Hello, everyone, and thank you for joining H.C. Wainwright's 28th Annual Global Investment Conference, held on September 14 to 16, 2026. My name is Patrick Trucchio. I am a Senior Healthcare Analyst at H.C. Wainwright. It is my pleasure to introduce our next speakers from Precision BioSciences. We have CSO, Cassie Gorsuch, and CFO, Naresh Tanna. Precision is a clinical-stage gene-editing company that is using its novel proprietary ARCUS platform to develop in vivo gene editing therapies for diseases with high unmet need. The whole-genome pipeline spans PBGENE-HBV, which in phase I ELIMINATE-B trial, as potential curative treatment for chronic hepatitis B and PBGENE-DMD, which recently began dosing in the phase I/II FUNCTION-DMD trial in Duchenne muscular dystrophy. Welcome to the panel here, and thank you for joining us again.
Maybe for those who are less familiar with the story, if you can give us the background on Precision's platform, the technology, and the science that underpins the pipeline.
Sure. Thank you very much, Patrick, for having us, and thank you all for joining us. It is really a pleasure to be here. So, as Patrick said, Precision is a clinical-stage gene-editing company, so the common thread across all of our programs is our technology, which we call ARCUS nucleases. They are a very unique platform of gene-editing nucleases that we developed. We design them wholly in-house. We own them. We own all the IP around them. They have a couple unique features that we think make them really excellent gene editors for therapeutic application. The differentiators, as we call them, come down to three unique features: the cut, the size, and the simplicity of ARCUS nucleases.
The cut allows us to take advantage of homology-directed repair for gene insertion, and that type of edit is being utilized in the context of an Ornithine transcarbamylase deficiency program in the hands of our partner, iECURE, really utilizing that overhang cut, that unique cut that ARCUS nucleases make to insert a healthy copy of the OTC gene. The size is really the second differentiator. ARCUS nucleases are very small, much smaller than your typical Cas9 protein in CRISPR-based systems, and this is really an advantage when it comes to delivery. Finally, simplicity, meaning it is a single component editor. One protein binds DNA, cuts DNA, versus multiple components needed in CRISPR-based systems, a guide RNA, a nuclease, potentially a base editor on top of the Cas protein.
We really think the simplicity, the elegance of this system really provides a lot of flexibility in terms of how we utilize this enzyme therapeutically. Our approach is to take advantage of those unique features of our platform and employ them in therapeutic areas where the differentiators matter, and that is being used today in the context of hepatitis B and Duchenne muscular dystrophy.
Great. Terrific. Moving on to hepatitis B, PBGENE-HBV is the only clinical program that aims to eliminate cccDNA, and unlike functional cure approaches that tend to work best in patients with lower baseline S antigen levels, doesn't appear to depend on baseline here. Walk us through why cccDNA is the best target, why editing the source gets you out of that baseline dependency that many of these other mechanisms have faced.
Sure. PBGENE-HBV is the first and only clinical stage therapy that is designed to directly target cccDNA and eliminate it. This is a completely differentiated approach from those that have been tried before in the context of chronic Hep B. Because of its unique mechanism, the way in which you think about the patient population is a little bit different. In the context of S antigen-targeting therapies, we have seen that their efficacy is better in the context of patients who have lower baseline S antigen. We're not targeting S antigen, we're targeting cccDNA. If you take a step back and you think about the virology of hepatitis B, cccDNA is the source of new infectious particles, the only source of new infectious particles. It has been the ideal therapeutic target for decades. We've never had a tool that could do it.
From a virology perspective, it's always made sense to go after cccDNA more so than S antigen. We now have a tool that can actually do that. What we've seen in our ELIMINATE-B program is the ability of PBGENE-HBV to directly target and eliminate cccDNA, driving durable pgRNA loss, driving durable S antigen reductions, and that effect has been independent of various factors like baseline S antigen levels.
The biopsy data has shown a one-log reduction in cccDNA-derived transcripts after two doses and cumulative editing with a third. Can you talk us through how we get from what we've seen so far to a functional cure?
Yeah. Our goal with PBGENE-HBV is really a viral cure. What we mean by that is eradication of the viral reservoir in the liver, cccDNA. If you can eliminate cccDNA in the liver, you can have long-term viral cure, meaning beyond even six months of the regulatory endpoint. Patients can achieve viral suppression cure forever. What we've seen in our biopsy data, this is really important proof of mechanism, proof that PBGENE-HBV can be delivered to the cells in the liver, that PBGENE-HBV can directly target cccDNA, and that you get loss of cccDNA-derived transcripts. Really important body of evidence demonstrating the mechanism of the drug works the way it was intended to work. What we're encouraged by in the biopsy data is that mechanism. Building on the biopsy data is really the circulating pgRNA data.
