Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — H.C. Wainwright Cell Therapy Virtual Conference 2023
47 slides from Precision Biosciences's conference presentation, February 2023
Slide 1: H.C. Wainwright Cell Therapy Virtual Conference
H.C. Wainwright Cell Therapy Virtual Conference February 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. All statements contained in this herein and in any related presentation that do not relate to matters of his
Slide 3: Allogeneic CAR T Programs
Allogeneic CAR T Programs Potential First-in-Class and Best-in-Class Approaches
Slide 4: Precision BioSciences: Allogeneic CAR T Program Executive Summary
Ex Vivo Precision BioSciences: Allogeneic CAR T Program Executive Summary 1. In autologous CAR T relapsed patients, azer-cel has shown high response rates1, with evidence of durability extending 1 greater than 18 months; including peak CAR T levels in the same range as autologous CAR T durable respo
Slide 5: Azer-cel: Target Product Profile for CAR T Relapsed Patient Population
Ex Vivo Azer-cel: Target Product Profile (TPP) for CAR T Relapsed Patient Population Azer-cel CAR T relapse 3rd line NHL Progression Free Survival (mPFS) > 3 months > 6-7 months ~35% CR at 6 months; Duration of Response (DoR) > 50% @ 3 months ~32% CR at 1 year plus Overall Response Rate (ORR) > 50%
Slide 6: Azer-cel: Efficacy Results
Ex Vivo Azer-cel: Efficacy Results1: Azer-cel 100% ORR, 73% CR with 50% durable responses at > 6 months ORR ≥ Day 28 n (%) 11 (100%) CR ≥ Day 28 8 (73%) n (%) CAR T relapsed ≥ 6 mo. DoR median 5+ prior lines n (%)3 3 (50%) of evaluable (n = 11 evaluable)2,3 Ongoing responders 6 (55%) n (%) PFS > 2 m
Slide 7: Azer-cel: Response Rates and Durability Exceed Current Standard-of-Care
Ex Vivo Azer-cel: Response Rates and Durability Exceed Current Standard-of-Care Azer-cel (SoC) for CAR T Relapsed Subjects Subject Current SoC A CR/CRi (MRD-) CR B PR ASH’ 21 Cohort C PD duration Death in ongoing response update D E F CNS PD • 100% ORR among 11 evaluable subjects G • 73% CR (8/11) •
Slide 8: Azer-cel: Peak Expansion Equivalent to Auto CAR T Levels
Ex Vivo Azer-cel: Peak Expansion Equivalent to Auto CAR T Levels in Long Term Azer-cel Durable Responders from ZUMA-1 Azer-cel exceeds ZUMA-1 durable responders1 Auto CAR T Durable Responders NHL, DL4b (mLD), CAR (ZUMA-1, n=39)2 T Relapsed (n=4) ★ Azer-cel program is first allogeneic CAR T to show p
Slide 9: Optimize Therapeutic Index: Maximize Safety While Maintaining Efficacy
Ex Vivo Optimize Therapeutic Index: Maximize Safety While Maintaining Efficacy Azer-cel Profile Remains Key Next Step 4 days Fludarabine dose of 30 mg/m2 per day Reduce total fludarabine exposure during lymphodepletion 3 days ★ Given CAR T relapsed patient population is extremely fragile and already
Slide 10: What to Expect in Q1 2023 Program Update
Ex Vivo What to Expect in Q1 2023 Program Update Azer-cel • Additional long-term follow up from ASH 2021 and ASCO 2022 cohorts • New subjects treated with optimized cells at DL4 (500M cells) and less intense LD − Peak expansion data (pharmacokinetics) & ctDNA clearance Precision − Safety − Response
Slide 11: Investor Deck
PRECISION BIOSCIENCES Investor Deck January 2023
Slide 12: Precision's Growth Strategy
Precision’s Growth Strategy: Leverage the ARCUS gene editing platform in oncology and genetic diseases 1 Advance a first-in-class and a best-in-class allogeneic CAR T treatment for hematologic cancer — Lead anti-CD19 allogeneic candidate, azercabtagene zapreleucel (azer-cel) potential first-in-class
Slide 13: ARCUS Platform: Clinical Stage Gene Editing Company
