Good afternoon. Thanks everyone for joining us. We're really pleased to have Sana here with us, and we have Steve Harr, who's President and CEO. Steve, Sana is a preclinical biotechnology company that's focused on cell engineering in a broad sense with a dual platform approach. Could you just give us a brief overview of both your ex vivo Hypoimmune and in vivo Fusogen technologies and remind us how your platform's differentiated versus others?
Yeah. First of all, thank you, Salveen, for having us. It's a beautiful location, and it's always nice to get out and see people again, and I appreciate everybody who's been going at it for a long day for joining us, and we'll try to make sure this is hugely entertaining part of your day and worthwhile. Thank you. We will make forward-looking statements just on the call to everybody. We do spend time running our risk factors and things, so feel free to peruse them. I think you'll learn a good bit about the company. It's a great question. When we started the company, I think a lot of you know, we really wanted to build the company around the idea of engineering cells, right?
Basically, every disease you can think of is caused more or less by damage to or, actually death of a cell. We would want to approach it from a lens where we could be agnostic. If the cell was still alive, then we could fix it in vivo, be able to modify the cell inside the body. If the cell were too far gone or already dead, to be able to really grow one or build one ex vivo and replace what was missing. You know, it was probably not something that a lot of people would have done. Most people went down one or the other track. It turns out that most of the capabilities we'd need to build are highly synergistic and utilizable across both platforms or areas of modifying cells.
The risks are really pretty idiosyncratic, which is something that's great from a portfolio construction perspective. When we started down the path of in vivo cell modulation, really what you're trying to do in a very simplistic way is deliver a payload that modifies the genome or the, you know, RNA downstream from the genome. It struck us that you can more or less do anything you want to the genome in vitro, right? In a petri dish. The real challenge is delivery. From the outset, we really focused on delivery. It's not to say we don't have a big program around gene editing and gene modification and RNA, but in epigenetic modifications and things like that, but it really is on delivery.
Our goal is really simple, is to be able to deliver any payload to any cell in a specific and repeatable way. To be really clear, we can't do that. But every time you take care of one of those four things, you open up whole new areas of medicine. What we started the company around was a technology that allows us to do cell-specific delivery. Just to T cells or just to hematopoietic stem cells or just to muscle cells. With that came along the ability to really deliver any payload. We can deliver DNA, RNA, protein. It allows us to deliver gene editing machinery like, you know, you can knock genes out, we can base edit, we can prime edit, you can do any of those with the technology. That's kind of part one.
We've chosen the first place to apply it is by delivering a gene to a T cell to make a CAR T-cell, right? We've shown in mouse models and in monkey models that we can do this in an efficient way, in a cell-specific way, and we're gonna hopefully get an IND in this year that will allow us to test whether we can do this in humans in a specific and efficient enough way to go after certain cancers. We'll start with the CD19 cancers just 'cause we'll talk about why in a little bit. On the ex vivo side, here what we're trying to do is manufacture cells at scale that will engraft, function, and persist, right? That's ultimately what all cell therapy is.
The real challenge in our industry has been the, I think, the tension between manufacturing cells at scale and cellular persistence. Basically, to overcome the problems of immune rejection of allogeneic cells, people have gone forward with autologous cells. It works, right? But it's really, really difficult to scale these products, and there are only a handful of cell types that you can actually manufacture that way. Our goal from the outset was to cloak cells from immune recognition so that we could do allogeneic cell transplants. We've chosen to really go after and for proof of concept, two areas where the field has already worked out how to get cells, what are the right cells to function, and how do you get them to engraft, right?
Starting with an allogeneic CAR T-cell, we do a donor-derived T-cell, we gene modify it. You know, we can show you data, which I'm happy to talk about, which, you know, suggests that our cells will really evade immune recognition and live at least as long as autologous cells, maybe longer, which would be transformational, I think, from an efficacy perspective. That's part one. Again, that will hopefully have an IND in this year. Part two is type 1 diabetes and making beta cells from iPS cells. Again, the field has already shown that you can take cadaveric islets, immunosuppress a patient, and transplant in these cells, and you will cure them of their diabetes for as long as they can tolerate the immunosuppression.
