Precision BioSciences Announces Early Safety and Antiviral Results for PBGENE-HBV in ELIMINATE-B Trial
Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS® platform to develop in vivo gene editing therapies for high unmet need diseases, today announced 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 0.2 mg/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 A. Abramson, MD, MPH, Head of Clinical Development. “We are proud to share this first in human proof-of-concept data with the Hepatitis B community as we plan additional administrations at this dose level and escalating dose levels.”
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 maximize 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.
The ELIMINATE-B global investigators are enthusiastic about the initial safety and activity profile of PBGENE-HBV and look forward to treating additional patients globally. Patient interest in this trial remains very high, and these data are re-assuring to me for my patients with chronic Hepatitis B,” said Alina Jucov, MD, PhD, Principal Investigator, Arensia Research Clinic, Moldova.
These data excite the entire Precision team, and we hope it instills confidence among the patients who are courageously embarking in our clinical trial. Progress against this wide-spread and devastating disease would not be possible without their participation,” said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences. “This marks an important step forward for Precision in a large patient population and the second clinical validation of ARCUS in vivo gene editing following the recent clinical data from the OTC-HOPE study being conducted by our partner iECURE in a dire rare disease.”
The ELIMINATE-B study is currently enrolling HBeAg-negative chronic Hepatitis B patients at world-class sites in Moldova, Hong Kong, and New Zealand. Investigators accrued the first cohort of patients within a month. The company is on schedule to provide additional administrations at this dose level and subsequently plans to escalate to higher dose levels to define the optimal dose and number of dose administrations for safely eliminating cccDNA and inactivating integrated HBV DNA. Precision expects to expand the study to the U.S. and U.K. and continue accelerating recruitment and evaluation of a genetically diverse patient population in the Phase 1 study. Precision plans to share detailed clinical data throughout 2025.
Prior to commencing the ELIMINATE-B clinical trial, we conducted numerous preclinical studies with PBGENE-HBV to understand the pharmacokinetics, safety, and impact on viral markers at various dose levels and following multiple dose administrations. 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, PhD, 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.
