8-K: Precision BioSciences Reports Positive HBV Gene Editing Trial Data

Precision BioSciences announced positive Phase 1 ELIMINATE-B clinical trial data for PBGENE-HBV, showing dose-dependent antiviral activity and a favorable safety profile for chronic Hepatitis B.

Summary

• Precision BioSciences presented late-breaking Phase 1 ELIMINATE-B study data for PBGENE-HBV, an in vivo gene editing therapy for chronic Hepatitis B, at AASLD The Liver Meeting 2025.
• Nine evaluable patients across three ascending cohorts (0.2, 0.4, and 0.8 mg/kg) received a total of 22 administered doses as of October 31, 2025.
• All treated patients showed measurable reductions in hepatitis B surface antigen (HBsAg), confirming on-target antiviral effects across all dose levels, regardless of baseline HBsAg (370 to 11,813 IU/mL).
• The magnitude and persistence of HBsAg declines increased with higher doses and repeat administrations, without cumulative toxicities.
• One patient in Cohort 1 (0.2 mg/kg) showed a durable ~50% HBsAg reduction 9 months after the initial dose.
• All three patients in Cohort 2 (0.4 mg/kg) achieved durable HBsAg declines, maintained for 8 weeks after the first administration, with reductions up to 66% after the third dose.
• Cohort 3 (0.8 mg/kg) demonstrated early (2 weeks) HBsAg reductions in all three patients after the first dose, with one patient showing a 64% decrease after two administrations.
• Patients in Cohort 3 achieved HBsAg levels as low as 188 IU/mL, suggesting a path to potentially stopping nucleos(t)ide analogs and testing for cure.
• A paired liver biopsy from Patient 5 (Cohort 2) confirmed ARCUS-mediated gene editing events (indel edits) within viral DNA, providing the first direct molecular evidence of HBV viral gene editing in humans.
• PBGENE-HBV was well tolerated across all cohorts with no dose-limiting toxicities. Adverse events were transient, generally resolved within 12 hours, and infusion-related reactions resolved without intervention.
• Transient elevations in ALT and AST were observed but resolved within days, with no associated changes in bilirubin or evidence of liver dysfunction. One reversible Grade 3 AST elevation resolved within 3 days.

Sentiment

Score: 9

Explanation: The filing reports highly positive clinical trial results, including dose-dependent efficacy, durable responses, direct molecular evidence of gene editing, and a favorable safety profile, indicating significant progress towards a potential cure for chronic Hepatitis B. The language is consistently optimistic and highlights breakthrough achievements.

Positives

• Consistent antiviral activity observed across all treated patients and dose levels, regardless of baseline HBsAg.
• Dose-dependent antiviral activity, with higher doses leading to greater magnitude and persistence of HBsAg reductions.
• Durable HBsAg reductions sustained over time, with one patient showing ~50% reduction at 9 months and another up to 66% reduction.
• First direct molecular evidence of HBV viral gene editing in humans confirmed by liver biopsy, supporting the mechanism of cccDNA elimination and integrated HBV DNA inactivation.
• Favorable safety and tolerability profile across all cohorts, with no observed dose-limiting toxicities and transient, resolving adverse events.
• Stable liver enzyme values across repeat administrations, with transient elevations resolving quickly and deemed not dose-limiting by independent committees.
• Emerging path to potentially stopping nucleos(t)ide analogs and testing for cure in the highest dose cohort.

Risks

• Forward-looking statements involve known and unknown risks, uncertainties, and other important factors.
• Risks referred to under the section "Risk Factors" in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and its Quarterly Reports on Form 10-Q for the quarterly periods ended March 31, 2025, June 30, 2025, and September 30, 2025.
• Limited ability or inability to assess the safety and efficacy of product candidates.
• Dependence on ARCUS technology.
• Uncertainty regarding the initiation, cost, timing, progress, achievement of milestones, and results of research and development activities and preclinical and clinical studies.
• Ability to advance product candidates into, and successfully design, implement, and complete, clinical trials.
• Changes in interim top-line and initial data that are announced or published.
• Current and future relationships with and reliance on third parties including suppliers and manufacturers.

Future Outlook

The company expects to complete all administrations in Cohort 3 and finalize in the first quarter of 2026. They plan to test for a cure by stopping nucleos(t)ide analogs when HBsAg becomes undetectable. Other cohorts are planned, including one to evaluate a 4-week dosing interval. After identifying the optimal dose and schedule, the company expects to advance PBGENE-HBV into the Part 2 expansion phase of the ELIMINATE-B study to evaluate the optimized regimen in a larger patient population, with paired biopsies expected in all Part 2 patients.

