Precision BioSciences, Inc. (DTIL) Earnings Call Transcript & Summary

Good morning, everyone, and thank you for joining us at Needham & Company's 24th Annual Healthcare Conference. My name is Ethan Markowski. I'm a member of the biotech research team here at Needham. Joining me today from Precision BioSciences are Michael Amoroso, President and CEO; and Cassie Gorsuch, Chief Scientific Officer, who will provide a presentation on the company, followed by a Q&A session with the remaining time. And with that, I'll go ahead and turn it over to Michael.

Thank you, Ethan, and thank you to our investor community for being with us today. I know there's some uncertain times, so I really like meetings like this where we can focus on the fundamentals. Fundamental science that change the standard of care in a given disease state regardless of modality, will always win the day in our business, and we feel very confident as we're in the clinic now and on the pinnacle of doing that for patients. Let's go ahead and proceed forward. Precision BioSciences for our friends out there who are not as familiar with us, is a full in vivo gene editing company on the back of a proprietary platform owned only by Precision known as ARCUS, not to be confused with the company. Precision, 3 short years ago, had some amazing science, still does have amazing science, but there was really 3 pillars of Precision. There was an agricultural business. There was an ex vivo gene application -- gene editing application of ARCUS for CAR T programs, allogeneic, and there was the in vivo programs. And when this management team came together, what I'll call the Chapter 2 management team, taking over from really the visionaries who started the platform of ARCUS and finding the science, I think it was really important for us based on market dynamics and where our greatest strengths were to find partners to progress our agricultural business and our CAR T business, and we did both of those, both accretive events for the organization to help fund forward in uncertain times, a clinical pipeline that we feel very certain about and have a great belief in. So today, Precision is a fully owned in vivo gene editing company. Our first program, which is in the clinic right now, is PBGENE-HBV standing for chronic hepatitis B. That is called the ELIMINATE-B trial. It's a Phase I/IIa, and it is in the trial now, and Cassie will spend most of today telling you about that. Here's where we've been getting most of our questions. It's a global trial, very proud of it, open in 5 countries. So we're accruing fast with some of the top infectious disease thought leaders in the world. Another program that's in the clinic as we speak through a partnership. So this is not a wholly owned program, but it's the ECUR OTC-HOPE trial, the 506 program. This is a very different program in babies that have OTC deficiency, which is a fatal disease, where we're inserting a functional copy of the OTC gene, our partners, iECURE. And very, very excited to announce both of these programs yielded clinical data this year. First in January from iECURE, a complete clinical response in a child who has OTC deficiency, now alive over a year, where 70-plus percentage of patients are not. And then just most recently, going in reverse order, PBGENE-HBV, we announced a full dosing of the first administration of cohort, our lowest cohort dose level 0.2 mg per kg LNP of PBGENE-HBV. And that had a wonderful safety and some very early efficacy that was exciting, so antiviral activity. Again, Cassie will tell you more about that today. And then our second wholly owned programs, which will yield clinical data. The first 2 programs I spoke about, PBGENE-HBV and iECURE are in the clinic this year, yielding data. Our second program, wholly owned muscle program for mitochondrial disease, 3243. It's about 20,000 patients afflicted a year who have real severe morbidity issues, where they don't have normal functioning mitochondria, therefore, not ATP and energy levels and they can't live normal lives. A very unique approach we have for PBGENE-3243, where ARCUS can cross the membrane of a mitochondrial barrier. Many other gene editors cannot do that. And the second muscle program that we took back in our portfolio this year is PBGene DMD for Duchenne muscular dystrophy, a market space that's crowded, but looking for permanent durability of functional improvement, which we haven't gotten to yet for patients. So again, PBGENE-HBV wholly owned. Second program, PBGene-3243, and we'll announce more plans on DMD, whether it be through a partnership or alone later this year. Cash runway of $109 million takes us well into the second half of next year, which gets us through 2 of our own wholly owned Phase I programs in addition to the work that iECURE is funding on the 506 program. Go ahead, Naresh. Sorry, I was ahead of you there. This just speaks a little bit to what I already touched, a really large win from our partners. We're very proud of them, small but mighty group at UPenn. This Phase I/II OTC HOPE trial. OTC deficiency, again, deadly disorder, about 10,000 patients worldwide and really, really large news this year that the first patient