Welcome to the afternoon sessions of the BofA Healthcare Conference. I'm Geoff Meacham. I'm the Senior Biopharma Analyst here. We're thrilled to have Sana Biotechnology, and then we have Steve Harr, President and CEO on stage with us. Steve, welcome.
Thank you, Geoff. Thank you for having us. Appreciate it.
Every second counts. We got a 15-minute spot.
Yeah.
Why don't I just turn to you, give us, like, the two-minute kind of background, and we'll get right to some questions.
Sure. First off, we'll make some forward-looking statements.
Yep.
We filed our Q last night, and we spent a lot of time on risk factors, so take a look. There's a lot of good information in there. The company was founded, I guess, about five years ago, around a couple of technologies, really trying to turn engineered cells into medicines. We have a handful of platforms. The one that's most advanced is something called a Hypoimmune platform , is what we call it. Since the advent of time, since the advent of modern medicine, we've been trying to transplant organs and cells into allogeneic recipients, and they are always rejected without immunosuppression. Our goal is to be able to transplant cells without immunosuppression, which we think can really unlock and unleash the power of cell therapy. We've two chances to get proof of concept in humans.
maybe I'll just start by saying, you know, we've made a ton of progress and have shown a lot of, I think, very compelling data, published in two Nature journals and in Science over the last month, related to this Hypoimmune technology in animals. The real key is, does what we've seen in non-human primates and mice models and other models translate to humans? We should know this year from two different programs. One is looking at an allogeneic CD19 CAR T-cell, starting out in blood cancers, and the other would be transplanting islet cells into patients with Type 1 diabetes.
In either scenario, hopefully in both, you know, the ability to see these cells live, without an immunosuppression could really, we think, unleash, not only these drugs, but a whole bevy of innovation. That's a little bit around where we are and what we're up to. We can go into more detail.
Yeah. Yeah. Let's talk about the CD19. There's a, you know, lot of companies in this, in this space. What does, I guess, success look like, you know, with respect to differentiation and...
Yeah.
you know, your initial kind of, re-release of data?
I kind of think of this in the biggest, the highest level. We've been spending about the last 25 years figuring out how to deplete B-cells and figuring out where that will have a clinical benefit. That's been shown across, you know, a range of lymphomas, a range of leukemias. Increasingly, we're seeing this in a whole host of autoimmune disorders, lupus and multiple sclerosis. As you move now in the last decade or so, we figured out that you can deplete B-cells much better with the greatest B-cell depleter man's created, which is the CAR T-cell. That has, you know, potentially curative effect actually for people in each of these types of indications. The challenge with all the antibodies, they don't deplete B-cells well enough.
The challenge with autologous CAR T-cells has been that, A, they don't work in everybody, but the bigger problem has just been manufacturing them at scale. What looks like You know, that means that just in cancer, blood cancers, 100,000 people a year die of lymphoma, leukemia, multiple myeloma, the diseases where it's been proven to work and approved by regulators. Yet in the history of humanity, only about 10,000 people have gotten a CAR T-cell. There's a massive supply problem, right? Success looks to me like the most basic level, look as good as an autologous CAR T-cell, we already improved drugs, but be able to manufacture at a scale that makes it like an antibody. If that's true, our ability to go after lymphoma, leukemia, multiple myeloma, lupus, multiple sclerosis, these large indications is really spectacular.
In so many medications, the winner in our spaces are first to market, and then do you have a chance to be best in class? I think here it's first to scale. Right? First to scale with at least as good of a product. What does that look like? I'd say there are three elements. There'll be three steps that we have this year or the next call it 18 months to develop evidence that our drugs work as we hope they will in the CAR T space. One, the way we make these CAR T-cells is we take a normal donor and we gene modify the cell. Some of the cells have all of the modifications, and some of them don't. Say about half of them have all of them.