Our goal is to be able to, in a single therapy, inject these cells and have patients who, with one treatment are euglycemic, so normal glucoses, off of all exogenous insulin, and with no immunosuppression. Again, we can go through why we think that will work in a second. That's kind of a little bit around what we've done. What's really different, I think, in what we've done is, first of all, the focus on delivery on the in vivo side, right? It's there aren't many things that you can look at where you can say, "You know what? They can actually maybe deliver cells to somewhere besides the liver." Right? That's really where everything goes, right? Everything, all LNPs bind to ApoE, and they bind the LDL receptor, which is mainly in the liver.
If you stay on the cell therapy side, really the focus on the immunology of transplant rejection, and we've shown now across multiple different cell types in non-human primates and in mice, and in humanized mice and in ferrets and things, that we can prevent these cells from being seen by the immune system and rejected. You know, there still is the hurdle of taking the word non away and moving from non-human primates into the human primate. But I think if it works in the human like it does in non-human, it can has the potential to be like Intel for every cellular therapy, right? Intel's in every computer. This type of immune cloaking really would be transformational for the entire field of cell therapy. It's gotta work though first. That's a long-winded answer to a very simple question.
You talked about being on track to file your first IND with CD19. Two questions. One, can you just walk us through your timelines for IND filings this year and next year? What programs they are? Two, I mean, I would assume CD19 is for platform optimization because you know the target CD list, and you can see how your platform's working. Is there really a commercial opportunity with the drugs going after CD19 at this point?
I'll answer the second one. It's the easiest question I can think of. It's absolutely yes, right? You know, today, if you just took CD19 and BCMA, I think there are 100,000 people in the U.S. and Europe alone that die of myeloma, leukemia, and lymphoma, okay? These drugs are pretty good, right? You've got a 35%-50% of patients really getting a long-term durable response to them. In the history of humanity, you can count the number of people who've gotten a CAR T-cell in the thousands, right? There are thousands and thousands of people dying every month that don't get access to these drugs. They can't make it, right? I'm absolutely convinced that if we can make. It's inconvenient if it's off-the-shelf available for infusion, you know, as soon as you want it, right?
Just get your lymphodepletion and off you go. We have data that are comparable or better 'cause I think you could do either to autologous, we'll be in a wonderful position. I think if it's inferior, which I think a lot of the field has been today, is there's a place for it, but it's gonna be highly fragmented and competitive, right? It does need to be different. It needs to be at least as good as what you see from autologous cells. We can get into, like, why we think that will happen. You know, in terms of why we did CD19, Yeah, I think you're getting this question. I kind of compartmentalize risk, right? In the simplest form, there are four major risks in our industry, right? If you're making a platform.
You got platform risk. Does my platform work, right? You have disease biology risk. Can I get it to intercede in really important disease biology? You have clinical trial risk. Can I prove it in a human, right? You have commercial risk, right? You're getting that by, you can create more commercial risk by focusing on the other three, but. What we chose of those scientific risks is to say, let's isolate platform risk. If it turns out that our platform does what it says it will do, we will have really clear evidence of human efficacy, right, with CD19. I think we're gonna make a really important drug that's really that has a big impact commercially.
Above and beyond that, you now have proven your platform risk works, so now we get the privilege of taking on more disease biology and target risk, right? That's how we've approached this from a stepwise perspective. If we did Target X, whatever Target X is, and it was going after ovarian cancer and it didn't work. We did Target X and a gene therapy, it's after Alzheimer's disease, and it didn't work. You'd say, "Well, I don't know if it was your platform or if it was the target you went after," right? We really wanna kind of isolate and stepwise go after. If things don't work, we know why, right? That's why we chose to go after CD19 out of the gate. It isn't like I think we'll do something really important if it works.
I think it gives us the privilege of taking on this other risk. You'll know, I mean, the great thing is, a year from now, if we are putting allogeneic cells and they're living for three, four, five, six months, right? As much as an autologous cell. You'll know we've got something, right? You will absolutely know that that will, one, translate into an important clinical drug, and two, that this hypoimmune platform really does cloak these cells from immune recognition. You can go all in on a whole bunch of different targets, both in oncology and cell therapy more broadly, things like type 1 diabetes. In terms of IND timelines, to ask the other part of the question, we hope to have. Our goal is to have two this year.
One is called SC-291. That's the hypoimmune allogeneic CAR T-cell targeting CD19. We're basically doing all the work for tech transfer to get this manufactured. It's a very complicated drug. There are six different GMP components, which means you're not just transferring the manufacturing, it's all the assays that go with it. It will happen, right? There's not a lot of technical risk in this. You know, could we slip up and miss a timeline by a week or two? We could do that. We could not get, you know, bags in on the right time, all those things, but it will happen. The second drug we're filing an IND this year, we hope, is called SG-295.
