Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Investor Presentation (January 2025)
39 slides from Precision Biosciences's investor presentation, January 2025
Slide 1: Corporate Deck
PRECISION BIOSCIENCES Corporate Deck January 2025 my
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: Precision BioSciences is a Clinical Stage In Vivo Gene Editing Company
Precision BioSciences is a Clinical Stage In Vivo Gene Editing Company Expected First Clinical Multiple Programs in or Nearing Clinical Data Data Timing PBGENE-HBV 〉 Multiple Clinical Trial Application (CTA) approvals received including in Moldova, Hong Kong & New Zealand In Vivo Gene Editing 〉 Firs
Slide 4: OTC Deficiency Program: First ARCUS in vivo Gene Editing Program Validated In Clinical Study
Ornithine Transcarbamylase (OTC) Deficiency Program: First ARCUS in vivo Gene Editing Program Validated In Clinical Study Initial Clinical Validation for ARCUS in vivo Gene Insertion First Infant Achieves Complete Clinical Response in Our Partner iECURE’s Phase 1/2 OTC-Hope trial ~10,000 People WW w
Slide 5: PBGENE-HBV is First Wholly Owned In Vivo Gene Editing Application of ARCUS
PBGENE-HBV is First Wholly Owned In Vivo Gene Editing Application of ARCUS
Slide 6: PBGENE-HBV Positioned to Impact More Patients than Other Gene Editing Programs
PBGENE-HBV Positioned to Impact More Patients than Other Gene Editing Programs Gene Editing Company - Lead Programs SCD and Transfusion- Dependent Beta Size based on worldwide prevalence Thalassemia 25M WW Prevalence 300 Million HeFH Patients 8M PiZ-AATD US Prevalence (Lung and Liver) >1 Million ATT
Slide 7: Chronic Hepatitis B Multi-Billion Dollar Market Opportunity
Chronic Hepatitis B Multi-Billion Dollar Market Opportunity: Large patient population currently on non-curative treatment options Ch > 300 Million U.S. Market Opportunity of ~$10 Billion1 cHBV infections globally Driven by the drug treated patient population today with total global aggregate revenue
Slide 8: Risk of Liver Cancer, Complications, and Mortality Remain on Current SoC
Risk of Liver Cancer, Complications, and Mortality Remain on Current SoC cHBV Patients Have Up to a 30% Risk of Liver Cancer Over 10 years on Nucleos(t)ide Analogs Up to 40% of patients with chronic HBV infections may develop life-threatening complications including cirrhosis and/or HCC1 cHBV Result
Slide 9: Phase 1 Clinical Momentum for PBGENE-HBV Program
Phase 1 Clinical Momentum for PBGENE-HBV Program Potentially Curative Finite Treatment for cHBV First-in-Human Trial Initiated Precision’s Hepatitis 〉CTA approved in Moldova, Hong Kong, and 〉Global Phase 1 multi-site clinical trial Scientific Advisory Board New Zealand initiated and moving to dose p
Slide 10: Advancement to Clinical Trials Supported by Strong Preclinical Rationale
Advancement to Clinical Trials Supported by Strong Preclinical Rationale
Slide 11: PBGENE-HBV Dual Mechanism: Designed to Drive Potential Cures
PBGENE-HBV Dual Mechanism: Designed to Drive Potential Cures By Targeting Root Cause of Disease & Eliminate Eliminate Inactivate cccDNA cccDNA IntegratedHBV Integrated HBVDNA DNA PBGENE- HBV + viral replication Functional Cure Two key viral markers (HBV DNA and HBsAg) undetectable for 6 months+ off
Slide 12: Only ARCUS is designed to eliminate cccDNA and inactivate HBV DNA
Only ARCUS is designed to eliminate cccDNA and inactivate HBV DNA Entry Inhibitors Immune Modulators HBV DNA HBsAg Hepatocyte NA and CAMs Gene Editing Eliminates cccDNA and inactivates HBV DNA cccDNA siRNA and ASO HBV RNAs Host DNA Integrated HBV DNA Nucleus Note: Trademarks are the respective prope
Slide 13: Very Few Patients Get To Functional Cure Today
Very Few Patients Get To Functional Cure Today: PBGENE-HBV has opportunity to be clinically meaningful by increasing functional cures Current Approved Drug Modalities or in Late-stage Development Clinically Meaningful show single-digit functional cure rates Average Functional Cure Rates (%) 30% 20%