Here, we can look at how much pgRNA is present in patients, and this gives us a little bit of a broader scope to look at. We have a couple patients who've received biopsies, but we can monitor pgRNA levels in every one. What we've seen, pgRNA, as a reminder, is a biomarker. It only comes from cccDNA, and it is the precursor to new infectious particles. It's the link between what's happening in the liver and new infectious particles in the blood. In 100% of patients who had detectable pgRNA at baseline, all of them have gone durably undetectable. Between the pgRNA blood biomarker data and the liver biopsy data, it's a really strong body of evidence that PBGENE-HBV mechanism is working at eliminating cccDNA and gives us optimism as we think about long-term viral cure.
Right. That's interesting. The pre-genomic RNA is your serum biomarker. Could you walk us through why pgRNA is the right surrogate endpoint for cccDNA elimination? I think there's two assays that are in use in the field, Abbott and Roche maybe.
Which are you using and why?
Of course. As I mentioned, pgRNA is the intermediate between cccDNA in the liver and HBV DNA in the blood. In patients who are on nucleoside analogues, they have undetectable HBV DNA. They're virally suppressed. Nukes work downstream of pgRNA, and so pregenomic RNA or pgRNA is still detectable in patients who are on Nukes, and it is an indicator of what's going on in the liver. It's a direct biomarker for cccDNA, only comes from cccDNA. It is specific to that target, which is our target. That's why it's really a great biomarker for us is our drug is designed at cccDNA elimination. pgRNA reads out what's going on on cccDNA, and it can be detectable in patients who are on Nukes, who are HBV DNA suppressed. There are two assays. They both have the exact same limit of quantitation. It's 10 copies per milliliter.
From a sensitivity perspective, they are equivalent. We're using the Roche assay. We selected that because that assay is specific to cccDNA, so it only picks up transcripts that come from cccDNA. Our goal is to eliminate cccDNA. We need to be able to measure that effect specifically. That's why we chose the Roche assay, using that as an indicator for cccDNA activity.
Can you talk about what you've seen from a safety profile and tolerability perspective and what you've seen in terms of repeat dosing?
Yeah. One of the unique things about the ELIMINATE-B study is that we are one of the first and only gene-editing clinical studies designed with prospective repeat administrations. That means our patients are designed to receive multiple administrations of PBGENE-HBV as part of their planned treatment course. With that, one of the things that we've learned as we've dose escalated is that there is an inflammatory response that can occur specifically on repeat doses of lipid nanoparticle. We've seen that in our study. Those look like hypotension observed on the day of dosing, as well as transaminase elevations. It's important to note that the transaminase elevations have been associated with lipid nanoparticle dosing. They've been not associated with any changes in bilirubin, no Hy's law in the study. Generally, the safety profile of the drug has been pretty good.
Repeat doses have been more of a challenge. One of the things that we implemented earlier this year is a new infusion protocol. Part of the goal of this infusion protocol was to mitigate those inflammatory responses we observed on dosing. We characterized really the etiology of it, increased cytokine activation, increased complement activation. By altering our infusion protocol, really simple mitigations, extending the infusion duration, increasing a dose of steroids they were already getting, and giving prophylactic saline. By doing that, we've improved the safety profile to the point where no hypotension has been observed on study, and no LNP-related transaminase effects have been observed. Really, those mitigations have been essential in improving the overall tolerability profile. We're continuing to dose patients under that new infusion protocol.
Can you tell us what the plan is for Part 2 expansion ELIMINATE-B, and how will you choose a dose schedule, and when could we expect to see patients begin taken off of nucleoside analogues or the standard of care drugs?
Our goal so far has really been through dose optimization to identify our go-forward dose. We've gained a lot of experience across 16 patients dosed, 38 administrations to date in that cohort of patients of data we released back in May. What we have found through that dose optimization is really where our tolerable sweet spot is and where we're seeing efficacy. I mentioned the pgRNA loss patients earlier. What was really fascinating about looking at our dataset comprehensively is we saw detectable pgRNA go undetectable in patients in four different dosing cohorts. That means we have a pretty wide option when we think about a therapeutically relevant dose. Where we are right now is continuing to dose patients at 0.1 mg per kg, 0.65 mg per kg, two of our dosing cohorts that were already opened.