When you put Geoff's cells in your body, your body would rej ect them as being foreign, unless we have all of our full set of gene changes in them. First body of evidence would be when we put those cells in, within about. You give them a little chemotherapy, and within about three weeks, the immune system's normal. If at one month and two months, all that's left is 100% fully modified CAR T-cells, we've proven that the immune evasion we see in animals is translated to humans. That to me is like the most important thing. We'll learn that very shortly. It's very simple. First few patients tell you. The second thing is...
That means a high probability that will translate if you evade the immune systems to seeing cells, CAR T-cells that persist over time, which means they can fight the cancer for months, instead of weeks. If that's the case, you know, that has a high probability of translating what we really care about, sorry, which is durable, complete responses from patients. We'll know the cell selection within a few months. We'll know the persistence within a few quarters, and we'll know the durable complete responses next year. It won't happen this year. That case will build.
Right. If we make that assumption. Let's say that you do have, you know, data that's de-risking. How do you allocate capital going for, you know, from liquid tumors to more autoimmune indications? You know, basically, like, down the risk curve, right?
Yeah.
Do you say, "I believe in technology, and therefore I'm gonna go after markets maybe that are more unmet?" Or do you go with the tried and true, like, let's go down the model of a lot of other folks have gone from, you know, CD19 to, you know, their logical indications?
First off, the way that we make these cells, it's essentially just a platform. We can swap in different CARs, where the CAR is the element that recognizes the cancer cell and activates the T-cell. We've licensed three different CARs against three different targets. All were validated in human studies with autologous T-cells. CD19, CD22, BCMA. The only difference we need to do to go from the first drug to all three is to make a very small change in the plasmid or the DNA. It's part of the supply. We change a release assay, and that's it. Really, if it works, you should be. Really the main risk is your question, which is capital and execution between us and three different drugs. Like, I think that's pretty rare because you'll sometimes have validated targets or-
Right.
you know, validated biology. Here we actually have validated almost drugs, right? Just put into our platform. We will need to make some tough choices around, kind of what indications to go after. I mean, there's pretty much no scenario where we can do all this on our own. I'll start with that.
Right.
We'll need help. You know, the second is I find it hard to imagine. If you look at Sana's pipeline slide today, I kinda find it hard to imagine we'll be doing all of those things one year from now. We will either have to put our chips into some of the things that are working and delay some things that are earlier, or we'll stop doing things that aren't working, right?
Right.
Be glad we have some of these other platforms to work on.
Yeah.
Right?
You're in a position where you don't need external capital to make.
Not now.
programs work.
No.
Right?
We do not. We do not need investor capital or partner capital to see if these work. Once they do work, you know, it will be a lot of money to push forward, and we'll need to figure out, you know, based on time and the world...
Right.
-kind of what the right way to build the company is. you know, fortunately, though, we own 100% worldwide rights to every drug in our portfolio, so we do still have the opportunity to do a number of different corporate partnerships over time. I always look back. There's almost no company, I can't think of one, that has globally launched their lead asset and built a regenerative R&D engine over time. Usually, you get to pick one or the other. The great companies or industry, like a Genentech, licensed their first drug outside the United States. Some of the great global companies like Gilead and Celgene really relied upon business development early on.
Right.
They have their own R&D. That... You know, if we... I think there's more value for us in pushing forward with our portfolio and our research.
Yeah.
we will almost certainly partner our drugs over time, at least in parts of the world.
I guess that begs the question, do end markets and economic opportunities, what part does that inform where you're going to invest next? I know you're gonna say the Science is what matters.
Well, no, everything matters. PTS, unmet need really is important, right?
Yeah.
You know, we're not anxious in running experiments. One of the things that I really am passionate about is trying to figure out how we turn cell and gene therapy into something that actually is utilizable for the diseases that most of our loved ones will suffer from, right? That we get above and beyond just kind of niche market indications.
Right.
Not that those aren't really important, and they have a big impact, but we really wanna try to do that. The size of the unmet need is very important. The one thing, though, you know, when you're dealing with gene modified products, you have to kinda start with big unmet needs.
