Precision BioSciences, Inc. · NASDAQ:DTIL
Precision BioSciences — Investor Presentation (January 2024)
77 slides from Precision BioSciences's investor presentation, Jan 12, 2024
Slide 1: Corporate Deck
PRECISION BIOSCIENCES Corporate Deck January 2024 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: Today's Agenda
Today’s Agenda 〉 Corporate Overview 〉 Technology Overview 〉 Chapter 1 – PBGENE-HBV 〉 Chapter 2 – PBGENE-PMM 〉 Chapter 3 – HDR Insertion and Replacement 2
Slide 4: Corporate & Technology Overview
Corporate & Technology Overview
Slide 5: Focusing on Our Foundation—In Vivo Gene Editing
Focusing on Our Foundation—In Vivo Gene Editing Precision—from dual to a single platform gene editing company Focused Execution 2023-2025 Ex Vivo CAR T In Vivo Accretive Event Gene Editing Go-Forward Singular Focus In Vivo Gene Editing Pivoting to Our Foundational Strength • ARCUS - wholly owned gen
Slide 6: Single Gene Editing Platform Funding Through Allogeneic CAR T Platform Deals
Single Gene Editing Platform Funding Through Allogeneic CAR T Platform Deals Unlocking $47 million in upfront and potential near-term payments Announced January 2024 Announced August 2023 • TG Therapeutics: Azer-cel for Autoimmune • Imugene Limited: Azer-cel for cancer; diseases; extends cash runway
Slide 7: End-to-End Research & Development Capabilities
Precision BioSciences End-to-End Research & Development Capabilities Nuclease Generation Gene Delivery & CMC Material Generation Regulatory and 1 & Characterization 2 In Vivo/In Vitro PoC 3 and Toxicology 4 Clinical Development 〉 Protein Engineering 〉 Gene Discovery 〉 Analytical and Process 〉 FDA Pr
Slide 8: Precision BioSciences Leadership Team
Precision BioSciences Leadership Team Michael Amoroso Jeff Smith, Ph.D. Alex Kelly Cindy Atwell Since Oct 2021 Since March 2006 Since Oct 2020 Since Apr 2019 President & Chief Research Officer, Chief Financial Officer Chief Business Officer Chief Executive Officer Co-Founder AMYLIN TM Alan List, M.D
Slide 9: Precision BioSciences Board of Directors
Precision BioSciences Board of Directors Kevin Buehler Michael Amoroso Melinda Brown Stanley Frankel, M.D. Since July 2019 Since Sep 2021 Since May 2022 Since Apr 2021 Board Chair President & Audit Chair Science & Technology Chair Chief Executive Officer Geno Germano Shari Lisa Pire, J.D. Sam Wadswo
Slide 10: ARCUS Focused on Sophisticated Edits Where Defined Outcomes Are Essential
ARCUS Focused on Sophisticated Edits Where Defined Outcomes Are Essential EDIT TYPE / CANDIDATE PROGRAM INDICATION TISSUE TARGET RESEARCH IND-ENABLING PARTNER DELIVERY SELECTION PBGENE-HBV Chronic hepatitis B Liver HBV Elimination/LNP m3243 primary mitochondrial PBGENE-PMM Muscle PMM Elimination/AAV
Slide 11: OTC Program is First ARCUS in vivo Gene Editing Program into the Clinic
Ornithine Transcarbamylase (OTC) Program is First ARCUS in vivo Gene Editing Program to Progress into the Clinic ARCUS in vivo gene editing now clinical stage following December 2023 approval: 28% Of liver cells in NHPs demonstrated durable expression of • iECURE received approval from the Australia
Slide 12: ARCUS Potential to Capture Genetic Medicines Market
ARCUS Potential to Capture a Significant Portion of the Genetic Medicines Market Versus Other Liver-focused Editors The Genetic Medicines Market Opportunity is Substantial Gene Therapy ~$25-$35B Gene Editing market size by 2030 Gene Editing Expected to Disrupt and Continue to Grow the Genetic Medici
Slide 13: Bringing the Dream to Reality with Creation of ARCUS
