Precision BioSciences KOL event

Please go ahead. Good morning, everyone, and welcome to the Precision BioSciences AASLD 2026 Investor Update, live from the liver meeting in Denver, Colorado.

Thank you all for joining today. Next slide, please. During this morning's call, we may make forward-looking statements. I would invite you to review our 10-Q, which was published last week on November 3rd. The 10-Q includes risk factors that could cause actual results to differ from any forward-looking statements made today. Next slide, please. I am joined today by Michael Amoroso, President and Chief Executive Officer, and Dr. Cassie Gorsuch, our Chief Scientific Officer. We are also honored to be joined by two leading hepatology infectious disease experts.

Next slide, please. Dr. Mark Sulkowski is Professor of Medicine and Director of the Division of Infectious Diseases at Johns Hopkins Bayview Medical Center.

Dr. Man-Fung Yuen is Chair Professor in the Division of Gastroenterology and Hepatology at the University of Hong Kong. All of today's speakers will be available during the Q&A portion. Without further ado, I will hand the call over to Michael.

Thank you, Naresh. Welcome to everybody, and welcome to our investor community. Thank you for being with us. We are very excited on the back of presenting our late-breaking oral presentation yesterday on Sunday. Today, I am joined by my esteemed colleagues. We will walk you through that data, what that data means, and what that looks like for patients and for Precision BioSciences going forward. Next slide, please. Viral cure. This will be a very important concept that we discuss throughout the day, the eradication and elimination with PBGENE-HBV of cccDNA, undetectable HBV DNA off of therapy. Next slide, please. The problem for the last 50-plus years in development of chronic hepatitis B is we have never been able to get at the replicating viral source, cccDNA, until now.

PBGENE-HBV is a lipid nanoparticle gene editing delivery system that targets the cccDNA, the viral source of replication and infectious particles, and eliminates that source. As you can see on your right-hand side, we have had breakthroughs through decades of drug development, but most and all drug development has truly focused on downstream RNA transcripts and proteins coming from the virus. The hope was that we would suppress these transcripts and proteins and allow the patient's immune system to eradicate the cccDNA on its own. Unfortunately, to date, that has been a long journey and an unattainable task. We hope now with the advent of a direct targeting cccDNA elimination agent like PBGENE-HBV, we can change the outcomes for patients going forward permanently. Next slide. When we last met, the end of May at EASL, Precision BioSciences and the team came out and told you phase I data, the first gene editor, the first targeting of cccDNA and elimination ever in chronic hepatitis B.

We told you about 100% treatment effect in 16 patients across 38 administrations. We told you about the advent of a key blood biomarker for intervening with therapy, for knowing when to stop your nucleoside analogue. We talked about the advent of the pgRNA blood biomarker. In six patients, everyone treated with PBGENE-HBV had 100% undetectable pgRNA post-treatment. We told you we were going to watch the durability. Permanence is critical for elimination. Next, we showed you the first evidence of cccDNA direct targeting and elimination by PBGENE-HBV through the gold standard molecular biopsies, tissue of the liver, log reductions of cccDNA, not viral proteins downstream.

Most importantly, we started to characterize the safety of PBGENE-HBV in patients with chronic hepatitis B across four different dose levels, 0.2, 0.4, 0.65, and 0.8, with a focus going forward on the 0.4 and 0.65 doses. The team told you we wanted to enroll more patients with the enriched blood biomarker of pgRNA. We wanted to get more experience in the 0.4 and 0.65 dose. We must see the critical durability of over six months after PBGENE-HBV. Remember, pgRNA is the proxy for HBV DNA, the FDA endpoint off therapy. We wanted to further look at our safety characterization and profile of these two different dose levels. I am very proud of this team, and I am proud today to be able to tell you Precision BioSciences has done just that.

25 patients, 59 administrations, with a go-forward plan to move success in phase I to move to phase II at a 0.4 milligram per kilogram dose. Next slide. The data behind the late-breaking oral presentation that MF Yuen had presented yesterday, and a wonderful job, Matt. Thank you very much. First, reproducible liver biopsies. We showed you the first proof at EASL, and now we show you another patient at 0.4 mg per kg, the go-forward dose, with one and a half log reduction, 35-fold decrease in cccDNA at the liver. Next, the pgRNA-enriched population, those with the blood biomarker indicative of cccDNA in the liver. pgRNA, now 11 patients. Green is good, 100% undetectable. When you go undetectable with pgRNA after PBGENE-HBV treatment, patients stay undetectable. Not one patient has come back. They stay green, as you can see in the swimmer's plot. Next, the toughest-to-treat population. Physicians asked, "How would PBGENE do when the disease burden is greatest?" The 20% of chronic hepatitis B, the early infected, HBeAg positive.

This is a population with two to three logs more wild-type cccDNA in their liver. PBGENE-HBV is potent at 0.4 milligram per kilogram, the go-forward dose, and with one dose, was able to eradicate 99% of pgRNA, starting in a patient with 5,600 copies per milliliter. After the second dose, as you can see by your purple arrow, completely undetectable, and the patient has stayed undetectable. So whether you have the blood biomarker or whether you don't, if you have lower disease or in the highest disease burden, PBGENE-HBV continues to have a treatment effect in all patients.

Heterogeneous disease, but a homogeneous impact, and is continuing to eliminate pgRNA, the HBV DNA biomarker, when on a nucleoside analog in all patients. Next, Mark, I'd love to get into a little bit, Mark Sulkowski. Dr. Sulkowski, can you please tell us a little what you think this data could mean for the field? What are you hearing amongst your peers in Denver?

Well, thanks, Michael. I'd like to just take a step back on this particular slide of the antigen-positive and think about people with hepatitis B, generally infected at birth, initially very high levels of infection. When we talk about an HBeAg-positive patient, we're talking about a tremendous amount of cccDNA in the liver, and the biomarkers, as depicted here, pgRNA, is quite high. The natural history and treatment with NUCs over decades, you may see reductions in this biomarker as they shift into the antigen-negative state. I think for me, one of the most remarkable things here is that with a single dose of PBGENE, that occurred in days and weeks, not decades. I think there's been a lot of excitement at the liver meeting about advances in HBV therapeutics, and PBGENE is part of that discussion.

Thank you, Mark. Look forward to continuing our conversation today. Next, please. As discussed, today marks an important chapter for patients, for Precision BioSciences, and the team, and we want to thank all the patients and our investigators. Today, we declare success in phase I, and the company is moving forward rapidly to phase II, where we will test for cure rates off drug therapy. I am going to turn it over to Cassie to tell you the evidence behind the late-breaking oral presentation and why we have such confidence to move forward into testing cures in the phase II setting.