Precision BioSciences: A Clinical Stage Gene Editing Company Built on Wholly Owned ARCUS Genome Editing Platform ARCUS® Platform for therapeutic drug development Diversified Pipeline Pioneers in genome editing technology development Scalable in-house manufacturing capabilities Ex Vivo: In Vivo: ARCU
Slide 14: Differentiating the ARCUS platform
Differentiating the ARCUS platform Highly Differentiated Genome Editing Platform for High Unmet Needs in Genetic Diseases
Slide 15: Three Distinct Advantages of ARCUS Genome Editing Platform
ARCUS Three Distinct Advantages of ARCUS Genome Editing Platform ARCUS® Platform • ARCUS is inactive until it binds to target DNA Precision for Therapeutic• Drug Development Off-target editing easier to detect and eliminate (Safety & Specificity) • Iterative nuclease optimization process to customiz
Slide 16: ARCUS: Engineering Nucleases that Mimic Nature's Genome Editing System
ARCUS ARCUS: Engineering Nucleases that Mimic Nature’s Genome Editing System The ARCUS nuclease is the only gene editor derived from a natural homing endonuclease Active state ARCUS Inactive state ARCUS Cuts with 3’ overhang that results in a unique jigsaw like pattern The ARCUS nuclease cuts DNA at
Slide 17: ARCUS is Capable of Simple Edits and Optimally Suited for Complex Edits
ARCUS ARCUS is Capable of Simple Edits and Optimally Suited for Complex Edits A deletion (also known as knock-out) is when a gene is made Simple Deletion inoperative through a permanent change in the DNA; therefore, Edit the gene no longer expresses a functional protein An insertion (also known as k
Slide 18: Precise 3' Overhang Cuts are Unique
ARCUS Precise 3’ Overhang Cuts are Unique - Designed to Enable Gene Insertion and Complex Edits and Provide Identifiable Signature for On-Target Editing Complex/Homology-directed Repair (HDR) Simple/Non-Homologous End Joining (NHEJ) ARCUS CRISPR/CAS GENE Cut with 3’ Blunt cut overhang GE NE N Repair
Slide 19: Effective Gene Editing Requires Both AAV and LNP Delivery Capabilities
ARCUS Effective Gene Editing Requires Both AAV and LNP Delivery Capabilities ARCUS can be effectively delivered with both AAV and LNP AAV LNP-mRNA • Sustained nuclease expression may provide increased • Potential to repeat dose to maximize therapeutic impact PROS efficacy PROS • Scalability for manu
Slide 20: Unlocking Greater In Vivo Editing Potential via Safe Harbor Gene Insertion
ARCUS Unlocking Greater In Vivo Editing Potential via Safe Harbor, ARCUS Gene Insertion Inactive state Active state A “safe harbor” ARCUS ARCUS ARCUS nuclease may be used Safe harbor to develop multiple products to insert a different gene for each disease Complex Edit Healthy gene Insertion Edited g
Slide 21: In Vivo Gene Editing Programs
In Vivo Gene Editing Programs Precision In Vivo Gene Insertion and Complex Gene Editing Programs Highlight Unique ARCUS Attributes
Slide 22: Broad and Deep In Vivo Pipeline Showcases ARCUS
In Vivo Broad and Deep In Vivo Pipeline Showcases ARCUS for Gene Insertion and Complex Edits COMPLEX EDIT CANDIDATE IND- PROGRAM INDICATION TISSUE TARGET RESEARCH PARTNER TYPE / DELIVERY SELECTION ENABLING PBGENE-HBV Chronic hepatitis B Liver HBV Deletion/LNP Sickle cell disease/ PBGENE-HbE HSCs — I
Slide 23: ARCUS Safety Supported by Long-term Non-Human Primate Data
ARCUS Safety Supported by Long-term Non-Human Primate Data Differentiated Ability to Track and Minimize Off-target Editing
Slide 24: Five Years of Follow-up for ARCUS in NHP
In Vivo Five Years of Follow-up for ARCUS in NHP; Longest, Publicly Known Gene Editing Data Non-Human Primate Animal Model One-time delivery of an AAV-ARCUS vector into PCSK9 safe harbor for deletion resulted in long-term reductions of serum PCSK9 and LDL1 (5-year timepoint approaching) with no addi
Slide 25: ARCUS Safety and Specificity for Tracking Off-Target Editing
