Conference Transcript - PRME 2026-09-16

Chris Yu, Analyst — Morgan Stanley

All right. Good morning, everyone. My name is Chris Yu. I'm on Terrence Flynn's team covering biopharma and biotech companies. I'm delighted to host Ellen Ryan, CEO of Prime Medicine. Before we start, for important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanding.com slash research disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. So, Ellen, thank you for joining us.

Alan Ryan, CEO

Thank you for having me here.

Chris Yu, Analyst — Morgan Stanley

Maybe we start with some high-level questions about a company. You know, in the past two decades, we have all witnessed the amazing evolution of gene editing technologies, and, you know, you guys are at the forefront of that. So maybe talk about how prime editing is different versus kind of the earlier generations of gene editing technologies.

Alan Ryan, CEO

Yeah, and I think you said it right. It really is a revolution. I think we're all very lucky to kind of be alive to see these technologies in others as they advance. I know they're just incredible, as you think of, where we were 20 years ago and where we are today. So I always think about the evolution of CRISPR kind of nucleus-based editing kind of to prime editing. And nucleus-based editing, we're looking at Nobel winning technology, really incredible for the first time. You could, with very high efficiency, go to a very specific point in the DNA and with a double-stranded break really make that cut and, you know, the result being very effective at knocking out targets, right, very effective at knocking out proteins or changing regulatory elements like they do in sickle cell, and an incredible technology. We have an approved drug now. We have others that are likely looking like they're close to approval, So this is becoming sort of that dream of 10-plus years ago is now becoming a reality for patients today, which is obviously what this is all about. That nucleus-based editing with double-strand breaks, there are some liabilities there, obviously some of the both on-target but also off-target consequences that can happen, chromosome-romal rearrangements, translocations, some off-target editing that can occur, but in general really, really promising technology. And then out of David Liu's lab came another type of gene editing called base editing. And now for the first time, you can not just knock something out, but with high efficiency, actually correct something, right? Make a change to the genome, a very specific change. And with base editing, they use what's called a DMNA's enzyme. And you can change kind of one base pair to another. So you can do an A to a G, G to an A, C to a T, T to a C. Those are the four base changes that you can make with base editing and very effective for certain diseases where you have that very specific type of mutation but limited to really only correcting those types of mutations or like CRISPR, you can use that to knock things out as well. It also uses, instead of a double-stranded break, you're using what we call kind of a Cas9-Nicase, which is creating a single-stranded break, which is a lot gentler on these cells and ultimately doesn't lead to the same rate of, you know, chromosomal rearrangements, translocations, and other off-target issues. So a nice step forward in doing things that nucleus-based editing could not do. With prime editing, we can do everything the kind of first-gen genetic technologies can do. We can do everything that base editing can do, but not just those four base changes. We can do all 12 changes, but we can also do so much more. So we have the ability to, instead of using a DMNA, also out of David Liu's lab, he came up with the idea of, well, let's use him and Andrew Anzalone, who our scientific co-founders came up with. We can now use a reverse transcriptase and actually create a template that goes right into the guide that gets transcribed right into your DNA. So instead of changing one base pair, you know, we think about this as a word processor Instead of it going after one letter, we can put in whole new sentences. And so the first time, we can make very much larger kind of full insertions of anything from, you know, 10 to 15 base pairs. But with our passage technology, we can actually do almost full gene insertions. So it's a really powerful technology. I like to say it's the most versatile gene editing technology that exists, given the number of different changes we can make. but it's also the safest as you think about the limited kind of off-target, on-target, and other consequences that you see with some of these other technologies.

Chris Yu, Analyst — Morgan Stanley

That's a great way to start this conversation. Certainly there are a lot of potentials for prime editing based on what you just described. The way I see it like with gene editing, a lot of efforts have been focused on delivering to the liver. Can you kind of talk about what are the remaining hurdles to kind of expand the technology kind of outside the liver to other organs and other diseases?

