First-in-human trial of PBGENE-HBV for chronic hepatitis B opens
Precision testing gene-editing therapy as treatment for chronic infections
Precision Biosciences has opened a first-in-human trial testing its gene-editing therapy candidate PBGENE-HBV in people with chronic hepatitis B infections, and says data are expected throughout next year.
For now, the Phase 1 clinical trial has only been approved by regulators in Moldova, where patient screening is underway, Precision said in a company press release reporting its latest financial and business updates.
According to the company, applications to regulatory authorities to expand the trial to additional countries are pending approval.
“Our team is moving quickly to dose patients and in parallel is leveraging our robust regulatory package to seek additional regulatory application approvals globally with the aim of rapidly accelerating enrollment in the PBGENE-HBV phase 1 trial,” said Michael Amoroso, Precision’s CEO.
The CEO also indicated that the company anticipates sharing additional plans for PBGENE-HBV’s clinical development in a virtual investor event on Nov. 15.
Precision seeking regulatory OKs to expand Phase 1 trial of PBGENE-HBV
Hepatitis B is characterized by liver inflammation caused by infections with the hepatitis B virus, known as HBV. While these infections often clear up on their own, some people will develop a chronic infection lasting six months or more.
Chronic HBV infection is associated with a risk of serious health complications, such as irreversible liver scarring and damage, or cirrhosis, as well as liver failure and liver cancer.
The current standard of care for chronic HBV infections involves a class of antiviral therapies called nucleoside/nucleotide analogs.
These treatments help lower circulating levels of the virus, but they don’t target the root cause of the disease — replication of viral DNA. As such, they only provide a 1% to 3% chance of a functional cure, in which the viral DNA and certain viral proteins are entirely undetectable at least six months after antiviral treatment ends.
PBGENE-HBV is a gene-editing therapy intended to directly suppress viral replication, which Precision expects will lead to a functional cure.
The hepatitis B virus uses two types of genetic material to replicate itself and cause infection. First, it forms rings of genetic material — called covalently closed circular DNA, or cccDNA — that reside in the nucleus of liver cells. The nucleus is the cellular compartment where all genetic information is stored. Second, HBV DNA can integrate itself into human DNA that’s also housed in the nucleus.
Developed with Precision’s proprietary ARCUS gene-editing platform, PBGENE-HBV is designed to target both of these types of viral DNA by cutting a highly conserved sequence of HBV DNA.
The gene-editing machinery is packaged into fatty vesicles called lipid nanoparticles that deliver their cargo to liver cells. There, the machinery makes cuts in cccDNA that ultimately result in its degradation. This strategy also cuts integrated HBV DNA and renders it unable to be used for virus replication.
Ultimately, Precision believes that by targeting both cccDNA and integrated HBV DNA, PBGENE-HBV offers a potential cure for chronic HBV infections.
We look forward to sharing [details] on our clinical plans for PBGENE-HBV.
“PBGENE-HBV represents the very first clinical-stage gene-editing program for chronic hepatitis B utilizing a differentiated dual modality targeting the elimination of cccDNA and inactivation of integrated HBV genomes — the root cause of viral persistence in chronic hepatitis B,” Amoroso said.
Preclinical data showed that the gene therapy gene therapy worked as intended in lab-grown, HBV-infected human liver cells, as well as in mouse and nonhuman primates models of HBV infection. PBGENE-HBV also showed no off-target effects on the DNA of human liver cells at therapeutically relevant doses.
Moreover, according to Precision, multiple doses of PBGENE-HBV were well tolerated in nonhuman primates. Some minor elevations in liver enzymes were observed, but were temporary and normalized within a couple of weeks after dosing.
“We look forward to sharing [details] on our clinical plans for PBGENE-HBV” at the upcoming investor event, Amoroso said.
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