Welcome to the first day of the BofA Healthcare Conference. My name's Geoff Meacham, I'm the Senior Biopharma Analyst. We are thrilled today to have Sana with us. Speaking on behalf of Sana is President and CEO Steve Harr. Steve, good to see you.
Great to see you, Geoff.
So we have some questions, but maybe just give us, for those on the webcast or in the audience that maybe are not as familiar with the story, just give us kind of the high-level view and then we'll get into right into some clinical programs.
Great, thank you for having us. I think all you guys know, we're making forward-looking statements and you can reference our recent 10-Q filing for risk factors. We spent a lot of time on them, so take a look. The company was founded on the idea of being able to make cell therapies for prevalent diseases, kind of at scale, broadly accessible. We went after some of the big problems of cell and gene therapy to start. One of those was the ability to transplant allogeneic cells, in particular to overcome immune rejection of allogeneic cells. Another was in vivo delivery, which I'm happy to get into a little bit later. We'll start with the rejection. When you try to put my cells into someone else, they'll be seen as foreign, like a virus, and rejected.
To date, the way the field's tried to overcome that is one of two things: either utilizing autologous cells, which are very difficult to scale, or immunosuppressing patients, knocking out their immune system, which can be very difficult to tolerate. Our goal has been to figure out really the underlying basis of transplant rejection, be able to make cells at a scale that could act as a therapeutic, and to be able to transplant them into anybody. If you take a step back, pretty much every disease you can think of is caused by damage to or a missing cell. So it's an opportunity to go after a lot of very prevalent and important diseases. We've made a lot of progress. I'll give you just a sense of the technology. There are two really important arms of the immune system you have to grapple with.
One is called the adaptive immune system, which is B and T cells. We can kind of all hear about that with vaccines and things. The other is the innate immune system, which is often evolved to deal with things that the B and T cells don't seem. The real challenge has been that we know how to knock out the recognition from B and T cells, but cancers and viruses figured that out a long time ago. Our innate immune system, in particular natural killer cells, will deal with those cells. The real key has been trying to figure out how to turn off, in particular, natural killer cells. We think we've done it. We've now shown we've transplanted cells across all kinds of different species, including non-human primates, in different locations for very long periods of time.
We haven't seen really any evidence of immunologic recognition or rejection. We've shown you some data, early data in humans, that are very consistent. We're now looking at developing drugs. Right now we have four clinical trials ongoing across seven different indications, all of which we hope to have data in this year, in big areas like blood cancers, lupus, type 1 diabetes, areas like that. That's a little bit about us.
Yes, perfect. So let's talk a little bit about the Type 1 diabetes program, probably the most topical in your meetings. So give us a background, Steve, on the non-human primate data, kind of what you learned and how you expect that to be one of the leading indicators of what you could see in humans, and also what are the challenges with that?
Yeah. So step back. Type 1 diabetes, the immune system of the patient recognizes and kills the beta cells, pancreatic beta cells in that patient. Beta cells make insulin. So up until 100 years ago, these people just died pretty quickly. And with the advent of insulin, people have done reasonably well, but there's still about a 10-15 years shorter expected lifespan and a lot of complications that come along the way. And so the goal is very simple, is to be able to replace those cells, transplant them into the patient, and for them to have normal blood glucoses off of insulin and with no immunosuppression. So today, what's known is that, one, people that have been for about the last 20 years have been doing primary islet transplants.
So they take islets from the pancreas of someone who recently died, a cadaver, and they are transplanting the patient with significant immunosuppression. And they work for a lot of patients. There are many people who have euglycemia or normal blood glucose off of insulin. But they have two challenges. One, it's very variable and difficult to scale manufacturing supply, and that leads to different outcomes for patients. And two, they're on immunosuppression their entire life. And there aren't that many people for whom lifetime immunosuppression is better than lifelong insulin, right? So then others have shown that you can make stem cells into beta cells and transplant those into people. And again, what you've seen is that patients can really do quite well off of insulin with normal blood glucoses. But again, there aren't that and you have a more scalable and replicable manufacturing supply.
