During the presentation, please feel welcome to submit questions using the Zoom Q&A interface at the bottom of your screen. After the presentation, we'll open to your questions. And with that, Alex, I'll turn it over to you.
Great. Well, thank you very much, Alex. It's great to be here again this year at the Sidoti Conference, and we thank you for the invitation. Next slide is just our forward-looking statements, so I'd encourage you to review those risk factors and other factors that could cause our actual results to differ materially from any statements we make today. With that, let's get on with it. Precision BioSciences is an in-vivo gene editing company based in Durham, North Carolina. And right now, we are focused on developing two programs, and that is really our exclusive focus in-house. Our first program is PBGENE-HBV for hepatitis B. We'll go into some detail about what hepatitis B is, but let's just suffice it to say it's a big opportunity. 300 million people around the world live with chronic hepatitis B.
They have no treatment that gets them to a cure on a predictable basis. So that's what we're looking to overcome. We got this program into the clinic late last year, and we've been generating data throughout 2025 and also going forward into 2026. PBGENE-DMD is our next program, a wholly-owned program by Precision BioSciences. We are running very fast right now in-house to get an IND filed for this drug in 2025. So we got about 20 days left to go, and our team is right on track to deliver the IND this year. This is a program for Duchenne muscular dystrophy. It's a well-known rare disease. The FDA has a very clear regulatory path for DMD, and there's also proven commercial opportunity in this marketplace. This program, as I said, will file an IND this year.
We'll be in the clinic in the first part of 2026, and we'll have our first data readout in probably three to five patients by the end of 2026. Now, what's also great is that we just did a financing. We raised $75 million from well-established current investors who were great participants before and also in this offering. But also, we also brought in new investors into the offering as well. That $75 million financing gives us a cash runway through 2028, and that's key because that will give us ample time to read out for these programs for all the phase 1 data, but also to progress beyond the phase 1 trial. Next. So if you look at ARCUS, ARCUS is our in-vivo gene editing platform that we developed in-house.
Our founders started this company almost 20 years ago in 2006, and since that time, they've been very focused, and the company is now extremely focused on in-vivo gene editing. And what we can tell you right now is that in the clinic, ARCUS works, right? We've got multiple examples of how ARCUS works for gene editing. We see that in our own hepatitis B product, which I will go into detail about the data that was just presented on November 10th from the phase 1 trial. We see that with our partner, iECURE, who's using an ARCUS gene editing nuclease for a disease called severe OTC deficiency. Severe OTC deficiency, unfortunately, has an extremely high mortality rate in the first year. Probably 74%-75% of the infants who are born with severe OTC deficiency, they unfortunately don't make it to their first birthday. So we're hoping to change that.
With the program with iECURE, they have reported the results, and the first patient that was treated, that patient achieved a complete response after receiving ARCUS, and they are now off of their ammonia-sparing medicines and they're consuming a normal protein diet. That patient is approaching two years old and is doing quite well, and it's a great accomplishment for iECURE, but also a great accomplishment for our team here at Precision that developed the nuclease for the OTC deficiency. We've also seen clinical validation for our ARCUS technology in the area of hematology. We had previously been developing azer-cel, a CAR-T product for hematologic malignancies, and our partner, Imugene, is now taking that forward, and they are covering the cost of the trials. They've just announced a successful meeting with the FDA, and they now have a clear path towards a pivotal clinical trial.
Great accomplishments there, but what it does is it shows that in the clinic, ARCUS works. Next slide. Let's start getting into hepatitis B for a moment if we can. This is the abstract that was presented on November 10th. It was a late-breaking oral presentation. If you're not familiar with the American Association for the Study of Liver Diseases, this is the biggest American liver conference. And at that conference, they rarely accept posters for phase one to be presented in oral presentations. We were quite proud to be recognized with an oral presentation for our data. And Man-Fung Yuen, who is one of our leading investigators in Hong Kong, he presented the data. Let's go on to the next slide. What we're seeing with h epatitis B is that there have been treatments that have been developed over many, many years.
