PBGENE-HBV shows early signs of targeting hepatitis B viral DNA
Phase 1 data showed reductions in key viral markers, company says
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PBGENE-HBV, Precision Biosciences’ experimental gene-editing therapy for chronic hepatitis B, showed early evidence of eliminating and inactivating hepatitis B viral DNA as designed, while reducing key viral markers, in an ongoing clinical trial.
That’s according to new analyses of data from the ongoing Phase 1 ELIMINATE-B clinical trial (NCT06680232). These were presented at the European Association for the Study of the Liver Congress 2026, being held May 27-30 in Barcelona, Spain, and online, and shared in a recent company webcast.
These data “represent a transformational step forward in the hepatitis B field,” as they suggest that “hepatitis B may be approaching a turning point where chronic care moves from lifelong suppression of an active virus toward a finite, biomarker-guided complete viral cure,” Michael Amoroso, Precision Biosciences’ president and CEO, said in a company press release. “There has never been a treatment that could directly target and eliminate the root source of hepatitis B viral replication and now there is.”
How hepatitis B persists in the liver
The hepatitis B virus (HBV) infects the liver and triggers liver inflammation, known as hepatitis. In some people, especially those infected at an early age, the virus can cause a chronic infection that raises the risk of life-threatening liver complications.
When HBV infects the liver, it delivers its DNA into liver cells. The viral DNA forms structures, called covalently closed circular DNA (cccDNA), which can act as a template for producing more virus and sustaining the infection.
Available antiviral medications can reduce the amount of circulating HBV, but they generally do not eliminate the cccDNA that serves as a reservoir for ongoing infection.
PBGENE-HBV is a gene-editing treatment that aims to destroy cccDNA, as well as viral DNA that has been integrated into the host cell’s DNA. The goal is to target the infection at its source and block the production of new viral particles. PBGENE-HBV is given by infusion into the bloodstream.
“The elimination mechanism of action for PBGENE-HBV directly aligns with the current [U.S. Food and Drug Administration] guidance that eradication of HBV DNA is the optimal [therapeutic goal] for approval,” Amoroso said.
Trial is testing different dosing approaches
The first part of the ELIMINATE-B study is testing different dose levels, dosing intervals, and numbers of administrations of PBGENE-HBV in adults with chronic hepatitis B. An optimal regimen will be evaluated in a larger number of patients in the study’s second, expansion part. The study is actively recruiting up to 45 participants at sites in the U.S., New Zealand, Hong Kong, and Moldova.
So far, 38 doses have been administered to 16 participants in five dose groups. PBGENE-HBV has shown what Precision described as a manageable safety profile, with no dose-limiting toxicities reported.
There were some cases of transient, reversible grade 3 or higher elevations in ALT and AST, enzymes used as markers of liver injury, but these did not cause symptoms. There were also cases of grade 3 low blood pressure, or hypotension, which can be triggered by lipid nanoparticles, the tiny fat-based particles PBGENE-HBV uses to deliver its gene-editing machinery to liver cells.
To minimize the risk of serious adverse events, the trial’s protocol was adjusted to include slower infusion rates and higher doses of corticosteroids, which are powerful anti-inflammatory medications. Since then, Precision said there have been no further grade 3 or higher cases of hypotension or lipid nanoparticle-related ALT and AST elevations.
Liver biopsy data showed that cccDNA-derived transcripts were reduced tenfold following two infusions of PBGENE-HBV at a dose of 0.4 mg/kg. And the less than 1% of cccDNA that remained also showed signs of further editing via indels, or small insertions or deletions that are introduced into the cccDNA so it cannot be used to make new virus.
“The quest for a highly effective treatment for hepatitis B has been frustrating and perplexing, for both patients and clinicians, because we have never had a treatment that directly targets the root cause of viral DNA replication,” said Man Fung Yuen, MD, PhD, an ELIMINATE-B investigator at the University of Hong Kong. “This exciting biopsy data from the ELIMINATE-B trial represents a first for the field.”
Blood tests supported biopsy findings
In addition, all six patients who had detectable blood levels of pgRNA before treatment had undetectable pgRNA after PBGENE-HBV. pgRNA, or pregenomic RNA, is produced from cccDNA and is needed for HBV DNA viral production. Furthermore, “loss of pgRNA in blood corresponded to undetectable pgRNA in post–PBGENE-HBV-treated liver biopsy,” the company wrote in its webcast.
The findings establish pgRNA “as the appropriate clinical biomarker for assessing PBGENE-HBV effect on cccDNA in the liver,” the release stated.
All 15 evaluable patients also showed pronounced reductions in blood levels of HBsAg, a key HBV surface protein and marker of infection.
Additional participants will be treated in the trial’s first part to further strengthen the dataset, which will help select the optimal dosing regimen for the trial’s second part. Precision is also working to define protocols for patients to be allowed to stop current antiviral medications. If patients can stop those medications without HBV recurrence, that would help researchers test whether PBGENE-HBV can lead to a viral or functional cure.
“Now that we have evidence that PBGENE-HBV is eliminating cccDNA as designed and has a clear therapeutic window, I look forward to finishing the dose and schedule optimization, stopping [antiviral] treatment and testing for viral cure,” Fung Yuen said.
Precision said it expects to provide further updates from the trial before year’s end.