But you still have the challenge of immunosuppression. So the last leg of this three-legged stool to get to a cure is to be able to say, we can get rid of the immunosuppression. So that's been our primary driver here. So what we've shown in non-human primates is that we can induce type 1 diabetes chemically and eliminate their beta cells. And that animal will have florid diabetes, insulin-dependent, transplant gene-modified islet cells with no immunosuppression. And that animal will be euglycemic off insulin with no immunosuppression for the duration of the study. We did this for six months. We then gave them a drug that would block one of our CD47, which you overexpress to hide it from the cells. And those cells were rapidly eliminated, and the animal went back to having diabetes.
So now you have proof of concept that really around showing in a non-human primate that you can transplant cells, get euglycemia with no immunosuppression. So we're taking that into humans. And the really only difference in what we did in the non-human primate in our ongoing human study is, one, it's humans, right? And that's important, right? There could be differences in the immunology of a non-human primate and a human primate, but they're probably pretty small. Two, is a mechanism of type 1 diabetes. It was chemically induced with the non-human primate, and it is autoimmune in the person. And we can get into it. I think we've done a really thorough job of showing why we're not too worried about the autoimmune reaction against these cells, but it's not a zero risk, right? And the third element is it will be a smaller dose.
It's a first-in-human study, right, and things like that. So our goal is not to see what we saw in non-human primates. We may get fortunate to see that, but in a first-in-human study, what we want to see is that these cells we'll transplant them into the arm of a person. The cells survive and that they function, right? And there's no immunosuppression. So the way you measure cell survival at its most base function level would be radiologically. So you get an MRI, see cells there, no immune response to the cells. That's baseline. The next best, and really what I think should be the goal of the study, is to see C -peptide levels that are stable. So when a beta cell makes insulin, what it does, it actually makes proinsulin. And when it's secreted, it makes you secrete C -peptide and insulin.
Proinsulin becomes C-peptide and insulin. So if you see C-peptide, you know the patient is making their own insulin. So if you see stable, no immunosuppression C-peptide, that said, these beta cells have survived and they're functioning. The third would be that we get rid of their insulin. I think that's not realistic in the first set of patients. It could happen, but it wouldn't be your base case. So that study should have data soon. It will tell us, hopefully, whether or not we've truly cracked the code on allogeneic and autoimmune rejection in the type 1 diabetic. If it works, I would say that at that point, a cure becomes more or less inevitable, right? We might screw it up. It may not be Sana that gets it done, but the field will figure it out.
And just along those lines, Steve, when you look at the persistent rates, what do you think success looks like? Is it one month, six months, like a year?
Success is a long, long time, right? But what should be true is that if you do an organ transplant into a person and you don't immunosuppress that person, that organ or those cells will be rejected in a matter of days. So they'll be gone within 7 to 10 days. If you have a patient who has to come off their immunosuppression for some reason, they will reject an organ within about a week. So by a couple of weeks, you kind of know if it's going to work or not, right? There's nothing that should pop up after that. We've kind of laid out arbitrarily a month is a nice time to see. Nothing should happen after that. I'd still like to see it last longer. We want it to last a lot longer than that for the patient's sake. A patient will benefit from this.
You should know if it works or not that early.
So this immune cloaking approach, if you want to call it that, outside of Type 1 diabetes, it obviously has many more other applications. What is sort of the menu of what you guys are thinking about?
The menu's broad. The focus of the company to date is around we have things in human testing, a few things behind them. In human testing, we've got the cloaked T cells, so allogeneic CAR T cells that we're developing for both B cell-mediated autoimmune disorders as well as blood cancers. We have the type 1 diabetes program. Behind that, we've got a glial progenitor cell program for different neurologic disorders. And you'll see other cell types over time. I mean, you can do a lot of things with this. You can do a lot more of it than we can, right? And so we'll think about that over time with potential partners and things. I mean, every one of these, to be really clear, every one of these stem cell-derived products is really complicated manufacturing. It's not a plug-and-play.
Let's talk about that just with respect to Sana's capabilities and kind of the steps that you've taken to build versus partner versus buy and how that could change over time as you potentially move up to larger clinical scale and then commercial down the road.
Yeah. So different in T cells and type 1 diabetes. Within the allogeneic CAR T cell space, first of all, it's a really complicated supply chain. So it's a combination of CDMOs and partners and things we do ourselves, right, to be clear. We're building out our own manufacturing plant in Bothell, Washington, where for a large portion of our portfolio, our goal is to run the registration study and launch the drug from there. We've kind of, I think, in the allogeneic CAR T cell program, we've probably solved the scale problem, right? We can make hundreds of doses per manufacturing run. We do still have to prove that when you get it's a donor that gives you these cells, and then across different donors, we have a consistent efficacy and safety profile, right? I think that's assuming that's cracked, we can make plenty of drug to treat.