Unfortunately, what we see is that they just don't get many patients to a functional cure. Most of the drugs that are available today, or even those that are being tested outside of PBGENE-HBV, are only trying to reduce S antigen, which is a viral marker that you have hepatitis B. They're going after this downstream marker, which doesn't really impact the root cause of the virus, which is the virus and the cccDNA is the viral source. That embeds itself in hepatocytes, the liver cells of patients with chronic hepatitis B. After years and years of studying S antigen and trying to reduce it to zero and keep it there, we just find that as soon as you stop the drugs, the S antigen starts coming back, meaning the disease is still present.
So what we are doing is a gene editing approach where we're not editing. We are going to edit directly into the virus and trying to eliminate cccDNA at its source. We have shown the data that you're going to see. We have studied this now in three different cohorts, all the way up to the highest dose so far is 0.8 milligrams per kilogram. We see safety with this drug at all three dose levels. We see a manageable side effect profile, and we are also importantly seeing dose-dependent antiviral activity. So we're seeing antiviral activity at the lowest dose, the middle dose, and the highest dose. So let's go forward and talk about the path of what we're seeing next. Go ahead, Naresh.
So if you look at this as a schematic kind of showing you what's going on inside a hepatocyte, which is the liver cells, and further in from there is the nucleus of the hepatocytes. So cccDNA and integrated HBV DNA are the two sources of what we call S antigen, hepatitis B surface antigen. And there are, but cccDNA itself is the only part that actually produces new infectious particles. So it's really critical that we eliminate cccDNA if we truly want to stop hepatitis B. So there are other drugs that are indicated on this slide: A, B, and C. A is the current standard of care, nucleoside analogs. There are also other drugs, a capsid assembly modulator or a CAM that's in the same area. And they are trying to work downstream of pgRNA to stop the development of infectious particles.
Sadly, they don't do that enough. They basically only result in a cure 1%-3% of the time. The other drugs that have been tried are indicated by B and C here, but unfortunately, even with combinations of drugs in category A, B, and C, we still don't see a high rate of functional cure in patients with chronic hepatitis B, and that ultimately can lead to severe cirrhosis of the liver or liver cancer. Next slide. So while those other drugs work downstream, what we're indicating here on this schematic is that PBGENE-HBV, our drug using ARCUS, is working at the root cause of the disease, the cccDNA and also the integrated HBV DNA. And you can see by doing so, we actually eliminate all those downstream particles, and we also, most importantly, we stop the infectious particles that come from cccDNA. So that's the mechanism.
Let me go further to the trial design. We call it the ELIMINATE-B trial, and this is our phase one trial for chronic hepatitis B. You can see on the left, there were designed to be at least three different cohorts, right? We have cohort one was the low dose, 0.2 milligrams per kilogram. We then went up to cohort two and cohort three. Now, what you see indicated in each of those boxes for the cohorts is that each patient receives three doses of our drug. So it's designed to be a finite course of treatment that can result in sustained viral suppression.
So we're also, once we establish the right dose for go forward and we have a safe and effective dose, then we'll expand from part one to part two, and we'll dose up to a total of 45 patients between part one and part two as we head towards a phase 2 clinical trial. Next slide. So what do we see so far in terms of safety? I think this is very important. Across all three doses, we see that PBGENE-HBV is well tolerated, even with repeat doses. Very important because with this virus, you need to keep coming at the virus more than one time to enable yourself to get to a functional cure. So we also see adverse events that were predictable based on the fact that our drug is used with a lipid nanoparticle or an LNP.
Those drugs have been used in the clinic before, so they have a very well-known safety profile, and we're seeing that safety profile and that predictable and manageable events in our trial as well, so for example, transaminases, we are seeing transient elevations in the transaminases, the liver enzymes, but we're not seeing a subsequent increase in bilirubin, and that's really important for a safety standpoint, and then what we're seeing is that the safety is being established, and that's really important. As I said, we need to work with multiple doses of this drug and find the right dose to move forward before we can stop the patients from taking their nucleoside analogs. Next slide. Go ahead, so what we're seeing in this trial is that we're seeing a clear trend as we increase in dose. You can see on the far left is cohort one.
