Right. It's my pleasure to introduce our next guest from Korro Bio, CFO Vineet Agarwal and COO Todd Chappell, so maybe to start, Vineet, maybe provide a few minutes of overview for people who are new to the story.
I'll let Todd go there in the terms of defining the story, but I think, you know, just as a very quick introduction to the company, I can provide. Look, the company was formed five years ago, almost. We took the company public last year, have raised $350 million from public market investors. We have cash runway into next two years. Very exciting space for us, our first indication being alpha-1 antitrypsin disease. We'll be filing a regulatory filing second half of this year, which is Q4 now. So looking forward to talking about that today. But just as in terms of people who are new to the story, what we do from ADAR, Todd, you want to go talk about it?
Yeah, sure. So, Korro is an RNA editing company. Like Vineet said, we were founded about five years ago. And, you know, we really have a vision to use genetic medicine to tackle both rare and common diseases. You know, the way that we do this is we use an oligonucleotide to co-opt an enzyme called ADAR. ADAR is a naturally occurring enzyme. Some of you, all of you probably, are editing RNA right now using ADAR. And so there's other organisms as well that edit RNA using ADAR. So there's many advantages here because we're using an oligonucleotide. It's, you know, it's a compound that or an approach that others have used, either, you know, with siRNAs or ASOs.
And so that's very attractive just from de-risking on the chemistry, the manufacturing, and the regulatory pathway, right, so we at Korro, you know, have really, you know, decided that we have to focus, you know, entirely on RNA editing. We don't think you can just be armchair RNA editors. We think that, you know, it's important to form an entire platform on it. There's a lot to be learned about ADAR. There's a lot to be learned about the chemistry, so we've endeavored to create that platform. Our first product is going after alpha-1 antitrypsin disease, and then we have a platform behind that that's also focused in liver, other liver diseases and CNS.
Great. So, you know, I think most of the people who are attending the conference are very familiar with DNA editing. You know, obviously, Nobel Prize-winning science, a lot of potential, a lot of good progress, but RNA editing is always gonna have advantages, safety being one of them, and reversibility. But talk about, in terms of disease targeting, you know, the ability, you know, not just to go after rare diseases, but, you know, the ability to go after more prevalent diseases. Talk about that potential.
Yeah. So, so obviously, you know, alpha-1 antitrypsin represents the, you know, kind of the therapeutic bucket of going after repair opportunities, right? Where there's a G to A mutation, and we are repairing it, back to wild type, A to G. So there are a lot of different mutations that, you know, have that same G to A mutation, so those pathogenic, SNPs are very common. So that is- that's one approach. There's also the other approach, where we can look at what we call the modulate approach, which is to look at, wild-type proteins to affect disease biology, which is really exciting to us, and we'll talk about it in a moment, but we just did this deal with Novo. They saw the same thing, right?
Where we can use RNA editing to make a single base change, and that single base change can have an effect on protein-to-protein interactions, post-translational modifications, look at microRNA binding sites to increase protein expression. So there's just this. It really opens a door to all these vast opportunities, expanding the target space.
You know, we'll get into your lead for alpha-1 in a second, but maybe tell us what have you learned about your platform design approach over the last year, such that you know you were able to entice a large pharma to enter into a collaboration deal?
Yeah, I think, Yeah, and it's been a really exciting last year, right? I mean, if you think about this time last year, we were marching towards a DC. We declared a DC. We went public, about this time last year, and got into the IND-enabling stage for our lead program, did this Novo deal. There's just been a lot going on with the company, so it's been exciting, and we've been learning a ton. I think probably what Novo saw to you know to do this deal was that they saw that the learnings that we were taking from our alpha-1 program could be applied to other targets, right?
It's not that you're going to be able to just, like, on day one, be able to, you know, do the lead optimization and declare a DC, but you are, you know, call it you're starting on second base or starting on third base now. We are understanding the rules of ADAR. You know, there are different ways in which you can you know, really, change the chemistry of the oligonucleotide. You could move the triplet, you know, from left to right, you can have different modifications, you can have different nucleotide bases. There's just many different ways in which you can attract ADAR and get it to edit efficiently.