Bringing the Dream to Reality with Creation of ARCUS • ARCUS is derived from the homing endonuclease I-CreI found in green algae • Evolved to safely edit by inserting in genome, adding function ― CRISPR-based editing tools engineered from enzymes evolved ARCUS to knockout DNA only • Extremely effici
Slide 14: 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 add function Degree of Difficulty ARCUS Remove portion of genome, high Capability To Perform
Slide 15: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity 14
Slide 16: It's All About The Cut
It’s All About The Cut ARCUS’s 3 prime, 4 base pair cut drives efficacy and safety DNA replication direction 3’ overhang DNA replication direction This unique cut drives high efficiency repair by HDR OR “Perfect” Re-ligation leading to Defined Outcomes • Due to ARCUS unique 3’ overhang cut, "sticky-
Slide 17: The ARCUS Cut is Uniquely Designed to Drive Defined Outcomes
The ARCUS Cut is Uniquely Designed to Drive Defined Outcomes ARCUS cut leads to HDR or “Perfect” Re-ligation Cas9 C C G TAT G C A AT TA G C TA G G T C G Blunt cut G G C ATA C G T TA AT C G AT C C A G C induces NHEJ The ARCUS Cut TALEN/ZFN Generates a DNA replication direction C C G TAT G C A AT TA G
Slide 18: ARCUS Inserts with High Efficiency in Adult Nonhuman Primates
ARCUS Inserts with High Efficiency in Adult Nonhuman Primates, Example Previously Thought to be Unachievable Nondividing High Efficiency Gene Insertion cells in vivo 50 44.6 40.6 Gene Insertion (%) 40 >3x 30 insertion efficiency of CRISPR-based 20 approach* + 10 ARCUS DNA Template 0 0 0 0.1 LNP AAV
Slide 19: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity
Slide 20: Size Matters for Where You Can Deliver
Size Matters for Where You Can Deliver ARCUS can use different delivery vehicles to target diverse tissue types ARCUS LNP AAV Liver Eye Muscle CNS Other 19
Slide 21: Size Matters for What You Can Deliver
ARCUS 1500 bp SaCas9 4200 bp AAV Genome Capacity ~4700 bp Size Matters for ARCUS Cas12a 4900 bp What You Can Deliver: Small ARCUS Size Allows SpCas9 Two Nucleases in One AAV 5100 bp ARCUS for Gene Excision in DMD Base Editor (ABEmax) 5800 bp – 6500 bp Prime Editor (PEmax) 7200 bp Sizes include edito
Slide 22: ARCUS Nucleases Excise Mutations and Restore Function in DMD
ARCUS Nucleases Excise Mutations and Restore Function in DMD ARCUS 1 ARCUS 2 Exon 44 Exon 56 Exon 57 Two complementary ARCUS nucleases Exons 45-55 delivered in a single AAV are used to excise a mutation “hot spot” in Exons 45-55 responsible for ~50% of DMD cases Exon 44 Exon 56 Exon 57 Exons 45-55 d
Slide 23: Size Matters for What You Can Deliver: Single AAV
ARCUS 1500 bp SaCas9 4200 bp AAV Genome Capacity ~4700 bp Size Matters for ARCUS Cas12a 4900 bp What You Can Deliver: Allowing Delivery with a SpCas9 DNA Template in a Single AAV for DNA Template 5100 bp Gene Insertion Base Editor (ABEmax) 5800 bp – 6500 bp Prime Editor (PEmax) 7200 bp Sizes include
Slide 24: Why does Size Matter for Safety? Potential for Lower AAV Dose
Why does Size Matter for Safety? Potential for Lower AAV Dose ARCUS + DNA Template gRNA + DNA Template CRISPR/Cas More Less AAV AAV Nuclear DNA Nuclear DNA 23
Slide 25: Why does Size Matter for Safety? Potential for Lower Total LNP Dose
Why does Size Matter for Safety? Potential for Lower Total LNP Dose mRNA quality is a driver of tolerability for LNP-based products 〉High purity mRNA is essential to prevent immunotoxicity. 〉Longer mRNAs are often associated with increased presence of “abortive transcripts,” which compromise purity.
