Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Investor Presentation (November 2024)
53 slides from Precision Biosciences's investor presentation, Nov 15, 2024
Slide 1: PBGENE-HBV Hepatitis B Program Investor Update
Precision’s Lead Program PBGENE-HBV Hepatitis B Program Investor Update November 15, 2024
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
Precision BioSciences Clinical Stage In Vivo Gene Editing Company With Goal to Cure Chronic Hepatitis B Michael Amoroso President & Chief Executive Officer Precision BioSciences, Inc
Slide 4: Precision BioSciences is a Clinical Stage In Vivo Gene Editing Company
Precision BioSciences is a Clinical Stage In Vivo Gene Editing Company Multiple Programs in or Nearing Clinical Data Expected First Clinical Data Timing 〉Multiple Clinical Trial Applications (CTA) filed PBGENE-HBV 〉Rapid CTA approval for Moldova Achieved in October 2024 In Vivo Gene Editing 〉First-i
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 SCD and Transfusion- Gene Editing Company - Lead Programs Dependent Beta Size based on world-wide prevalence Thalassemia 25M WW Prevalence 300 Million HeFH Patients 8M PiZ-AATD US Prevalence (Lung and Liver) >1 Million AT
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 HBV 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 Results
Slide 9: HBV Driven By Two Distinct Drivers of Disease
HBV Driven By Two Distinct Drivers of Disease cccDNA Integrated HBV DNA + viral replication 8
Slide 10: PBGENE-HBV Dual Mechanism
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 + AAA viral replication Functional Cure Two key viral markers (HBV DNA and HBsAg) undetectable for 6 months+
Slide 11: Robust Preclinical Proof-of-Concept Data Supports Advancement of PBGENE-HBV
Robust Preclinical Proof-of-Concept Data Supports Advancement of PBGENE-HBV 10
Slide 12: Demonstrating Efficacy: Preclinical Evidence Supports First-In-Human Studies
Demonstrating Efficacy: 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 Multiple Models Supports PBGENE-HBV to Safel
Slide 13: Phase 1 Clinical Momentum for PBGENE-HBV Program
Phase 1 Clinical Momentum for PBGENE-HBV Program Potentially Curative Finite Treatment for cHBV Clinical Program Quickly Moving Towards Dosing Patients Precision’s Hepatitis 〉CTA approved in Moldova 〉Global Phase 1 multi-site clinical trial Scientific Advisory Board initiated and moving to dosing pa
Slide 14: Discussion with Expert Clinical Investigators & Scientific Advisory Board Members
Discussion with Expert Clinical Investigators & Precision Scientific Advisory Board Members Murray Abramson, MD, MPH Mark Sulkowski, MD Jordan Feld, MD, MPH Head of Clinical Development Professor of Medicine Section Head, Hepatology, Division of Precision BioSciences, Inc Director, Division of Infec
Slide 15: A Patient's Journey From cHBV Infection to Treatment
A Patient's Journey From cHBV Infection to Treatment Chronic Treatment Infected Diagnosed Functional Cure with Nucleoside Analogs HBV RNA HBV DNA Initial Exposure Chronic HBV (cHBV) Chronic Treatment with Nucleoside Analogs Only 1-3% Virus enters the liver and 〉 HBV becomes chronic 〉 Of patients on
Slide 16: HBV Primer: Monitoring HBV Activity Through Biomarkers
HBV Primer: Monitoring HBV Activity Through Biomarkers Patient serology levels demonstrate HBV viral load and activity Biomarkers 1 HBV RNA 1 HBV RNA Source: cccDNA HBV RNA is the predecessor to HBV DNA. It is reflective of Hepatocyte the presence and transcriptional activity of cccDNA 2 HBV DNA 2 H
Slide 17: A Patient's Journey From cHBV Infection to Treatment
A Patient's Journey From cHBV Infection to Treatment Chronic Treatment with Infected Diagnosed Functional Cure Nucleoside Analogs "NUCs" Measuring Viral Load Impact from NUCs HBV RNA Detectable Initial Exposure Only 1-3% of patients Two sources of virus HBV DNA Undetectable achieve functional cure o
