Sana Biotechnology, Inc. (SANA) Earnings Call Transcript & Summary

There might be. I don't view that longer follow-up is that important anymore, right? Just to be clear, I've said that since 28 days though. So it's likely going to continue to be around. There isn't really an immunologic issue that's likely where it's headed. You may -- we're not really -- we're not transplanting these cadaveric islets next time. And so you're not going to learn a lot about the durability of the cells we transplant. Our cells could be worse, our cells could be better. My expectation is that these cells will last for at least for a while longer. I don't know how long before they exhaust. They came from a 60-year-old person who died who had a hemoglobin A1c of 6.2%. And so it's not like they were probably already getting, kind of, petered out, and we'll just have to see, kind of, how it all goes. Okay. Actually, I'm not sure what he's presenting. I mean I think that's still a month away and to be determined.

Great. Great. So I think maybe this is definitely an exciting time for type 1 diabetes and for the company's very differentiated platform, definitely looking forward to the initiation of the trial and data next year.

Yes, me too. I joke around sometimes, it feels like sometimes we're waiting for Godot and Godot is finally showing up. So hopefully, we'll have an opportunity to understand in people. Again, I kind of -- I sometimes have given this analogy that it's like others in the field have made an electric car, right? The people who have done the islet transplants before. It turns out it wasn't that useful to have you plugged in, right? And so we showed with that New England Journal of Medicine paper that we could make a lithium battery essentially, right? And now we need to put together the whole thing and see can we really get this to go. Everything suggests that this should work, right? I think I've been around long enough to know that biology, in particular, immunology, have a distinct way of humbling us. And so I'll be excited to see the data. And hopefully, we'll be delivering something that's really helpful for people who deserve a better and new treatment.

Yes. Well said. Let's rotate to another area that you pioneered and years ago, that is in vivo CAR T. So this area has seen a lot of activities over the last couple of years. As we watch the number of acquisitions and partnerships formations across the space, I was wondering what do you think are the pharma companies going after? And how is your program positioned in this landscape?

Yes. A lot of them going after things they think work. Whether or not they end up working, we'll have to see. I mean, again, just to go to biology, nothing ever plays out like -- not everything will play out like I hope it does. But what we did, that's different. So at the very beginning of this program, we made 3 really, kind of, intentional choices. And we'll end up seeing how these were really good choices to make or we make things complicated. One is we believe cell specificity is super important. And that includes not going into the liver and not going into antigen-presenting cells. And I think if you look at our data to date, I'm pretty confident we have a best-in-class therapy around that. Now that may not -- the alternative hypothesis is that it isn't that important. You just need to get enough into the target cell, which is the T cell. And if that turns out to be right, we will overcomplicate things, right? The second is because you have, let's call it, you and I probably have 100 billion B cells. And if you have cancer, you probably have 100 billion more cancer cells, and you're only maybe making 100 million CAR T cells. We've always believed you need to integrate the DNA into the target cell, so you can get that multi-logarithmic expansion and growth to kill because you have way more target cells to kill than you have CAR T cells. And that may be right. I think that early human and animal data suggests it's likely to be right. But if that's not right, I mean mRNA is a lot easier to do, and that's people don't like the idea of the integrating signal because it does have some at least theoretical risks. The third thing we did is we've dissociated entry from activation, right? And what I mean by that is most of these companies are using something like CD3 to enter the cell. And that, and what you've seen to date is a new category of side effects come across in this field with a per-infusion toxicity. It's being dealt with high-dose steroids. We're optimistic that we will have something better around that. We don't know that for sure because we don't know exactly. We have to put in people and see. But we use a different molecule to enter the cell, which allows us to titrate in activation of the cell, not overly stimulate the T cell and hopefully have a safer therapy and maybe a longer-lasting therapy because you won't exhaust the cells with the CD3 activation. But if you're using your CD3 as your activation and entry portal, you may end up overstimulating these cells. Those are the 3 things we've done differently. They may turn out to be really valuable in the clinic and they may not. And you don't really know until you get into people. It definitely has slowed us down to do it this way, right? We -- as you said, we, kind of, pioneered this and been at this for a while and companies have jumped ahead of us in line. So I hope that they turn out to be really important for patients because they were intentional choices we made.

Can I follow up on the point of not targeting through CD3 -- is that the CD8 targeting method? Or is it...

Yes. So we're using CD8 to enter the cell. Those are your -- kind of your effector, here's your killer cells. Now the flip side of that, again, everything has a cost, right, is we're not entering CD4 helper cells or regulatory cells, right? It doesn't look like that's going to be important based on what we know and the information we have, but I think that's still plausible that you wish you had a bit more activity by having made CD4 cells. But the benefit of it is it's a much more specific delivery. And we're able to, again, titrate in the activation of these cells with a little CD3 co-display on the VLP, on the virus-like particle rather than using it -- and if you're using your portal of entry, you can't turn down your activation without lowering your potency because you're using CD3. Just CD3 is a very potent activator. It's what is -- everybody who makes an ex vivo CAR T cell in some way binds to CD3, they, kind of, get these cells going. There's an old drug called OKT3, which is a CD3 activator that was used. I remember from when I was in medical school and residency just being a very difficult medicine to administer because of again, the cytokine storm or per-infusion toxicity took place.

Okay. Any comment on CD7? So some companies are using CD7. Does that stimulate the T cell? Or could it achieve entry without activation data?

I'd like to see some more CD7 data before you can make a true determination on that.

Got it. Yes. Yes. So that's super helpful to understand the differentiation and potential. So I think you alluded to this earlier. I think you were thinking about data this year. So that's apparently you're referring to activities in China that you're working on, but perhaps 1 or 2 quarters, even some recent development. So any thoughts on -- maybe let me ask you this question. So once this study enters the clinic, how quickly do you think -- this is the cancer study, right? So maybe 2 questions here. Does this mean that you are more focused on cancer than autoimmune disease? Two, for a cancer study, how quickly can you get a sense of how well the drug works?

