Slide 1: EASL 2026 Investor Update: PBGENE-HBV ELIMINATE-B Program
EASL 2026 Investor Update: PBGENE-HBV ELIMINATE-B Program May 27, 2026
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward- looking statements
Slide 3: EASL 2026 Investor Update: PBGENE-HBV ELIMINATE-B Program
EASL 2026 Investor Update: PBGENE-HBV ELIMINATE-B Program Michael Amoroso President & Chief Executive Officer Precision BioSciences, Inc.
Slide 4: Key Hepatitis Expert Presenters and Panelists
Key Hepatitis Expert Presenters and Panelists MF Yuen, MD, PhD Mark Sulkowski, MD Cassie Gorsuch, PhD Chair Professor Professor of Medicine Chief Scientific Officer Division of Gastroenterology & Hepatology Director, Division of Infectious Diseases Precision BioSciences, Inc. Li Shu Fan Medical Foun
Slide 5: HBV at the Turning Point: From Lifelong Suppression Toward Finite, Biomarker-Guided Viral Cure
HBV at the Turning Point: From Lifelong Suppression Toward Finite, Biomarker-Guided Viral Cure “True cure of HBV “…assessing response to chronic “First clinical evidence infection requires hepatitis B therapies is unclear of reservoir-elimination eradication, degradation because of inconsistent corr
Slide 6: A Direct Antiviral Therapy Targeting & Eliminating cccDNA Is Needed to Cure HBV
A Direct Antiviral Therapy Targeting & Eliminating cccDNA Is Needed to Cure HBV 〉 Current therapies do not eliminate the Current Therapeutics Rarely sole source of infectious particles: cccDNA Achieve Cure Because 〉 Downstream targeting agents only They Do Not Eliminate cccDNA achieve single-digit f
Slide 7: FDA Regulatory Pathway: Elimination of HBV DNA Is Required for Approval
FDA Regulatory Pathway: Elimination of HBV DNA Is Required for Approval PATHWAYS TO FDA APPROVAL1 GUIDANCE DOCUMENT 1 2 Chronic Hepatitis B Virus Infection: OR Developing Drugs for Treatment HBV DNA HBV DNA + APRIL 2022 undetectable HBsAg both only undetectable Loss of HBV DNA Is the Common Therapeu
Slide 8: PBGENE-HBV Primary Mechanism: Directly Targets and Eliminates cccDNA
PBGENE-HBV Primary Mechanism: Directly Targets and Eliminates cccDNA cccDNA ARCUS mRNA Target Site Protein (Polymerase) Protein (HBsAg) cccDNA pgRNA HBV DNA cccDNA, covalently closed circular DNA; HBsAg, hepatitis B surface antigen; mRNA, messenger RNA; pgRNA, pregenomic RNA. 1. Gorsuch CL, et al. M
Slide 9: PBGENE-HBV Secondary Mechanism: Also Targets and Reduces HBsAg by Editing Integrated Viral DNA
PBGENE-HBV Secondary Mechanism: Also Targets and Reduces HBsAg, a Replication-Incompetent Protein, by Editing Integrated Viral DNA Indel Integrated Viral DNA S S-antigen Gene ARCUS mRNA Target Site Protein (HBsAg) HBsAg Decreased HBsAg, hepatitis B surface antigen; mRNA, messenger RNA. 1. Gorsuch CL
Slide 10: Late-Breaking Data Prove PBGENE-HBV Directly Targets and Eliminates cccDNA
LATE-BREAKING DATA Prove PBGENE-HBV Directly Targets and Eliminates cccDNA, Providing Path Toward Viral Cure 〉Primary antiviral mechanism established through multiple biopsies, confirming targeting and elimination of cccDNA 〉Potent cccDNA targeting drives direct antiviral effect — 10-fold (1-log) re
Slide 11: NEW EASL DATA: pgRNA Is the Appropriate Blood Biomarker