treated is more than 6 months out from treating, has not had a breakthrough attack. These are toxic ammonia level attacks that really impaired these children to be able to have normal nutrition level intake. They're taking a normal protein level. Their safety was very well managed through the first dose administration, and we're very excited. Our partner, Joe, who leads the program, Joe Truitt and team has made a public comment, he'll give updates on this program operationally that they continue to have results like that in the next 1, 2 or 3 patients, they would go speak to the FDA about a possible BLA path. This, again, is a smaller disease area. So really one patient complete response is tremendous for these patients and these parents of these afflicted children. Go ahead, please. Just a quick update on ARCUS and how we apply it as I send it over to Cassie, our superstar, who's really the brains behind the PBGENE-HBV program. There's not one gene editing company that's better than the other. You really need to understand your technologies. There won't be one winner. You need to apply them of what your technology does best. ARCUS is highly differentiated. First and foremost, it doesn't come from bacterial restriction enzymes, which most gene editors do, which were really made in evolution to cut, cut, cut, cut, cut, cut. ARCUS was actually engineered kind of biochemically neutral, where it comes from green algae. And what you do, it does not have a guide RNA. It's a single protein component that takes years of some smart scientists knowing how to do protein reengineering. I'd say Precision out of Durham, North Carolina, right outside the outskirts of the Duke campus. Many of our muscle come from there is really experts in protein reengineering. This technology has over 65 patents issued, which gives us a very nice ownership of ARCUS. Anybody who touches this homing endonuclease bound ARCUS really is given this program or access to this nucleus through Precision BioSciences. And there's 3 differentiating factors. One I've touched upon already, 2 of them, which are very important. Actually, all of them are important for 2 of the programs we just talked about in the clinic this year, the cut really important for any gene insertion programs. This is a 3 prime overhang, which allows gene editors for really the first time to repair predominantly from homology-directed repair versus non-homologous end joining. This really matters when inserting DNA for high-efficiency insertion. Size and simplicity really apply to our first wholly owned program, the PBGENE-HBV program. One of the biggest problems of ever going at root cause has been getting into really the nooks and crannies of the closed -- the cccDNA, covalently closed circular DNA that drives replicating virus for hepatitis. The size of ARCUS is the smallest of all gene editors, about 1,000 base pair. That's advantageous for delivering it through an LNP or an AAV, depending on what tissues of the body you're going to. But that size is a huge advantage in the PBGENE-HBV program. And then the simplicity. Most gene editors must deliver multiple components at one time, in order to really have a PK profile that gives you the editing output you're looking for. The beauty of ARCUS is it has one single protein. Recognition and catalytic activity cutting occur in the same single protein. So we're not reliant on higher doses of delivery vehicles like LNP or AAV. We don't need multiple delivery vehicles, and we have a better chance of getting the desired edited outcome. These are 3 of the unique differentiating backgrounds of the ARCUS platform. And again, we think about these very carefully when we make a therapeutic application. Will we go into a disease state where we dramatically improve the standard of care better than anything out there, regardless if it's a gene edit or not? And can anybody follow us? Can anybody gene edit the way we can if we're able to bring permanence to these disease states because cure is always the goal. Next. Very quickly here, gene editing, very general term. Most gene editors today apply to a more limited number of therapeutic areas where you're being delivered to the liver through an LNP. Most gene editors are very large. We talked about ARCUS being the smallest, about 1,000 base pairs. And most programs for gene editing today are knocking out, getting rid of something bad, a mutation, causing a scar that stops something deleterious in the body. But as you go up and we call the gene editing tree here, you heard me talk about the insertion program with our iECURE partner. You've heard me talk about the DMD program, which is an [indiscernible] program, the purple bubble. And the HBV program is elimination of a viral genome. These open up much more therapeutic applicability, bigger patient numbers if your technology is meant to do that. You also heard me say there won't be one winner. Know your technology and apply it where you've got the greatest advantage. This tree really shows that. Next. We believe our gene editing platform is the best suited for where we apply it. And now I'm going to hand it over to our CSO and the brains behind our PBGENE-HBV program. Cassie?

