Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — American Association for the Study of Liver Disease (AASLD) 2023
32 slides from Precision Biosciences's conference presentation, Nov 13, 2023
Slide 1: Investor Update on PBGENE-HBV Program
Investor Update on PBGENE-HBV Program American Association for the Study of Liver Disease (AASLD) November 13, 2023
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: Opening Remarks
Opening Remarks Michael Amoroso President & Chief Executive Officer 2
Slide 4: Today's Overview
Today’s Overview Singular Focus ARCUS Potential Curative Strategy KOL Perspective: Quest for a on Gene Editing for HBV Elimination Functional Cure Through ARCUS with ARCUS HBV Elimination Strategy Internal Lead Program 〉ARCUS only modality to eliminate cccDNA Dr. Geoffrey Dusheiko PBGENE-HBV and ina
Slide 5: ARCUS for the More Sophisticated Gene Edit
ARCUS for the More Sophisticated Gene Edit Designed by nature for a multitude of applications versus other gene editing modalities Replace Remove defective and insert functional gene Insertion Insert gene to cause expression Degree of Difficulty ARCUS Remove portion of genome, high Capability To Per
Slide 6: PBGENE-HBV Leverages the ARCUS Advantages of Size and Simplicity
The Cut PBGENE-HBV Leverages the ARCUS Advantages of The Size Size & Simplicity PBGENE-HBV Program The Simplicity 5
Slide 7: ARCUS Potential to Capture a Significant Portion of Genetic Medicines Market
ARCUS Potential to Capture a Significant Portion of Genetic Medicines Market The Genetic Medicines Market Opportunity is Substantial Gene Therapy ~$25-$35B Precision’s PBGENE-HBV program Gene Editing market size by 2030 represents a market opportunity to treat Total Estimated Sales ($MM) CAGR 200-30
Slide 8: ARCUS Potential Curative Strategy for HBV Elimination
ARCUS Potential Curative Strategy for HBV Elimination Cassie Gorsuch, PhD Vice President, Head of Gene Therapy Discovery 7
Slide 9: PBGENE-HBV Program Accomplishments
PBGENE-HBV Program Accomplishments Finalized mRNA optimization of payload and LNP formulation leading to 8x improvement in protein expression FDA INTERACT Meeting in July Final Clinical Candidate Nominated on-track Submit IND/CTA in 2024 site-selection Initiate First-in-Human (FIH) Clinical Studies
Slide 10: ARCUS Approach to Eliminate cccDNA and Inactivate Integrated HBV DNA
ARCUS Approach to Eliminate cccDNA and Inactivate Integrated HBV DNA to Drive Durable Antigen Loss with Goal of Functional Cure Therapeutic Outcomes 1 Elimination by exonuclease ARCUS DNA break HBV DNA and HBsAg loss occurs “Indel” via DNA repair HBV cccDNA HBV cccDNA HBV DNA and HBsAg loss 2 ARCUS
Slide 11: AASLD 2023 Data Update
Summary of New PBGENE-HBV Data Presented • Enhanced Specificity With No Detectable Off-Target Editing at Maximal On-target Editing Dose AASLD 2023 • NHP Study Demonstrates Up to 99% Viral Engagement Data Update • • Eliminates cccDNA and Inhibits Viral Markers in PHH ~95% Durable HBsAg Reduction Acro
Slide 12: Safety: Final Clinical Candidate Shows Enhanced Specificity
Safety: PBGENE-HBV Final Clinical Candidate Shows Enhanced Specificity With No Detectable Off-Target Editing NEW DATA PBGENE-HBV Final Clinical Candidate 70 60 50 No Off-Target % Editing 40 1.2 Editing 1 Detected 0.8 0.6 0.4 Limit of Detection = 0.2 0.2 0 On- and Off-Target Sites Notes: 1. The final
Slide 13: ARCUS Eliminate cccDNA
ARCUS Eliminate cccDNA HBV cccDNA 12
Slide 14: Efficacy: NHP Study Demonstrates Up to 99% Viral Engagement
Efficacy: Non-Human Primate (NHP) Study Demonstrates Up to 99% Viral Engagement, Suggestive of Strong Potential Efficacy Profile of PBGENE-HBV NEW DATA Prior Optimized Nuclease 99% viral engagement Nuclease at highest dose in NHP study 100 99% 95% 93% 18% Viral Engagement (%) 81% 80 indels 81% 60 el
Slide 15: Efficacy: Eliminates cccDNA in Primary Human Hepatocytes
Efficacy: PBGENE-HBV Eliminates cccDNA and Inhibits Viral Markers in HBV-Infected Primary Human Hepatocytes (PHH) NEW DATA 100 ARCUS mRNA (µg) 90 Medium 0.001 80 0.003 0.01 0.03 HBV DNA NUC % Inhibition 70 0.1 0.3 HBsAg 60 HBeAg 50 HBV RNA 40 30 cccDNA 20 10 0 *siRNA also do 0.001 0.003 0.01 0.03 0.