I think that's what was so exciting about, you know, what we've been able to demonstrate over the last year.
I think what I'd say is like, look, we haven't publicly talked about our second program, but I think all those learnings over 12 months, as you said, Kate, right, is gonna be relevant in terms of every program we bring forward. Hopefully, you know, there's learnings from that so that we can move faster. I think specifically, your question on Novo partnership, if you look at that, why it was exciting for us is, given the amount of capital and the focus for us in near term, cardiometabolic diseases, which are large indications, we wouldn't have gone after them ourselves. We knew it would open up common diseases for us.
So in terms of bringing a pharma, which is, you know, one of the leaders in that space, coming in, you know, working with us, and in respect also funding all the R&D for us in those programs up to DC, where we learn on our platform, it's not only those programs, but that learning will go across different tissue types and different, how we design our oligos. So I think that was critical for us. And I think, you know, also not giving away our house in terms of five, seven targets to Novo and opening up more targets there, so.
Yeah, so great. So, so, let's talk about your lead, alpha-1 antitrypsin. I think as you described, you know, single point mutation, I think what's interesting, it's a relatively large disease. And, you know, there are solutions out there or solutions going after, the what's called the toxic gain-of-function, which, you know, leads to a mutant protein that aggregates in the liver. That's a problem. But then you also have a loss of function. It's not doing its intended job of clearing the lung. We do have protein replacement products to deal with the lung side of it, and the siRNAs that are being developed really only deal with the liver aggregation. So talk about why this is the best indication for you to have as a lead.
Obviously, your solution can solve both of those problems, but what else? Why, why else have you chosen this for your lead?
First, you know, you're absolutely right on all those points. And, you know, what I would say is, what we have seen as we talk to, you know, physicians, patients, payers, is that they prefer going after genetic medicine with a drug-like product like ours, right? There's a lot of concern with you going after, you know, DNA and editing DNA, and that's one of the other alternatives in terms of going after both the liver and lung manifestations. And so that's very clear. I think there's obviously the commercial aspect of it.
There's 100,000 patients here in the United States, there's 100,000 patients in Europe, there's a lot of unmet need with augmentation therapy, and as you pointed out, it's even if there is a therapy that goes after, you know, the disease, it's only relevant for the lung, right? There is no therapy out there for the liver, and so having a disease-modifying therapy like ours or potential for a disease-modifying therapy, you know, is just, it's just really exciting. So that's the kind of the commercial aspect of it and the opportunity. But so alpha-1 itself is, you know, released from the liver at, you know, very high amount, right? I think it's one of the top five proteins that's released from the liver in the body.
So what that gives us is an opportunity in an early clinical study to demonstrate that we are editing and returning the, what they call Z protein, the mutant protein, back to normal, which is called the M protein. And so, in an early study, we can use homozygous ZZ patients and demonstrate that our mechanism is working, which is really exciting, of course, for you know a new modality.
You know, talk about the preclinical data you have to date, and how is that informing the design of your phase I?
Yeah, sure. So we have a robust data set, right? That obviously starts, you know, using human-like cells. We also use patient-derived cells. We think that we need to get around 50% editing to have a clinically meaningful result in patients, and we've been able to demonstrate that in vitro. In addition to that, we've, when we do these studies in vitro, we've shown no off-target effect, which is very important, right? And then, probably the most notable data that we've been releasing is using a transgenic mouse model. That's an alpha-1 transgenic mouse model, where we did a 13-week study. It's called the NSG model. And using our drug product, and by the way, it's KRRO-110.
KRRO-110 uses an LNP formulation, LNP that we licensed from Genevant. In these models, we were able to demonstrate very high levels of alpha-1. Both the M normal protein and then total protein as well. Nearly 45 micromolar of the M-AAT by the end of that 13-week study was demonstrated, and over 60 micromolar for total AAT. We took that extraction, looked at the functionality of that protein, and demonstrated that at high levels, it's inhibiting neutrophil elastase, which is really important.