Alan Ryan, CEO

Yeah, so you're asking the billion-dollar, $100 billion question. You know, I think the initial promise as we looked at gene editing was there were just so many different diseases, both genetic and non-genetic, that would benefit from this type of technology. And it was just a matter of, okay, let's get the delivery technology, you know, towards all these different tissue types. Well, that's proved, I think, a lot more challenging than probably initially thought. And I think today we've shown that these, and it's not just, you know, it's not just gene editing. It's other technologies, too, that are RNA-based that require delivery. But I think we can very effectively today get delivery into the liver for gene editing. We've seen that proof of concept for both nucleus-based editing, base editing, and soon-to-be prime editing. We've obviously seen this done with these technologies, both prime-based and nucleus-based editing, ex vivo. So it can obviously be done in cells. We've shown that in our chronic granulitis disease program. Obviously, it's been shown in sickle cell with those two other technologies. But as you go beyond that, it gets more challenging. I think we've seen good delivery to the eye. And I know Editas had an earlier program where they could at least effectively deliver, and we've got some early pre-clinical data showing that we got really good eye delivery as well. We think we can get delivery to the ear. So it becomes like, are there real opportunities there to go after from a commercial standpoint? But where I see kind of the biggest opportunity for prime editing would be if we can get successful delivery to the brain. I think there are a couple of, you know, maybe AAV-based approaches today that may work. But I don't think there's anything today that we've said that we've seen to say we think this is a solved issue. I would say we continue to scour the world for advancements in these types of delivery, because I do strongly believe this is a case of when, not if. But I don't know if that when is in one to two years or in five to ten years. But as soon as that gets solved, we are going to be there to explore those areas, because, again, there's a tremendous amount of unmet need in the brain where prime editing can make significant impacts in the lives of patients. And, you know, in five to ten years, I hope to be treating many of those diseases with prime editing. And then beyond that, obviously, there's heart, there's muscle, there's kidney, there's other organs that we'd like to get to as well. And there's, you know, varying levels of advancement. Again, we're staying very close attention to those so that when we do see something that looks promising, we can jump right on it. I think the lung would be a good example where, in collaboration, obviously, with the Cystic Fibrosis Foundation here, we've got programs in Cystic Fibrosis that we're developing where we think lung delivery looks very promising. We've seen AV, we've seen HSV with other companies, and we've seen LNP be successful, at least in delivering that cargo, and we think prime editing has the potential to be a best-in-class therapy as we think about Cystic Fibrosis. So that's an area we think is in the process of being solved, where others we think are probably more in the future. But again, tons of opportunities that delivery question gets solved. But it's a great question and one we spend a lot of time talking about and thinking about.

Chris Yu, Analyst — Morgan Stanley

Yes, that sounds good. And recognizing that in the past year there has been a lot of changes at FDA, and now I think we have seen some stability there. Just how supportive in general is the FDA on gene editing? That's part one. And then second, how has your interaction been with them recently?

Alan Ryan, CEO

Yeah, I mean, I think in general the FDA, and I know that we've all been through a lot over the last year in terms of kind of what's gone on there, but I think even over that entire period of time, even with all the changes, it's been in the right direction. I think when it's at least come to cell and gene therapy for the most part, especially when it's come to, I think, gene editing. I think they seem very supportive. There's a lot of different measures and endeavors going on at the FTA where they're trying to help these companies create more products for patients in need, especially when you go down to the rare and ultra-rare indications. And so I think that's going to continue. And these efforts are both on the CMC side, the ease of getting to the clinic. I mean, for us, I mean, we went and the FDA, you know, essentially gave us alignment that we can file for approval on two patients' worth of data. I mean, that's incredible flexibility. Obviously, it's an unmet need. We showed a really strong data set in curing two patients. But that's showing a lot of flexibility and that real desire to get these drugs to patients in need. In terms of recent conversations, like, we don't comment, you know, on specifics on our dialogue with the FDA. What I would say is we continue to have constructive conversations across the board with the FDA. And, you know, for the most part, it seems like business as usual. I think it's nice that we have leaders that are not interim, that are now in place at SEVER, well, for us SEVER, but also CEDAR. I think Kareem is going to do a fantastic job there. We're sort of excited that that whole agency can now go in the right direction going forward. That's great.

Chris Yu, Analyst — Morgan Stanley

So let's kind of talk about the specific programs that you are running right now. Wilson's disease is your most advanced in vivo program, and the IND recently got cleared. Can you kind of walk us through the Phase 1-2 design specifically, and then kind of what are the key biomarkers that you will be measuring?

