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. We'll provide a presentation on the company, followed by a Q&A session with the remaining time. I will 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 this is some uncertain time, so I really like meetings like this where we can focus on the fundamentals. Fundamental science that changes the standard of care in a given disease state, regardless of modality, will always win the day in our business. 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, three short years ago, had some amazing science, still does have amazing science, but there were really three 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 were the in vivo programs. When this management team came together, what I'll call the Chapter Two 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. 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 great belief in.
Today, Precision's 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. Usually, there we'll be getting most of our questions. It's a global trial, very proud of it, open in five 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 our wholly owned program, but it's the ECUR OTC- HOPE t rial, 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+% of patients are not. Just most recently, going in reverse order, PBGene-HBV, we announced a full dosing of the first administration of cohort, a lowest cohort dose level, 0.2 mcg per kg LNP of PBGene-HBV. That had wonderful safety and some very early efficacy that was exciting, some antiviral activity. Again, Cassie will tell you more about that today.
Our second wholly owned programs, which will yield clinical data, the first two programs I spoke about, PBGene-HBV and ECUR, 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. Very unique approach we have for PBGene-3243, where an ARCUS can cross the membrane of a mitochondrial barrier. Many other gene editors cannot do that. 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.
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 two of our own wholly owned phase one 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 for our partners. We're very proud of them, small but mighty group at UPenn. This phase one, two 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 six months out from treating, has not had a breakthrough attack.
These are toxic ammonia level attacks that really impair 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 if they continue to have results like that in the next one, two, or three 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. ARCUS was actually engineered kind of biochemically neutral, where it comes from green algae. 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 re-engineering. I'd say Precision out of Durham, North Carolina, right outside of the outskirts of the Duke campus, many of our muscle come from there, is really experts in protein re-engineering.
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 nuclease through Precision BioSciences. There are three differentiating factors, one I have touched upon already, two of them, which are very important. Actually, all of them are important for two of the programs we just talked about in the clinic this year. The cut, really important for any gene insertion programs. This is a three-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 to 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 what tissues the body is going to, but that size is a huge advantage in the PBGene-HBV program. 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. We are 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 three of the unique differentiating backgrounds of the ARCUS platform. Again, we think about these very carefully when we make a therapeutic application. W e will go into a disease state where we dramatically improve the standard of care better than anything out there, regardless if it's a gene editor or not? 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.
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. As you go up, we call the gene editing tree here. You heard me talk about the insertion program with our iECURE partner. You have heard me talk about the DMD program, which is an excise program, the purple bubble. 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 will not be one winner. Know your technology and apply it where you have 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. Now I'm going to hand it over to our CSO and the brains behind our PBGene-HBV program. Cassie.
Thank you, Michael. I'm going to start by talking through our PBGene-HBV program. 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. Let's jump into PBGene-HBV. When we look at really the drivers for chronic hepatitis B, it's really two viral reservoirs that exist in patients within their livers that lead to chronic hep B. What those two viral reservoirs are called are cccDNA, Michael already mentioned this, covalently closed circular DNA. This is a mini genome that persists chronically in infected cells and gives rise to new infectious particles within patients.
You can also, patients also have integrated fragments of the viral genome into their host chromosomes. We call this integrated HBV DNA. It is really both of these reservoirs that give rise to infectious particles and different viral antigens. PBGene-HBV is designed to eliminate cccDNA and inactivate integrated DNA in order to address both viral reservoirs. If you go to the next slide, please. We mentioned that we intentionally apply ARCUS where it is well suited based on its unique features. Michael mentioned this PBGene-HBV program really is leveraging the two features of ARCUS in the single component nature, the simplicity of the platform, where ARCUS is a single protein that we engineer to recognize a DNA target sequence, and that protein can also elicit the catalytic activity, can cut the DNA.
It recognizes DNA and cuts DNA, no guide RNA required. It's also a very small protein, and 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. It is really taking advantage of these two unique features of ARCUS nucleases that we are applying to be able to eliminate cccDNA and inactivate integrated HBV DNA. When we look 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. 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. Up to 30% of patients, even on nucleoside analogs over a 10-year timeframe, 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.
Unfortunately, more than a million people each year still die from chronic hepatitis B. 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. 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's nucleoside analogs, the goal for hepatitis B patients is to be cured, of course. What that means is achieving undetectable levels of HBV DNA and S antigen off treatment for at least six months. That's the regulatory defined functional cure definition. Today, nucleoside analogs almost never achieve that for patients.