That's the low-dose cohort. You can see that there was an impact quickly in almost every patient, a quick reduction in their S antigen. But what you see in this low-dose cohort is that only one of the three patients is able to maintain the S antigen reduction to 50% reduction after 20 weeks after the last dose. The other two treatments, they tended to bounce back up to baseline after their first dose. Now, if you progress to cohort two, you can see a different trend is emerging. One, you see the same trend that each dose knocks down the S antigen, but what you're not seeing in cohort two is the same kind of rebound effect that you see in cohort one, right? All the patients are staying below baseline and maintaining a reduction in their S antigen.
Now, when you progress to cohort three, and maybe I'll build the trend lines here, you can see that the trend line is changing. We don't have as many doses in cohort three yet. Cohort three right now represents two doses at the 0.8 milligrams in one of the patients, and two of the patients have only had one dose so far. But the trend line is pretty impressive because you see a dramatic reduction in S antigen, and you see even with a second dose in the lead patient in cohort three that you're seeing sustained reductions, no effect of bouncing back up towards the baseline. So this is the trend line that we showed at the AASLD conference, and I think that the clinicians who treat hepatitis B for a living every day are quite impressed to see a profile like this emerging for a gene editor.
Next, this is specifically looking at just cohort three. As I mentioned, patient seven or the first patient in cohort three had two doses of drug, whereas patient eight and patient nine had only one dose of the drug. But you're seeing we're getting to a place where their S antigen is being reduced to a substantial level, and they're getting closer to zero. The goal really is getting to zero S antigen, and if we can do so, then we will be able to stop their nucleoside background therapy and test for a cure. Now, there's emerging data in Europe and other countries that's showing that you could also look at stopping after different, and if you don't get to zero, you could consider stopping somewhere south of 100 international units per milliliter on S antigen.
So you can see with this top dosing level, we're getting patients close to that place where we can have a discussion about is it time to test for a cure? Not there yet, but the data is looking promising. Next slide. This is kind of a schematic to show you using the patient number seven that you just saw as an example. You see a dramatic reduction after dose level one. You see a further reduction in their S antigen after dose level two. We have not given dose level three yet, but our hope is that when you do give it, you will see once again a further reduction in their S antigen. So let me go back to the basics. This is the only mechanism targeting the root cause of the disease, which is cccDNA. It's well tolerated and with a manageable safety profile.
All patients so far, whether it's at the low dose or the high dose, have demonstrated antiviral activity, and we're seeing that response is being maintained as we look at the later cohorts. Next slide, please. Here's where we are. Next, we want to complete the dosing for cohort three. We want to, then we can get patients to either undetectable or to a very low level of S antigen. We want to stop the nukes and test for a cure. That means we'll stop and watch. If the S antigen stays low, we have a patient to a cure. If they go back up, we're not there yet. Once we find the right dose, we want to expand into part two with more patients.
Now, in parallel, we're also looking at some other plans, other cohorts where we're actually shortening the dosing interval. Every patient so far has received the drug every eight weeks. We want to now look at it to see what happens if we treat patients every four weeks. Do we get to a cure faster, or can we give additional administrations to get to a cure even at the lower doses? Next slide. Let me hand off to Naresh now to talk about PBGENE-DMD, our lead program for Duchenne muscular dystrophy. Great. Thank you, Alex. As Alex mentioned, this is a program that's quickly marching towards clinic and one that's got us very excited. You can see here we're calling the trial Function-DMB, and I'll tell you a little bit more about it in the next few slides. So why are we developing this program, right?
It's really because there's a huge unmet need. Despite therapies that are currently approved or in development, there's a huge unmet need. You'll see a lot of Xs here, right? There's really no drug that's improving muscle function over time today, which is something really that patients need. These are boys that unfortunately are afflicted with this genetic disease at a very young age and become immobile and non-ambulatory over time and unfortunately succumb to muscle loss and heart or lung failure by the time they reach their 20s. So very important that we show muscle function over time and we have a durable effect. We also want a therapy that's broadly applicable to patients. Exon skipping therapies today are limited to very small subsets of patients, and hence, you can see we're designing PBGENE-DMD really to take benefit of all these key unmet need parameters in the market.
