Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Investor Presentation (June 2024)
54 slides from Precision Biosciences's investor presentation, June 2024
Slide 1: Corporate Deck
PRECISION Bulrers'e WENGE S Corporate Deck June 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: 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 Overview
PRECISION Bil@mre WEINI@IES Corporate Overview i
Slide 5: Focusing on Our Foundation—In Vivo Gene Editing
Focusing on Our Foundation—In Vivo Gene Editing Through our gene editing platform ARCUS Focused Execution 2024-2026 Ex Vivo CAR T Accretive Event Go-Forward Singular Focus In Vivo Gene Editing Pivoting to Our Foundational Strength • ARCUS - wholly owned genome editing platform Expected cash • Optimi
Slide 6: 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 7: 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 Alan List, M.D. Juli Bla
Slide 8: 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 9: ARCUS Focused on Sophisticated Edits Leveraging Unique Advantages
ARCUS Focused on Sophisticated Edits Leveraging Unique Advantages EDIT TYPE / PROGRAM INDICATION TISSUE TARGET RESEARCH IND-ENABLING CLINICAL PARTNER DELIVERY PBGENE-HBV Chronic hepatitis B Liver HBV Elimination/LNP m3243 primary mitochondrial PBGENE-PMM Muscle PMM Elimination/AAV myopathy PBGENE-DM
Slide 10: OTC Program is First ARCUS In Vivo Gene Editing Program in 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 the human OTC gene at the 1-year 〉iECURE rece
Slide 11: 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 12: ARCUS Technology Overview
PRECISION Bil@mre WEINI@IES ARCUS Technology Overview @
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 Clear Differentiation Versus Other Gene Editing Modalities
ARCUS is a Sophisticated Editing Tool With Clear Differentiation Versus Other Gene Editing Modalities All About The Cut Size Matters Keep It Simple • 3 Prime Overhang Cut • Smallest gene editor (~1500 bp) • Only single component editor that • Small size enables delivery of MORE recognizes and cuts D
Slide 15: 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 16: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity 15
Slide 17: 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 18: 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 T A T G C A A T TA G C T A 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
Slide 19: ARCUS Can Drive Efficient HDR in 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 20: 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 40 >3x Gene Insertion (%) 30 insertion efficiency of CRISPR-based 20 approach* + 10 ARCUS DNA Template 0 0 0 0.1 LNP AAV
Slide 21: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity
Slide 22: 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 21
Slide 23: 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 24: ARCUS Nucleases Excise Mutations and Restore Function in DMD
ARCUS Nucleases Excise Mutations and Restore Function in DMD PBGENE-DMD Program 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 Ex
Slide 25: ARCUS-Edited Dystrophin Preserves Majority of Protein Domains
The Size: ARCUS-Edited Dystrophin Preserves Majority of Protein Domains With the Goal of Improving Function Normal ABD R1-R3 R4-R19 R20-R24 CR CT Dystrophin ELEVIDYS (Sarepta) Received accelerated ABD R1-R3 R24 CR approval in US ARCUS ABD R1-R3 R4-R17.5 R22.5-R24 CR CT Edited Dystrophin ABD: actin b
Slide 26: Maximum Force Output in ARCUS-Treated Mice Significantly Improved
Maximum Force Output in ARCUS-Treated Mice was Significantly Improved 350 ARCUS-treated mice achieved: *# 300 *# • Editing in heart, diaphragm, *# and skeletal muscle 250 • Evidence of edited dystrophin *# in muscle satellite cells Force (mN) 200 150 *# • Leading to: 100 *# Treated (hDMDdel52/mdx) #
Slide 27: 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: 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 28: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity 27
Slide 29: 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 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 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: PBGENE-HBV
Target CTA/IND 2024 PBGENE-HBV Viral Elimination
Slide 33: PBGENE-HBV Designed For Broad Patient Applicability
> 300 million PBGENE-HBV Designed For cHBV infections globally Broad Patient Applicability 〉Only modality designed to eliminate cccDNA and inactivate integrated HBV DNA -> essential for functional cure (undetectable HBV DNA and HBsAg) 〉Precision Advancing Next Steps: > 1,000,000 ― Final PBGENE-HBV c
Slide 34: 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 35: Size & Simplicity Optimal to Target cccDNA and Integrated HBV DNA
Size & Simplicity Optimal to Target cccDNA and Integrated HBV DNA ARCUS ~1000 base pairs (bp) Small size and single component 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
Slide 36: 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 Cas9 2 domain dCas9 or Cas9n 2 1 2 3 Transcription effector domain 3 deaminase Efficacy Single component of ARCUS means more efficient packaging and delivery
Slide 37: 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 38: 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 Nuclease 100 99% 95% 93% Viral Engagement (%) 81% 80 60 0% ARCUS 40 LNP Control AAV + AAV + AAV + AAV + 2mg/kg LNP 2mg/kg LNP 1mg/kg
Slide 39: PBGENE-HBV Demonstrates Up to 95% Durable HBsAg Reduction
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% viral 150 ARCUS LNP 0.03 mg/kg vira
Slide 40: PBGENE-HBV Significantly Reduces HBV DNA 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 41: 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 Saturating On- 0.8 0.6 Target Dose 0.4 Limit of Detection = 0.2 0.2 0 On- and Off-Target Site
Slide 42: 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 2023 Final Clinical Candidate Nominated FDA Pre-IND Meeting in January 2024 on-track Submit IND/CTA in 2024 site-selection underw
Slide 43: PBGENE-HBV Phase 1 Clinical Considerations
PBGENE-HBV Phase 1 Clinical Considerations Phase 1 Clinical Study Design Considerations Phase 1 Clinical Parameters To Be Considered • Global clinical trial across all genotypes • Safety Considerations: • Tolerability (DLTs, AEs and ALT flares) • Adult patients currently treated with SoC • PK • Nucl
Slide 44: PBGENE-PMM
Target CTA/IND 2025 PBGENE-PMM Mutant Mitochondrial DNA Elimination
Slide 45: Primary Mitochondrial Myopathy Currently Lacks a Curative Treatment
Primary Mitochondrial Myopathy (PMM) Currently Lacks a Curative Treatment 15-25K m.3243 PMM patients in the US alone Mitochondrial diseases (MDs) Primary mitochondrial myopathies (PMM) are the most common are genetically defined disorders leading to defects in hereditary metabolic energy production
Slide 46: 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 47: 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 46
Slide 48: 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 ~15-25k 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’
Slide 49: 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. 48
Slide 50: 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. 49
Slide 51: 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 52: 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. 51
Slide 53: PBGENE-PMM Program Accomplishments
PBGENE-PMM Program Accomplishments Final Clinical Candidate PoC and Dose Finding Studies underway on-track Initiate GLP Tox In-process Identify First-in-Human Study Sites on-track CTA/IND in 2025 52
Slide 54: Focusing on Our Foundation—In Vivo Gene Editing
Focusing on Our Foundation—In Vivo Gene Editing Through our gene editing platform ARCUS Focused Execution 2024-2026 Ex Vivo CAR T Accretive Event Go-Forward Singular Focus In Vivo Gene Editing Pivoting to Our Foundational Strength • ARCUS - wholly owned genome editing platform Expected cash • Optimi
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