Thank you, Michael. So I'm going to start by talking through our PBGENE-HBV program. And as Michael mentioned, we're really intentional about Precision of utilizing our technology in spaces where we see a high unmet need, spaces where we need some innovation in the clinical development space as well as indications where our technology can really shine, where we can leverage those unique advantages of the ARCUS platform. So let's jump into PBGENE-HBV. When we look at really the drivers for chronic hepatitis B, it's really 2 viral reservoirs that exist in patients within their livers that lead to chronic hep B. What those 2 viral reservoirs are called are cccDNA, and Michael already mentioned this covalently closed circular DNA. And this is a mini genome that persists chronically in infected cells and gives rise to new infectious particles within patients. And then you can also -- patients also have integrated fragments of the viral genome into their host chromosomes. We call this integrated HBV-DNA. And it's really both of these reservoirs that give rise to infectious particles and different viral antigens. And so PBGENE-HBV is designed to eliminate cccDNA and activate integrated DNA in order to address both viral reservoirs. Go to the next slide, please. We mentioned that we intentionally apply ARCUS where it's well suited based on its unique features. And so Michael mentioned this PBGENE-HBV program really is leveraging the 2 features of ARCUS in the single component nature, the simplicity of the platform where ARCUS is a single protein that we engineer to recognize the DNA target sequence and that protein can also elicit the catalytic activity can cut the DNA. So it recognizes DNA and cuts DNA, no guide RNA required. It's also a very small protein. So ARCUS is encoded by about 1,000 bases of sequence, and this really allows us to generate very high-quality mRNA that can be packaged into an LNP very efficiently, delivered to the liver very efficiently to give us very high efficiency editing, which we know will be needed for HBV. And so it's really taking advantage of these 2 unique features of ARCUS nucleases that we are applying to be able to eliminate cccDNA and inactivate integrated HBV DNA. When we look at across various gene editing platforms and gene editing companies, we're really excited about the opportunity here for chronic hep B patients. There are more than 300 million patients globally that live with chronic hepatitis B. In the United States, there's up to 2.4 million people living with chronic hep B. And so when you look across various indications that are currently being pursued with gene editing, we see this PBGENE-HBV program as really having major upside in terms of the applicability to patients and the potential opportunity to really impact a number of people across the world. The unfortunate truth today is that patients who live with chronic hepatitis B, while there is a standard of care with nucleoside analogs, even with the standard of care, there are still some very serious complications that go hand-in-hand with living with chronic hepatitis B. So up to 30% of patients even on nucleoside analogs over a 10-year time frame still experience hepatocellular carcinoma and up to 40% of patients can also develop more serious liver complications like cirrhosis that can ultimately lead to liver failure. And unfortunately, more than 1 million people each year still die from chronic hepatitis B. And so when we look at this, we say there's a huge patient population. There's still a huge unmet need regardless of the availability of nucleoside analogs. And so we really see this as a very good approach for us to be able to apply an ARCUS technology in a disease indication that really matters for a number of people. When we look at that standard of care, I mentioned today is nucleoside analog. So the goal for hepatitis B patients is to be cured, of course. And what that means is achieving undetectable levels of HBV DNA and S-antigen off treatment for at least 6 months. That's the regulatory defined functional cure definition. Today, nucleoside analogs almost never achieved that for patients. So only 1% to 3% of patients are functionally cured with the standard of care. Interferon is available in some places, although it's not broadly used because it is a really challenging course of treatment. And even there, only 3% to 8% of patients experience functional cure rates. With the most developed -- for this advanced clinical development today with ASOs, still, we're not seeing double-digit functional cure rates. It's still unfortunately not really meaningful for the vast majority of patients. And so our goal with PBGENE-HBV is really to change this. It's to provide functional cure benefits for the largest number of patients we can. And we think by going after a very different strategy here, which we'll talk about in a second, we're really well positioned to be able to provide functional cures for patients. So what we're looking at here is the viral life cycle. And it's important to walk through this to truly understand how impactful the PBGENE-HBV mechanism is and how differentiated it is against the current clinical development landscape. And I think by understanding our mechanism, you can better appreciate why we're so excited for this idea of providing higher functional cure rates. So what you see here is really the viral life cycle. And we mentioned earlier that within hepatocytes in chronically infected hepatocytes, there's really 2 viral reservoirs, cccDNA and integrated HBV DNA. You can see those in the nucleus in the cell. cccDNA is the