I would really like to think that we're able to develop this medicine in both the oncology setting and the autoimmune diseases. That being said, I think what you've seen even over the last few weeks from others in the field is that the safety bar is higher in the autoimmune space. And so we feel it's appropriate to start in the oncology setting and really understand the potency and safety and efficacy of this program. And if it works as we hope it does, which includes both potency and a really tolerable side effect profile, we'd like to move rapidly into autoimmune diseases. But we have to see what the clinical profile looks like. And so how quickly can you see, is that the question?

Right.

It's a little hard to know. Again, you're -- the way that these -- one of the reasons these VLPs, these particles are complicated is that they're all like derivations in some way of lentivirus, which is in some way a derivation of HIV. And actually, that's a species-restricted virus, right? So it doesn't infect most nonhuman primates. And so you're using some surrogate vector into a normal monkey, right, because they don't have cancer, right? It's not a disease model. The mice model are simple, like that's easy. But I think you really need to get into humans to understand dose, right, because you're using a surrogate in a nonhuman primate. And so you could have something where you've seen a company that's dosed too high, patients almost died. We've seen another company that started out and it took them a few doses to get to the therapeutic dose. And we've seen one that it seemed like from the outset, the first -- they were, kind of, in the right ballpark with their dose. And which one we end up being, I don't think we know, right? And so it could happen very quickly. I doubt we're too high. I think we've learned enough that you want to, kind of, come in carefully. But we may be too low. We may be just right, and that will determine how long it takes us because it's just -- you have to get through the dose-finding portion. It's a novel therapy, a very -- it's a first-in-class type of technology. And it just -- sometimes you get fortunate and you're at the right dose and more frequently, you got to kind of go through some of the dose finding. So we'll see. I do think it's pretty quick once you get here to know does it work. To really understand is it -- if you take just a big 10,000-foot 50,000-foot view, B cell depleters is a very, very competitive space, right? You've got pills, antibodies, ADCs, T cell engagers, you've got CAR T cells, you've got in vivo CAR T cells, you've got different technologies in the in vivo space and kind of how we fit into that competitive landscape will take more patients than a handful, right, of efficacy. But that early efficacy can be very, very helpful in understanding does this technology really work like we hope it does.

Got it. Got it. So I think you alluded to this very -- I hope we can get some of your insights. This is regarding the autoimmune indication, Novartis and BMS announcing study pause due to severe immune or inflammatory reactions after their rapidly manufactured CAR Ts were administered to autoimmune disease patients. You have a lot of experience with CAR T. Can you talk about what you think the cause there might be? Does it have anything to do with this rapid manufacturing process? And maybe related to in vivo CAR T, like could there be any read-through given that their T cells are pretty -- very quick turnaround, whereas in vivo, I think no turnaround at all.

Well, I take a step back. This -- the side effect that they've described is a well-known side effect of CAR T cells, right? And if you -- it's this immune-mediated hemolytic syndrome, right? And -- it was probably missed in the very early days of the CAR T field is probably underrepresented on labels based on kind of what is reality because it smells a lot like cytokine release syndrome. It happens just a little bit later, and it actually has a different treatment, right? And so first thing I'd say is this is -- anybody who thinks that this is not their problem is in the CAR T space is fooling themselves. This is all of our problem, right? I think we have to -- it's just like you're going to have cytokine release syndrome, you're going to have neurologic toxicity. You're going to have this stuff over time. It's been seen across different targets, across different manufacturing platforms, across different diseases, right? So those things are true, right? Number 2, is there something about this patient population or something about the medicines that these companies are making that specifically are heightened risk. I don't think we know enough. I think it would be way too premature to kind of -- they haven't told us what happened. You do know that this is often a very treatable issue. So it might just be that there's some physician education that needs to take place, but you need to treat really early in the course of this hemolytic syndrome. And again, if they were treated for cytokine release syndrome, that's not going to have done the trick. So I look forward to learning more. I like to think that you won't have this issue in at least our technology, where, again, we're hopefully activating the T cell less. I don't think we could confidently say that without a lot of experience. It's a rare side effect. But if you're treating hundreds of people, you may start to see a little bit. And I don't think you can say you don't have the issue after 5, 10, 15 people. It's just -- it's going to take us more time. So stay tuned. I do think this is something that it's a great reminder that these are amazingly wonderful medicines and they give people potentially a very rapid cure to some very dismal diseases, but they are very potent medicines, and we have to be careful and mindful as we're treating people with them.

Got it. Got it. I really appreciate the perspective. In the remaining time, I was wondering, can you talk about your cash runway? And how do you think about capitalizing the company?

Yes. I see our clock at 0, so we're better than that. But I'll try to be brief. I'll try to be brief. We have about $160 million. We've said it will last us into the middle of next year. We've got a lot of things coming up with a number of data points. We've generally said managing through 2026 and until we get to data, we're going to be pretty tactical about things and just make sure that we maintain some buffers so that if things don't go as we hopefully do, we've got a little bit of time. If we're fortunate enough to have some good data across either one or both of these programs, I think we'll be in a strong position to rebuild the balance sheet and capitalize the company more fully. We certainly would like to have multiple years of cash on our balance sheet at some point in the not-too-distant future. But that may be through business development, that may be through raising equity, it may be through something else. We'll have to see.

Great. Great. Thank you. As you said, we have come to the end of the session. I want to thank you again, Steve, for a very, very helpful and enlightening session.

Thank you, and thanks, everybody, for your time and attention.

Great. Thanks, everyone.