That's in vivo delivery to T-cells of a CD19 CAR. We're finishing up the pharm/tox studies now. There's always some risk. We've done non-human primate studies before, we've done mouse studies before. There's always some risk you find something that slows you down a little bit, right? That's ongoing. Again, goal is this year. You know, once those are done, we're looking for two next year. Those two are a drug called SC-271. That's looking at CD22 and CD19 together, really going after mechanisms of failure and resistance. That's the type 1 diabetes program I mentioned earlier. Hopefully we get both of those in as we move through 2023. That's a little about that.
Help us understand if your CD19 works from both
Say it again.
If both platforms have positive data.
Yeah.
With CD19, who's the ultimate winner here?
Great question that I would love to have the privilege of answering. You know, my general view would be that they will both be important and within the CAR-T field, and they will serve different masters, right? With the in vivo delivery, we're relatively capacity constrained in how much we can put into the cell at this point. It will be great for things like, you know, current hematologic malignancies. With the Hypoimmune platform, we can really 'cause we're outside the body and you know, we can do a lot of gene modification to these cells.
I think it will ultimately be what's necessary to go after some things like solid tumors, where it's pretty clear that, just going with the same old, you know, manufacturing the same cells with the different target is probably not gonna be enough, right? It would give us a platform to go after some of that. It also. They both will have all kinds of orthogonal uses. If we can deliver cells, if we can deliver genes efficiently in vivo, we're not gonna do just T-cells, right? We're gonna do HSCs, we're gonna do other cells, right? We're gonna make that happen. If we can hide cells from the immune system, we're not just gonna do CAR T-cells, right? It's gonna end up doing a whole bunch of other things.
Like, I would love to be in the position where we're all debating which is better and how are we gonna divide the world up. That would be a wonderful place to be. We'd probably take one right now and be pretty happy, but two would be great. I'd love to have that problem.
Let's talk about you have a pretty vast portfolio that you could move forward. How are you thinking about capital allocation in these times and where do you stand on cash and runway here?
Yeah. Important question. You know, as I think, in case you guys haven't noticed, it's a little bit dicey out there right now in the public markets, right? You know, we really started the year. We actually, our stock did pretty well last year, and it got kind of beat up as we went through the end of the year and early this year. We actually, at the beginning of the year, really sat down and had to make a choice. Are we gonna just kind of put our head down, execute, and hope that the market's in a better place when we're next to raise capital?
Are we gonna make the assumption that at least for the medium term, our cost of capital has changed and we need to change how we operate? We went down the latter path, right? This morning we put out a little 8-K that we have money that will last us, our balance sheet will last us into 2025. We can make it go further if we need to. You know, with that, what we prioritize were the four drugs we already talked about, really with no change to our investment into them. We prioritized building our own and controlling our own manufacturing. We did announce about three weeks ago, we're changing where we do that, and it saved us about $100 million.
We prioritized ensuring that we were continuing to really hold on to investing in some of these platforms. Everything that's earlier, we slowed down. You know, that has a consequence. We talked about wanting to do two and three INDs, two to three INDs per year. We'll do it for the next few years. We probably won't be able to hold on to that for some period in the middle, medium term. We'll be alive, right? That's a good thing. That's how we've decided to. We have slowed some things down. We've changed where we're manufacturing. We've slowed down our overall growth rate. We'll make sure this lasts for a while. The great thing is we'll have time with that runway to turn over the CART on at least four drugs.
We'll know if this allogeneic CAR T works with CD19. We'll know if our in vivo delivery works. We'll be able to see if we can get euglycemia off immunosuppression in type 1 diabetes, and hopefully we'll have a chance to look as well at, you know, the CD19-22 drug.
You've talked about the importance of manufacturing. Is this plan change solely financial, the benefit solely financial or are there other aspects for why you moved here?
I'm not even sure the benefits are financial at this point. I think we'll figure that out over time. I'm very confident that the benefits are dramatic in risk reduction. I'll give you two examples of things that didn't go so well for us. One of them was the simple manufacturing of our gene editing reagents, right? Doing them at GMP and hearing from CDMOs that basically you have a couple opportunities for slots. It's like three months from now or it's 20-some months from now. Having to go forward three months, which was a while ago, with GMP manufacturing runs before we were really done with all of our work. That's just risk, right? I kinda think one of my main jobs is to figure out how to reduce risk, right?