So I guess a couple of things there. Again, you know, those are very high numbers. How is that informing who you might have in your phase I, or let's call it the phase I-a, when you actually get to patients? Do you start with the ZZs, or do you go to a different set of patients?
Yeah, I think it's likely that we'll be using ZZ patients both. You know, and we haven't disclosed what we're doing exactly in the clinical study yet, but, you know, one can obviously imagine it's a kind of SAD, MAD, you know, design study, and you can use ZZ patients in both of those parts. So, you know, and we'll be able to demonstrate, I think, in that MAD portion, you know, probably meaningful levels of alpha-1 antitrypsin return to wild type.
Okay, so you've talked about completing a filing by the end of the year. So what are the remaining critical path items to before you're able to do that?
Yeah. So, so we haven't disclosed, you know, where we're filing, but we've said publicly that by the end of the year, we will file, we'll have a regulatory filing. So you can imagine that, you know, we're, you know, we believe we're on track for that. So getting everything together in terms of the, the package, the regulatory package, finishing up, you know, key areas and writing that package is where we're at.
Let's go back to your choice to use LNP. So I think, you know, people who look at small RNA, and especially with a deliverer, you know, they assume almost immediately you're gonna use GalNAc. So why, for you folks, does LNP make sense?
So first off, when we think about delivery, I think everybody here is probably pretty aware of the challenges that face the oligonucleotides, you know, area of this space. You know, I think what you have to ask yourself, you know, is so what we do is we do a fit for purpose delivery approach, right? We look at the indication, and we say, "All right, what is needed the most for these patients?" Right? "And what delivery mechanism will be the most relevant for these patients?" And so when we look at alpha-1 antitrypsin, what is the most important thing for these patients? Is it safety versus augmentation therapy? Is it dosing frequency, or is it levels of alpha-1 antitrypsin?
And so we believe that alpha-1 levels of alpha-1 antitrypsin is the most important thing for these patients, right? You talk to KOLs, it's clear to us that more is better. Okay? So sometimes people talk about the threshold at 20 micromolar being normal. You know, getting more than that is even, you know, even more exciting. In addition to that, you want oligonucleotide, the oligonucleotide that you've delivered to be present when there's an acute phase response as well. So when there's an acute phase response, the body is saying: We need more of it. And so if you have the oligonucleotide there ready to go to pump that up, it's fantastic, right?
That's why, because we think that LNP versus GalNAc at this point offers the best opportunity to increase alpha-1 levels to normal levels.
Okay, so let's go back to the Novo Nordisk agreement you talked about. Can you further describe, you know, the scope of that agreement?
Yeah, no, happy to do that. So it's for two undisclosed targets in cardiometabolic diseases. It includes, we disclosed in our 8-K, it comes with $10 million upfront for the first target. Total deal value is $530 million, equally weighted, I would say, between development and commercial milestones. We're responsible to taking these, you know, indications to DC, and Novo Nordisk reimburses us for all the R&D costs. So from my perspective, it's not dilutive on our P&L, and as I said earlier, we do learn on the platform side, which is an upside from that side of things, and in a post DC, Novo takes it to IND, and then that triggers further milestone payments from that.
The other thing, as we're talking about, is it wasn't in part of our focus in next 24-36 months, so obviously opens up another tissue type and indications for us, and doing it with somebody like Novo was exciting. So...
So, how does this change your strategy? So, you know, if you're thinking about what your next target might have been before this, now you've got, say, this commitment to do the work, but you're getting paid for it. So, you know, how do we think about beyond, say, these two cardiometabolic targets, where else do you think your technology is best suited to further advance something?
Yeah, so it doesn't change anything for us. Yes, there is, this becomes a priority for us with Novo Nordisk, but, this, our focus is still on the liver indications and CNS as the next, two areas that we're focused on. The second indication most likely is liver indication. We haven't publicly talked about the target yet. Once we have DC, you know, we'll come out and talk about it, and then CNS is key area of focus that is all, you know, part of the plan.