source that gives rise to additional viral particles, which we call HBV DNA. You can see that's secreted into the blood here. And both cccDNA and integrated HBV DNA can give rise to S-antigen, which is also shown there as an important biomarker. And so you have to be able to go after both of these viral reservoirs in order to reduce or eliminate both HBV DNA and S-antigen. Go to the next slide, please. When you look at the clinical development landscape today, you can see most of these various modalities are really aimed at impacting parts of the viral life cycle that are downstream of cccDNA and integrated DNA. And all of these different components are really transient parts of the viral life cycle, not really addressing the root cause. Next slide, please. So PBGENE-HBV, as I mentioned, is really designed to go right after the root cause. And to be fair to all of those who've gone ahead of us, everyone agrees that if you eliminate cccDNA and you inactivate integrated HBV DNA, you will cure hepatitis B. There's been a desire in the field for a long time to be able to do that. We just haven't had the tools to actually be able to go after it. And so PBGENE-HBV is the first drug in clinical development that's really designed to eliminate cccDNA and inactivate integrated HBV DNA. And we're very excited because we think this approach is really differentiated from what's been tried before and has the potential to provide really differentiated outcomes for patients. So now I'm going to talk a little bit about our ELIMINATE-B study. So this is our Phase I/IIa study to evaluate PBGENE-HBV. We are intending to conduct this study in up to 5 countries, up to 45 patients. You can see here, we're currently active and enrolling in Moldova, Hong Kong and New Zealand. We recently announced that we had clearance for our IND in the U.S., and I'm also happy to share that we have received CPA clearance in the U.K. as well. And so now we have 5 geographies that we have approved through the regulatory processes and we'll be bringing the U.S. and U.K. site on board here soon. We're starting this trial in HBV e-antigen negative patients who are currently controlled on nucleoside analogs. Next slide. We chose E-negative patients for a couple of reasons to start in. E-negative patients are the vast majority of patients, almost all or all actually chronically infected hepatitis B patients will eventually become E-negative. They may start in an E-positive phase of the disease course, and they all typically graduate into this E-negative state. And so you can see here, over 80% of patients, whether they're on nucleoside analogs or not are E-negative. So this patient population represents a real-world segment within chronic hep B patients. The other reason for choosing E-negative patients is that these patients are a little bit more progressed in terms of how long they've had chronic hepatitis B. So they aren't in sort of the acute phase of the infection where there's more likely to be liver flares and other things like that, that may complicate some of the safety parameters in the study. Next slide, please. So this is the way that the ELIMINATE-B study has been designed. And I'm really excited about this multiple ascending dose escalation design that the team put together because it allows us to really evaluate a couple of different parameters at once. And so what you're looking at here, you can see there's intended to be up to 3 dose levels, within each dose level, there are 3 dose administrations. And this design was really borne out of a very vast set of preclinical data that demonstrated you could continue to push increased efficacy through allowing for subsequent administrations. And so each dose level, each patient can receive up to 3 administrations at that dose level. What's neat about this design is once 3 patients have been administered that first dose, so let's say, dose level 1, 3 patients received their first dose administration. We can pull together our data safety monitoring committee and evaluate the safety of that dose level in those patients. And once we have that meeting, we can achieve alignment in order to start the next dose level. So we can move up in dose level while also progressing those 3 patients through their next 2 administrations to complete out the dosing cohort at that initial dose level. And this design allows us to really move quite rapidly through this multiple ascending dose escalation part of the study. And this design allows us to identify the correct dose level and number of dose administrations that gives us the highest safety profile and, of course, efficacy profile. And once we have identified that dose level and dosing schedule, we can move into Part 2 of the study, which is the dose expansion phase of this study. Next slide, please. So the primary endpoints in this ELIMINATE-B study are, of course, safety. So we'll be looking for DLPs across all of our patients enrolled. And then we'll also be looking at efficacy. And I mentioned earlier, the goal in the chronic hep B field is really to provide functional cures. So undetectable HBV DNA and S-antigen off treatment for at least 6 months. And so we'll be using serology markers of HBV DNA and S-antigen to really follow towards that functional cure rate. And we have a number of novel biomarkers as well that we'll be following such as core-related antigen and HBV RNA, which can give us a little bit of a sense in patients who express these markers about activity on specifically cccDNA. And so it's a really robustly designed trial to give us a very comprehensive look at the mechanism of