Slide 26: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity 25
Slide 27: Simplicity: ARCUS is the Only Single Protein Component Editor
Simplicity: ARCUS is the Only Single Protein 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 efficiency Single component requi
Slide 28: 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-PMM 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 m
Slide 29: Safety Outcomes Accomplished Through ARCUS Advantages
The Cut Safety Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity 28
Slide 30: Why does Simplicity Matter for Safety?
Why does Simplicity Matter for Safety? ARCUS Integrated Cleavage and Binding Activity Allows for Precise Targeting Targeted Editing Potential for guide independent effector off-target activity Base Editor Prime Editor ARCUS 1 dCas9 or Cas9n 2 1 Cas9n 1 2 pegRNA 3 deaminase Reverse 3 transcriptase Si
Slide 31: ARCUS Safety and Durability Supported By Longest Ongoing Gene Editing NHP Study
ARCUS Safety and Durability Supported By Longest Ongoing Gene Editing NHP Study NHPs have been on study without any serious adverse events 10 NHPs on study for >6 years 80 Stable & Durable Reductions Total in PCSK9 & LDL-C maintained Years throughout study 6 NHPs on study for >3.5 years 16 NHPs trea
Slide 32: Precision Only Focused On ARCUS Differentiation By Edit Type
Precision Only Focused On ARCUS Differentiation By Edit Type Wholly-Owned Partnered Programs Replace Degree of ARCUS Differentiation Future Precision Programs PBGENE-NVS PBGENE-LLY2 Insertion iECURE-OTC Excision PBGENE-DMD PBGENE-LLY3 (CNS) Edit Type and Delivery Undisclosed PBGENE-HBV Elimination P
Slide 33: ARCUS Differentiation By Edit Type
ARCUS Differentiation By Edit Type Strategic Overview of Precision Programs
Slide 34: Chapter 1: PBGENE-HBV
Chapter 1: PBGENE-HBV Viral Elimination Back to Menu
Slide 35: Executive Summary on PBGENE-HBV Program
Executive Summary on PBGENE-HBV Program ARCUS Potential Curative Strategy for HBV Elimination Ready For Clinic in 2024 〉ARCUS only modality currently designed to eliminate cccDNA and inactivate integrated HBV DNA -> essential for functional cure (undetectable HBV DNA and HBsAg after a finite treatme
Slide 36: Only ARCUS designed to eliminate cccDNA and inactivate HBV DNA
Only ARCUS 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 property
Slide 37: PBGENE-HBV Leverages the ARCUS Advantages of Size & Simplicity
The Cut PBGENE-HBV Leverages the ARCUS Advantages of The Size Size & Simplicity PBGENE-HBV Program The Simplicity 36
Slide 38: Size Optimal to Target cccDNA and Integrated HBV DNA
Size Optimal to Target cccDNA and Integrated HBV DNA ARCUS ~1000 base pairs (bp) Small size may allow easier access to DNA for target site editing —impact of DNA methylation and chromatin structure is less relevant for ARCUS due to small protein size ARCUS ARCUS is efficient at targeting cccDNA + in
Slide 39: Simplicity: ARCUS is the only single component editor
Simplicity: ARCUS is the only single component editor ARCUS Epigenetic Editor Base Editor CRISPR 1 1 Methylation effector 1 domain DNA binding 2 domain dCas9 or Cas9n 2 1 Cas9 2 3 Transcription effector domain 3 deaminase Efficacy Single component of ARCUS means more efficient packaging and delivery
Slide 40: Targeting cccDNA: ARCUS Versus Other Genetic Modalities
