Joining the PBGENE-HBV (ELIMINATE-B) Phase 1 trial - anyone else? Thoughts on off-target / cancer risks?

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Hello everyone,

I am a long-time follower of this community, and I wanted to share some big news. I have been accepted for the screening process of the Phase 1 ELIMINATE-B clinical trial (NCT06680232) for PBGENE-HBV by Precision BioSciences. My screening appointment is next week at the Matei Bals Institute in Bucharest, Romania.

I am feeling very optimistic and confident about this. I saw the recent late-breaking data presented at the EASL 2026 Congress a few weeks ago, where they showed actual human liver biopsy data proving a 1-log (10-fold) reduction in cccDNA transcripts after just two doses, and total pgRNA clearance in 100% of patients who had it at baseline. It feels incredible that we finally have a therapy that physically targets and destroys the cccDNA reservoir rather than just suppressing it.

Link to the latest data I read: https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-announces-new-and-late-breaking-pbgene-hbv/

Because this is a brand new in vivo gene-editing technology (using their ARCUS platform delivered via LNPs), I wanted to open a discussion here to ask for your thoughts.

Specifically, I would love to hear what the science-savvy members of this forum think about long-term safety. Is there any real, practical risk of off-target edits to human DNA that could potentially trigger mutations or cancer down the line? Precision BioSciences states that ARCUS is highly specific to the 22-base-pair HBV sequence and that the mRNA degrades quickly, but as a patient moving forward with this, I want to be as informed as possible.

Is anyone else here currently enrolled or looking into the ELIMINATE-B trial? I would love to connect and hear your perspectives!

Thank you all for being such a supportive community.

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Hi @learnandshare ! That’s super exciting that you’ve been given the opportunity to participate in this trial! I’m not a scientist (just another patient), but I understand your concern about the risk of off-target gene edits. I personally would not be comfortable with participating in a first-in-human trial, but I acknowledge that the decision of whether or not to participate is a personal decision. Everyone has a different level of risk tolerance. I’m in a later-stage trial, and I know other patients who think even that is too risky for them, and they would rather stay on tenofovir/entecavir.

I’m also curious to hear what the experts have to say about this.

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Hi @et5656,

Thank you so much for your reply and for sharing your perspective! You are completely right, everyone has a different risk tolerance, especially when it comes to a first-in-human gene-editing trial.

Interestingly, the Bepirovirsen hits very close to home for me. I was actually a participant in that GSK Bepirovirsen trial back in 2023!

To share a bit of my journey: before that treatment, my HBsAg quantity was around 7,000 IU/mL. I was in the full-dose cohort, receiving 2 shots weekly for the first part, and then after 3 months, my dose was reduced to 1 real shot and 1 placebo shot per week. While I was on Bepirovirsen, my HBsAg successfully dropped all the way to 0! Unfortunately, about a year after finishing the treatment, I experienced a rebound, and my surface antigen is now sitting around 1,000 to 2,000 IU/mL. However, thanks to that trial, I completely lost my HBeAg, which was a huge win. I was, and currently still am, taking daily TAF (Vemlidy) as well.

In terms of side effects, I found Bepirovirsen super easy to handle. The only major thing you really have to watch out for with that specific drug class is keeping an extra close eye on your kidney function to prevent any potential damage.

Because Bepirovirsen ultimately left the cccDNA intact in my liver, causing that rebound, that is exactly why I am looking toward PBGENE-HBV now. Since it aims to permanently destroy the viral reservoir at the DNA level, it feels like the logical next step for my journey, even if it comes with the unique anxieties of a Phase 1 gene editor.

I totally understand why staying on standard, safe antivirals like Tenofovir or Entecavir is the right choice for many, but I am hopeful this next step might finally lead to a permanent fix. Still very curious to see if any science experts here can weigh in on the structural risks of the ARCUS platform!

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Hi @learnandshare,
I have so much respect for anyone who volunteers to participate in clinical trials and public health/social research. Hats off to you. I agree with @et5656

However, the idea of programming a substance that can edit some parts of my genes to treat my viral infection does not sit well with me. Could the programmed tool miss its target and edit the wrong section of my genes? That can be possible, and that is a risk I don’t want to take. Personally, I don’t feel the need, nor do I feel desperate to get cured. Whenever it happens, I will take it. For me, some risks are just not worth taking.

Kudos and more respect to you. Without knowing exactly what will happen when off-target gene editing occurs, or the harm and long-term consequences, it makes this risky. And I am not willing to volunteer for it.

I wish you all the best as you take part in this clinical trial. Bansah1

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That’s really cool that you were in the bepirovirsen trial. I’m sorry to hear your surface antigen came back, and I’m actually a bit surprised that it would come back a year after stopping treatment. The data that I’ve seen seem to show that most people who rebound have their surface antigen come back within 1-6 months. That must have been so disappointing. I’m glad to see that you haven’t given up. I also think that HBsAg 1,000 puts you in a better position for new treatments to potentially work for you, compared to where you started at 7,000.

Best of luck with everything! Let us know if you ultimately decide to participate.

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Hope all goes well!!! It will go very well! sanatate Criprian

thank you for the very good news

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Hi @learnandshare,

Great questions and indeed agree with the others about anyone who joins a trial to further our knowledge in developing better ways of addressing hepatitis B.

It is unclear what the off-target edits could be, though I believe they could not find strong signals of this in the petri dish. Other aspects may be at play though, which have previously been discussed in another thread: Precision BioSciences Announces Initial Safety and Antiviral Activity. Hope the points here help you in contextualising the risk/benefit.

Cheers,

Thomas

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Hello everyone,

I wanted to give you all an update regarding my upcoming screening appointment at the Matei Balș Institute for the PBGENE-HBV trial. After a lot of deep reflection, research, and soul-searching over the last few days, I have decided to back off and cancel my screening.

To be completely honest, I just wasn’t convinced enough to fully commit to joining a Phase 1 trial. I also realized it wouldn’t be ethical for me to go through the screening process, consuming valuable trial resources and clinic time, knowing deep down that I would likely drop out later. I’d rather leave that spot open for someone who is 100% ready to move forward.

Right now, I am still looking very closely at the two gene therapies (PBGENE-HBV and TUNE-401). The data and the science behind them sound incredibly promising, and a part of me is upset with myself for letting the fear of theoretical dangers get the best of me. But yeah… to be transparent, I just don’t have enough courage to take that leap into Phase 1 right now.

I’m going to keep following the progress of these therapies closely from the sidelines. Thank you all again for being such a supportive community and letting me think out loud here.

P.S. Another curiosity that puzzles me is how they manage to harvest and recruit people for this. The inclusion criteria require patients with already well-controlled Hep B, meaning these are people who have a stable, functioning baseline and a lot to lose if something goes completely wrong. Yet, there are people out there who genuinely have the courage to step up, and PBGENE-HBV already has patients who have successfully joined them. It’s a fascinating dynamic that I still can’t quite wrap my head around.

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Why did gene editing failed to eliminate hepatitis b

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Well done :+1: happy for you and thank you for your generosity to offer to take part and paving the way for the rest of us.

keep us updated. How long will it take?

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Thank you for bringing attention to trial like this. Keeps hope alive! The fact that you even considered to participate already speaks volumes.

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@learnandshare Thank you for letting us know about PBGENE-HBV the first gene-editing therapy designed to treat chronic hepatitis B by directly targeting HBV cccDNA and integrated HBV DNA.. This is great news and I wonder why did you gave up participanting in the trial?!. A lot of us dream of such opportunities.

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