Alan Ryan, CEO

Yeah, so the IND was cleared back in July. We also had a CTA cleared back in New Zealand in June, and this is going to be a global study, so we'll be enrolling in other geographies ultimately as well. The design of the study is going to be a dose escalation. We'll be looking at a few, you know, call it initially planning for three cohorts. You can always add cohorts if needed. We'll be looking at three different dose levels. The lowest dose is potentially a biologically active dose as we start to get to the second and third dose levels. There could be a lot of biologic activity if the preclinical data translates well to the clinical data. I think from everything that we've seen from other programs across different gene editing approaches, we've seen fairly good translation as you kind of look even just mouse to human. And so within those studies, we'll obviously be assessing safety. I think safety is paramount. With our LNP, and this will be the first time this LNP has gone into the clinic, we appear to have a very wide therapeutic index, much wider than some of the LNPs that have gone into the clinic that we've actually benchmarked doing experiments internally. So excited about the prospect there. Then obviously looking at efficacy. I think the good thing with gene editing, if you're in the right indication, is, and if you have a good biomarker, you can get a really early read, right? If you're making that precise correction and you're doing it with high enough efficiency and you have a good biomarker, you know pretty early if your drug is working. For alpha-1, which I'm sure we'll talk about, which investors are very familiar with because there's a number of programs out there, you know, obviously you can look at, very simply look at blood levels of AAT and look at the differential between MAAT and Z in the systemic circulation. You know, Wilson doesn't have a biomarker that's that easy because most of these patients are on standard of care, so we can't just look at copper. But what we can do, another way to do that, is we're going to be doing radio-labeled copper PET scans. We'll be doing those scans both at baseline and then about six to eight weeks after treatment. And we have really nice images that are in our deck that I encourage people to go look at, which are these mouse models showing what the copper pet looks like. And in a diseased mouse, which you'd expect to see similar in a diseased human, and there's some publications that actually kind of show what this looks like in a human as well, you could see these livers completely lit up with copper because they lack the enzyme and the ability to effectively shuttle it into the bile for normal fecal excretion. as you look at what a wild-type mouse or human would look like, you have very normal copper metabolism. You don't see that copper lighting up in the liver because it's been normally metabolized. And if you look at even just a lower dose of 0.4 mg per kg and a somewhat higher dose of 0.8 mg per kg, if you look at the images that we have, we look very much like that wild-type mouse, like we're almost completely normalizing copper metabolism. And you really only need to get to a heterozygote level. You only have to get to that level, a heterozygote level. within a copper PET study, which isn't quite normalized copper metabolism, but those patients don't have disease. So even if you can get to that level, you could feel very comfortable removing standard of care and knowing that these patients won't have a copper burden that is going to continue to add to their disease.

Chris Yu, Analyst — Morgan Stanley

So just to follow up on that point, I mean, obviously everything is going to depend on the data, but is it reasonable to assume that if the data looks good, the kind of the radio-labeled copper biomarket could potentially serve as an end point for accelerated approval, or it's still early to say?

Alan Ryan, CEO

Yeah, I think it's still early to say. You know, I always like to say things, it's always dependent on, everything's always data dependent, and the better your data, you know, the more flexibility that might get awarded to you. I kind of use a base case as, hey, let's get patients off of standard of care for some period of time as a potential registrational endpoint. You know, if your data looked incredible that you're getting all these patients to, you know, vastly improve copper metabolism and that's very predictive of getting patients off standard of care, You know, there's always an upside scenario where the FDA can be a little bit more flexible there. But we're kind of using our base case as, you know, some period of time off standard of care ultimately for registration. And, you know, depending on strength of the data, there could be upside to that. And just maybe just two other things to add. The other things we'll look at, it's not just the radiolabeled copper PET, but we'll look at an enzyme called seroplasmin, which is very low in patients with Wilson disease. It's something that kind of helps to bind a copper and shuttles it through the circulation. In the absence of this ATP7B enzyme that's mutated, that doesn't occur, and that seroplasmin degrades very rapidly. So as you treat these patients and you have normalized enzyme function, you should see those levels of seroplasmin go up. We'll also be looking at urinary copper, which in disease patients is very high because the main mode in disease patient of copper excretion is through the urine, not through the feces. So in these patients, we'll also test if you see that urinary copper come down. So there's a mix of different endpoints that we can look at, not just the radiolabeled copper PET, and they should all start to point in the right direction if we're having the right impact.

Chris Yu, Analyst — Morgan Stanley

Okay, sounds good. And then you guided proof of concept clinical data in 2027. So what kind of initial clinical data do you expect to disclose? And do you know how many patients that they would disclose those data for?

