for immunosuppression? So there are two elements of the immune system we have to overcome. There's allogeneic.
We showed you these non-human primate data earlier. I think that's something where... And we've shown you the human data that from another setting that seemed to indicate that the non-human primate and preclinical data are translating to people. So the real question now became: Can we overcome autoimmune rejection? And this is where the patient's own immune system recognize islet cells. It's difficult to study because there are no islet cells left in the patient. So our team, what they did is, they took blood from a type 1 diabetic and did two things: took some of that blood and made a humanized immune system in a mouse. So now you have a mouse that has the B-cells and T cells of the patient.
Then they gave that mouse STZ to knock out its pancreas, so now it's a diabetic mouse with a human immune system. We took that same patient's blood and reprogrammed back into pluripotent stem cells and then divided into two groups. One, we gene-edited with our hypoimmune cells, and the other we didn't, and then grew them into islet cells to transplant into this mouse. So now you have a mouse that is receiving its own islet. What you have is a person's islets and that person's immune system inside of the mouse. And what you see on the right-hand side is the system works as it should. This is unmodified cells, and within a couple of days, the mouse's the human immune system will kill those cells, and there's full-blown diabetes.
What you see on this slide is that actually, with our gene-modified cells, it works as we hope it will. So what you see is, for the life of the study, the islets survived, they functioned, it's a measure of C-peptide, and you can see glucose control from that. So now we've shown in the preclinical setting that we can overcome both allogeneic and autoimmune rejection with absolutely no immunosuppression. Next up is people. And so just in the fourth quarter of last year, we had a CTA allowed through an investigator-sponsored trial, where we will gene-modify primary islet cells and transplant them into type 1 diabetes patients with no immunosuppression.
And this is a study we're really excited to see the data from, and it's, we just got our manufacturing license to move forward this morning, so now there's nothing stopping us, and we're ready to go. And what will happen here is they'll take donor cadaveric islet cells. They will be gene-modified and placed into the forearm of the patient. It's a phase 1 study, so the first thing we want to see is safety. But really what we're trying to see is cell survival and immune evasion, and the best marker for that will end up being C-peptide levels. So all patients here. So what, the way our beta cells make insulin is you make proinsulin, and it's secreted in the blood. You secrete insulin and C-peptide. All patients here have no detectable C-peptide.
All of their islets or their beta cells are gone. So if you see stable, detectable C-peptide over time, you will know that we have survival of these cells in the context of no immunosuppression. At that point, all three of those boxes will be checked, right around what you need for a curative therapy, for type 1 diabetes. Not saying we'll nail it, it may take us time, but from a scientific perspective, it's all done. So our goal, what we're doing over time, is we're trying to make hypoimmune islet cells from stem cells. We call that drug SC451. We'll manufacture that at scale and deliver, as a single therapy into the arm. And, you know, stay tuned. That's coming at us quickly.
I think that this program is the one that is probably the most transformative for the company, and it really could change the way we all think about the ability to treat a host of different diseases. Cell replacement with no immunosuppression at scale. 2024 is going to be a lot of fun. I hope it will be very value-creating. We'll see. Clinical data have a way of playing out, and we're optimistic based on what we've seen. We have a couple of different ongoing studies in different indications in blood cancers. We have a study in B-cell-mediated autoimmune disorders across three different indications, and we'll get our first data in type 1 diabetes as the year progresses. We'll share, hopefully, information from all of them in the not-too-distant future with you.
So look forward to seeing you. And with that, we'll take questions and answers. I think I'm going to be joined up here by a couple of people. Doug Williams, who's our Head of R&D, Sonja Schrepfer, who runs this hypoimmune platform. So, you know, so much of what you see comes from her brain and hands and her team's brain and hands, and Nate Hardy, our Chief Financial Officer. So with that, questions? Do you want... Oh, if you have a question, use the microphone because it is being webcast, and I'm deaf, so those are both problems.
I have a question. So it's good talk, good science. So I have two questions. So in the CD19 CAR therapy, so what's the dose you show in the slide, you show 20 million, 60 million. This is total dose or the per kilo dose?
Just say the last part again.
The cell dose.
Yeah.
You show in the slide, there's 20 million, 60 million. So these are total dose in a single regimen, injection, or this per kilo dose?
So the dose is based upon CAR-positive cells.
Ah, okay.
So-
Just total up-
So-
... positive cells.
