Slide 1: In Vivo Gene Editing Update
Precision BioSciences In Vivo Gene Editing Update April 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 Speakers
Today’s Speakers Michael Amoroso Jeff Smith Alex Kelly Alan List, M.D. President and Co-Founder, Chief Chief Financial Officer Chief Medical Officer Chief Executive Officer Research Officer 2
Slide 4: 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 2024-2026 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 5: Sufficient Cash Runway to Realize Multiple Near-Term Opportunities in 2024-25
Sufficient Cash Runway to Realize Multiple Near-Term Opportunities in 2024-25 Near-term clinical & regulatory validation of ARCUS In-Clinic Lead Partnered Program with iECURE for OTC deficiency now in clinic with clinical data expected in 2024 or 2025 On-Track Wholly owned PBGENE-HBV program IND &/o
Slide 6: 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 7: ARCUS is a Differentiated & Sophisticated Editing Tool
ARCUS is a Differentiated & Sophisticated Editing Tool 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 DNA • Drives Homology-Directed Repair (HDR) payl
Slide 8: The Cut: ARCUS Inserts with High Efficiency in Adult Nonhuman Primates
The Cut: 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
Slide 9: The Size: ARCUS Nucleases Excise Mutations and Restore Function in DMD
The Size: 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 Exo
Slide 10: The Size: 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 11: Maximum Force Output in ARCUS-Treated Mice was 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 *# Force (mN) 200 in muscle satellite cells 150 *# • Leading to: 100 *# Treated (hDMDdel52/mdx) #
Slide 12: 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 13: OTC Program is First ARCUS In Vivo Gene Editing Program to Progress 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 the human OTC gene at the 1-year 〉iECURE rece
Slide 14: 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 15: 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 16: 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 17: 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 18: Sufficient Cash Runway to Realize Multiple Near-Term Milestones in 2024-2025
Sufficient Cash Runway to Realize Multiple Near-Term Milestones in 2024-2025 In-Clinic Lead Partnered Program with iECURE for OTC deficiency now in clinic with clinical data expected in 2024 or 2025 Wholly owned PBGENE-HBV program IND &/or CTA expected filing in 2024 with Phase 1 clinical data in On
Slide 19: Q&A
PRECISION BIOSCIENCES Q&A my