Precision BioSciences reports safety, efficacy data for ELIMINATE-B trial cohort

Precision BioSciences (DTIL) announced ELIMINATE-B results as of the data cutoff of July 28. Data include completed Cohort 1, the lowest dose level of the ELIMINATE-B trial, and initial safety data from Cohort 2. The ELIMINATE-B trial is designed to investigate PBGENE-HBV at multiple ascending dose levels with three dose administrations per level in patients afflicted with chronic hepatitis B who are Hepatitis B e-Antigen-negative, treated daily with nucleos(t)ide analog therapies, and have =200 IU/mL HBsAg without an upper limit. Cohort 1 of the Phase 1 ELIMINATE-B study consisted of three patients, each of whom received three planned administrations of 0.2 mg/kg of PBGENE-HBV dosed approximately eight weeks apart. The patients treated in Cohort 1 possessed different baseline characteristics: age of infection, duration of infection, and baseline level of HBsAg with no upper limit. The primary objective of the study is to characterize the safety of PBGENE-HBV. The low dose in Cohort 1 was selected with endorsement of global regulators to maximize the safety margin for first-in-human investigation. This starting dose in humans is significantly less than the dose administered in the non-human primate proof of efficacy study where viral DNA editing was observed. PBGENE-HBV was well-tolerated and active in all three patients in Cohort 1. Across Cohort 1, no patient experienced above a Grade 2 treatment-related adverse event, a serious adverse event, or a dose-limiting toxicity. Additionally, no clinically significant lab abnormalities were observed, including liver enzymes and platelets. At 0.2mg/kg, PBGENE-HBV demonstrated a substantial HBsAg reduction in all three patients with best response reductions of 56%, 69% and 47% compared to baseline levels in patients one, two and three, respectively. One of three patients in Cohort 1 achieved a durable HBsAg reduction of approximately 50% from baseline that was maintained as of the data cutoff-date, which was seven months after the initial dose of PBGENE-HBV. These results are evidence of the ability of PBGENE-HBV to drive a durable antiviral response by editing the viral DNA at the source of chronic hepatitis B infection and give further reason to believe in the ELIMINATE-B trial objective of achieving durable undetectable levels of HBsAg in some patients. The other two patients in Cohort 1 demonstrated antiviral response after each dose administration and eventually returned to baseline levels of HBsAg. Transcriptional upregulation from unedited viral DNA remaining after administration at the lowest dose is likely responsible for the HBsAg increase in these patients. Cohort 2 in the ELIMINATE-B study is evaluating PBGENE-HBV at 0.4 mg/kg. As of the data cut off, 1 patient received three dose administrations with two weeks of follow-up, and two patients received one dose administration with four weeks of follow-up. In these patients, no adverse events above Grade 2, no serious adverse events, nor dose-limiting toxicities were observed. There were no clinically significant liver transaminase elevations noted. One additional patient did not complete their dose due to a transient infusion-related serious adverse event that led to dose interruption at minute two. This event quickly resolved within minutes of ceasing the infusion, and the patient is doing well. The Data Monitoring Committee deemed the event not dose-related or dose-limiting. The Company is on track to complete dosing of all three patients with three planned dose administrations in Cohort 2 and commence dosing Cohort 3. The company intends to evaluate PBGENE-HBV at increasing and more frequent doses until a maximum tolerated dose is reached, with the goal of establishing the right dose and administration schedule leading to a complete cure and optimal therapeutic index. The company expects to provide a data update later in 2025.