Only 1% to 3% of patients are functionally cured with a standard of care. Interferon is available in some places, although it is not broadly used because it is a really challenging course of treatment. Even there, only 3% to 8% of patients experience functional cure rates. With the most developed, furthest advanced clinical development today with ASOs, still we are not seeing double-digit functional cure rates. It is still unfortunately not really meaningful for the vast majority of patients. Our goal with PBGene-HBV is really to change this. It is to provide functional cure benefits for the largest number of patients we can. We think by going after a very different strategy here, which we will talk about in a second, we are really well positioned to be able to provide functional cures for patients. What we are looking at here is the viral life cycle.
It is 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. I think by understanding our mechanism, you can better appreciate why we are so excited towards this idea of providing higher functional cure rates. What you see here is really the viral life cycle. We mentioned earlier that within hepatocytes, in chronically infected hepatocytes, there are really two viral reservoirs, covalently closed circular DNA (cccDNA) and integrated HBV DNA. You can see those in the nucleus in the cell. The cccDNA is the source that gives rise to additional viral particles, which we call HBV DNA. You can see that secreted into the blood here. Both cccDNA and integrated HBV DNA can give rise to S antigen, which is also shown there as an important biomarker.
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. All of these different components are really transient parts of the viral life cycle, not really addressing the root cause. Next slide, please. PBGene-HBV, as I mentioned, is really designed to go right after the root cause. 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.
It'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. PBGene-HBV is the first drug in clinical development that's really designed to eliminate cccDNA and inactivate integrated HBV DNA. 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. Now I'm going to talk a little bit about our ELIMINATE-B study. This is our phase I/IIA study to evaluate PBGene-HBV. We are intending to conduct this study in up to five 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 US. I am also happy to share that we have received CTA clearance in the UK as well. Now we have five geographies that we have approved through the regulatory processes. We will be bringing the US and UK site up on board here soon. We are starting this trial in HBV e antigen negative patients who are currently controlled on nucleoside analogs. Go to the next slide. We chose e negative patients for a couple of reasons to start in. The 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.
You can see here over 80% of patients, whether they're on nucleoside analogs or not, are e negative. 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. 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. This is the way that the ELIMINATE-B study has been designed. 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.
What you're looking at here, you can see there's intended to be up to three dose levels. Within each dose level, there are three dose administrations. This design was really born out of a very vast set of preclinical data that demonstrated you could continue to push increased efficacy through allowing for subsequent administrations. Each dose level, each patient can receive up to three administrations at that dose level. What's neat about this design is once three patients have been administered that first dose, so let's say dose level one, three patients receive their first dose administration, we can pull together our data safety monitoring committee and evaluate the safety of that dose level in those patients. Once we have that meeting, we can achieve alignment in order to start the next dose level.
We can move up in dose level while also progressing those three patients through their next two administrations to complete out the dosing cohort at that initial dose level. This design allows us to really move quite rapidly through this multiple ascending dose escalation part of the study. This design allows us to identify the correct dose level and number of dose administrations that gives us our highest safety profile and, of course, efficacy profile. Once we have identified that dose level and dosing schedule, we can move into part two of the study, which is the dose expansion phase of this study. Next slide, please. The primary endpoints in this ELIMINATE-B study are, of course, safety. We will be looking for DLTs across all of our patients enrolled. We will also be looking at efficacy.
I mentioned earlier the goal in the chronic hep B field is really to provide functional cures. Undetectable HBV DNA and S antigen off treatment for at least six months. We will be using serology markers of HBV DNA and S antigen to really follow towards that functional cure rate. We have a number of novel biomarkers as well that we will 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. It is 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.
As we're following these biomarkers in the blood, if we can get a patient to undetectable HBV DNA and S antigen for two serial testings, we will be able to look at functional cure by withdrawing their nucleoside analog and monitoring those serology markers. 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 go to 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. That would really be an exciting functional cure, maybe even sterilizing cure for patients. Next slide, please.
We recently, earlier this year, shared some initial readouts from this study. We were very excited to share that we had dosed our first three patients at that first dose level, first administration. It is early on in the study, but we felt it was important to share with the world that PBGene-HBV was well tolerated in all three of the first patients dosed. We observed substantial S antigen reductions in two out of those three patients. This was 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 will 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. 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. First and foremost, of utmost importance for a phase one study is safety. 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. This is where we think the small size of ARCUS really has an advantage. A thousand bases to encode a nuclease means a very short mRNA that you have to produce. Shorter mRNA means higher quality mRNA.
What we were excited to see, this is some data from one of our non-human primate toxicology studies. You can see here, after a dose of LNP, you see, as you'd expect, a transient elevation in transaminases. These go back to baseline within about two weeks. Importantly, the overall magnitude of these elevations is less than three times 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 mg per kg dose in non-human primates. Very well tolerated, no adverse changes in blood parameters. These transaminase elevations were transient, returned to baseline, and were not associated with any total bilirubin changes. Overall, very good safety profile from the preclinical data. We are really seeing that bear out as we translate that into clinical data now. Next slide, please.