Anytime you're changing PTS of a program to negative, that's just not helpful, right? It turned out it worked out. Another example is we were doing toxicology runs for our Fusogen program. Five of the first six times they tried to manufacture it, they failed. It was like, it wasn't because our process didn't work. We actually never got to test it. It's like they forgot to hook up the oxygen. They dropped a bag one time, right? There's like a, there's a 50% turnover, a lot of these CDMOs right now per year. You're taking on another element of risk, right? When you're transferring these products into them.
It's to me, the main reason to control this is you control your timelines, and you control the people who are doing the work that's really essential to the company's success, right? I do think over time it will save us money on cost of goods, but in the short term, it's clearly a more expensive way to operate. It's pretty clear to me that the whole industry can't go build their own manufacturing, particularly as cost of capital has changed, right? The fact that we're gonna be able to do this, I hope is a competitive advantage to us, both in terms of risk and access to drugs, partnerships and things. We'll have to see. It's really about risk. It's very little about financial.
Got it. You've also announced a number of licensing deals, and you did a deal with Beam for their CRISPR-Cas12b recently. Was there a reason you bypassed base editing? Just curious why of all the, you know, enzymes you went after Cas12b.
Why not use Base editing? You could ask them. It's a wonderful technology. We were looking for five things when we were putting together our gene editing reagent access. We needed to have an efficient system, right? Because we're doing multiple edits, so it has to be really efficient. By the way, if you're knocking something out, a nuclease is probably better than putting in a stop codon 'cause you can read through them, right? You can actually see in some published literature that happens, right? We want efficiency. That's first and foremost. Second is specificity, right? Third is ability to manufacture for a GMP. Fourth is freedom to operate, right? That's really difficult in a lot of these things, right?
One of the great things about the Cas12 assets is that the intellectual property is much clearer than some other areas, right? 5th is, could we get to a commercially reasonable agreement? Really, Beam was terrific in all five. It's a great company, and they've been a wonderful partner in this.
You've been in this field for a long time. I mean, you're a pioneer in the field of gene and cell therapy.
Yeah.
The FDA draft guidelines that came out, was there anything surprising to you in your
There were two sets of draft guidelines, right? One was around gene therapy, another one was around CAR T-cells. There really was nothing in there that was in any way different. You know, we have had pre-IND discussions with the FDA around different programs. There's nothing in there that's different than what we expected. Not a thing. I do think, though, that there's kind of this misconception that the FDA is on a one-way track to being more complicated, right? I think what is true is there are elements around where as we've learned more, they've raised the bar, right? And there are elements where they've made things much easier. A great example is like RCL testing, replication-competent lentivirus. You have to do that.
You used to have to do that before you could release a product, right? There's never been an episode, there's never been an incident. That has become a much more simplified area for testing. I don't think it's irrational. Like it's, they're moving targets in both directions. You know, justifiably when, you know, our field is one where we're taking two steps forward and occasionally take a step back, right? We take that step back, we learn things, and we have to make sure that all of us apply it because patient safety is of paramount, right?
Yeah. The Hypoimmune technology, you talked about diabetes, type 1 diabetes and moving forward there. How do you think about what we're seeing out of the stem cell programs with Vertex and CRISPR? How would this be differentiated?
Yeah. First of all, this is a gigantic problem with type 1 diabetes, right? It's millions of people in the U.S. and Europe alone. The average patient with all of these pumps and devices and monitoring lives 15 years less than a non-diabetic. During that time, they have all kinds of challenges with hypoglycemia and hyperglycemia. Like, we could be so fortunate to have all three of us work, right? Because I'm not sure how we're gonna meet demand if all three of us really do one. That being said, you know, what really is different about our approach is, you know, we actually started from an immunology perspective, right? With transplant immunologists who understand transplant rejection and rejection of allogeneic cells, and trying to cloak these cells first from allogeneic recognition.
You know, as we've come to learn, we actually are really good at cloaking them from autoimmune recognition, as well. I think what's really different is that we kind of started out by approaches from an immunologic perspective. We brought in, you know, there are a couple of people who really drove the field. There's one seminal paper, right, from Doug Melton's lab, who originally looked at taking stem cells and turning them into a beta cell. The two first co-authors, one went to Semma and one's at Sana, right? They have different approaches now to how they manufacture cells. I don't really know what Semma and Vertex does. They seem to make good cells, though, right?