NEW EASL DATA: pgRNA Is the Appropriate Blood Biomarker as it Directly Comes From cccDNA and Is the Necessary Precursor of HBV DNA Replication Based on Clinical Biopsy and Biomarker Data, PBGENE-HBV’s Primary Mechanism of Eliminating cccDNA Results in Durable pgRNA Loss 〉Loss of blood pgRNA in 100%
Slide 12: NEW EASL DATA: PBGENE-HBV Drove Durable pgRNA Loss in 100% of Patients
NEW EASL DATA: PBGENE-HBV Drove Durable pgRNA Loss in 100% of Patients Who Had Detectable pgRNA at Baseline* cccDNA pgRNA HBV DNA Cohort 2, Pt 6 0.4 mg/kg Q8W Cohort 3, Pt 7 0.8 mg/kg Q8W Cohort 3, Pt 9 0.8 mg/kg Q8W Cohort 4, Pt 10 0.4 mg/kg Q4W Cohort 4, Pt 12 0.4 mg/kg Q4W Cohort 5, Pt 14 0.65 mg
Slide 13: Destroying Hepatitis at Its Source Is Foundational to Viral Cure
Destroying Hepatitis at Its Source Is Foundational to Viral Cure Hepatitis C Virus Hepatitis B Virus RNA Virus DNA Virus SOVALDI® (sofosbuvir)1 PBGENE-HBV HCV RNA Loss Direct Elimination of correlates to sustained virologic response HBV cccDNA Undetectable Levels of Virus HCV RNA HBV DNA = Lack of R
Slide 14: PBGENE-HBV Product Profile: Designed to Directly Target and Eliminate cccDNA
PBGENE-HBV Product Profile: Designed to Directly Target and Eliminate cccDNA and Drive Viral Cure PBGENE-HBV Target Product Profile A curative antiviral therapy would achieve the following: 〉 Directly target & destroy cccDNA – the only source of new infectious virus (HBV DNA) 〉 Permanent mechanism w
Slide 15: PBGENE-HBV Primary Mechanism of Targeting cccDNA Is Now Validated
PBGENE-HBV Primary Mechanism of Targeting cccDNA Is Now Validated Cassie Gorsuch, PhD Chief Scientific Officer Precision BioSciences, Inc.
Slide 16: Chronic Hepatitis B Disease Biology
Chronic Hepatitis B Disease Biology
Slide 17: cccDNA Is the Only Source of New Infectious Virus and Therapeutic Target
cccDNA Is the Only Source of New Infectious Virus (HBV DNA) and the Therapeutic Target to Cure Hepatitis B HBV DNA (infectious HBV DNA is only produced from cccDNA particles) pgRNA cccDNA- derived cccDNA transcripts iDNA RNA Integrated DNA (iDNA) transcripts Nucleus Hepatocyte cccDNA, covalently clo
Slide 18: Integrated DNA Cannot Produce HBV DNA and Is Less Important Than cccDNA
Integrated DNA Cannot Produce HBV DNA (Infectious Virus) and Therefore Is Less Important Than cccDNA cccDNA- derived cccDNA transcripts HBsAg HBsAg is expressed from both cccDNA and integrated DNA iDNA RNA Integrated DNA (iDNA) transcripts Nucleus Hepatocyte cccDNA, covalently closed circular DNA; H
Slide 19: In HBeAg-Negative Patients, HBsAg Is Primarily Produced From iDNA
In Fact, in HBeAg-Negative Patients, HBsAg Is Primarily Produced From iDNA, Limiting Its Utility as a Biomarker for Antiviral Effect on cccDNA Years With Chronic Hepatitis B HBeAg-positive HBeAg-negative ~20% of patients ~80% of patients • Higher cccDNA • Lower cccDNA • Higher pgRNA • Lower pgRNA •
Slide 20: The Problem: The Field Has Focused on the Wrong Target and Biomarker
The Problem: Because the Field Lacked Tools Directly Targeting cccDNA, We’ve Been Focused on the Wrong Target and Biomarker 〉 Hepatitis B is a viral infection in the liver that can cause cirrhosis and liver cancer 〉 cccDNA is the source of the viral infection 〉 The goal of therapy MUST be to elimina