Targeting cccDNA: ARCUS Gene Editing Versus Other Genetic Modalities in Development Base Editor ARCUS Epigenetic Editor1 CRISPR Editor3 (Development Paused2) Designed to eliminate cccDNA Silences cccDNA Mutates and Creates cccDNA indels vs. Edit Result directly at high efficiency via methylation Ina
Slide 41: PBGENE-HBV Designed For Broad Patient Applicability
> 300 million cHBV infections globally PBGENE-HBV Designed For Broad Patient Applicability > 1,000,000 cHBV infections in the US 40
Slide 42: ARCUS Recognizes a Highly Conserved Sequence in cccDNA
Broad Patient Applicability: ARCUS Recognizes a Highly Conserved Sequence in cccDNA Target site conserved in ARCUS >92% Target Site of isolates 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. 202
Slide 43: ARCUS Recognizes a Highly Conserved Sequence in Integrated HBV DNA
Broad Patient Applicability: 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.20
Slide 44: 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 Demonstrated Up to 99% Viral Engagement Data Update • • Eliminated cccDNA and Inhibited Viral Markers in PHH ~95% Durable HBsAg Reduction Acr
Slide 45: PBGENE-HBV Final Clinical Candidate Shows Enhanced Specificity
Safety: PBGENE-HBV Final Clinical Candidate Shows Enhanced Specificity With No Detectable Off-Target Editing PBGENE-HBV Final Clinical Candidate 70 60 50 No Off-Target Editing % Editing 40 1.2 Detected at 1 Maximally- 0.8 Saturating On- 0.6 Target Dose 0.4 Limit of Detection = 0.2 0.2 0 On- and Off-
Slide 46: 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 47: Eliminate cccDNA
ARCUS Eliminate cccDNA HBV cccDNA 46
Slide 48: 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 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 eliminated
Slide 49: PBGENE-HBV Eliminates cccDNA and Inhibits Viral Markers in Hepatocytes
Efficacy: PBGENE-HBV Eliminates cccDNA and Inhibits Viral Markers in HBV-Infected Primary Human Hepatocytes (PHH) 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 0.1 0.3 not
Slide 50: Up to 95% Durable HBsAg Reduction in Episomal Mouse Study
Efficacy: PBGENE-HBV Demonstrates Up to 95% Durable HBsAg Reduction Across Dose Levels in Episomal Mouse Study 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 150 vira
Slide 51: Inactivate Integrated HBV DNA
ARCUS Inactivate Integrated HBV DNA Integrated HBV DNA 50
Slide 52: PBGENE-HBV Reduces HBV DNA as a Monotherapy in Transgenic Mouse Model
Efficacy–New Model: PBGENE-HBV Significantly and Sustainably Reduces HBV DNA as a Monotherapy in New Transgenic Mouse Model 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 (higher dose)
Slide 53: ARCUS Potential Curative Strategy for HBV
ARCUS • Size Optimal: Target cccDNA and Integrated HBV DNA Simplicity of ARCUS: single component editor offers advantages Potential Curative • when applied to HBV elimination Strategy for HBV • mRNA Sequence Optimization: 8x improvement in protein expression permitting dosing flexibility ARCUS Dual
Slide 54: 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 55: Chapter 2: PBGENE-PMM
Chapter 2: PBGENE-PMM Mutant Mitochondrial DNA Elimination Back to Menu
Slide 56: Primary Mitochondrial Myopathy Currently Lacks a Curative Treatment
Primary Mitochondrial Myopathy (PMM) Currently Lacks a Curative Treatment Mitochondrial diseases (MDs) Primary mitochondrial myopathies (PMM) are the most common are genetically defined disorders leading to defects in hereditary metabolic energy production predominantly affecting skeletal muscle dis
