Precision BioSciences has announced positive initial results from the first administration of PBGENE-HBV in cohort 1, the lowest dose level of the ELIMINATE-B trial.  

The ELIMINATE-B trial is designed to investigate PBGENE-HBV at multiple ascending dose levels with three dose administrations per dose level in patients afflicted with chronic Hepatitis B who are HBeAg-negative. 

PBGENE-HBV, which comprises an ARCUS-encoding mRNA encapsulated in a lipid nanoparticle (LNP), was safe and well tolerated in all three participants in cohort 1 after the first administration of a 0.2mg/kg dose.  

The planned dosing schedule in ELIMINATE-B allows for two additional administrations at this dose level while in parallel investigating the next higher dose level.  

The participants treated in cohort 1 possessed different baseline characteristics: age of infection, duration of infection and level of HBsAg. Across the three participants dosed, none experienced a Grade ≥2 treatment-related adverse event or serious adverse event. 

“This exciting initial safety data set provides evidence that ARCUS encapsulated in a LNP was well tolerated in chronic Hepatitis B patients upon first dose administration at dose level 1. When studying novel technologies and drug mechanisms it is important to monitor safety closely, and we believe the extensive preclinical safety experiments Precision conducted along with several rounds of mRNA optimization were critical steps to ensure patient safety,” said Murray Abramson, Head of Clinical Development. 

Reduction in Hepatitis B surface antigen 

In addition to safety, PBGENE-HBV demonstrated a substantial reduction in Hepatitis B surface antigen (HBsAg) in two of the three participants following the first administration at dose level 1.  

The ELIMINATE-B protocol is designed for three dose administrations at each dose level, with the goal to maximise cumulative viral editing to achieve undetectable levels of HBsAg.  

With a well-tolerated safety profile and early antiviral activity established at pre-specified timepoints, Precision will complete subsequent administrations in all cohort 1 patients. 

Precision expects to expand the study to the US and UK and continue accelerating recruitment and evaluation of a genetically diverse patient population in the Phase I study. 

“Importantly, the early data in the first cohort of patients is consistent with the safety and HBsAg reductions observed in our preclinical models,” said Cassie Gorsuch, Chief Scientific Officer. “The safety and early reduction of HBsAg suggests that PBGENE-HBV is doing what no previous treatment has been able to accomplish, eliminating the source of viral replication in cccDNA and inactivating integrated disease.” 

>>> Read the DDW interview with Cassie Gorsuch, Chief Scientific Officer, Precision BioSciences. 

Diana Spencer, Senior Digital Content Editor, DDW