Precision BioSciences, Inc. · NASDAQ:DTIL
Precision BioSciences — Investor Presentation (November 2024)
40 slides from Precision BioSciences's investor presentation, November 2024
Slide 1: Corporate Deck
Corporate Deck November 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: Corporate Overview
PRECISION BIOSCIENCES Corporate Overview rm
Slide 4: 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 Leveraging Our Foundational Strength • ARCUS - wholly owned genome editing platform Expected cash • Optimiz
Slide 5: ARCUS Focused on Sophisticated Edits Leveraging Unique Advantages
ARCUS Focused on Sophisticated Edits Leveraging Unique Advantages PROGRAM INDICATION TISSUE TARGET US Patient Pool RESEARCH IND-ENABLING CLINICAL PARTNER 1-2 PBGENE-HBV Chronic hepatitis B Liver HBV Million Mito 20 PBGENE-3243 m3243 mitochondrial disease Muscle Disease Thousand 8 PBGENE-DMD Duchenne
Slide 6: ARCUS Potential to Capture a Significant Portion of the 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 7: ARCUS Technology Overview
PRECISION BIOSCIENCES ARCUS Technology Overview 2)
Slide 8: 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 9: 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 10: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity 9
Slide 11: 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 AT G C A A T TA G C TA G G T C G Blunt cut G G C AT A C G T TA A T C G AT C C A G C induces NHEJ The ARCUS Cut TALEN/ZFN Generates a DNA replication direction C C G T AT G C A A
Slide 12: 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 13: Gene Insertion to a “Safe Harbor” Locus in Hematopoietic Stem Cells
Gene Insertion to a “Safe Harbor” Locus in Hematopoietic Stem Cells Safe Harbor HSC Antisickling Gene ARCUS Promotes Repair by HDR Repair template Safe Harbor Antisickling Gene ARCUS will be used to add an Permanent integration of an antisickling gene into a “safe harbor” antisickling gene to hemato
Slide 14: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity
Slide 15: 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 14
Slide 16: 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 ARCUS 5100 bp for Gene Excision in DMD Base Editor (ABEmax) 5800 bp – 6500 bp Prime Editor (PEmax) 7200 bp Sizes include edito
Slide 17: 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 18: 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) Missing Functional Domains Received accelerated ABD R1-R3 R24 CR approval in US ARCUS ABD R1-R3 R4-R17.5 R22.5-R24 CR CT Edi
Slide 19: Defined Outcomes Accomplished Through ARCUS Advantages
The Cut Defined Outcomes Accomplished Through The Size ARCUS Advantages The Simplicity 18
Slide 20: 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 21: Simultaneous Delivery of Multiple Components Results in Lower Efficiency
Simplicity: Simultaneous Delivery of Multiple Components in Separate Delivery Vehicles Results in Lower Efficiency CRISPR Base Editor Prime Editor 1 Cas9 2 gRNA 1 dCas9 or Cas9n 2 gRNA 1 Cas9n 2 pegRNA 3 deaminase Reverse 3 transcriptase 20
Slide 22: PBGENE-HBV
CTA Approved PBGENE-HBV Viral Elimination
Slide 23: PBGENE-HBV Designed For Broad Patient Applicability
PBGENE-HBV Designed For > 300 million cHBV infections globally Broad Patient Applicability 〉Only modality in development designed to eliminate cccDNA and inactivate integrated HBV DNA -> essential for functional cure (undetectable HBV DNA and HBsAg) 〉Precision Advancing Next Steps: ― CTA approved in
Slide 24: 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 25: 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 26: Non-Human Primate Study Demonstrates 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 Nuclease 100 99% 95% 93% Viral Engagement (%) 81% 80 60 0% ARCUS 40 LNP Control AAV + AAV + AAV + AAV + 2mg/kg LNP 2mg/kg L
Slide 27: 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 28: Safety: PBGENE-HBV Final Clinical Candidate Demonstrates Robust Safety Package
Safety: PBGENE-HBV Final Clinical Candidate Demonstrates Robust Safety Package Supporting Advancement Towards Clinical Trials • PBGENE-HBV specifically cuts HBV DNA leading to elimination of cccDNA and inactivation of integrated HBV DNA without impacting any genes in the human genome • No increased
Slide 29: 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 genotypes • Safety Considerations: • Tolerability (DLTs, AEs and ALT flares) • Adult patients currently treated with SoC • PK • Nucleos(
Slide 30: PBGENE-HBV Program Accomplishments
PBGENE-HBV Program Accomplishments FDA INTERACT Meeting in July 2023 Final Clinical Candidate Nominated FDA Pre-IND Meeting in January 2024 Clinical Trial Material Manufactured Clinical Trial Sites Identified Multiple CTAs Submitted Submit IND/CTA in 2024 In-Progress Initiate First-in-Human (FIH) Cl
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 PMM 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 mitochondrial Chronic
Slide 33: 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 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: PBGENE-3243 Program Accomplishments
PBGENE-3243 Program Accomplishments Final Clinical Candidate PoC and Dose Finding Studies underway FDA INTERACT Meeting in December 2023 on-track Initiate GLP Tox In-process Identify First-in-Human Study Sites on-track Submit CTA/IND in 2025 38
Slide 40: $121M Cash Runway Into 2H 2026
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 $121M Potential to Advance 3 Programs to Phase I Clinical Data Cash1 As of 9/30/24 Expected Inflection Point
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