So what are we exactly doing? PBGENE-DMD is really the first and only approach that's going after a gene editing approach to really affect up to 60% of patients with DMD who have a mutation in this region called exons 45 to 55. You can see that in the blue box on the right. This is a large segment. As I mentioned, up to 60% of patients have mutations in this region, and what we're doing is by AAV, we're delivering two ARCUS nucleases that go into the muscle cell and excise that mutated region so the gene can then come back together, repair itself, and produce a functional dystrophin protein. That protein is absolutely essential for proper muscle function. It's almost a scaffolding that allows the muscle to keep its integrity, and we know this type of protein works.
There's actually patients that are known as Becker phenotype that when they have at least 5% or more expression of this functional protein that I mentioned, you can see on the right, they have a lifespan that they can live into their 60s or 70s. This is vastly different than what you see on the left with the typical DMD patient, as I mentioned, will succumb to death in their late teens or early 20s. Clinically, this is also very different. You can see the Becker patient on the right, what we call the Del 45-55 patient, can be asymptomatic or very mild symptoms, or they can have normal respiratory function, normal muscle strength, and these are patients that are living and walking around today. Vastly different than what you see on the left.
We’re very excited by this approach because we know if we can restore almost only as little as five% functional dystrophin, we can potentially get a patient to the phenotype on the right. Keep that five% number in mind because what we see in a preclinical study in the disease mouse model, which is the gold standard, is we’re able to restore functional dystrophin protein higher than that five%. You can see whether it’s the heart, the calf, or the quadriceps, all very important muscles for patients who have DMD, we’re increasing these dystrophin protein levels above that threshold, right? This is very compelling. Most importantly, we’re also seeing this increases over time, right? This is important as a proxy for a child who would obviously age over time.
So what we're doing about that is we've designed the Function-DMB Study, which is a phase one, two, three study design, which we hope to start in clinic early next year. This first part, we would do a phase one, two, which is a single dose level design, right? We would go in with our best and most efficacious dose there to really give these patients the best chance. The goal would be to enroll five to eight ambulatory patients. And once we treat up to 10 to 15 patients, we would look to move to pivotal. So this is a study that can work very quickly given the high unmet need and a clear regulatory pathway that's already dictated by the FDA. So this would be our goal here. I think one other thing that's important is we're keeping safety top of mind. These are boys and children.
We're going to make sure that we're keeping an aggressive immunomodulation regimen, that we're going to top world clinical sites. We really want to make sure we're giving the patients the best chance at efficacy, but keeping safety top of mind.
So let me close down. We're happy to take questions, Alex, from you or from the audience. But as noted, we have multiple data readouts coming for these programs, and 2026 is just going to be the continuation for the Hepatitis B trial. As you saw, we've already shown good data across three cohorts, but we're going to complete the third cohort, and we're also looking at additional cohorts for this. So we'll see data readouts in 2026. I would say that for the audience, how do you think about that?
There's a major European liver conference every year in the first half of the year, and there's a major U.S. conference for liver disease in the second half of the year towards the end of the year. So those are kind of good events and good opportunities for us to roll out new data. We'll see what data we have when those events come up, but I think that there's a number of readouts coming this year, sorry, in this coming year for Hepatitis B. For DMD, as Naresh said, we're running ahead with this Function-DMB trial, and we will begin enrolling patients in 2026 and expect our first data readout towards the end of 2026.
So if the data progresses, as we hope, this could be in a place to file a Biologics License Application or a BLA by the end of 2028, which will enable us to sell the drug commercially with approval of the BLA. As we mentioned before, we have financing from top-tier fundamental and long-term oriented investors to help fuel the development of these programs. And I think that we're well on our way to having successful data readouts in 2026 and beyond. So with that, let's open it up to questions.
Great. Well, thank you very much, Alex and Naresh. Let's start on the PBGENE-HBV program. I think you alluded to this in your remarks that patients are often on lifetime background treatments.
But I just kind of want to dwell on what is the standard of care for these patients and what's the closest that treatments have come to what you're doing and what's the difference? Because I think there's not many treatments that are demonstrating what you are, even at the earliest stages, the durable decline that might well become a cure at higher doses.
Yeah. So look, we see nucleoside analogs are the background therapy. Most patients who are treated in clinic are treated with those drugs. They're commercially available, well-established safety profiles. The challenge with the nucleoside analogs is that they don't really touch cccDNA. So as a result, you can see that your HBV DNA is under control, but your S antigen is still present, indicating that the liver is still producing viral particles. So other drugs are being developed simultaneously. There are CAM inhibitors.