Slide 21: PBGENE-HBV Mechanism of Action
PBGENE-HBV Mechanism of Action
Slide 22: Direct Antiviral Targeting: PBGENE-HBV Eliminates cccDNA as Designed
Direct Antiviral Targeting: Late-Breaking EASL Data Demonstrate PBGENE-HBV Eliminates cccDNA as Designed, Providing Path Toward Viral Cure Targeting the viral source HBV DNA PBGENE HBV PBGENE-HBV potently eliminates cccDNA as the primary mechanism and pgRNA drove undetectable pgRNA in all patients w
Slide 23: Deep Dive Into PBGENE-HBV Mechanism: Two Productive Editing Outcomes
Deep Dive Into PBGENE-HBV Mechanism: Potently Targeting cccDNA Through Two Productive Editing Outcomes The Reason Why: Predominant Outcome (~90%) Primary PBGENE-HBV targets Mechanism Elimination cccDNA, which is more Replication effective because there are Incompetent two editing outcomes. HBV cccDN
Slide 24: pgRNA Is the Specific Blood Biomarker for Measuring Elimination of cccDNA
For a Direct Targeting cccDNA Mechanism Like PBGENE-HBV, pgRNA Is the Specific Blood Biomarker for Measuring Elimination of cccDNA1-2 Source of pgRNA/HBV DNA Source of HBsAg 100% from cccDNA <10% from cccDNA 0% from integrated DNA (iDNA) >90% from integrated DNA (iDNA) *NUC cccDNA pgRNA HBV DNA cccD
Slide 25: Undetectable pgRNA Is Associated With Success of Stopping Nucleoside Analogs
Studies Demonstrate Undetectable pgRNA Is Associated With Success of Stopping Nucleoside Analogs and Increasing Probability of Cure Probability of Cure Stratifies on pgRNA 10X Increase in Probability of Cure With Non-quantifiable pgRNA pgRNA is a specific marker for cccDNA indicating viral load, whe
Slide 26: Phase 1 ELIMINATE-B Trial Continues to Rapidly Progress
Phase 1 ELIMINATE-B Trial Continues to Rapidly Progress
Slide 27: Broadening Patient Experience: Doses Across 16 Patients in 5 Cohorts
Broadening Patient Experience and Confidence: 38 Doses Across 16 Patients in 5 Cohorts to Date W0 W4 W8 W12 W16 Patient 1 Cohort 1 0.2 mg/kg Patient 2 Q8W Patient 3 Cohort 2 Patient 4 0.4 mg/kg Patient 5 Q8W Patient 6 Dose Cohort 3 Patient 7 administered 0.8 mg/kg Patient 8 Q8W Patient 9 Dose planne
Slide 28: Efficacy: PBGENE-HBV Shows Potent Elimination of cccDNA
Efficacy: PBGENE-HBV Shows Potent Elimination of cccDNA as Primary Mechanism of Action
Slide 29: Multiple Datasets Support cccDNA Targeting and Permanence of Effect
Multiple Datasets Support cccDNA Targeting and Permanence of Effect by PBGENE-HBV Liver Biopsies pgRNA HBsAg CONFIRMATION OF POTENT cccDNA SUBSTANTIAL ANTIVIRAL cccDNA ELIMINATION EFFECT ACTIVITY IN ALL PATIENTS 〉 10-fold (1-log) reduction in 〉 100% of patients (6/6) with 〉 Durable HBsAg reductions
Slide 30: Multiple Datasets Support cccDNA Targeting and Permanence of Effect
Multiple Datasets Support cccDNA Targeting and Permanence of Effect by PBGENE-HBV Liver Biopsies pgRNA HBsAg CONFIRMATION OF POTENT cccDNA SUBSTANTIAL ANTIVIRAL cccDNA ELIMINATION EFFECT ACTIVITY IN ALL PATIENTS cccDNA, covalently closed circular DNA; HBsAg, hepatitis B surface antigen; pgRNA, prege