Slide 18: Majority of Modalities Target HBV Downstream, Leaving Root Cause Intact
Majority of Modalities in Development Target HBV Downstream to Disrupt the Viral Lifecycle but Leave the Root Cause of Disease Intact No therapies today target the root cause of disease by eliminating the cccDNA and inactivating the integrated HBV DNA ANTISENSE NUCLEOS(T)IDE ANALOGS OLIGONUCLEOTIDES
Slide 19: PBGENE-HBV Directly Targets Root Cause of Disease
However, PBGENE-HBV Directly Targets Root Cause of Disease Targeting the origin of viral genesis ANTISENSE NUCLEOS(T)IDE ANALOGS PBGENE OLIGONUCLEOTIDES CAPSID ASSEMBLY HBV SMALL INTERFERING RNA MODULATORS HBV DNA HBV RNA Hepatocyte NUCLEIC ACID POLYMER HBsAg Eliminates cccDNA HBV transcripts THERAP
Slide 20: Finite PBGENE-HBV Treatment Designed To Eliminate Root Source of Viral Replication
Finite PBGENE-HBV Treatment Designed To Eliminate Root Source of Viral Replication Finite treatment with Infected Diagnosed Functional Cure PBGENE-HBV Measuring Viral Load Potential Impact from PBGENE-HBV HBV RNA Undetectable Initial Exposure Two sources of virus HBV DNA Undetectable 〉 cccDNA (the f
Slide 21: 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 22: PBGENE-HBV is Designed to Meet The Needs of the Patient
PBGENE-HBV is Designed to Meet The Needs of the Patient Based on Hepatitis B Foundation Expert Workshop & Patient Perspectives1,2 What does an ideal treatment look like for patients with cHBV? 〉 Cures Hepatitis B By Targeting Root Cause of Disease and Degradation of cccDNA 〉 Safe, Tolerable and No L
Slide 23: Advancement to Clinical Trials Supported by Strong Preclinical Rationale
Advancement to Clinical Trials Supported by Strong Preclinical Rationale Cassie Gorsuch, PhD Head of Gene Therapy Discovery Precision BioSciences, Inc
Slide 24: 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 25: ARCUS is Only Clinical Stage Gene Editor Designed to Eliminate cccDNA
ARCUS is 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 integr
Slide 26: Robust Preclinical Safety and Efficacy Profile
Robust Preclinical Safety and Efficacy Profile Nonhuman primates Human HBV cell lines Multiple Models and Viral Endpoints Achieved Transgenic Mouse Model Primary human hepatocytes Episomal AAV Mouse Model 25
Slide 27: Preclinical Safety: High Specificity and Good Tolerability Across Models
Preclinical Safety: High Specificity and Good Tolerability Across Models SAFETY: SAFETY: Multiple doses were Comprehensive off-target well-tolerated analysis demonstrates high specificity June 2024 Nonhuman primates Nov 2023 Human HBV cell lines Multiple Models and Viral Endpoints Achieved SAFETY: T
Slide 28: Safety: 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 29: Safety: Robust Safety Package Supporting Advancement Towards Clinical Trials
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 30: Preclinical Efficacy: cccDNA Elimination is Essential for Cure
Preclinical Efficacy: cccDNA Elimination is Essential for Cure cccDNA ELIMINATION: 99% viral engagement at highest dose Nonhuman primates Nov 2023 Human HBV Episomal AAV cell lines Mouse Model Multiple Models and Viral Endpoints Achieved Transgenic cccDNA Mouse Model ELIMINATION: Primary human Dose-
Slide 31: 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 0% 40 Control AAV + AAV + AAV + 2mg/kg LNP 1mg/kg LNP 0.5mg/kg LNP Increased editing observed with 2 dose a
Slide 32: Efficacy: Broad Distribution Across NHP Liver
Efficacy: PBGENE-HBV Achieves 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 33: Preclinical Efficacy: Integrated DNA Inactivation Necessary For Functional Cure
Preclinical Efficacy: Integrated DNA Inactivation Necessary For Functional Cure IntDNA INACTIVATION: Dose-dependent editing and HBsAg reductions Nonhuman primates Nov 2023 Human HBV cell lines Multiple Models and Viral Endpoints Achieved IntDNA INACTIVATION: Transgenic Significant and sustainable Mo