Slide 14: Eliminate cccDNA to Cure Hepatitis B
Eliminate cccDNA to Cure Hepatitis B "Realization of a functional “At present, the cccDNA cannot or complete cure for chronic be completely eliminated by “The ideal therapeutic HBV infections requires standard treatments. There is strategy for curative innovative therapeutic an urgent need to develo
Slide 15: ARCUS is The Only Clinical Stage Gene Editor Designed to Eliminate cccDNA
ARCUS is The Only Clinical Stage Gene Editor Designed to Eliminate cccDNA ARCUS Gene Editing Single-component ARCUS protein interacts with cccDNA directly, not through use of a guide RNA Small size Enables delivery efficiency Designed to ELIMINATE cccDNA and and accessibility to cccDNA INACTIVATE in
Slide 16: Demonstrating Efficacy & Safety: Preclinical Evidence for PBGENE-HBV
Demonstrating Efficacy & Safety: Preclinical Evidence for PBGENE-HBV Supports Advancement of PBGENE-HBV to First-In-Human Clinical Studies Nonhuman primates Human HBV Robust Preclinical Evidence, cell lines Including in Gold Standard NHP Models Triangulated Across Supports PBGENE-HBV to Multiple Mod
Slide 17: Safety: PBGENE-HBV Demonstrates Robust Safety Package
Safety: PBGENE-HBV Demonstrates Robust Safety Package Supporting Advancement Towards Clinical Trials Robust and thorough specificity pipeline demonstrated high degree of specificity for PBGENE-HBV with no increased risks of translocations or integrations in HBV-infected PHH PBGENE-HBV does not distr
Slide 18: Safety: PBGENE-HBV Showed Minor and Transient Elevations in Liver Transaminases
Safety: PBGENE-HBV Showed Minor and Transient Elevations in Liver Transaminases NHP data supports safety of multi-dosing to achieve functional cure 1.5 1000 1000 1.5 mg/kg PBGENE-HBV Control 800 800 1.0 AST (U/L) ALT (U/L) TBIL (mg/dL) 600 600 400 400 0.5 200 200 PBGENE-HBV 0 20 40 0 20 40 0 20 40 T
Slide 19: 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 Optimized Nuclease 100 99% 95% 93% Viral Engagement (%) 80 60 HBV LNP 2nd dose administration 0% 40 1st dose administration Control AAV + AAV + AAV + 2mg/kg LNP 1mg/kg LNP 0.5mg
Slide 20: Efficacy: PBGENE-HBV Achieved Broad Distribution Across NHP Liver
Efficacy: PBGENE-HBV Achieved Broad Distribution Across NHP 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; ~7
Slide 21: Efficacy: PBGENE-HBV Significantly and Sustainably Reduced HBV DNA in Mouse Model
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 22: PBGENE-HBV: Robust Preclinical Safety and Efficacy Profile
PBGENE-HBV: Robust Preclinical Safety and Efficacy Profile cccDNA ELIMINATION: 99% viral engagement at IntDNA INACTIVATION: highest dose Dose-dependent editing and HBsAg reductions Nov 2023 Nov 2023 Nonhuman primates SAFETY: SAFETY: Multiple doses were Comprehensive off-target well-tolerated analysi
Slide 23: Phase 1 Clinical Trial – Targeting Functional Cure
Phase 1 Clinical Trial – Targeting Functional Cure
Slide 24: Up to 5 Countries, Up to 45 Patients
Up to 5 Countries HBeAg-negative patients controlled on nucleos(t)ide analogs Up to 45 Patients ClinicalTrials.gov identifier NCT06680232. 23
Slide 25: Eliminate-B Trial is Starting in Largest Real World Patient Segment
Eliminate-B Trial is Starting in Largest Real World Patient Segment More than 80% of HBV Patients are E-Negative 81% of Diagnosed 84% of Patients Treated on Patients are E-Negative Nucleos(t)ide Analogs are E-Negative 16% 19% Still only 1-3% achieve functional cure and up to 30% 10-year cumulative i
Slide 26: 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 & Stagg
Slide 27: PBGENE-HBV Finite Treatment Duration
PBGENE-HBV Finite Treatment Duration: Increased Cumulative Viral Editing Through Up to Three Dose Administrations Treatment Duration Dose Administration Dose Administration Dose Administration 1 2 3 8 weeks 8 weeks later later Increase in cumulative editing of Viral DNA ClinicalTrials.gov identifier