Yeah. So it's total dose of CAR-positive cells. This is how all CAR T cells are dosed.
I see.
Right? And so if you look, most of the approved CD19, that all the approved CD19 CAR T cells, the dose is somewhere between 100 million and about 150 million cells. When you start with these donor-derived cells, these are healthy individuals who give them to us, so they could be more potent. They may not be. So we start at 60 million for safety-
Okay
... went to, you know, really the range of 120, which is kind of in the range of the approved cells, and we also have 200 million cells around that. Doug, anything to add to that?
No. I think you covered it well.
Okay.
Okay. The last question is, what's your manufacturing time for to make those cells?
Well, I'm gonna start. That question doesn't really matter, right? Because you're used to the autologous CAR T cell, where the patient takes--has an apheresis. The, the patient has to first... There's a pen, right? The doctor says: "I'd like to give you the drug.
Yeah.
They then try to find an apheresis center, where they take off the white blood cells, send them to a factory-
Okay
... manufacture them, test them-
Typically home
... and send them back. What we're doing is we make these off the shelf. So, the-
Ah, you make them.
the patient's CAR, the product is available today.
I see.
If the patient comes in and says they're ready for a prescription, it is on the shelf and ready today. And so, the manufacturing timelines are generally pretty similar to an autologous cell. But it doesn't matter, 'cause we can have 1,000 or 10,000 patients of drug product sitting in the background. We do do a bit more testing, 'cause we do a lot of gene editing, than what's done on an autologous cell. And so I think we can hopefully offer physicians and patients more comfort, around the predictability and the safety of our cells. But, you know, just to give you a sense, at that middle dose, 120 million cells, from a single manufacturing run-
Mm-hmm.
We make enough drug to treat about 500 patients.
Wow!
To put that into context, right?
That's interesting.
Yeah, so if you make 100 doses-
Okay
... of an autologous CAR T cell, you can treat 100 people. If we do 100 doses of our drug, we can treat 50,000 people.
Right.
That's a totally different scale.
Thank you.
We'll go here, and then there's one in the back after that.
Okay, thanks for the talk. How do you compare the kind of editing efficiency of Cas9 versus Cas12b in your early research?
Do you want to take that, Doug?
Sure.
Is your mic... Yeah, yeah, there you go.
Yeah, it's... You hear me okay?
Yeah.
Okay. I think, you know, Cas12b, one of the advantages is that the editing fidelity that we're seeing is actually quite high.
Mm-hmm.
Relatively, I'd say probably higher than Cas9. And I think, you know, we've now had the benefits of being able to actually make several batches of drug and be able to go back and do the analytics on that. So we're feeling actually quite good about the editing fidelity that we're seeing with the reagents that we've developed. And we've now got a data set that continues to grow to back that up.
Okay, thanks.
So when we did this, we had four criteria. We wanted, you know, potency or efficacy-
Mm-hmm.
specificity, which gets to safety, GMP manufacturability, and freedom to operate, right? Those are kind of before you got to deal terms.
Yeah.
So one of the big problems on specificity are impurities in your guide RNA for Cas9, because they're manufactured from five prime to three prime.
Yeah.
It's the three prime then binds to DNA. That last bit can be a little unstable.
Mm-hmm.
When that's not quite exactly what you think, it could bind anywhere in a patient's genome. The way Cas9 works, it's flipped, and so, it's the initial part that binds to the patient's DNA. And so if it doesn't, if you have impurities in the product, you end up just not binding to the Cas. So that gives you a much higher level of specificity. But, you know, the second element that Doug didn't get into is, the Cas9 intellectual property estate, I think, as most people recognize, is kind of, it's kind of messy, right? And it sits in different geographies in the world, with different entities. One of the nice things about the Cas12 intellectual property estate is it all resides in a single party. We license it from that single party.
And that gives us, we hope, global, you know, ability to take these drugs everywhere in the world over time.
Wow! Thanks a lot. And my second question is, so, for, like, CD19, I think, CAR T treat, resistant patients, some lost CD19. How do you, like, you know, deal with those patients? They lost the target.
Screening for the, you know, screening for the antigen upfront.
Uh-huh.
You know, certainly in the CD22 case, you know, there's evidence of that happening in that situation as well. So, you know, we'll, we'll obviously confirm that the patients have the antigen first.
Okay. Got you. Thank you.
There's a question in the back.