The fact that it's the agreement's focused on cardiometabolic. Was that them driving the ship? Or obviously, when we think about cardiometabolic diseases, we generally think of larger diseases, you know, cardiovascular outcome trials, you know, that kind of stuff. So is that why it's more amenable from your side to partner, and obviously, they came and got what they wanted, but talk about those dynamics.
Yeah, I think I can start, and Todd, obviously, feel free to jump in. I think, look, I think Novo was very clear, and that as you can imagine, these partnerships or any partnership takes time. They wanted to get into cardiometabolic with RNA editing modality, and they've probably seen the space of players who can go after, and they did some work with us and saw the data in some of the indications or target site, and they got excited about it. And so for us, what was more important was it opens up the common diseases, but also the commitment from very senior folks at Novo from an R&D standpoint is this is where they wanna focus, you know, progressing these to, hopefully to the clinic.
For us, the more important thing was this was not five, six target deal, because to your point earlier, then the focus is, quote, unquote, "We become kind of a CRO-type player" and not focusing on other important pipeline programs for us, which obviously is not. This is just two target deal. So I think, you know, it did come in from again, we were talking to some other pharma players, but I think just the commitment from Novo in this space and what we learned from them and collectively moving this forward, probably differentiated it. Given that cash on the balance sheet gets us already into late 2026, I think the focus was to getting right partner than just non-dilutive funding, so.
So yeah, I mean, you were alluding to this earlier, right? It's, there's, we don't have any business running a long, long-term, you know, cardiovascular outcome study, right, and at least right now, not right now, and so, you know, to get into that space, to demonstrate our ability to go after a wild-type protein, and that unique way in which we can affect the disease biology, you know, is, so we can take these learnings, right, that we work on with Novo and take our platform to the next step, you know, all at the same time, so, you know, that's very exciting to us, you know, remember that, you know, I think that the way that Novo looked at this was, "This is a target that we wanna go after.
This is a target that we think is uniquely suited for RNA editing. It's not something that we can just knock down. It's not something that we can just attach a monoclonal antibody to or whatever. This is, this is where RNA editing fits. It's perfectly suited for that," right? And so, that's those are the kinds of things that we really wanna be moving towards, you know, outside of the, and getting away from the, just the monogenic disease area.
Yeah, and again, it speaks to the potential to address these larger prevalent diseases. So factoring in the partnership, talk to us about your cash, and you know, how far is the runway now that that supports?
Yeah. So, we had $155 million cash and balance sheet as of Q2 of this year. The runway is into second half of 2026, and so, you know, as we report Q3 later this year, the guidance will come out and talk about it, but nothing should change. This does not include, you know, cash runway or $10 million that we got from Novo or other milestones, or the cash reimbursement we get from doing the work with Novo, but we're well-funded till 2026.
Okay, great. So let me ask you a final question. So what do you think, investors are either missing or really need to understand to fully appreciate the Korro story?
I think right now is a very unique time for RNA editing space. We have Wave, which is gonna come out with clinical data very soon, and that will obviously have a read-through for entire space, and so we wish them luck, and hopefully, the data reads you know, in a way which, does well for all the players. I think for us, it's just, just execution on getting the regulatory filing, getting into clinic, and showing that we have a best-in-class profile next year with our clinical data. In terms of what investors are missing, there is a lot of other indications and opportunities behind AAT, which obviously, we need to generate data and start talking about it and, and showcasing before we get any credit or value for it in public markets, and you know.
I think alpha-1 is just the tip of the iceberg, but you know, as this gets a little bit more validated with clinical data this year, I think you'll see more excitement around it.
Yeah, and I'll just expand on that and see that we're almost out of time. But, you know, I come... My background after being in biotech for nearly 20 years, or I guess it's over 20 years now, is, you know, it's all been in small molecules. And so, you know, using RNA editing at that post-transcriptional level is just an exquisite way to go after, you know, wild-type proteins, to affect disease biology. And so, you know, I really hope that we get an opportunity to showcase that more.
All right. Well, great. Well, we have reached the end of our time here, but thank you so much for being with us today.
Thank you for hosting us.
Yeah, thank you.
Thank you. Good questions.