Precision BioSciences, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

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.

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.

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.

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 pre-genomic 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 mil.