Thank you. Just curious, your thoughts on Allogene's announcement to try and kind of leapfrog into an earlier line of therapy. Do you think that's feasible, to kind of jump ahead of autos?
So it's feasible to go into earlier lines of therapies with allogeneic CAR T cells?
Just to leapfrog, to go from, you know, being targeting patients who've failed in a prior auto, to jump ahead and be treated with allogeneic CAR T before failing off an auto.
Is the question... I'm just kind of missing that. It's hard. Is the question whether it's-
Is that on?
Yeah.
Just the question of, like, do you think that's feasible as a kind of marketing strategy?
To what... is what feasible?
To jump ahead of autos-
Oh.
into an earlier line.
Yeah, so there are two different settings. Sorry, just to be really clear. There's oncology and autoimmune disorders, right? In the oncology setting, right, you know, in fairness, you know, autologous CAR T cells have a good bit of data, right? They have long-term survival data that's emerging in CD19 and BCMA, and they're moving into early and earlier lines of therapy. So our road is more complicated.
You know, if you talk to physicians, the ability to have this drug off the shelf, right, versus, you know, the complexity of apheresis, waiting for drug, having 5% failures or some number of failures, is something where we're quite comfortable that we have the chance to move ahead of autologous CAR T cells for some clinicians and some patients. We'll probably never get everybody, right? It will be a competitive dynamic, and we'll have to grapple with bispecific antibodies as well. With CD22, you know, we're not very... Well, we're kind of running in a pretty competitive race with autologous. And most likely, as you move in the autoimmune setting-... We're kind of-- We have a manufacturing process. It will be locked shortly and ready for registration studies and commercial launch.
We have a scale that allows us to move a lot faster than the autologous cells. And so if our drug works as we hope it does, we're optimistic that we can, you know, really kind of move more rapidly than they can, and you'll be asking them the question you're asking us about in oncology. But we'll have to see, right? I mean, data has a way of doing what it does.
Just regarding the type 1 diabetes IST, can you help us understand when would be the earliest time that they can treat the first patient? Can you pre-manufacture the cells before you identify the patient, or you have to find the first patient, then do the manufacturing?
So are you asking about the investigator-sponsored trial?
Yes.
Yeah, because just to, you know, I think you recognize in the stem cell space, you edit this master cell bank once, and you grow these cells forever from that. It's a little bit like an antibody that spits out antibodies. The master cell bank continue to spit out cells. In the investigator-sponsored trial, Sonja, you've been really our architect around this. Do you want to take that question?
Thank you. Yeah, the IST will be done like an islet transplantation, so you have your wait list with different recipients, and the cadaveric donor will then be matched to the right recipient. So the only new thing is that the strategy is in hypoimmune islet cell without immunosuppression, but everything else is like in an islet, cadaveric islet transplant.
Thank you for the presentation. I was very excited to see mention of your next iPSC programs. Would love to hear a little bit more about that.
The next one?
Yes.
Yeah, so, you know, the next pluripotent stem cell program, and probably the first one that will be in the clinic, are glial progenitor cells. Glial progenitor cells are bipotent cells in the brain that can become either astrocytes or oligodendrocytes. It's very context dependent. You know, increasingly, it's become recognized that there are many, many CNS disorders that are white matter driven. So this is a program that we've had going for a while, and we're kind of moving into GLP toxicology studies as we speak. We're quite optimistic that we'll have an IND filed later this year. And we'll see. I think that, you know, unlike something like beta cells, where you see D-- you have C-peptide, and does it survive?
You know very quickly if you're having a clinical benefit or in CAR T cells, where we expect to see a very rapid improvement for the patient. It may take us a little bit longer to kind of find the signal as you're fixing the white matter in a patient. So, you know, the time to the clinical readouts probably not three or five months after you begin human testing, but it's something where we think it could have just a tremendous impact for patients. Doug was at Biogen for a long time and knows CNS quite well. So, Doug, yeah, what-
I think, having tried to remyelinate the brain at Biogen and having had limited success there, the data that I've seen from Steve Goldman's team, at least in the preclinical setting, is just, it's really stunning, the degree to which you can get remyelination. So it's, I think it's a real opportunity to transform MS and other diseases of myelin that, you know, we're gonna be starting with a disease called PMD, which is a genetic disorder of dysmyelination. So imaging and some of those endpoints will be the way in which we get a feel for how the drug is working, but, pretty exciting stuff.
I guess we're out of time, so thank you, everybody, for your time and attention and interest.