Slide 31: NEW EASL DATA: Biopsies From Two Patients in Cohort 2
NEW EASL DATA: Biopsies From Two Patients in Cohort 2 (0.4 mg/kg, Q8W) Dose 1 Dose 2 Dose 3 Patient 5 Post-treatment Pre-treatment Biopsy Biopsy Patient 6 Post-treatment Biopsy Only Liver Transcript Sequencing Methodology biopsy • Quantitate levels of cccDNA transcripts pre- and post-treatment analy
Slide 32: Primary Mechanism: Elimination of cccDNA Resulted in 10-fold Decrease
NEW EASL DATA: Primary Mechanism - PBGENE-HBV Elimination of cccDNA Resulted in 10-fold (1-log) Decrease in cccDNA 1 Normalized cccDNA transcripts 0.8 10-fold (1-log) Patient 5 decrease 0.6 Patient 5 Cohort 2: 0.4 mg/kg 0.4 Biopsy after 2 administrations Elimination 0.2 <1% Remaining 0 Pre-treatment
Slide 33: Remaining cccDNA: Indels Permanently Inactivate Viral Replication
NEW EASL DATA: Of the <1% cccDNA Remaining, PBGENE-HBV Indels Permanently Inactivate Viral Replication by Knocking Out Polymerase Function 1 Patient 5 | Post dose 2 Normalized cccDNA transcripts 0.8 Elimination 0.6 Key: 0.4 23% Inactivating Indels Wild Type 0.2 <1% Remaining 0 Post-treatment Biopsy
Slide 34: Additional cccDNA Inactivation Occurs Upon Subsequent Administrations
NEW EASL DATA: Additional cccDNA Inactivation Occurs Upon Subsequent Administrations of PBGENE-HBV Patient 5 | Post dose 2 Patient 6 | Post dose 3 Key: 23% 80% Inactivating Indels Inactivating Edits Wild Type Editing in remaining cccDNA reached 80% after 3 administrations, supporting that cumulative
Slide 35: Secondary Mechanism: All Indels in cccDNA Knock Out Polymerase Function
NEW EASL DATA: Secondary Mechanism – All Indels in cccDNA Knock Out Polymerase Function, Resulting in Complete Viral Inactivation 1⁰ MOA cccDNA elimination (~90% of edits) ARCUS results in complete loss of Target Site polymerase protein 2⁰ MOA cccDNA inactivating indels cccDNA (~10% of edits) result
Slide 36: Multiple Datasets Support cccDNA Targeting and Permanence of Effect
Multiple Datasets Support cccDNA Targeting and Permanence of Effect by PBGENE-HBV Liver Biopsies pgRNA HBsAg CONFIRMATION OF POTENT cccDNA SUBSTANTIAL ANTIVIRAL cccDNA ELIMINATION EFFECT ACTIVITY IN ALL PATIENTS cccDNA, covalently closed circular DNA; HBsAg, hepatitis B surface antigen; pgRNA, prege
Slide 37: PBGENE-HBV Drove Durable pgRNA Loss in 100% of Patients
NEW EASL DATA: PBGENE-HBV Drove Durable pgRNA Loss in 100% of Patients Who Had Detectable pgRNA at Baseline* cccDNA pgRNA HBV DNA Cohort 2, Pt 6 0.4 mg/kg Q8W Cohort 3, Pt 7 0.8 mg/kg Q8W Cohort 3, Pt 9 0.8 mg/kg Q8W Cohort 4, Pt 10 0.4 mg/kg Q4W Cohort 4, Pt 12 0.4 mg/kg Q4W Cohort 5, Pt 14 0.65 mg
Slide 38: Patient 6 – Undetectable pgRNA in Both Blood and Liver Biopsy
NEW EASL DATA: Patient 6 – Undetectable pgRNA in Both Blood and Liver Biopsy After Third Administration Undetectable pgRNA Patient 6 had detectable in the liver corresponds blood pgRNA at baseline with pgRNA loss in blood Cohort 2, Pt 6 0.4 mg/kg Q8W -4 0 4 8 12 16 20 24 28 32 36 40 Weeks From First
Slide 39: Multiple Datasets Support cccDNA Targeting and Permanence of Effect