I mean, certainly, that one patient has benefited a lot. Based on what's in the public literature in terms of how these cells do in terms of glucose-sensitive insulin secretion, we seem to do really well. We won't use, you know, we won't need things like any kind of encapsulation. You know, we won't use immunosuppression. Our goal is a single injection with no immunosuppression. You know, currently what Vertex does, which really works, but these patients get transplant-level immunosuppression, right? It's really, really heavy immunosuppression. That's really important for some people. For many patients, lifetime immunosuppression is not better than lifetime insulin therapy, right? You know, our goal, if we can do this, it will be very different, right?
It will allow patients to get a single therapy and come off of injections and no immunosuppression for life. It's obviously a high bar. You know, we're optimistic that this has a pretty good chance of working.
When you look at your two platforms and you think about the platform risk, right? Validating it through these two programs coming up, CD19 programs, where does the risk stand?
For what?
Where does the risk stand for the platforms? Like, why would it not be successful in CD19?
Sure. If you look at the allogeneic cloaking, right? We'll present three new cell types this week, cardiomyocytes, RPE cells and cadaveric islet cells. Sorry, islet cells, where we show that we can, you know, immuno-cloak these cells and that they are able to evade immune recognition in non-human primates. The risk is that there's something different in humans, right? What we've already shown is that with human serum and other things, like the T cells don't see this. There's no antibody recognition. The NK cells don't see these cells. Macrophages don't see. In my mind, it would be something, the unknown unknown. Maybe something like something we weren't thinking about could still get us. Right? I'll be pretty surprised if it doesn't work somewhat well, right?
Immunology has a way of humbling us, right? We wanna see it in humans. You know, we cannot test this system anymore preclinically. We've done it. We've done pretty much everything we can think of, and we really need to get it to humans and see what happens. That will start happening, you know, hopefully this year.
Yeah. Any questions from the audience? One last one for you, Steve. There's just been a lot of news flow, whether it's regulatory, and how they're interacting with companies or just many cell therapy companies with news coming, you know, from solid tumors and blood cancers. How do you think about that? Has any of that impacted your vision for how, you know, Sana can move forward? Are there any changes that you're implementing from learnings around this?
Any changes, sorry, what?
To the business model or to your programs that you're incorporating as a result of what's happening around you?
Macro-wise or regulatory-wise?
Science and regulatory.
Yeah. I think the greatest scientific challenge in our portfolio right now is understanding what is an acceptable level of genomic and epigenomic heterogeneity in a stem cell-based product, right? It's inevitable that every time a cell divides, you get like one mutation, right? You're gonna do billions of divisions, and then you're gonna differentiate things. These cells are gonna be different, right? I think that there is no doubt that when you're watching, you know, others in the field sometimes have signals that may be related to their drug or it could have been, and it's not, right? Either one of those. It's a great reminder that we need to be as careful as we can in characterizing that kind of genomic and epigenomic drift that occurs or heterogeneity that occurs. That's part one.
we need to be really able to monitor if something goes wrong, right? I think that's something where maybe the field could have done a little bit better, in that there are predictable challenges ahead of us and having, you know, serum blood tests that just will look for, hey, have you gotten some tumor that you weren't expecting, right? The third is being able to intervene, right? Every one of these drugs will have some type of a kill switch on them, right? So that we can do something if something goes awry. It has made it so it's much more granular to me that we have to do all three of those really well, right? I think we may not have as a field always done all three really well. That's definitely been impactful.
There's no question that we invest. When you're looking at gene editing and gene modification, understanding where you're inserting and modifying the genome is challenging. We've made a gigantic investment in analytical genomics and computational biology. It's like child's play compared to stem cells. It's total child's play. That's made us much better at really analyzing things for the gene editing. 'Cause the gene editing is like you're looking at one thing, you're trying to figure out what happens. It's not that complicated. With stem cell-based products, you need to really look at the entire genome over many, many cells. You're putting them in cells where you're actually picking cells that grow well, right? That's what you're doing when you're growing cells ex vivo.
We need to make sure that we're not selecting for cells that are more likely to grow really well into a tumor, right?
Great. Well, with that.
What's that?
Thank you so much, Steve.
Yeah.
Oh, did I interrupt you?
No.
Did I cut you off?
No.
I apologize. Yeah. Thank you. Really appreciate it.
Yeah. Thanks, everybody.