If you look at what the likely dose is in autoimmune as an example, if it works like the autologous setting, we'd make 700-ish doses per manufacturing run. That means out of 100 manufacturing runs a year, you'd get 70,000 patients. It just isn't that complicated to think of an autologous company doing 70 manufacturing runs. I mean, we'll have more safety studies we do, but generally, it's pretty straightforward. So that's not that challenging. Type 1 diabetes is more complicated, right? And there are three kind of critical manufacturing risks along the way. I kind of think of them. One is making a gene-modified master cell bank where you're comfortable with the genomic integrity over time. Because every time a cell divides, you make a couple of mistakes. That's kind of what allows us to evolve.
We want to make sure that that doesn't occur in a way that we're selecting for cells that become cancerous, right? So that's part one. We spend a lot of time on that. Part two is being able to make enough cells at adequate purity, potency, and yield for a phase 1, 2 study. I feel like we're pretty good at that, right? I wouldn't put that into your big risk category. I mean, it's not zero, but then part three is being able to make enough drug to be able to supply a market that has eight million people, right? That's a big, big step. And we have a lot of work to do to be able to do that. And you have to do that to a certain extent at the time you begin a registration study. It's not that far in the future.
So it's a scientific leap to be able to do that, right? And we can do some of it, but we'll need to really grow that capability. A lot of that's science. Some of that's capital, right? It's not really just scaling up, right? We're kind of building more factories. It's really we have to kind of get more from every run, right?
Makes sense. So let's talk about SC 291. So we talked about the Type 1 diabetes and B cell malignancies. I guess to take a step back, I mean, when you guys first IPOed, the idea is CD19 and leukemias, lymphomas, BCMA for myeloma. And that kind of model has evolved since then, right? I mean, these markets have gotten pretty competitive. There's lots out there. And you guys have sort of shifted a little bit with respect to Type 1 diabetes. So the focus has evolved. But for 291, talk about kind of what we could expect from the first set of data. Maybe set the stage for that. How about that?
Yeah. I guess I might characterize it a bit differently, but it's not way off. I mean, there's no question that when you look at lymphoma, leukemia, multiple myeloma, they're very competitive landscapes. And that as we go into those with an allogeneic CAR T cell, if we assume it works as well as we hope it does, we still have to grapple with autologous CAR T cells and bispecifics and things like that. And they're entrenched. They're getting survival data. They're moving upstream, all of those things. Those are things we kind of thought would happen, but they definitely it's a competitive marketplace. We have to grapple with that. And we have had, though, this we've always had an interest in autoimmune disorders. But the data that came out of Germany from Dr.
Schett's are just so transformative in terms of kind of how you think about that, the B cell-mediated autoimmune diseases. This idea that you might have curative intent at the time of a treatment is not really was in the lexicon of people five years ago or even three years ago. And we have to be focused on that because in there, one, there are a lot more people that we can help, right? Two, I would argue that the allogeneic players have a much bigger impact. And we're running alongside them, or we can even maybe beat everybody to market because we've invested already in the manufacturing. And if it really works, they'll have to grapple with us instead of us having to grapple with them. So there is something to that.
But the autologous CAR T cells work in that space, and they'll have a place. The bispecifics work. They'll have a place. And we'll still have to grapple with them over time.
So if you look at autoimmune, though, overall, including some of the more orphan-ish inflammatory conditions, compared to classic sort of HemOnc, right? I mean, you have a different risk-benefit profile, chronic therapy versus somebody who has a cancer. And I think it's just the FDA and EMA look at that a little bit differently from a risk-benefit. Talk about that in terms of the context of the platform at Sana and what you could do to kind of have a competitive safety tolerability profile in addition to, obviously, efficacy, which leads a lot of these cases.
Yeah. So these diseases are different within themselves, and they're different from blood cancers in some regards, right? You have to do some arm wrestling to convince me that a lot of lupus nephritis is different in risks in an early-stage lymphoma patient, right? They both have pretty difficult outcomes in front of them with a lot of toxic medicines and things. If you can offer people a one-time curative medicine, that would be really just spectacular, right? It's probably the same with multiple sclerosis and certain lupuses. Wegener's granulomatosis or ANCA-associated vasculitis. Again, some of these are really bad. If you go into something like an IgA nephropathy, it's more middle of the road. It's not quite as it's a bad disease, right? I'm not saying minimize what they have, but it's not quite as grim of an outcome.
