Precision Biosciences has received clearance from regulators in the Eastern European country of Moldova to begin a human trial of a gene editor for chronic hepatitis B, marking the first such test in the world.
Precision’s ultimate goal is to use gene editing to functionally cure chronic hepatitis B, which to date is treatable but not curable. It’s a herculean task — a cure thus far has been elusive because the hepatitis B virus hides in a stable form in liver cells where it continues to make more copies of itself.
“This is a disease indication where new therapies have really had a challenge, and patients have really been looking for better treatment options for a really long time,” Precision CEO Michael Amoroso said.
People with chronic HBV can receive daily antiviral pills and interferon injections to treat the disease. Functional cure rates are around 2% on the antiviral pills alone and around 10% when combined with the injections but with significant side effects.
The company’s Phase 1 trial will recruit from Moldova and up to four other countries. Amoroso declined to name those countries in an interview ahead of the announcement, though he confirmed Precision is pursuing an IND in the US.
Precision uses its own gene editing platform it calls ARCUS, which was developed by North Carolina scientists who founded the company in 2006. Instead of CRISPR/Cas9, ARCUS uses an editing enzyme derived from algae.
For chronic hepatitis B, Precision calls its experimental therapy PBGENE-HBV. The gene editor is delivered via a fatty acid envelope called a lipid nanoparticle, which accumulates in the liver. The gene editor is targeted to a sequence in HBV DNA that codes for the virus’ polymerase, which is an enzyme that helps make more copies of viral DNA.
In doing so, Precision hopes gene editing can eliminate two forms of the hepatitis B viral DNA in liver cells that other approaches can’t get to: covalently closed circular DNA, or cccDNA, as well as HBV DNA that has integrated into the host DNA. cccDNA is a feature of certain viruses including HBV where its genetic code makes a stable ring inside the cell, and it also makes the virus very hard to cure.
“The factory that makes replicating virus is that cccDNA,” Amoroso said. “So we’re not looking to cure symptoms, we’re looking to go at the root cause.”
In May, Excision BioTherapeutics reported that its attempt to gene edit HIV failed. Like Precision, Excision’s goal is to use gene editing to excise hidden viruses from cells. However, there are some key differences — including that HIV is found in cells beyond the liver and Excision used viral envelopes called AAVs to try to reach those cells.
Excision is likewise developing a gene editing therapy for HBV, for which it hopes to start clinical studies in 2026. Beam Therapeutics was also working on a gene editing approach to HBV but the company stopped work on the program in October last year as part of larger cost cuts and layoffs.
It’s been a long road to this moment for Precision, which once developed CAR-T therapies before offloading that work to Imugene and in April saw Eli Lilly end a partnership on three programs. Gilead had signed on to Precision’s hepatitis B program in 2018, but axed the partnership in 2020, returning the rights to the gene editing company.
In a May note to investors, BMO Capital Markets analyst Kostas Biliouris wrote that Precision “remains a ‘show me’ story wherein positive clinical data from the PBGENE-HBV program are needed to improve investor sentiment.”