Multiple Datasets Support cccDNA Targeting and Permanence of Effect by PBGENE-HBV Liver Biopsies pgRNA HBsAg CONFIRMATION OF POTENT cccDNA SUBSTANTIAL ANTIVIRAL cccDNA ELIMINATION EFFECT ACTIVITY IN ALL PATIENTS Durable HBsAg reductions across all patients treated; highly supportive of cccDNA elimin
Slide 40: Proof of Editing in Evaluable Patients Across All Cohorts
NEW EASL DATA: PBGENE-HBV Demonstrates Proof of Editing in 100% of Evaluable Patients Across All Cohorts, Regardless of Baseline S-Antigen Levels Maximal HBsAg Declines 0 -10 HBsAg % Decline From Baseline -20 -30 Significant maximal -40 declines in HBsAg -50 -60 supporting PBGENE-HBV -70 activity ac
Slide 41: Biomarker Proof of cccDNA Elimination: pgRNA Loss and S-Antigen Decline
NEW EASL DATA: Biomarker Proof of cccDNA Elimination – 100% of Patients With pgRNA Complete Loss and S-Antigen Decline Across All Evaluable Patients pgRNA (n=6) HBsAg (n=13) Durable biomarker; proof Supportive biomarker of cccDNA elimination correlated with cccDNA elimination 〉6 patients detectable
Slide 42: Permanent Editing Effect in First Patient Now >1 Year Since Treatment
NEW EASL DATA: Permanent Editing Effect in First Patient Treated With PBGENE-HBV Now >1 Year Since Initiating Treatment Patient 1 – Sustained HBsAg Reductions Dose 1 Dose 2 Dose 3 120 600 % of Pre-Treatment HBsAg 100 HBsAg (IU/mL) 80 400 60 40 200 20 0 0 0 7 14 28 42 71 0 7 14 28 Time 42 0 7 14 28 4
Slide 43: Efficacy Summary: PBGENE-HBV Potentially the Foundation for Viral Cure
Efficacy Summary: PBGENE-HBV Potentially the Foundation for Viral Cure Liver Biopsies 〉 First evidence of cccDNA elimination by a direct antiviral gene-editing modality 〉 1-log / 10-fold reduction in cccDNA-derived transcripts after only 2 dose administrations 〉 Of the <1% of the cccDNA that remains
Slide 44: Safety: Clinical Safety Update From ELIMINATE-B
Safety: Clinical Safety Update From ELIMINATE-B
Slide 45: PBGENE-HBV Safety Profile Executive Summary
PBGENE-HBV Safety Profile Executive Summary 〉 38 doses administered across 16 patients in 5 cohorts 〉 No dose-limiting toxicities observed 〉 Most common adverse events include infusion-related reactions consistent with LNP effects, with onset and resolution within 24 hours of infusion 〉 While transi
Slide 46: Safety Profile Summary – Clear Evidence of Therapeutic Window
NEW EASL DATA: PBGENE-HBV Safety Profile Summary – Clear Evidence of Therapeutic Window Number of patients with 0.2 mg/kg Q8W 0.4 mg/kg Q8W 0.4 mg/kg Q4W 0.65 mg/kg Q4W/Q8W 0.8 mg/kg Q8W treatment-related and possibly Cohort 1 Cohort 2 Cohort 4 Cohort 5 Cohort 3 treatment-related AEs: n=3 n=3 n=3 n=
Slide 47: Safety Measures Have Mitigated Hypotension and Liver Lab Abnormalities
Simple and Mechanism-Driven Safety Measures Have Mitigated Hypotension and Liver Lab Abnormalities LNP-inflammatory response 〉 Rapid onset of complement and cytokine elevations after LNP dosing which resolve in 24 hours 〉 LNP-driven transient elevations of complement and cytokines drive hypotension
Slide 48: Tolerability of PBGENE-HBV Has Improved After New Safety Mitigations
NEW EASL DATA: Tolerability of PBGENE-HBV Has Improved After Implementing New Safety Mitigations Across 5 Patients and 7 Administrations With Repeat Administrations Across Cohorts 0.4 mg/kg Q4W 0.65 mg/kg Q8W* 〉New prophylaxis and infusion measures Number of AEs associated with doses given Cohort 4