PBGENE-HBV and its ability to eliminate cccDNA and inactivate integrated HBV DNA with, of course, the goal of providing functional cures. And so as we're following these biomarkers in the blood, if we can get a patient to undetectable HBV DNA and S-antigen for 2 serial testings, we will be able to look at functional cure by withdrawing the nucleoside analog and monitoring those serology markers. And if you really think about the mechanism here of eliminating cccDNA and inactivating integrated HBV DNA, you can really think that if you see those biomarkers goes undetectable and you remove the nucleoside analog and it stays down, there's no reason to think if you've eliminated cccDNA that it's going to come back. And that would really be an exciting functional cure, maybe even sterilizing cure for patients. Next slide, please. So we recently, earlier this year, shared some initial readouts from this study. We were very excited to share that we had dosed our first 3 patients at that first dose level, first administration. So it's early on in the study, but we felt it was important to share with the world that PBGENE-HBV was well tolerated in all 3 of the first patients dosed, and we observed substantial S-antigen reductions in 2 out of those 3 patients. And so this is a really exciting time for us to be able to share these initial clinical results. We expect to be able to continue to share clinical results from this study throughout this year as we continue to dose more patients and complete the entire cohort for patients within each dose level, we'll be able to share more data -- more descriptive data from the clinical study. I mentioned that the clinical trial was really built on the back of a lot of preclinical data to support it. And so I just wanted to take the opportunity to talk through a couple of pieces of preclinical data that we think is really contributing to what we're seeing in the clinic. So first and foremost, of utmost importance for a Phase I study is safety. And I've talked before about when you think about LNPs and the overall safety profile for LNPs, it's not just about the lipid nanoparticle, it's about the mRNA that goes inside the lipid nanoparticle. And this is where we think the small size of ARCUS really has an advantage. 1000 basis to encode a nuclease means a very short mRNA that you have to produce and shorter mRNA means higher quality mRNA. So what we were excited to see, this is some data from one of our nonhuman primate toxicology studies. And you can see here after a dose of LNP, you see it, as you'd expect, a transient elevation in transaminases. These go back to baseline within about 2 weeks. And importantly, the overall magnitude of these elevations is less than 3x the upper limit of normal for these primates, which is a very good profile overall for a high dose of LNP. This is a 1.5 milligram per kilogram dose in nonhuman primates. So very well tolerated, no adverse changes in blood parameters. And these transaminase elevations were transient, returned to baseline and weren't associated with any total bilirubin changes. So overall, very good safety profile from the preclinical data, and we're really seeing that bear out as we translate that into clinical data now. Next slide, please. And just one last piece of preclinical data, and I think this is one that gets me really excited when we think about efficacy for our clinical data set. And so at Precision, we really put a lot of emphasis on trying to ensure that our preclinical data would translate as best as possible into the human scenario. And so we actually developed our own nonhuman primate HBV model because, unfortunately, nonhuman primates don't get hepatitis B, the same virus that humans get. And so we gave these primates a surrogate virus in order to establish an infection that looks very much like HBV. It has a mini chromosome that sits in hepatocytes very tightly wound there and chronically infects those hepatocytes, just like cccDNA does. And then we administered 2 doses of our LNP. And what you can see here is that after the first dose, we achieved about 50% editing overall in this nonhuman primate model. And after that second dose, we achieved about another 50%. So a good second boost in efficacy after that second administration in order to achieve about 99% overall editing at this top dose here. And so it's really this study that I think you can start to see 2 doses, we get to 99%, 93% at the lowest dose. This study has really informed how we designed the clinical trial, allowing up to 3 dose administration to allow for best chances of efficacy for our patients. So just to close here, we talked a lot about our PBGENE-HBV program today. We're excited to continue to progress through enrolling patients and collecting data. And as I mentioned, we anticipate continuing to share data from this trial throughout the remainder of 2025. We're also evaluating at Precision, 2 different muscle-directed programs. And Michael mentioned these earlier. Our second internally owned program is PBGene-3243. And we're also -- we obtained the rights back to a DMD program, which is currently under assessment, looking for opportunities to be able to progress this program. We're really excited about the potential differentiation that this program provides within the DMD space. And so we'll continue to look for opportunities to advance that program that could be applicable in up to 60% of DMD patients and offer a permanent functional cure at the root cause leading to durable functional responses for those patients. And so with that, I'd be happy to turn it over for any questions.