Slide 57: Multi-Copy Mitochondrial DNA 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 56
Slide 58: PBGENE-PMM Distinguishes a Single Base Difference at m.3243
PBGENE-PMM Distinguishes a Single Base Difference at m.3243 • Mutation Prevalence of 1/5001 m.3243 associated PMM m.3243A>G • ~36% of Mitochondrial Diseases are driven by estimated at ~14k patients in the US alone3 m.3243A>G2 Mutant mtDNA sequence 5’-C A G G G C C C G G T A A T C G C A T A A A-3’ 5’
Slide 59: 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. 58
Slide 60: mitoARCUS Therapeutic Approach to Shift Heteroplasmy
mitoARCUS Therapeutic Approach to Shift Heteroplasmy Cytoplasm mitoARCUS MTS ARCUS mito-targeting polyA sequence WT MTS ARCUS mtDNA Mitochondrial matrix mutant ARCUS mtDNA mtDNA, mitochondrial deoxyribonucleic acid; MTS, mitochondrial targeting sequence; WT, wild-type. 59
Slide 61: PBGENE-PMM Improved Mitochondrial Function
PBGENE-PMM 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-PMM Control PBGENE-PMM mutant mtDNA WT mtDNA mtDNA, mitochondrial DNA; WT, wild-type
Slide 62: mitoARCUS Shifted Heteroplasmy in In Vivo Mouse Model
mitoARCUS Shifted Heteroplasmy in In Vivo Mouse Model Heart Tibialis Anterior Quad Calf Kidney Liver Spleen 20 0 % Change mutant mtDNA -20 (normalized to brain) -40 -60 -80 -100 -120 Control mitoARCUS mtDNA, mitochondrial DNA. Zekonyte U, et al. Nat Commun. 2021. 2021;12(1):3210. 61
Slide 63: Reasons to Believe in Precision's Approach to Treat PMM
Target CTA/IND Reasons to Believe in Precision’s Approach to Treat PMM 2025 Simplicity of ARCUS single component editor enables targeting mutant mitochondrial DNA whereas other guide RNA-based editors cannot Opportunity for a one-time, potentially curative treatment for adult patients who today are
Slide 64: Chapter 3: Road To HDR Gene Insertion & Replacement
Chapter 3: Road To HDR Gene Insertion & Replacement Back to Menu
Slide 65: Derisking Through Internal Program Development, Delivery, and Select Partners
Derisking Through Internal Program Development, Delivery, and Select Partners Current Program Development Future HDR Gene Insertion/Replace Program LNP AAV LNP AAV Future Delivery at and Beyond + the Liver In the Outside In the Liver the Liver Liver Leveraging PBGENE-HBV and Leveraging PBGENE-PMM De
Slide 66: ARCUS HDR Gene Insertion Validated by Big Pharma and Biotech Partners
ARCUS HDR Gene Insertion Validated by Big Pharma and Biotech Partners 2020 2021 2022 Key Accomplishments Key Accomplishments Key Accomplishments 〉 AAV + LNP delivery for gene 〉 Robust in vivo liver insertion data 〉 Novel approach to bring sophisticated insertion in liver with ~20% insertion across a
Slide 67: ARCUS Can Drive Efficient HDR in Both Dividing and Non-Dividing Cells
ARCUS Can Drive Efficient HDR in Both Dividing and Non-Dividing Cells… …Previously Thought to be Nearly Impossible for Gene Editing “However, traditional HDR "By the late 1980's, dogma “Inability to correct genes has very low efficiency in most in the field of DNA repair in non-dividing cells human
Slide 68: ARCUS Inserted with 17x Higher Efficiency than CRISPR
ARCUS Inserted with 17x Higher Efficiency than CRISPR A true head-to-head comparison ARCUS vs CRISPR insertions 40% 36% 32% 28% Head-to-head comparison at same site, Insertion Efficiency % 24% 17x same dose, with same DNA template. 20% higher 16% 12% ARCUS was More Efficient 8% 4% 0% Mock DNA Templa