Slide 34: Efficacy: Significantly and Sustainably Reduced HBV DNA in Transgenic 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 35: 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: (NHPs) Multiple doses were Comprehensive off-target well-tolerated
Slide 36: Excitement Continues Into Clinic
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 analysis demonstrates high specificity Exciteme
Slide 37: Phase 1 Clinical Trial – Targeting Functional Cure
Phase 1 Clinical Trial – Targeting Functional Cure Murray Abramson, MD, MPH Head of Clinical Development Precision BioSciences, Inc
Slide 38: Eliminate-B Trial: 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. 37
Slide 39: 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 40: Key Inclusion / Exclusion Criteria
Key Inclusion / Exclusion Criteria Inclusion Criteria Exclusion Criteria • HBeAg-negative cHBV • No history of liver cirrhosis regardless of any subsequent improvement in histology • cHBV infection documented by serum HBsAg-positivity for ≥ 12 months • No hepatitis A virus infection, hepatitis D vir
Slide 41: 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 42: 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 43: 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 44: Expert Clinical Investigators Panel
Expert Clinical Investigators Panel Murray Abramson, MD, MPH Head of Clinical Development Precision BioSciences, Inc
Slide 45: 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 46: Moldova Enables Operational Speed Towards Dosing First Patient
Moldova Enables Operational Speed Towards Dosing First Patient Moldova 〉 High Unmet Need ― High diagnosed prevalence rate resulting in large patient population (>215,000 patients) 〉 Clinical Trial Feasibility ― Highly centralized medical system provides easier access to patients suffering from cHBV
Slide 47: New Zealand is a Pioneer for Gene Editing Studies & Infectious Disease
New Zealand is a Pioneer for Gene Editing Studies & Infectious Disease New Zealand 〉 Sizable patient population ― Approximately 100,000 people in New Zealand live with chronic HBV, and many require lifelong monitoring due to the risk of liver damage and liver cancer2 〉 New Zealand Clinical Research
Slide 48: Hong Kong is on the Forefront of cHBV Drug Development
Hong Kong is on the Forefront of cHBV Drug Development Hong Kong 〉 Clinical Trial Feasibility ― Nearly 70 Phase 1/2 studies completed or on-going for investigation in HBV1,2 ― Clinical center offers access to Asian-specific genotypes for inclusion into clinical studies 〉 Large Patient Population ― A
Slide 49: U.K. is a Global Center of Excellence for cHBV & Pioneers in Gene Editing
U.K. is a Global Center of Excellence for cHBV & Pioneers in Gene Editing United Kingdom (U.K.) 〉 Growing Diagnosed Patient Population1 ― UKHSA initiatives in place to improve the diagnosis rate for people living with hepatitis B ― ~90,000 prevalent patient population today, but estimated up to 270,
Slide 50: Clinical Summary
Clinical Summary Murray Abramson, MD, MPH Head of Clinical Development Precision BioSciences, Inc
Slide 51: 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 target cccDNA and integrated DNA, addressing the root cause of HBV Right Clinical Design Backed by Robust Preclinical Data & Regulatory Alignment Demonstrate
Slide 52: Closing Thoughts
Closing Thoughts un
Slide 53: Next Steps Focused on Operational Excellence & Generating Clinical Data
Next Steps Focused on Operational Excellence & Generating Clinical Data Finalize Regulatory Submissions Continued Clinical Execution Evaluate Potential for Stopping Nucleos(t)ide & Drive Clinical Operations & First Data Readout Analogs & Initiate Phase 1b 〉 Secure additional CTA and IND 〉 Enroll pat
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