Alan Ryan, CEO

Yeah, I mean, I think we'd be looking at, you know, at a minimum we'll be looking at those kind of three endpoints that I talked about, radiolabeled copper pads through a plasma and urinary copper, safety obviously as well. You know, this is kind of standard where you do a few patients per cohort. You know, we've talked about, you know, at least three cohorts. So you can kind of do the math on what a potential, you know, first data set could look like. You always have the ability to backfill in certain cohorts if you feel like you're at a good dose level. So, you know, we'll wait and see kind of where we are. If things translate well, then, you know, then you'd expect somewhere between, you know, kind of 6, 9, 12 patients essentially as we get to that first data set.

Chris Yu, Analyst — Morgan Stanley

Great. Thanks. And then with that POC data that you're going to get in 2027, what kind of data will be sufficient to give you the confidence to move the program forward? it?

Alan Ryan, CEO

Yeah, I mean, I think what we're going to want to see to gain, so I think at a minimum, are you improving copper metabolism? Like, that's the bare minimum, right? If we're not improving, and if we're making that edit, you should be improving copper metabolism. So are we able to achieve the level of editing efficiency that we've seen pre-clinically, or even some level that's similar to that, which is not that high to see a really strong effect, Even at high 20s whole liver editing, we're getting to almost normalization of liver copper metabolism in a mouse model. So as long as we can see vastly improved copper metabolism and these other markers are going the right way, we know we have a drug. And then I think the secondary question to that is, is this something that is effective in every person? Right. Is there any reason why we're not getting kind of widespread efficacy, which is the expectation based off animal models? And so, you know, if you have like one of six patients, six people responding, then, you know, you know, you can have a response or something going something wrong there. So you'll want to see pretty consistent responses across the majority of patients. And I think if you have that, that tells you you've got a drug.

Chris Yu, Analyst — Morgan Stanley

OK, yeah, that makes a lot of sense. And for Wilson's disease, your current candidate only covers one mutation. I think it's the H1069Q mutation. There are other mutations for Wilson's disease. So kind of talk about how you're going to broaden that program to cover other mutations in the timeline to do so.

Alan Ryan, CEO

Yeah, so the H1069Q mutation covers about, we say, 30% to 50% in the Caucasian population. So we think about predominantly, you know, the U.S. and European populations. You know, other numbers we've looked at, maybe that's closer to 40, 45 percent, but somewhere within that range. We think ultimately with a handful of additional editors, we can get to about 60 percent of the population in the U.S. and Europe. And the ability to get those studied is we know, or at least we have alignment, that we can do additional mutations under the same IND. and we can leverage all the information, the majority of the information that we have from the first mutation for subsequent mutations. So it's a lot faster, and it's a lot cheaper to do each additional mutation, and hopefully, given genotype to phenotype is pretty similar across Wilson disease, there's not a lot of, you know, not significant difference. Hopefully, it's going to be a small number of patients that need to be studied as well, you know, to ultimately get those to licensure. As we go into Asia, it's a little bit different. The mutational backdrop's a little bit different. The prevalence actually seems to be a little bit higher, and the most prominent mutation there, R778L, is even, you know, potentially 40, 45, or even more percent of those patients, and with a handful of vetters, we might even be able to get to, like, 70 percent of that population. So we think we can pretty quickly get to the next mutations. Our 778L is, you know, pretty close to ready to go. There's some additional, like, off-target and other work we'd have to do to get ultimately to the IND, but we've got a pretty good editor right now, you know, and we're trying to determine the right time to kind of layer that in to this current study, even though it's a prominent mutation in Asia. There are patients we've identified in the U.S. that do have that mutation. So you could start studying that outside of Asia first before you go into Japan. But that would be the plan for that program.

Chris Yu, Analyst — Morgan Stanley

A competitor is developing a gene therapy for Wilson's disease. What are you watching in this space when it comes to gene therapy?

Alan Ryan, CEO

Yeah, I mean, look, I think first off, you know, I mentioned that we're probably going after 60% in these geographies and 70% in Asian geographies. So there's a market beyond what we're doing, so there is a place for other therapies to play. We think a gene therapy and a gene editing approach are very different. You know, a gene therapy, they're using a, you know, you can't fit the full gene in an AAV, so it's a truncated version of that gene, which, you know, can or can't have the exact same type of functionality. It's something that's not under endogenous control, So you're under the regulatory controls of the AV that you're putting in there, where when we're making a permanent change at that mutation location at that gene in that genome, so you're under the normal endogenous or the, you know, normal regulation of that gene. So we always say, like, you don't want zero copper, right? It's always going to be some balance that you're trying to get with many of these things and being under endogenous controls is the right answer. But the other thing is every daughter cell that has the correction is going to have that correction. So this is something that's durable and gets maintained over time. You know, some data suggests that you even have a positive selection bias over time. But even without that, this is something that's a durable fix. For gene therapy, that, you know, hepatocytes, you know, they're not dividing like, you know, epithelial cells, but they do divide over time. And so it is something that will get diluted out over years because every daughter cell, only one of the daughter cells will have that vector. So there's a durability, long-term durability question there, too. So I really feel for this specific disease or most diseases where you're going after the liver, a gene editing approach where available is a better approach than a gene therapy approach. but yeah and we're hopeful that we'll see data to validate that.