In Vivo ARCUS Safety and Specificity for Tracking Off-Target Editing Oligo Capture: A genome-wide assay for ARCUS off-target editing ARCUS Step 1: Transfect cells with ARCUS DNA “tag” and a DNA “tag” + + AGCT TCGA Step 2: The “tag” is captured at DNA breaks resulting from ARCUS cleavage 5’-CGCTGCTAG
Slide 26: ARCUS for Gene Insertion
ARCUS for Gene Insertion Wholly Owned and Partnered Programs, Including Those for Large Gene Insertions
Slide 27: Hemophilia B Gene Insertion: Stable Transduction of Factor IX in Macaque
In Vivo Hemophilia B Gene Insertion: Stable Transduction of Factor IX in Newborn and Infant Macaque Liver (Non-Human Primates)1 Newborn 3-mo infant 6-mo infant 3-month biopsy 1-year biopsy 3-month biopsy 1-year biopsy 3-month biopsy 20-196 (d84) 20-196 (d366) AH0120 (d98) AH0120 (d364) 21-120 (d100)
Slide 28: OTC Clinical Candidate Shows Stable Gene Insertion at Year 1
In Vivo Ornithine Transcarbamylase Deficiency (OTC) Clinical Candidate Shows Gene Insertion Stable Gene Insertion at Year 11 for OTC > Delivery of twin AAV-based vectors carrying ARCUS Long-term stability of the edited genome nuclease vector (GTP-506A) and therapeutic donor vector in NHPs was demons
Slide 29: Gene Insertion to a Safe Harbor Locus in Hematopoietic Stem Cells
In Vivo Gene Insertion to a “Safe Harbor” Locus in Hematopoietic Stem Cells Gene Insertion for SCD and Beta Thal > Permanent integration of an antisickling gene into a ARCUS will be used to add an antisickling gene to “safe harbor” locus in HSCs is expected to prevent the hematopoietic stem cells (H
Slide 30: ARCUS for Complex Edits
ARCUS for Complex Edits 〉HBV approach edits DNA at two locations 〉DMD approach makes a 500,000 base pair edit
Slide 31: Precision Approach in HBV: Excision in Two Locations in the Liver
In Vivo Precision Approach in HBV: Excision in Two Locations in the Liver Gene Excision for Curing HBV requires targeting two key viral components – cccDNA and integrated HBV DNA Chronic HepB > 1. cccDNA Degradation by exonuclease cccDNA is a pool of minichromosomes HBV DNA break HBV that hangs out
Slide 32: ARCUS HBV Program Has Shown Efficacy Data During In Vivo POC Studies
In Vivo ARCUS HBV Program has Shown Exciting Efficacy Data During In Vivo POC Gene Excision for Studies Demonstrating Ability to Reduce Both HBV S-Antigen and HBV cccDNA Chronic Hep B > 200 150 (% of baseline) Data from in vivo models1 treated with ARCUS-HBV HBsAg 100 PBS nuclease via LNP showed pot
Slide 33: ARCUS to Restore Dystrophin Expression for Duchenne Muscular Dystrophy
In Vivo ARCUS to Restore Dystrophin Expression for Duchenne Muscular Dystrophy Gene Excision for DMD > Restore dystrophin expression Deleting exons 45-55 using a pair of ARCUS nucleases intended to remove a mutation hotspot responsible for >50% of DMD ARCUS 1 ARCUS 2 GOAL Exon 44 Exons 45–55 Exon 56
Slide 34: 2023 Priorities
PRECISION BIOSCIENCES 2023 Priorities
Slide 35: 2023 Priorities and Milestones
2023 Priorities and Milestones 〉Complete Phase 1b for azer-cel to support decision point for Phase 2 〉Complete Phase 1 dosing trial for PBCAR19B 〉Host CAR T update in first quarter of 2023 〉Nominate the final drug candidate for HBV in vivo program 〉Advance the first ARCUS in vivo nuclease to CTA thr
Slide 36: Building the leading therapeutic gene editing company
Technology: ARCUS, a premier genome editing platform Building the leading therapeutic gene editing People: Fortified Senior Leadership Team with 15+ years perfecting company focused on high ARCUS protein engineering unmet needs in oncology and Focus & Discipline: Fiscal resources genetic diseases su
Slide 37: Precision BioSciences: Senior Leadership Team