Great. Yes. Great. Thank you, Cassie. Thank you, Michael. Thank you. Very nice presentation. As a reminder, any viewers who are watching through our conference portal are able to submit questions via Ask a Question feature. But while that's compiling, maybe I'll start us off. So I do promise I won't spend too much time on the markets and the external environment we have right now, but given there's gene editing and given your modality, do you want to ask what your thoughts are on recent changes at the FDA? Have you noticed any differences so far in your interactions? Or do you expect any -- I know it's a very evolving climate right now, but let me start there.

Yes. I think the short answer that people do want to hear, I hope you believe it is no, right? And I'll give you an example. So look, when you're applying any application, genetic therapies to an area with great unmet need, this is a world where you have 30% to 40% still experience mortality. It's over 1 million people, 2.4 million in the U.S. alone. That's not to talk about the worldwide pandemic. We need cures, sterilizing cures in this disease state. The FDA as well as all of the other regulators around the world. So just to give you a heads up, Moldova, New Zealand, Hong Kong, the U.S. and the U.K. starting simultaneous. I think it's the first gene editor to be able to start simultaneous because we did all the work that was asked for in representative models, nonhuman primates for safety. The big areas are on and off-target editing, we call it genomic integrity, using a genome that's similar -- most similar to a human, a primate and delivering the final candidate at representative doses. So our toxicology with the LNP we use was given 3x like we're going to do in the trial and to make sure you do the work on germline and make sure there's no reproductive editing. Cassie, I give her all the credit in the world, is very robust when we put the package together. We were able to get approval simultaneously in the market because we really want to accrue this trial quickly. And if you take a look at prior to the new administration and RFK coming in, taking over kind of the FDA, and obviously, we know there's a changed with marks. Just this last month, all the feedback we had gotten for the last 1.5 years was consistently came to fruition where we got an IND approval. So if you're clear on your safety parameters, if you deliver on those things, if there's high unmet need, if the clinical protocol is understood of what the TPP, the target product profile is, we don't think with the levels of need and the programs and the high unmet need we're talking about that any changes at the FDA. We've had nothing but consistency so far. The IND approval this March is really proof of that under the new administration.