Slide 49: Summary of PBGENE-HBV Clinical Data
Summary of PBGENE-HBV Clinical Data
Slide 50: Safety and Efficacy Findings Substantiate a Clear Therapeutic Window
Safety and Efficacy Findings Substantiate a Clear Therapeutic Window for Driving Potential Viral Cures in Chronic Hepatitis B 〉 Established primary mechanism of direct cccDNA elimination through liver biopsy, pgRNA, and HBsAg data — 1-log reduction in cccDNA transcripts observed in liver biopsies —
Slide 51: Next Steps
Next Steps Mark Sulkowski, MD Michael Amoroso Professor of Medicine President & Chief Executive Officer Director, Division of Infectious Diseases Precision BioSciences, Inc. Johns Hopkins Bayview Medical Center Johns Hopkins University & Medicine
Slide 52: Transforming the Natural History of cHBV Through Direct Viral Targeting of cccDNA
Transforming the Natural History of cHBV Through Direct Viral Targeting of cccDNA CONTINUE STOP NUC EXPAND 〉 Expand number of patients 〉 Confirm global alignment for NUC 〉 Select optimal dosing schedule in cohort 4 (0.4 mg/kg) and withdrawal framework with clinicians for phase 1 expansion and phase
Slide 53: HBV at the Turning Point: From Lifelong Suppression Toward Finite Viral Cure
HBV at the Turning Point: From Lifelong Suppression Toward Finite, Biomarker-Guided Viral Cure Eliminating cccDNA drives undetectable HBV DNA → consistent with FDA approval guidance Destruction of replication-competent virus by PBGENE-HBV directly eliminating and inactivating cccDNA pgRNA is the bio
Slide 54: Multiple Near-Term Data Catalysts Through Wholly Owned Programs
Multiple Near-Term Data Catalysts Through Wholly Owned Programs Clinical-Stage Programs Validating ARCUS Wholly Owned In Vivo Gene-Editing Programs PBGENE-HBV for Chronic Hepatitis B PBGENE-DMD for Duchenne Muscular Dystrophy 〉 Viral gene elimination program with 38 doses delivered across 16 patient
Slide 55: Q&A
Q&A MF Yuen, MD, PhD Mark Sulkowski, MD Michael Amoroso Chair Professor Professor of Medicine President & Chief Executive Officer Division of Gastroenterology & Hepatology Director, Division of Infectious Diseases Precision BioSciences, Inc. Li Shu Fan Medical Foundation Johns Hopkins Bayview Medica
Slide 56: Appendix
Appendix my
Slide 57: Viral Replication Drives Increased Integrations and Higher Risk of Cirrhosis and Liver Cancer
Viral Replication Drives Increased Integrations, Resulting in a Higher Risk of Liver Cirrhosis and Liver Cancer cccDNA HBeAg-positive HBV DNA Host genome integration Integrated DNA (iDNA) Liver Cancer Cirrhosis pgRNA cccDNA, covalently closed circular DNA; HBeAg, hepatitis B e antigen; pgRNA, pregen
Slide 58: Undetectable pgRNA Is Associated With Success of Stopping Nucleoside Analogs
Studies Demonstrate Undetectable pgRNA Is Associated With Success of Stopping Nucleoside Analogs and Increasing Probability of Cure Probability of Cure Stratifies on pgRNA 10X Increase in Probability of Cure with Non-quantifiable pgRNA 3% ~30% Probability +pgRNA -pgRNA Probability of cure of cure Ad