Slide 28: Phase 1 Study Goals to Demonstrate Both Safety and Efficacy
Phase 1 Study Goals to Demonstrate Both Safety and Efficacy Key Endpoints Safety determined by: Efficacy determined by: Frequency and severity of dose-limiting Antiviral activity through fixed duration toxicities (DLTs) PBGENE-HBV treatment Monitoring Biomarkers Reduction/Negativity in HBsAg: Sustai
Slide 29: Phase 1 Clinical Investigators: United Kingdom, Moldova, Hong Kong, New Zealand
United Kingdom Moldova Hong Kong Kosh Agarwal, MD Alina Jucov, MD, PhD Hepatologist and Transplant Principal Investigator, ARENSIA Physician Institute of Liver Studies, Research Clinic, Chisinau, Moldova King’s College Hospital NHS Assistant Professor, Department of Foundation Trust Gastroenterology
Slide 30: PBGENE-HBV: Establishing A New Paradigm for Cures in cHBV
PBGENE-HBV: Establishing A New Paradigm for Cures in cHBV Goal of Sterilizing Cure with Initial Target of Functional Cure Uniquely designed to eliminate cccDNA and inactivate integrated DNA, addressing the root cause of HBV Right Clinical Design Backed by Robust Preclinical Data & Regulatory Alignme
Slide 31: PBGENE-3243
Target CTA/IND 2025 PBGENE-3243 Mutant Mitochondrial DNA Elimination
Slide 32: m.3243 Mitochondrial Disease Currently Lacks a Curative Treatment
m.3243 Mitochondrial Disease Currently Lacks a Curative Treatment ~20K m.3243 mitochondrial disease patients in the US alone m.3243-associated mitochondrial diseases often lead to defects in energy production affecting high energy-demand tissues (e.g. skeletal muscle) m.3243A>G m.3243-associated mit
Slide 33: Multi-Copy Mitochondrial DNA (mtDNA) is Critical for Mitochondrial Function
Multi-Copy Mitochondrial DNA (mtDNA) is Critical for Mitochondrial Function Essential for energy production Mitochondrial DNA (mtDNA) Human Cell Mitochondria 32
Slide 34: PBGENE-3243 Distinguishes a Single Base Difference at m.3243
PBGENE-3243 Distinguishes a Single Base Difference at m.3243 • Mutation Prevalence of 1/5001 m.3243 associated mitochondrial disease m.3243A>G • ~36% of Mitochondrial Diseases are driven by estimated at ~20k patients m.3243A>G2 in the US alone Mutant mtDNA sequence 5’-C A G G G C C C G G T A A T C G
Slide 35: mtDNA Mutations Are Commonly Heteroplasmic
mtDNA Mutations Are Commonly Heteroplasmic Situation where two or more mtDNA variants exist in same mitochondria Clinically asymptomatic Clinically symptomatic 40% mutant 60% mutant 70% mutant 80% mutant Biochemical threshold Mutant mtDNA Wild-type mtDNA mtDNA, mitochondrial DNA. 34
Slide 36: mitoARCUS Therapeutic Approach to Shift Heteroplasmy
mitoARCUS Therapeutic Approach to Shift Heteroplasmy Cytoplasm mitoARCUS MTS ARCUS NES mito-targeting nuclear export sequence signal WT MTS ARCUS NES mtDNA Mitochondrial matrix mutant ARCUS mtDNA
Slide 37: Simplicity: ARCUS Can Go Where Few Other Gene Editors Can Follow
Simplicity: ARCUS Can Go Where Few Other Gene Editors Can Follow Prime ARCUS CRISPR + gRNA Base + gRNA + gRNA PBGENE-3243 Program Highlights 〉 Single component nature of ARCUS allows specific editing of mutant mtDNA with no off-target editing 〉 ARCUS-induced heteroplasmy shift resulting in improved
Slide 38: PBGENE-3243 Improved Mitochondrial Function
PBGENE-3243 Improved Mitochondrial Function On target efficacy Impact on energy production 120% 4 Relative mtDNA copy number 3.5 100% OCR (pmol O2/min/1000 cells) 3 80% 2.5 60% 2 1.5 40% 1 20% 0.5 0% 0 Control PBGENE-3243 Control PBGENE-3243 mutant mtDNA WT mtDNA mtDNA, mitochondrial DNA; WT, wild-t
Slide 39: Precision BioSciences Offering Meaningful Catalysts in Next 6-18 Months
Precision BioSciences Offering Meaningful Catalysts in Next 6-18 Months Ample cash runway to fund multiple potential regulatory submissions and clinical data readouts CASH RUNWAY INTO 2H 2026 ~$109M Potential to Advance 3 Programs to Phase I Clinical Data Cash1 As of 12/31/24 Expected Inflection Poi
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