Slide 16: Efficacy: Up to 95% Durable HBsAg Reduction in Mouse Study
Efficacy: PBGENE-HBV Demonstrates Up to 95% Durable HBsAg Reduction Across Dose Levels in Episomal Mouse Study NEW DATA Final Clinical Candidate 200 PBS Prior Nuclease ARCUS LNP ARCUS LNP 0.3 mg/kg 95% administration HBsAg Inhibition (% of baseline) ARCUS LNP 0.1 mg/kg 90% ARCUS LNP 0.03 mg/kg viral
Slide 17: ARCUS Inactivate Integrated HBV DNA
ARCUS Inactivate Integrated HBV DNA Integrated HBV DNA 16
Slide 18: Efficacy: HBV DNA Reduction in New Transgenic Mouse Model
Efficacy–New Model: PBGENE-HBV Significantly and Sustainably Reduces HBV DNA as a Monotherapy in New Transgenic Mouse Model NEW DATA HBV DNA 1st 2nd ARCUS ARCUS Dose Dose 5 Log [HBV DNA (copy/µl)] Saline 4 NUC 0.003 mg/kg ARCUS 0.1 mg/kg (lower dose) 3 ARCUS 1 mg/kg (higher dose) ARCUS 1 mg/kg (high
Slide 19: ARCUS Potential Curative Strategy for HBV
ARCUS • Simplicity of ARCUS: single component editor offers advantages when applied to HBV elimination Potential Curative • mRNA Sequence Optimization: 8x improvement in protein expression permitting dosing flexibility Strategy for HBV • ARCUS Dual Mechanism: eliminates cccDNA and inactivates integr
Slide 20: The Quest for a Functional Cure Through ARCUS HBV Elimination Strategy
The Quest for a Functional Cure Through ARCUS HBV Elimination Strategy Dr. Geoffrey Dusheiko, MD, FCP(SA), FRCS Emeritus Professor of Medicine King's College Hospital & University College London 19
Slide 21: HBV Currently Lacks a Curative Treatment
HBV Currently Lacks a Curative Treatment Hepatitis B is a leading cause of morbidity in the US and death globally, with no current curative options > 300 million An estimated 15% to 40% of patients cHBV infections globally > 1,000,000 cHBV infections in the US with HBV infections may develop complic
Slide 22: Hepatitis B – ARCUS is Differentiated Versus Other Approaches
Hepatitis B – ARCUS is Differentiated Versus Other Approaches ENTRY INHIBITORS HBV DNA HBsAg Hepatocyte NUCLEOS(T)IDE ANALOGS CAPSID ASSEMBLY MODULATORS NUCLEIC ACID POLYMER THERAPY cccDNA HBV RNAs ANTISENSE ARCUS OLIGONUCLEOTIDES Host DNA SMALL INTERFERING RNA Integrated HBV DNA 21 Nucleus
Slide 23: The Quest for a Functional Cure Through HBV Elimination Strategy
The Quest for a Functional Cure Through HBV Elimination Strategy Sustained Undetectable Circulating HBV Surface Functional Cure = Antigen (HBsAg) and HBV DNA After a Finite Course of Treatment. “Ability to achieve functional cure today is extremely limited… Gene editing therapies would enhance the p
Slide 24: Q&A
Q&A Cassie Gorsuch, PhD Dr. Geoffrey Dusheiko, MD Vice President, Head of Gene Therapy Discovery Emeritus Professor of Medicine Precision BioSciences, Inc. Royal Free Hospital & University College 23
Slide 25: Near-Term Catalysts Include Filing CTA/IND for PBGENE-HBV in 2024
Near-Term Catalysts Include Filing CTA/IND for PBGENE-HBV in 2024 1 2 Drive Organic Development Establish Premium Partnerships Focus on Eliminations, Excisions and Insertions Work with leading Big Pharma/Biotech to drive differentiated programs forward Current PBGENE-DMD Lead PBGENE-HBV PBGENE-LLY2
Slide 26: Appendix
Appendix my 25
Slide 27: PBGENE-HBV Program Enhancements: mRNA Optimization
Through Our PBGENE-HBV Program Enhancements, We Have Conducted mRNA Optimization ARCUS Protein Expression in Mice 10000 ARCUS Protein (ng/g tissue) 8000 6000 mRNA Sequence Optimization 8x 4000 increase 2000 0 Current ARCUS mRNA Future ARCUS mRNA 26
Slide 28: Taking Advantage of ARCUS Simplicity for HBV
Taking Advantage of ARCUS Simplicity for HBV ARCUS is The Only Single Component Editor ARCUS Single protein with a DNA recognition motif and catalytic 1 activity all in one; no guide RNA required Editing outcome not dependent on simultaneous delivery of multiple components leading to higher efficien
Slide 29: ARCUS Approach for a Functional Cure
ARCUS Approach for a Functional Cure ARCUS eliminates cccDNA and inactivates integrated HBV to drive durable antigen loss HBV DNA HBsAg HBV-infected Hepatocyte cccDNA HBV RNAs Integrated HBV DNA 28 Nucleus
Slide 30: ARCUS Approach for a Functional Cure
ARCUS Approach for a Functional Cure ARCUS eliminates cccDNA and inactivates integrated HBV to drive durable antigen loss Elimination of cccDNA HBsAg and inactivation of integrated DNA reduces HBV DNA HBV RNA, HBV DNA, and HBsAg potentially leading to a functional cure HBV-infected Hepatocyte cccDNA
Slide 31: Selecting Target Site: Highly Conserved Sequence in cccDNA
Selecting Target Site: ARCUS Recognizes a Highly Conserved Sequence in cccDNA Target site conserved in 92% ARCUS of isolates Target Site across genotypes1,2 Core S PreS1 X PreS2 1. Gorsuch CL, et al. Mol Ther. 2022;30(suppl 9):2909-2922. 2. Image source adapted from: Tu T, et al. Viruses. 2021;13(2)
Slide 32: Selecting Target Site: Highly Conserved Sequence in Integrated HBV DNA
Selecting Target Site: ARCUS Recognizes a Highly Conserved Sequence in Integrated HBV DNA ARCUS Targeted region is present in Target Site the vast majority of integrations1 Core S PreS1 X PreS2 1. van Buuren, N, et al. JHEP Rep. 4.4 (2022): 100449. Published 2022 Feb 12. doi:10.1016/j.jhepr.2022.100
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