Chris Yu, Analyst — Morgan Stanley

That makes sense I would like to talk about AATD now, it's another very important program of yours so recently the arbitration panel ruled in favor of you guys so now you can move ahead with your program I think Beam said that that decision was somewhat narrow, they still have some rights in developing AATD with prime editing so just can you help us square away what each party's rights are in this base. Sorry, what? Yeah, each part is right, and you're right, and they're right.

Alan Ryan, CEO

So, yeah, we've never contested whether Beam has rights to prime editing in Alpha 1. So, as part of the collaboration agreement that we did with Beam back in 2019, they have rights to prime editing for doing certain types of edits, which are transition-only edits, essentially what you can do with base editing. What I think this decision, and we always felt, okay, we're operating under the prime field where we're not just doing transition-only edits, we're also doing non-transition edits. What this decision says is it clearly defines what the beam field is and what the prime field is, which is, again, back to what we believe the beam field and the prime field were before. And so as long as we're operating within the prime field, which means we are doing, you know, non-transition edits as well, then, again, that has a material impact that's within the prime field. Okay, that makes sense. That's a clear definition across the fields. Okay.

Chris Yu, Analyst — Morgan Stanley

So AATD is a somewhat crowded field for gene editing, and for good reasons, just because there's a really high amend need and there's a large patient population. So there are two companies that already have some clinical data for AATD. So where do you think your candidate can potentially differentiate from those two?

Alan Ryan, CEO

Yeah, so there's two base editing companies that have had data. You know, Beam's got probably the largest collection of data to date, And I think they're showing somewhere in the, you know, mid-teens level of systemic levels of alpha-1, which is kind of right square into what you'd expect for, you know, a potential heterozygous patient, which typically don't get disease. And I think it seems, looking at kind of MZ levels, that they're probably near levels of saturation. with that other company out of China they've released a few patients worth of data I think the first patient which had a higher baseline that looked much higher I think the next two patients that came out kind of look maybe in a similar range to where Beam is maybe a touch higher so it looks like the data that we've seen to date from those two companies look very similar from what I'm told the company out of China Yoltec has a lot less bicentered protein that Beam has, which, you know, we can debate if there's some theoretical potential risks there. But it seems like everyone's kind of getting to saturating levels and then potentially getting to kind of similar levels of alpha-1. I think what becomes really important as you go out is not just what levels of alpha-1 you're getting to, but also it's going to be safety. How safe is your LMP? It's one thing to dose, you know, five patients, 10 patients, even 30 patients. What are things going to look like when you've dosed 100 patients, 200 patients, 300 patients? And again, you know, we think we've got a LMP that is a pretty wide therapeutic index. And from a safety standpoint, we think we're going to be in a good place. And then from an efficacy standpoint, yeah, I think we're gonna have to wait and see. I mean, we still, I still believe a prime editing approach where you're taking a patient back to wild type protein where there's no bystander edit or anything else going on that you're purely, you're fully at wild type protein to me is it should be the the sort of preferred therapy here um and even though we're not first i think there's still the potential to be best for that reason um but we'll see how all the data you know plays out over the next couple years and as you said it's a crowded space but it's a it's a large market and there's a lot of patients to treat out there yeah that makes sense and um is the lmp use in aatd program the same as the one used in abusing disease it is it is and And for that reason, we've been able to leverage a lot of what we did in Wilson's to Alpha And for future liver indications, we think we can, you know, take that to another level, leverage even more, scale even more, et cetera.

Chris Yu, Analyst — Morgan Stanley

Okay, that's great. I know you guys are working on an IND right now for IATD. What are the remaining gating factors in there?

Alan Ryan, CEO

We are still reiterating our guidance of a regulatory filing this quarter. Okay.

Chris Yu, Analyst — Morgan Stanley

All right, so soon. So similar to what I asked about the Wilson's program, you expect to provide initial proof of concept data in 2027. Again, like what kind of data will you provide for how many patients?