Just one last piece of preclinical data. I think this is one that gets me really excited when we think about efficacy for our clinical data set. 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. We actually developed our own non-human primate HBV model because, unfortunately, non-human primates do not get hepatitis B, the same virus that humans get. 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, sits there and chronically infects those hepatocytes, just like cccDNA does. We administered two doses of our LNP.
What you can see here is that after the first dose, we achieved about 50% editing overall in this non-human primate model. After that second dose, we achieved about another 50%. A good second boost in efficacy after that second administration in order to achieve about 99% overall editing at this top dose here. It is really this study that I think you can start to see two doses, we get to 99%, 93% at the lowest dose. This study has really informed how we designed the clinical trial, allowing up to three dose administrations to allow for best chances at efficacy for our patients. Just to close here, we talked a lot about our PBGene-HBV program today. We are excited to continue to progress through enrolling patients and collecting data.
As I mentioned, we anticipate continuing to share data from this trial throughout the remainder of 2025. We are also evaluating at Precision two different muscle-directed programs. Michael mentioned these earlier. Our second internally owned program is PBGene-3243. 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 are really excited about the potential differentiation that this program provides within the DMD space. We will 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. With that, I would be happy to turn it over for any questions.
Great. Yeah, great. Thank you, Cassie. Thank you, Michael. Thank you. Very, very nice presentation. As a reminder, any viewers who are watching through our conference portal are able to submit questions via the ask a question feature. While that's compiling, maybe I'll start us off. I do promise I won't spend too much time on the markets and the external environment we have right now. Given there's gene editing and given your modality, I do 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 maybe start there.
Yeah, I think the short answer that people do want to hear, I hope you believe it, is no, right? I'll give you an example. Look, when you're applying any application, genetic therapies, to an area with great unmet need, this is a world where you have 30-40% still experience mortality. It's over a million people, 2.4 million in the US 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 US, and the UK 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, non-human 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. Our toxicology with the LNP we use was given three times, like we're going to do in the trial. 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.
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 change with Marks just this last month, all the feedback we had gotten for the last year and a half consistently came to fruition where we got an IND approval. 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.
Right. No, that's very helpful. You did mention there that obviously LNP and safety, tolerability in general is a big focus. With multiple administrations, how do you guys mitigate or mitigate the best you can the risk of toxicity? Is it spacing out? The spacing intervals? I know the cargo is important, like you mentioned. What are your thoughts?
I'm going to turn to Cassie in one minute because it's her baby. The short answer that she's been saying for two 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?
Yeah, 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. I mentioned the size of our ARCUS nuclease really helps with creating high-quality mRNA, the drug substance that goes into it. It is also a single component. We only have one thing that has to go into the LNP versus a guide RNA and an mRNA like CRISPR-based technologies.
I definitely think that the quality of the drug substance and the drug product matters when you think about, especially when you are trying to do multiple administrations. You will see in the toxicology data that I showed, it is the ALT and AST elevations that you have to be really cognizant of with LNP-based products. You can see our transaminase elevations, one, overall are very mild, and two, they resolve quickly. That is actually without any background pretreatment in that study.
I think it's important just to note that this study actually dosed 28 days between first and second administration. Our clinical study is at eight weeks right now just to give us an additional buffer. We're very confident in terms of the ability to safely multi-dose in the clinical setting.
Right. 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. Obviously, it's an exciting space. You now 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 needs still is, and go from there.
Yeah, I'll ask Cassie to comment here in a closing moment. First and foremost, I think the Duchenne muscular dystrophy right now, 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. We need fast solutions. I know everyone's working hard, and I give a lot of credit to my peers.
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've 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. C onventional gene therapies need to push their AAV dose, and they're giving a truncated protein, synthetically made dystrophin to try to get expression. 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, exons 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 re-ligating and taking advantage of the native gene, not synthetic gene, native dystrophin. 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 myofibers with the corrected dystrophin gene. It is a very different approach.
It is basically episomal expression is where the world has been at versus permanent gene correction. That is what would really 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 is 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 is a microdystrophin approach that requires that AAV to be persistent, and we know really has not been. 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.
Yeah, Ethan, 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's going to get a chance to turn their cards over and see if the data can speak for us. We're excited about that. Right now, we're just going to focus on controlling what we can control on.
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 multi-billion dollar opportunities, more importantly for patients, their cures. I think the fundamentals will speak for themselves regardless of macro-level dynamics.
Great. Thank you. Thank you for the closing. Thank you, Michael and Cassie, for joining us today. Best of luck to Precision on the year.
Thank you for having us.
Thank you, Ethan.