Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Global Hepatitis Summit 2025
19 slides from Precision Biosciences's conference presentation, Mar 18, 2025
Slide 1: PBGENE-HBV Definitive Preclinical Toxicokinetic and Toxicology Data
PBGENE-HBV Definitive Preclinical Toxicokinetic and Toxicology Data Enables Advancement to Clinical Trials for a Potentially Curative Gene Editing Treatment for Chronic Hepatitis B Global Hepatitis Summit | March 18-21, 2025 | Los Angeles Emily B. Harrison, PhD | Senior Scientist
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements, as may any related presentations, within the meaning of the Private Securities Litigation Reform Act of 1995. The Company intends such forward-looking statements to be covered by the safe harbor provisions for forward-
Slide 3: Disclosures
Disclosures Emily Harrison is an employee of Precision BioSciences, Inc. (Nasdaq: DTIL) 2
Slide 4: PBGENE-HBV First in Class Gene Editor for HBV
PBGENE-HBV First in Class Gene Editor for HBV Dual Mechanism: Designed to Drive Potential Cures By Targeting Root Cause of Disease ARCUS LNP HBV Infected Chronic Hepatitis B affects Hepatocyte ~300 million people eliminate Risk of Liver Cancer, cccDNA Complications, and Mortality Remain on Current S
Slide 5: PBGENE-HBV: Robust Preclinical Safety and Efficacy Profile
PBGENE-HBV: Robust Preclinical Safety and Efficacy Profile IntDNA INACTIVATION: cccDNA ELIMINATION: Dose-dependent editing and 99% viral engagement HBsAg reductions at highest dose AASLD Nov 2023 AASLD Nov 2023 Nonhuman primates SAFETY: SAFETY: Comprehensive off-target SAFETY: Multiple doses analysi
Slide 6: Preclinical data supports the activity of repeat dosing to target cure
Preclinical data supports the activity of repeat dosing to target cure
Slide 7: Efficacy: NHP Study Demonstrated Up to 99% Viral Engagement
Efficacy: NHP Study Demonstrated Up to 99% Viral Engagement, Suggestive of Strong Potential Efficacy Profile of PBGENE-HBV 99% 100 100% 95% 93% Viral Engagement (%) 50% 50 2nd dose administration HBV LNP 1st dose administration 0% 0 Control AAV + AAV + AAV + 2mg/kg LNP 1mg/kg LNP 0.5mg/kg LNP Increa
Slide 8: Efficacy: PBGENE-HBV Significantly and Sustainably Reduced HBV DNA as a Monotherapy
Efficacy: PBGENE-HBV Significantly and Sustainably Reduced HBV DNA as a Monotherapy in Transgenic Mouse Model HBV DNA 1st 2nd ARCUS ARCUS Saline Dose Dose NUC Log [HBV DNA (copy/µl)] 5 PBGENE-HBV + NUC 4 No Viral Rebound 3 start NUC stop LLoQ=2.08 2 -4 0 3 7 10 14 1721 2428 3135 38 42 Days Even afte
Slide 9: Preclinical data supports the safety of repeat dosing to target cure
Preclinical data supports the safety of repeat dosing to target cure
Slide 10: Safety: Extensive nuclease specificity screening of PBGENE-HBV supports repeat dosing in clinic
Safety: Extensive nuclease specificity screening of PBGENE-HBV supports repeat dosing in clinic 1 Orthogonal Assays to Identify and 2 Account For Population Diversity Confirm Any Potential Off-target Sites 〉 Location and possible off-target sites created 〉Genomic location and frequency of cutting by
Slide 11: Safety: Repeat Dosing in Clinic supported by Definitive Pre-Clinical Toxicology Studies
Safety: Repeat Dosing in Clinic supported by Definitive Pre-Clinical Toxicology Studies in Non-human Primates GLP Toxicokinetic / Adult Biodistribution GLP Toxicology Study Biodistribution Study Study 〉Study designed to reflect the 〉PBGENE-HBV; 2 dose 〉Evaluate risk of heritable edits clinical plan
Slide 12: Biodistribution: PBGENE-HBV distributed primarily to the liver
Biodistribution: PBGENE-HBV distributed primarily to the liver PBGENE-HBV NHP Liver Control NHP Liver 〉 ARCUS mRNA reaches all hepatocytes1 〉 ~10,000 ARCUS mRNA molecules per cell are detected in liver2 1. ISH quantification shows that ≥ 80% of cells are ARCUS+ after PBGENE-HBV administration; ~70-8
Slide 13: Safety: PBGENE-HBV did not distribute to germ cells
Safety: PBGENE-HBV did not distribute to germ cells Colocalization between germ cell marker DDX4 and ARCUS mRNA evaluated in sexually mature NHPs Ovary: >4,000 DDX4+ objects evaluated Testes: >20,000 DDX4+ objects evaluated DDX4+ Objects ARCUS mRNA No distribution of PBGENE-HBV to germ cells. Evalua
Slide 14: Safety: Toxicokinetics in NHPs supports safety of repeat dosing
Safety: Toxicokinetics in NHPs supports safety of repeat dosing Plasma Liver 2E+13 2x1013 800 8.E+09 25 ARCUS mRNA; 8x109 ARCUS mRNA; Copies/mL (Copies/mg tissue) ARCUS mRNA (Copies/mg tisssue) Aminolipid; ARCUS Protein ARCUS mRNA (Copies/mL) ARCUS Protein (ng/mL) ug/mL (ng/mg tissue) 20 Aminolipid
Slide 15: Safety: NHP data supports safety of multi-dosing to achieve functional cure
Safety: NHP data supports safety of multi-dosing to achieve functional cure 〉 Good laboratory practice (GLP) toxicology study with 3 dose levels and 3 dose administrations 〉 Liver Function Tests ― Minor and transient elevations in liver transaminases normalized within 2 weeks ― There were no treatme
Slide 16: Phase 1 Clinical Trial – Targeting Cure
Phase 1 Clinical Trial – Targeting Cure
Slide 17: Phase 1 Trial Overview and Key Endpoints
Key Endpoints Up to 5 HBeAg-negative Safety determined by: Frequency and Efficacy determined by: Antiviral activity Countries patients controlled on severity of through finite nucleos(t)ide analogs dose-limiting duration PBGENE- Up to 45 Patients toxicities (DLTs) HBV treatment ClinicalTrials.gov id
Slide 18: Phase 1 Study Design
Phase 1 Study Design Potential for rapid evaluation of safety and efficacy of PBGENE-HBV in 2025 Part 1: Multiple Ascending Dose Escalation Part 2 : Dose Expansion N= 3-6 Patients at Each Dose Level Finite Treatment: Patient Receives up to 3 dose administrations Dose Level 3 | High Dose Safety & Go
Slide 19: Phase 1 Clinical Momentum for PBGENE-HBV Program
Phase 1 Clinical Momentum for PBGENE-HBV Program ELIMINATE-B Safety and antiviral activity Clinical data Global Trial Ongoing after one administration at presentation expected in 0.2 mg/kg dose level 2025 Acknowledgements • Andrew Van Cott • Adepeju Aseyiga • Arpan Mukherjee • Ying Tam • Chengwei Wa