So we have to, first of all, start in diseases where patients are quite sick, right? But patients are trading off chemotherapy, steroids, other diseases that are really toxic for potentially a one-time treatment, and they're done with their disease, right? So that's part one. Part two, within the allogeneic platform, we have a couple of potential advantages. So if you look at that lymphoma risk that's popping up, right, within the T cell space, I've said the CAR T cell space and B cell malignancies, what you've seen it looks like is that these are secondary malignancies related to either viruses in the patient's T cells or as a consequence of all the chemotherapy they've gotten, right? They haven't really seen it from CAR insertion, right? And so if that's true, we have a couple of advantages. We can screen out pre-existing T cell viruses, right?
We can actually screen out certain insertions if we need to, right? And we will be donating in terms of the patient's, I should say the drug will come from a healthy donor instead of somebody who's been undergoing T cell toxic therapies for many, many years. So there's at least a theoretical benefit in terms of fewer T cell lymphomas and infection risk. But I like our chances in the autoimmune setting for that reason. And I think there will be a number of patients for whom it will be transformative. I don't think it will work as well for everybody. And as the early data out of Germany were, which were 100% complete responses with no one recurring, right? Life doesn't work that well. Drugs don't work that well. It will work in some. Some people will probably recur.
Hopefully, we don't have any meaningful toxicities, and we go forward. I think it can be a really, really important drug class. If you look at the B cell depleting agents, they've transformed a number of different therapies. They've done very well commercially. And these are substantially more potent than the antibodies.
Right. Yeah. And just I guess along those lines, when you look at one side of the spectrum where you have sickle cell and the gene-edited products that look to be very clean and had a straightforward regulatory path, but others, TILs or some of the AAV-related therapies, right, for hemophilia have had a little bit more of a regulatory kind of a bumpy road. Where do you think regulators are today, U.S. and Europe, on understanding the subtleties of cellular technologies like you guys have? And do you think that they'll be able to sort of be able to capture that when you design your studies and understand the risks?
I think that people might differ in what you said, right? If you were to go to, for example, some of the early pioneers in HSCs, they did a lot of work around conditioning regimens and things that allowed you so we do benefit from the fact that there are companies who have done autologous CAR T cells. They figured out certain elements of the therapy, both for the oncology and the B cell-mediated autoimmune setting. And we benefit from what people are learning in the field in type 1 diabetes with stem cell-derived islets. So I hope that we get the same benefit that some of the later companies did in coming along in the sickle cell space where they learned from others in the field, right?
I think with TILs or AAVs, the challenge there is a lot of the challenges. Those are very complex medicines with substantial variability in the manufacturing product from run to run. And that just takes a lot of time for a company to get their hands around. And kudos to them, people who have done it. And it takes a lot to scale and to convince yourself and then regulators that you have a consistent safety and efficacy profile. I mean, hopefully, we're just like the same every time at a reasonable scale, and we're able to kind of skip that hurdle. But we will learn from people who have been playing around this space, the cadaveric islet space. We learn a lot from them, right?
As an example, transplanting cadaveric islets has taught us a lot about product composition, how you get these cells to engraft better, elements that impact ability to store, all these simple but kind of steps you have to get through in drug development that you can learn from others in the field, right? So we do benefit from that. All right. Glial progenitor cells, we'll be the first people to ever transplant those. It's more complicated, right? It carries more biology risk and more risks around getting it in, getting it at the right place, at the right time, in the right regimen.
Along those lines, I mean, if Sana is the expert here and you sort of blaze a trail, does a partner add anything other than capital, right? I mean, I feel like there's not really you could. I mean, it seems to me you could really benefit from taking all these candidates, right, in the pipeline through to market. Maybe the only thing that you may need is commercial, but I feel like that's moving forward.