Right.
Prove your safety with pretty morbid outcome for patients and prove your safety before you can gradually move, hopefully, with good safety data into patients who may benefit longer.
Right.
for longer periods of time, right?
Yep.
For whom the risk isn't there.
Gotcha. kind of the same question on the islet cell data coming up?
Yeah.
You know, what would you say, you know, does success look like?
Yeah. The experiment, just for people who just take a step back, Type 1 diabetes is an immune attack, autoimmune attack of a person's pancreatic beta cells. These beta cells are what we all have, they secrete insulin in response to fluctuating glucose and rising glucose. You know, up until 100 years ago this year, patients who developed Type 1 diabetes just died. With the advent of exogenous insulin in 1923, people have done increasingly better over time. That being said, you know, the average Type 1 diabetic has a very complicated life, where they also face many long-term sequela, the best care, about a 10-year shortened lifespan. It's still a very big unmet need.
You know, what we're trying to do is the ultimate place is, say, if a cell's missing, just replace it, right? You've seen. There are three levels of things we have to do. People have been taking for about the last 15 years islets or pancreatic beta cells from cadavers and transplanting them into patients with substantial immunosuppression. What you see is that those Type 1 diabetics can stay off of insulin with normal blood glucose for years and years and years, more or less as long as they can tolerate the immunosuppression. It works.
Two problems: It's not scalable, and there aren't that many people for whom lifetime immunosuppression is better than lifetime insulin. We've seen others in the field who have, at least in a patient or two, shown that you can take stem cells and turn them into beta cells, transplant that into a patient with immunosuppression. Again, patient can live without insulin, at least in that case, for a year and a half or so. Stem cell-derived products should be scalable. Again, though, the immunosuppression is a problem. The real limit here is can you figure out how to hide these cells from autoimmune and allogeneic rejection so you can transplant them and a patient gets euglycemia, normal blood glucoses with no insulin, no immunosuppression, and it lasts hopefully for life, but at least for years and years and years.
The missing element is immunosuppression. We're trying to do this in a gene-modified stem cell that we will grow into islet cells and make, hopefully, into a product IND next year. That's our goal. This year, what we're trying to do is do a first test in humans by gene modifying cadaveric islet cells and transplanting those into a patient. It will tell you if we're able to hide the cells, it should tell you, from auto and alloimmune rejection. If we can, this would be my supposition, a cure for Type 1 diabetes goes from being possible to being inevitable. We could still screw it up. It may not be us, right? I think it could be us. It will happen because all the component parts have been proven now. Right?
Our goal is to transplant these cells this year. First level of evidence, do the cells live? You can just scan them and see. If they live for two, three, four weeks, it's over. We won. The immune system, when you transplant, you know, when you transplant a cell in, we'll kill it within about those cells in a week or two. Two or three, four weeks, it's over, we won. If they're still alive. A better level of evidence would be that you can see something called C-peptide. When we secrete insulin, we make insulin as proinsulin, and when you secrete insulin, it gets cut into C-peptide and insulin. If you have cells making insulin, you have C-peptide floating around your blood.
It's a definitive level of evidence that you are making insulin. Those cells are surviving. You can see if it's stable. The third would be, I don't think this will happen because we'll start at lower doses, if these patients are able to come off insulin, they're normal. That would be spectacular. Our goal is to do that this year, take that as a learning, and hopefully it works. If it doesn't work, we get to figure out early why it didn't work and, you know, hit reset.
Go from there.
If it does work, we just go right into this, hopefully this IND with the stem cell-derived product next year. We've been working on that for a while. Making a gene-modified stem cell-derived product is a complicated endeavor. We think we've got our arms around it, and we're really optimistic about, you know, this going forward.
Big year coming up.
Big year. Big, big year.
Okay. Thank you, Steve.
That was your 15 minutes. Thank you.
Yes.
15 minutes of fame.