We're expanding those dosing cohorts, continuing to build the experience at those dose levels with the goal of continuing to follow pgRNA as the marker for evidence of activity in the liver, of viral elimination in the liver. We're continuing to follow the patients that we released data back in May, continuing to enroll additional patients in those dosing cohorts with the goal of selecting a go-forward dose to expand into expansion phase II studies. That's really the goal, pgRNA is the guiding biomarker and continuing to build the experience to select that dose and move into expansion.
Have you said when that next update is expected in ELIMINATE-B?
Yeah. We anticipate data before the end of the year, another data update for this study. As we're typically pretty active around scientific conferences. We've got AASLD coming up in November. That's a conference that is always a good hepatitis B field update, one that we like to participate in as well. More to come this year on ELIMINATE-B.
Right. Terrific. Maybe just moving on to Duchenne. The first patient was recently dosed in DMD study. Where does that program stand? Beyond safety, is there anything else we could expect from the initial data expected later this year?
Yeah, I can give a quick update there. So yeah, great news. We were able to provide an update, and earlier in August, we did dose the first patient. This dosing took place at Arkansas Children's Hospital, Dr. Veerapaneni and Dr. Panda, who is the PI there. Terrific leader in the field and has great experience working with AAV-based therapies. Then we've also announced that we activated our second site at Washington University in St. Louis, so that's another great site. We'll provide more updates as that program goes through. We did commit to providing a safety data update this year, initial safety data. So you can expect that by the end of the year as well.
So when do you expect to get the first look at dystrophin expression, and what level of near full-length dystrophin would you consider clinically meaningful?
Yeah. So again, at the end of this year, just a quick step back here. The protocol requires about an eight-week interval between dosing patients, so patient one, two, and three. So we'll look to have a safety update by the end of the year. Biopsy data will shortly follow with functional data through next year. So Cassie, maybe give an update a little bit on the biopsy and the near full.
Yeah, of course. So the way the study's designed is patients are undergoing muscle biopsies pre-treatment, three months, and 12 months. We decided to do two post-treatment biopsies, really because in our preclinical data, it was very exciting to see dystrophin protein expression increase over time. We think that's an effect of both satellite cell editing and accumulation of a very stable near full-length dystrophin protein. So we'll continue to collect biopsy data, as Naresh mentioned, as we enroll and dose more patients on study. That's probably a 2027 type of data set for initial look at biopsy data. Patrick, to your question of how much dystrophin do you need to see in those biopsies?
I think it's important to keep in mind our approach is to restore at the DNA level a near full-length dystrophin protein, in contrast to micro-dystrophin approaches, which are very truncated versions of the dystrophin protein. We expect that as little as about 5% of this near full-length dystrophin protein could be therapeutically meaningful based on natural history studies. And of course, pre-clinically, we demonstrated far above that 20%- 25% dystrophin protein. Very excited to see how that translates now that we are on our way in clinical dosing.
If I could add, we did coin the clinical trial to FUNCTION-DMD for a reason, right? We want to make sure the biomarker is linked to function. That's ultimately what matters for these children and something that we're really committed to.
Partially I've answered this, but want to maybe ask a little bit differently with the PBGENE-DMD excise exons 45 through 55, that addressed roughly 60% of DMD patients. Could you walk us through why this is a differentiated approach and how it compares to those micro-dystrophin and exon skipping strategies?
Yeah. It's interesting because in my mind, PBGENE-DMD sort of sits between a micro-dystrophin and an exon skipper, but it is its own thing. It is a first-in-class gene editor designed to excise exons 45 to 55, so applicable for up to 60% of patients who have mutations in that hotspot region. The way it's similar to an exon skipper is that we are delivering, or we are resulting in a near full-length dystrophin protein by altering the genetics within that patient. Exon skippers skip an exon resulting in a near full-length dystrophin. We're removing that region of exons resulting in a near full-length dystrophin protein. And that's really, I think, helps kind of set the stage for what's the expectation around dystrophin protein expression.
We've seen in the context of exon skippers, even 2.5% of dystrophin in the Dyne study being clinically meaningful for these kids. I think that's how I would compare to an exon skipper. However, it's a one-time treatment with ours. Exon skippers have to be repeat administered weekly. This is a one-time administration that corrects at the DNA level, resulting in this near full-length dystrophin.
Right.