Well, we need more. I'm really clear. I'll just start with the most basic global regulatory and commercial pricing expertise. I mean, every country's different. Every geography's different. I've yet to see a company in our industry that launched their first drug globally and built a regenerative pipeline successfully. Pretty much all of the companies that have built the kind of regenerative R&D engines have partnered their first asset. All the companies that went global with their first asset began the next phase of their growth through acquisitions and licensing just because it's so hard. We just don't have the human capital bandwidth, let alone the balance sheet capital bandwidth to do it. The second is if you look at all of the best drugs in our industry's history, almost all of them had a similar drug.
We could argue the nuance, but same mechanism that was in the same class that was dramatically less successful. That typically has a lot to do with R&D strategy and development strategy and bandwidth. Look at type 1 sorry, not type, B cell-mediated autoimmune disorders as an example. The probability that we're going to be able to go as broad and quick as we could, alone as we could with a partner, is pretty small, right? At some point, we will really benefit from the expertise of a partner, maybe not today, but sometime soon. Type 1 diabetes, because stem cells are so new, not a lot of companies have invested a lot in stem cell biology and manufacturing.
All that being said, there are a lot of companies that understand metabolic disease, a lot of companies that understand scaling cell-based drugs, and there are a lot of companies at lower cost of capital than ours. So I think we will benefit by more than just cost of capital and anything that we do. And if we can't, we probably shouldn't do it because you sell a lot of the company in any partnership. And so early on, we tried to avoid them just because decision-making is so complicated. And if you were to just kind of pick only competitive advantage we have is faster decision-making, right? Everything else, big pharma companies should be better enough. They have more systems, more capital, more people, more plants, more everything, right? So it's decision-making.
When you start a partnership, you have to kind of align on what you're going to do going forward. So there's a time for that because it's a time when the decisions need to be right. Early on, the company that wins is often the company that learns the fastest, right? So we want to move quickly. But that time will change soon. So we will partner all these drugs over time. It's inevitable.
It'll start with initially turning the card over on early human proof.
We want to turn cards over ourselves. It's a human-proof concept. But we're just not that far from it. I mean, all those things will happen this year, hopefully.
Yep. And when you think about that conversation as informing the strategy, does further expansion of your manufacturing capability play a role there, or do you feel like that's a box that you have mostly checked at this point?
In the CAR T cell, it's mostly checked. It's not entirely checked, but it's mostly checked. I think we can deal with it ourselves. If you were to take a long 10, 20-year view, we'd need to build more, right? But launch, we can do. In the stem cell-derived stuff, that box is barely even drawn, let alone checked, right? So we got some work to do, right? And being at a place where you'd call that a checkbox, a lot of work. We don't really have a commercial strategy yet, right? We've been working very hard on a phase one, two strategy. And that is something that we have to work through.
Yep. And along the evolution of your pipeline, you have developed technologies which are really very innovative, and sometimes it's not clear what to do with them. And I think the Sana X piece of it is really unique to you guys in that you put a lot of the cool projects, if you to put it so. Talk a little bit about that as providing what kind of optionality is something like that provide you guys?
I'll use something different as an example. Same idea. So we spent a lot of time on the ability to deliver because you can do anything you want to a gene in a Petri dish, more or less, right? In vitro, super easy. And you can't do it really at all on a human, right? And so spent a lot of time on delivery. And the goal was to be able to deliver any payload, DNA, RNA, protein to any cell in a specific and repeatable way. And we've made a ton of progress. And we've shown that we can deliver gene editing, base editing reagents in cell-specific ways to multiple different cell types and that it's very specific. We completely avoid things like the liver, macrophages, other things. And we just haven't had the bandwidth or capital to push that forward.
We had to make some choices as we went through the last couple of years. So we have one more experiment we're running that we want to just, I guess, kind of the killer internal experiment. And then we have to make a choice because we could sit there and just hold on to it. Ultimately, people's capabilities walk, though, right? We could partner it. We could spin it out, or we could develop it ourselves. And we'll have to make some choices in things like that. The in vivo delivery is probably the most proximal in that. And the team's done a wonderful job of making really good progress. I mean, we'll do knockout and all the models you can think of for sickle cell. We can do HSC-specific delivery and change the hemoglobin gene and that kind of thing. So we'll figure it out.
We can't let it sit here forever.
It's a good problem to have, though.
It is. It was a bad problem the last year or two because it led to us having to make some tough choices on prioritization. Those always include not just programs but people that are no longer with the company. At this point, it's a good problem to have because we've kind of hit reset. From here, we can grow with it or spin it out into something different for others.
Yep. Okay.
Thank you very much.