Slide 69: 3' Overhangs Promoted Insertion Through HDR
3’ Overhangs Promoted Insertion Through HDR Chewing off the 3' overhangs impacts insertion efficiency Impact of 3’ overhangs made by ARCUS 60% 49% 50% • TREX1 removes 3’ overhangs of ARCUS Insertion Efficiency % 40% Loss of • TREX1 generates CRISPR-like blunt cuts 30% 3’ overhangs • Blunt cut ablate
Slide 70: Gene Insertion Efficiency and Outcomes are Context-Dependent
Gene Insertion Efficiency and Outcomes are Context-Dependent 1 2 3 4 Dividing cells Non-dividing, primary Dividing cells in vivo Non-dividing cells in vivo in culture cells in culture (infant/child) (adults)* Increasing Level of Evidence & Difficulty *Note: Data in adult non-dividing NHPs already sh
Slide 71: ARCUS Inserted with High Efficiency in Dividing Cells in Culture
ARCUS Inserted with High Efficiency in Dividing Cells in Culture High Efficiency Gene Insertion Mechanism of Repair 1 100 75.9% 75 Gene Insertion (%) 50 92% Dividing cells HDR 25 in culture 0 0 0.2 Mock DNA Template DNA Template + Alone ARCUS Data on file 70
Slide 72: ARCUS Inserts Efficiently in Both Copies of Target Gene
ARCUS Inserts Efficiently in Both Copies of Target Gene Resulting in High Functional Impact - Dividing Cells in Culture ARCUS inserts in both alleles* Bi-allelic editing results in high 1 functional impact 60 Therapeutic Gene Induction (%) 51.4% 50 40 37.1% 91% 30 Dividing cells Bi-allelic 20 in cul
Slide 73: ARCUS Inserts Efficiently in Non-Dividing Cells in Culture
ARCUS Inserts Efficiently in Non-Dividing Cells - in Culture High Efficiency Gene Insertion Mechanism of Repair 2 40 28.6% 30 Gene Insertion (%) 20 57% Nondividing HDR 10 primary cells in culture 0 0% Mock DNA Template + ARCUS ARCUS Ability to Insert by HDR in Non-Dividing Cells is Attributable to t
Slide 74: ARCUS Inserts with High Efficiency in Infant Nonhuman Primates
ARCUS Inserts with High Efficiency in Infant Nonhuman Primates; Sustained Effect Demonstrated at 12 months 3 Dividing cells High Efficiency Gene Insertion Day 84 Day 365 25 in vivo 19.9 NHP #1 NHP #1 15.3 20 Gene Insertion (%) 15 NHP #2 NHP #2 10 + 5 ARCUS DNA Template AAV AAV 0 1e13 vg/kg 3e13 vg/k
Slide 75: ARCUS is Ideal for Therapeutic Gene Insertion
ARCUS is Ideal for Therapeutic Gene Insertion High efficiency insertion rates Designed to Increase High HDR observed Therapeutic Effect Biallelic editing demonstrated Breadth in Level of Evidence Demonstrating Insertion in Dividing and Non-Dividing Cells In Vitro and In vivo 74
Slide 76: Therapeutic Breadth: ARCUS is Best Suited to Insert or Replace Genes
Therapeutic Breadth: ARCUS is Best Suited to Insert or Replace Genes Insert or replace >2000bp of a gene ARCUS Editor Broad Therapeutic Applicability Gene Correct small (50-100 bp) segment of gene Prime Editor Limited Therapeutic Applicability Gene KO a gene or correct a single base Very Limited Bas
Slide 77: Examples of Opportunities for Gene Insertion & Replacement Through HDR
Examples of Opportunities for Gene Insertion & Replacement Through HDR Hemophilia B Cystic Fibrosis ARCUS can unlock Gene Insertion & Replacement ARCUS Retinitis HIV through HDR across Pigmentosa a broad range of tissue types at the Liver and beyond Cardiomyopathy Angelman Syndrome Examples and info
Precision BioSciences — Investor Presentation (January 2024) on 6ix