They're being developed. Interferon has been tried before as well, and there are a number of different drugs all targeting this S antigen and seeing, "Hey, what if we can take it down to 99%? What if we can take it down to 99.9%? Does that change the cure rate?" and sadly, initially, it looks great, right? When you treat a patient and you get their S antigen down by 99.9% or a three log reduction, you start feeling pretty good. We got this under control, but in time, after you stop the drug and you stop the nucleoside analog therapy that's in the background, you see S antigen comes back up, and you might start with even 25%-30% of the patients getting to a place where they can stop the nukes initially, but within six months, that's usually back up to where it was.
So we only see 1%-3% of patients on nucleoside analogs getting to a functional cure, even with newer drugs like one being developed by GSK. It's a pretty substantial advance, but we're still getting less than 10% of the patients to a functional cure.
Yeah. Alex, if I can add to that, you're absolutely right. We are the only therapy that's targeting to eliminate that cccDNA, the root cause of that disease. And hence, we do feel very uniquely positioned there from a therapeutic approach.
Great context. Thank you. And we have a question from the audience. How do you think about finding strategic partners for the PBGENE-HBV program, and what stage might that occur?
Yeah. Great question. I think that with PBGENE-HBV, it's such a vast disease that is endemic in many parts of the world.
We definitely have the wherewithal to do phase one development for this program and also phase two. I think that that's certainly within our realm. But I think as we think about launching a bigger phase three trial or commercializing PBGENE-HBV, partnering would be really important because there are some partners that are in the hepatitis B space now with existing drugs that could make very good partners for us from a commercial standpoint. And really, our company is less than 100 people right now. So taking on a big disease like HBV from a commercial standpoint, probably more than we would envision doing. So we already have partner discussions that are ongoing for PBGENE-HBV, but I think it's common for investors as well as potential biopharma partners to say, "Hey, show me the next cut of the data. Show me the complete phase one data.
Show me the phase two data." And then we think that there's more interest in partnering as they see further evidence of these drugs being effective at reaching a cure. For DMD, it's a different story. This is a smaller population of patients who have this disease. They are generally treated in very specialized institutions who treat patients with Duchenne muscular dystrophy. And I think that we have the ability to take DMD all the way through BLA if we choose to, and even towards commercial. Now, it's such a well-known disease with an existing commercial opportunity that I think if we have successful data for DMD, we will also have opportunities to partner this, whether it's partnering individual markets, whether it's having a partner to help us develop it further and bear some of the cost of doing so.
But I think if these two programs, while they're very different, they're both hitting diseases with high unmet needs. And I think that if we can demonstrate that the gene editing approach works for these diseases, we'll have plenty of partners knocking on our door to take them forward.
Great context. And as we're coming up on time, maybe I'll just sort of zoom out and say, right, I think there's been a lot of progress that you've demonstrated. But for investors who are sort of, they're interested in the space, they believe in the transformative power of gene editing, they're not sure now is the right time. What would you say to them to encourage them to have a conversation or think about investing?
Yeah. I think if you look at Precision BioSciences, we have a unique tool that is proprietary to Precision BioSciences.
These are the first two programs that we're focused on. We're trying to be extremely focused with the capital that our investors have provided to us. We want to be exceptionally good stewards of that cash. So we're focused on these two programs right now. These each have opportunities to create value inflection points throughout 2026 and beyond. And I think that in addition to that, there's more opportunities beyond these programs we could pursue. But right now, we're being very disciplined and focused on these programs, and we're executing extremely well in both cases. Just want to make one point. One year ago, we dosed our first patient for Hepatitis B, and this year, we've already dosed nine patients, and there's other cohorts that are underway as well. And data readouts have already happened for PBGENE-DMD.
We just declared this to be a program in May of 2025, and we're already in a position to file the IND by the end of this year. So the company is executing, very focused, and there's more coming in the future.
Great. Well, thank you so much for sharing context on that question. And thank you both, Alex and Naresh, for sharing the presentation and taking Q&A with us. And lastly, thank everybody listening for tuning in with us as well. Great.
Thank you again, Alex, and to the audience, thanks for joining us. Happy to take any follow-up questions that you may have. Thank you.