Management Comments

• "These new late-breaking data represent a milestone for Precision BioSciences and for the entire field of chronic Hepatitis B because it is the first time clinicians have been able to target the root viral source of the disease." Michael Amoroso, CEO.
• "The safety data and tolerability profile, along with dose-dependent durable reductions in hepatitis B surface antigen and the first liver biopsy data provide evidence that antiviral activity is being achieved through directly editing the viral genome in patients with chronic Hepatitis B. This further validates ARCUS as a differentiated platform with true curative potential." Michael Amoroso, CEO.
• "With no observed dose-limiting toxicities to date, we look forward to finishing dosing the third cohort to generate additional data for PBGENE-HBV in our pursuit of a cure that has been so elusive in the field of Hepatitis B drug development." Michael Amoroso, CEO.
• "For the first time, we have clinical biopsy evidence that a gene editing therapy aimed at elimination of cccDNA can directly modify HBV DNA in infected human liver tissue—a step that we believe could redefine what is achievable in HBV drug development." Dr. Man-Fung Yuen, lead investigator.

Industry Context

Chronic Hepatitis B affects an estimated 300 million people globally, with 1-2 million in the U.S., and current antiviral therapies provide long-term viral suppression but rarely lead to functional cure as they do not eradicate cccDNA. PBGENE-HBV is positioned as the only clinical-stage gene editing therapy targeting direct viral elimination by addressing cccDNA and integrated HBV DNA, aiming for a permanent halt to viral transcription and antigen production, potentially redefining HBV drug development.

Comparison to Industry Standards

• Unlike existing therapies, PBGENE-HBV is designed to target the source of viral infection by directly eliminating cccDNA and inactivating integrated HBV DNA, which current treatments do not eradicate.
• PBGENE-HBV is the first and only potentially curative gene editing program to enter the clinic specifically designed to eliminate the root cause of chronic Hepatitis B (cccDNA) while inactivating integrated HBV DNA.
• The paired liver biopsy from Patient 5 confirmed the first direct molecular evidence of HBV viral gene editing in humans, a landmark moment for the HBV field.
• The ARCUS platform is differentiated from other technologies in its cutting mechanism, smaller size, and simpler structure, enabling more intended, defined therapeutic outcomes.

Stakeholder Impact

• Shareholders/Investors: Positive clinical data could lead to increased investor confidence and potential share price appreciation due to the promising therapeutic potential and market opportunity in chronic Hepatitis B.
• Patients with Chronic Hepatitis B: Offers hope for a potentially curative treatment where current options are limited to long-term suppression.
• Medical Community: Provides novel insights into gene editing for infectious diseases and could redefine treatment paradigms for HBV.
• Employees: Positive clinical progress validates the company's ARCUS platform and R&D efforts, potentially boosting morale and attracting talent.

Next Steps

• Complete all administrations in Cohort 3, expected in Q1 2026.
• Test for a cure by stopping nucleos(t)ide analogues when HBsAg becomes undetectable or approaches undetectable on a sustained basis.
• Plan other cohorts, including one to evaluate a 4-week dosing interval.
• Advance PBGENE-HBV into the Part 2 expansion phase of the ELIMINATE-B study after identifying the optimal dose and schedule.
• Conduct paired biopsies in all patients in Part 2 to provide robust biologic evidence of gene editing and cccDNA elimination.
• Expand the study to clinical trial sites in the United Kingdom.
• Continue accelerating recruitment and evaluation of a genetically diverse patient population in the Phase 1 study.

Key Dates

Recommendation

The filing presents exceptionally strong and groundbreaking clinical data for PBGENE-HBV, demonstrating consistent, dose-dependent, and durable HBsAg reductions, coupled with the first direct molecular evidence of HBV viral gene editing in humans. The favorable safety profile across all cohorts further de-risks the program. This represents a significant milestone in the pursuit of a functional cure for chronic Hepatitis B, a disease with a large unmet medical need. The potential to stop nucleos(t)ide analogs and achieve a cure positions Precision BioSciences as a leader in this therapeutic area, suggesting substantial future value creation.

Keywords

gene editing, Hepatitis B, HBV, PBGENE-HBV, ELIMINATE-B, clinical trial, Phase 1, ARCUS, cccDNA, HBsAg, antiviral, liver disease, biotechnology, Precision BioSciences, DTIL