Precision BioSciences: Senior Leadership Team Michael Amoroso Derek Jantz, Ph.D. Jeff Smith, Alex Kelly Cindy Atwell Since Sep 2021 President & Since Mar 2006 **Chief Science Advisor, Ph.D. Since Oct 2020 Since Apr 2019 Chief Business Officer Since Mar 2006 Chief Financial Officer Chief Executive Of
Slide 38: Precision BioSciences: Board of Directors
Precision BioSciences: Board of Directors Kevin Buehler Michael Amoroso Melinda Brown Stanley Frankel, M.D. Since Jul 2019 Since Oct 2021 Since May 2022 Since Apr 2021 Board Chair Audit Chair Science & Technology Chair Geno Germano Shari Lisa Piré, J.D. Sam Wadsworth, Ph.D. Since Mar 2020 Since Nov
Slide 39: Appendix
PRECISION BIOSCIENCES Appendix
Slide 40: PBCAR19B: Anti-CD19 Allogeneic CAR T Designed to Evade Immune Rejection
Ex Vivo PBCAR19B: Anti-CD19 Allogeneic CAR T Designed to Evade Immune Rejection PBCAR19B and Displace 2nd/3rd Line Auto CAR T 3rd line+ NHL Target Product Profile to Replace Auto CAR T Anti-CD19 CAR TCR is knocked-out to prevent GvHD Median Overall Survival ~26 months1 (mOS) 1 Anti-beta-2 microglobu
Slide 41: PBCAR19B: Designed to Overcome Rejection by T Cells and NK Cells
Ex Vivo PBCAR19B: Designed to Overcome Rejection by T Cells and NK Cells in Mixed PBCAR19B Lymphocyte Reactions Rejection by T cells Rejection by NK cells (n=4 mismatched donors) (n=3 mismatched donors, strong activation protocol) 70 120 % Killing of CAR T Cells % Killing of CAR T Cells 60 100 50 80
Slide 42: ARCUS for Chronic Hepatitis B Virus Targeting cccDNA
In Vivo ARCUS for Chronic Hepatitis B Virus (cHBV) Targeting cccDNA Gene Insertion for Chronic Hep B ARCUS-mediated inactivation of cccDNA and integrated HBV could result in a functional cure ARCUS HBV Infected Hepatocyte LNP Chronic HBV is one of greatest racial health disparities in the U.S. > 860
Slide 43: Novartis Collaboration Complementary to Existing Lilly Partnership
In Vivo Novartis Collaboration Complementary to Precision’s Existing In Vivo Gene Gene Insertion Editing Partnership with Lilly for DMD Research collaboration and license agreement aimed at treating + challenging genetic diseases Pre-IND R&D IND to Commercial 3 Initial collaboration for three target
Slide 44: Duchenne Muscular Dystrophy Currently Lacks a Curative Treatment
In Vivo Duchenne Muscular Dystrophy Currently Lacks a Curative Treatment Gene Insertion for DMD Mutation on the X chromosome interferes On average, with dystrophin protein production, which children lose is needed to form and maintain healthy muscle their ability to walk by Affects approximately age
Slide 45: In Vivo Gene Insertion Collaboration with Novartis for Hemoglobinopathies
In Vivo In Vivo Gene Insertion Collaboration with Novartis for Hemoglobinopathies Gene Insertion for Hemoglobinopathies Builds on the unique gene insertion capabilities + of ARCUS® and further validates ARCUS as a Develop single Preclinical to premium genome editing platform ARCUS nuclease commercia
Slide 46: Hemoglobinopathies are a Major World Health Problem
In Vivo Hemoglobinopathies are a Major World Health Problem Gene Insertion for Hemoglobinopathies Sickle Cell Disease (SCD) Beta Thalassemia Affects the structure/function of hemoglobin, One of the most common genetic diseases caused by a disruption reducing the ability of red blood cells to transpo
Slide 47: OTC is a Severe, Ultra Rare Genetic Condition With High Unmet Medical Needs
In Vivo OTC is a Severe, Ultra Rare Genetic Condition With Extremely High Unmet Gene insertion Medical Needs Across Phenotypes for OTC Ornithine Transcarbamylase (OTC) Deficiency ~ 4,200 People with OTC in the US2 • OTC deficiency is the most • OTC deficiency is also associated Neonatal-onset Late-o
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