Great. No, that's very helpful. And then you did mention there that obviously, LNP and safety, tolerability in general is a big focus. How -- with multiple administrations, how do you guys mitigate any -- or mitigate the best you can the risk of toxicity, is that spacing out the spacing intervals. I know the cargo is important, like you mentioned. What are your thoughts?

I'm going to turn it to Cassie in 1 minute because it's her baby. But the short answer that she's been saying for 2 years is all LNPs are not alike and the quality of the mRNA makes all the difference in the world. Cass, why don't you talk a little bit about what you did in optimization?

Yes. So we put a lot of effort into optimizing the mRNA that goes into our lipid nanoparticle as well as the process by which we manufacture the mRNA and the drug product, the lipid nanoparticle. And so I mentioned the size of our ARCUS nuclease really helps with creating high-quality mRNA, the drug substance that goes into it. It's also a single component. And so we only have one thing that has to go into the LNP versus a guide RNA and an mRNA like CRISPR-based technologies. And so I definitely think that the quality of the drug substance and the drug product matters when you think about -- especially when you're trying to do multiple administrations. And you'll see in our -- the toxicology data that I showed, it's the ALT/AST elevations that you have to be really cognizant of with LNP-based products. And you can see our transaminase elevations, one, overall are very mild and two, they resolve quickly, and that's actually without any background pretreatment in that study. And so I think it's important just to note that we -- this study actually dosed 28 days between first and dose -- and the second administration. Our clinical study is at 8 weeks right now, just to give us an additional buffer. But we're very confident in terms of the ability to safely multi-dose in the clinical setting.

Great. And I know we're coming up on time here soon. But maybe one more on DMD just because I know I didn't get a chance to talk about a whole lot. But obviously, it's an exciting space. You have at least one gene therapy approved and several next-gen therapies in development. Maybe if you could just touch on how you're hoping to differentiate? What do you think the unmet need still is and go from that.

Yes, I'll ask Cassie to comment here in a closing moment. First and foremost, I think Duchenne muscular dystrophy right now is it's a hot area because it's predictable with what you just asked about the FDA. There's a biomarker. They know there's a limited number of patients needed. That's not a good sign. That means what's out there isn't working for these children, and we need fast solutions. And I know everyone is working hard, and I give a lot of credit to my peers. But right now, this is very different than with HBV. This is a rare disease and you've got one shot on goal with viral delivery, which to date, all of us need viral delivery to get to muscle, unlike the liver with PBGENE-HBV, which means the payload we deliver matters most. We spent the entire time talking about better capsids. We all want to be liver sparing and delivering our dose. The difference between gene editing and what's out there, conventional gene therapies. Conventional gene therapies need to push their AAV dose, and they're giving a truncated protein synthetically made dystrophin to try to get expression. And while we've impacted biomarker very well, we industry, we've not had that translate to real large functional outcomes for patients, unfortunately. When you have a gene editing approach, and this is the first gene editing approach, [indiscernible] 45 to 55 where there's a problem, is about 60% of the population. These are not point mutations. It's a large homogeneous group. What you're doing is you're religating and taking advantage of the native gene, not synthetic gene, native dystrophin. And what you do here by making this cut and cutting out the problematic area, you don't need to deliver the highest doses of AAV safety. You need to deliver enough AAV to edit the satellite cells, stem cells of muscle. Now that correction gives birth and bears more mild fibers with the corrected dystrophin gene. So it's a very different approach. It's basically episomal expression is where the world has been out versus permanent gene correction. That's what would merely differentiate us. Cassie, also one of your babies, is there anything you would add there?

No, I think you covered it really nicely. I think gene editing has the ability to permanently correct the dystrophin gene at the root cause, which has the potential to be much more durable when you think infinitely durable, if you think about it compared to an AAV that's a microdystrophin approach that requires that AAV to be persistent, and we know really hasn't been. So I think we're very excited to offer this differentiated approach for patients where, as we said, really looking for creative ways to continue to push this program forward.

Just in closing, what I would say is thank you to our investors. I know it's a very distracted day. We're going to continue to control what we can control across administrations, across differences at the FDA and other world markets, the diseases we're in, with the feedback we've gotten from regulators and the clear clinical hurdles being laid out and the cash runway to accomplish it, Precision is going to get a chance to turn their cards over and see if the data can speak for us. We're excited about that. And right now, we're just going to focus on controlling what we can control. I know my partners are having a tough day with the markets. But if we're able to deliver with PBGENE-HBV and in a program like this for DMD, these are multibillion-dollar opportunities, more importantly for patients, they're cures. And I think the fundamentals will speak for themselves regardless of macro level dynamics.

Great. Thank you. And thank you for the closing. And thank you, Michael and Cassie for joining us today and best select Precision on the year.

Thank you for having us.

Thank you, Ethan.