Alan Ryan, CEO

Yeah, I don't know patient numbers yet for that, but what I would say is we've kind of seen from others, You can get pretty quick readouts looking at serum alpha-1 levels and percentage M versus percentage Z, and you could see that as early as, you know, a week to two weeks. So you can get pretty quick readouts there. And so, you know, again, probably not dissimilar to Wilson as we think about patient numbers potentially, depending on how many cohorts we need to get to to get to the right dose level. But, yeah, expect to have that data sometime next year as well.

Chris Yu, Analyst — Morgan Stanley

And then, similarly, what kind of proof of concept data would give you the competence to move the program forward?

Alan Ryan, CEO

Yeah, I mean, I think, you know, we're not kind of recreating things here. I think we've seen what other companies have been able to do. I think similar types of development paths are likely for all of us where you're going to do some small number of patients, as long as you're seeing pretty consistent levels, response rate in these patients and levels, that you can very quickly transition to a registrational trial for accelerated approval where you're using serum levels as your kind of main endpoint.

Chris Yu, Analyst — Morgan Stanley

Right. Okay. All right. Perfect. Now I want to switch to your CGD program, your ex vivo program, that you had two patient data. We have all read in the news how those two patients are doing so much better thanks to your drug. So kudos to you guys. So in June, you talk about that FDA is willing to kind of accept those two patient data as a filing package. Where is that conversation now? Can any update on the timing?

Alan Ryan, CEO

Yeah, so we're planning for a filing sometime in the first half of next year. There is just some, you know, small kind of CMC requirements that are needed, and that's kind of what's gating to that filing. So, yeah, we think we're in a good position there.

Chris Yu, Analyst — Morgan Stanley

Okay. And if it's approved, what is your commercial strategy there?

Alan Ryan, CEO

Yeah, I mean, there's not a lot of patients out there with the disease. It's an important therapy, so we want to make sure it's available. You know, we're not looking at this as a massive commercial opportunity for us, But we think with a very kind of minimal amount of expense, we can get this drug to the patients in need. Okay, great.

Chris Yu, Analyst — Morgan Stanley

In the last two minutes, I want to touch upon the other programs that you have in your portfolio, cystic fibrosis. You talked about that earlier. Maybe talk about just an overview of the status of that program right now.

Alan Ryan, CEO

Yeah, so we continue to make good progress there. where that's an area where we're looking at predominantly LNP as the delivery technology to the lung. We've gotten to a number of editors that look like we're getting high-efficiency editing, definitely seeing really high-efficiency editing as we look at ALI cultures and other things that kind of people look at to try and de-risk this. Next step is to really getting to really good in vivo data and getting to a drug candidate to ultimately hopefully get this into the clinic in the next couple of years.

Chris Yu, Analyst — Morgan Stanley

And you touched upon this earlier, like delivery to the lung, it has been a challenge for the industry. So like, can you talk about your progress there and like, what have you seen so far in that area?

Alan Ryan, CEO

Yeah, we're evaluating both external and internal LMPs. But as you look at LMP to the lung. I think that, and there's some mRNA and other therapies and gene therapies, that's more been HSV or AV, but there's been some therapies where I think you can get the drugs delivered, right? Then it's a question of, do you have the right cargo? Are you getting the right amount of expression of the CFTR gene in the right cells? And so there's a couple of different approaches here as I think about cystic fibrosis. There's one, can we get enough editing in the right cell type and sort of those basal lung cells that are going to give you that sort of that long-term benefit, and that would be sort of a great result. But this is also an indication where even if you can hit those bronchoepithelial cells that are going to turn over at some rate, you know, this could be a possibility of, hey, maybe I have a little bit more frequent dosing, and I'm dosing this every twice a year or a few times a year instead of a once and done. So I think there are different approaches here that can ultimately lead to success, and I think we'll probably test a number of them and figure out, you know, what's best for these patients. Because we can go after, you know, all the patients that really are not amenable to tracafta and other treatments because of the mutation set that they have, but there's no reason we also can't go after that DEL508 population in the future as well.

Chris Yu, Analyst — Morgan Stanley

Yeah, that makes sense. And so when should we expect to see some preclinical data in that area?

Alan Ryan, CEO

Yeah, I think we hope to share some additional data, you know, later this year or sometime next year as we get to Proof of Concept.

Chris Yu, Analyst — Morgan Stanley

Time is up. So, Adam, thank you so much for joining us.

Alan Ryan, CEO

Great questions, and thank you for having us.