As it compares to micro dystrophins, the commonality is that we utilize AAV for delivery, but that's really where the similarities stop. The micro dystrophins are much smaller dystrophin protein. They're synthetic, meaning they don't occur in nature. To be determined how well that dystrophin protein functions in the context of human muscle. With our dystrophin protein, that protein occurs in nature in a subset of people who have Becker muscular dystrophy and are phenotypically very favorable. We know that the protein that we make works in humans because it already occurs in humans. I think it's a really unique approach, very differentiated, can leverage learnings from both of the different classes of dystrophin approaches or micro dystrophin approaches, but really offers, we think, meaningful differentiators.
Right. The DMD gene therapy field's had some safety setbacks. I'm wondering how do your AAV and dosing strategies differ, and how are later stage programs approaching approval informing your regulatory strategy?
Yeah, great question. I mentioned that we utilize AAV for delivery. That means we can leverage learnings from the micro dystrophin studies for AAV class effects. Dose selection is really important when you think about AAV related class effects. Our dose is 1 x 10^14 viral genomes per kilogram. That's on the lower end of all micro dystrophin. You see REGENXBIO up to 2E14 vg/kg. Even ELEVIDYS is dosed 30% higher than that. Dose selection is really important for overall tolerability, but manufacturing, I think, can't be understated. We have up to 90% full capsid ratio, meaning very few empty capsids come along for the ride when we deliver our dose.
We know historical programs can have up to 50% empty capsids, meaning not almost, twice the capsid dose when you think about the empty capsids that come along. We know that that can't generate any efficacy. It can only generate toxicity.
Right.
Manufacturing is extremely important. We're really proud of the CMC team at Precision that developed our manufacturing process. I forgot the second part of your question. I'm sorry.
I think just how those late-stage programs-
Oh, yes.
approaching approval are informing your strategy.
Yeah, I forgot about that.
Yeah, look, I think what's also important here is even as we're thinking about our immune modulation regimen, right? I think we're taking a safety-first approach here. I think that's one big difference that I think we're going to make sure we employ forward here.
Now you have the Orphan Drug and Fast Track designation, plus eligibility for Rare Pediatric Disease Priority Review Voucher. So, maybe you can talk about how that will shape your regulatory plan specifically.
Sure. There's a lot of designations in this space, and what that clearly articulates is there's a huge unmet need in this space. Families and children are waiting, right? So what that does is it opens up the opportunity to engage with the FDA often and frequent and make sure we're having that dialogue, to make sure we're safely and effectively taking this program forward as quickly as possible. We'll make sure we leverage all of those opportunities as they surface.
Can you discuss the cash level and the runway, which I think takes you through 2028?
Sure.
Does that get us through some of these key catalysts?
Yes, absolutely. So at the end of Q2, we reported a little over $112 million in cash and cash equivalents. That does get us through 2028, as you mentioned. Really lets us realize the clinical catalyst from both programs, both from the expansion phase of both PBGENE-HBV as well as PBGENE-DMD. So we're in a pretty good place right now, and we feel really good executing through next year.
And just, iECURE's OTC program and azer-cel, these are both advancing on Precision originated assets. How much platform validation do you take from those, and do you expect any meaningful near-term milestones?
Yeah. So, those are great programs that speak to both our scientific capabilities, both from, as Cassie alluded to, from a gene insertion perspective, but also all the great work we did previously in CAR T. So we do get platform validation from it, but of course, those programs run through our partners. All milestones that have been realized in our runway, so those are all just upsides. But typically, you would expect development and sales-based types of milestones. Typical for these types of deals.
Right. And just as a final question, what do you think investors are missing about the Precision story?
I think Precision has evolved over the years, and where we are today is we're a clinical stage gene editing company, two clinical programs. And I think sometimes that gets lost in who we've been in the past and who we are today. But we've got near-term catalysts in both HBV and DMD and really differentiated programs. DMD is an AAV-based therapy in a rare disease population, super motivated population, clear regulatory path, potentially accelerated approval options. I think it's its own unique program. Hepatitis B, on the other hand, is this huge patient population using a lipid nanoparticle to the liver. Both utilize key features of the ARCUS platform in really unique ways, but they're quite different programs.
What that means for us is that we think we've got two equally opportunistic shots on goal, two abilities to deliver clinically meaningful data that can be catalyst drivers and two really different types of approaches. I think that's really a unique situation for a gene editing company.
Right. Terrific. It's a big year for Precision. So Cassie and Naresh, thank you so much for being with us. Thanks for everyone for attending the conference. Have a great rest of your day and conference.
Thank you.
Thank you guys.