Precision BioSciences, Inc. · NASDAQ:DTIL
Precision BioSciences — Investor Presentation (May 2023)
68 slides from Precision BioSciences's investor presentation, May 2023
Slide 1: Precision BioSciences Corporate Presentation
Precision BioSciences Corporate Presentation May 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: 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 4: ARCUS Platform
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 5: Agenda
Agenda 〉2022 Accomplishments 〉Allogeneic CAR T Program Update 〉Differentiating the ARCUS Platform 〉ARCUS In Vivo Gene Editing Program Highlights 〉2023 Priorities & Milestones 5
Slide 6: 2022 Accomplishments
2022 Accomplishments Presented compelling clinical allogeneic CAR T data to date; 100% ORR 73% CR1 Secured $75M for in vivo gene editing collaboration with Novartis for hemoglobinopathies Raised $50M in equity financing from new and existing investors Extended the cash runway; Runway greater than 2
Slide 7: Allogeneic CAR T Programs
Allogeneic CAR T Programs Potential first-in-class and best-in-class approaches
Slide 8: Executive Summary
Executive Summary Azer-cel: Potential First-In-Class Opportunity for CAR T Relapsed CD19+ DLBCL Azer-cel is Precision’s Lead CAR T Program Demonstrating Efficacy and Improved Safety Across Hematologic Malignancies • Precision has amassed a robust data package (n = 84) for Azer-cel in NHL and ALL, wi
Slide 9: Azer-cel Total Body of Evidence
Azer-cel Total Body of Evidence: Azer-cel Has Meaningful Clinical Activity Across B Cell Malignancies 84 23 + B-ALL Patients Patients Treated With Azer-cel 61 23 NHL Patients B-ALL Patients 58% ORR All Doses / All LD 61% ORR Regimens 41% CR 61% CR/CRi ★ Tailoring Azer-cel for the right patient, with
Slide 10: Azer-cel is Active in CAR T Relapsed Patients
Azer-cel Azer-cel is Active in CAR T Relapsed Patients: Demonstrated High Response Rates and Durability Across All Subjects 61 All Doses / All LD Regimens NHL Patients CAR T Relapse Pts2,3 18 83% ORR DL3, DL4b / All LD Regimens Patients 61% CR Rate 55% DoR ≥ 6-months1 *Median duration in ≥ 6-month r
Slide 11: Azer-cel Approach is Biologically Rational for CAR T Relapse Population
Azer-cel Azer-cel Approach is Biologically Rational for CAR T Relapse Population • Azer-cel from healthy donor may be more effective than an autologous product • Autologous products made from cancer patients with impaired Azer-cel: Optimally immune system may result in suboptimal product attributes1
Slide 12: Majority of CAR T Relapse Patients Continue to Have CD19+ Disease
Azer-cel Majority of CAR T Relapse Patients Continue to Have CD19+ Disease ~85% of patients1 continue to have CD19+ disease Patients In our prospective data, patients continue to have antigen positive disease Note: Retrospective Literature states that 12-28% of patients have antigen negative relapse
Slide 13: CAR T Relapse Setting Has No Approved Standard of Care
Azer-cel CAR T Relapse Setting Has No Approved Standard of Care and Poor Prognosis CAR T Relapse Outcomes Proposed TPP For U.S. Consortium Actual Data / RWD1,2,3 CAR T Relapse Patients Overall Response Rate (ORR) ~20-30% > 50% Progression Free Survival (mPFS) ~1.8 months > 3 months Overall Survival
Slide 14: CAR T Relapse Market is Large and Growing
Azer-cel CAR T Relapse Market is Large and Growing 60-65% of patients currently treated with Auto CAR T will relapse1 ★ By 2025, Global CAR T Relapse Patient Pool Is Expected To Grow ~4x as Auto CAR T Drugs become the SoC in 2L+ Estimate total Global G8 markets to be ~18k patients per year2 1. Estim
Slide 15: Azer-cel: Allogeneic CAR T
First-In-Class Opportunity Azer-cel: Allogeneic CAR T For CD19+ CAR T Relapsed Patients
Slide 16: One Year Ago, Precision Showed Compelling Data in CAR T Relapse
Azer-cel One Year Ago, Precision Showed Compelling Data in the CAR T Relapse Setting Data Update n (%) ORR ≥ Day 28 11 (100%) CR ≥ Day 28 9 (82%) CAR T relapsed Median 5 lines (n = 11) ≥ 6 mo. Duration of Response 6 (55%) of evaluable PFS > 2 months 8 (73%) U.S. Consortium/RWD Threshold ClinicalTria
Slide 17: Significant Progress Made to Improve Azer-cel Therapeutic Index
Azer-cel Significant Progress Made to Improve Azer-cel Therapeutic Index • Optimized manufacturing process using ARCUS leading to improved product attributes resulting in improved potency and control • Received favorable CMC feedback from the FDA for ongoing development path • Reduced lymphodepletio
Slide 18: Two Levers Designed to Improve Therapeutic Index
Azer-cel Two Levers Designed to Improve Therapeutic Index Reduced LD Dose Intensity: Potency with Control: 1 Reducing the Fludarabine Dose in Lymphodepletion 2 Improving Product Attributes Process improvement led to improved fitness measured by 4 non apoptotic cell fraction days Fludarabine dose of
Slide 19: Optimizing Lymphodepletion Regimen to Drive CAR T Expansion
Azer-cel Optimizing Lymphodepletion Regimen to Drive CAR T Expansion: An Important Factor to Drive Molecular Remission (MRD-) Mean CAR T Peak 44K CART T cells (DL4b/FluCy750) Reduced to sLD Transitioned To to Improve Safety FluCy750 Outcome: Modest Expansion1 Outcome: Increased Expansion ~1K CART T
Slide 20: Azer-cel Safety Update
First-In-Class Opportunity Azer-cel Safety Update CD19+ CAR T Relapsed Patients
Slide 21: Optimized Product Attributes and Reduced Fludarabine Improve Safety
Azer-cel Optimized Product Attributes and Reduced Fludarabine Exposure Significantly Data Update Improves Safety Profile Latest Cohort Latest Cohort Number (%) of subjects experiencing events with max grade DL3a/eLD Cohort DL4b/mLDCohort (DL4b FluCy750 or sLD) (DL4b FluCy750) (n=6) (n=6) (n=7) (n=5)
Slide 22: Azer-cel CAR T Specific AE Profile is Comparable
Azer-cel In Latest Cohort, n = 5, Azer-cel CAR T Specific AE Profile is Comparable to Data Update Approved Autologous CAR T Autologous CAR T Allogeneic CAR T Yescarta1 Kymriah2 Breyanzi3 Azer-cel (n=5) Number (%) of subjects experiencing events with max grade (CAR T Relapse DLBCL) (r/r LBCL) (r/r DL
Slide 23: Azer-cel Efficacy Update
First-In-Class Opportunity Azer-cel Efficacy Update Durability and Molecular Response Update from ASCO ’22, n = 11 patients
Slide 24: Durability Favorable vs. Current Treatment
Azer-cel Update Since ASCO 2022 Data: Durability Favorable vs. Current Treatment Data Update Current Treatment Defined in U.S. Consortium Data/RWD First Subject Assessment D28 CR A CR, post SCT B PR C Prior to first response DL3a2 /eLD D Gr5 event in ongoing response E Disease progression F Stem cel
Slide 25: Molecular Remission (MRD-) Key Predictor of Durability
Azer-cel Molecular Remission (MRD-) Key Predictor of Durability PFS by Day 28 MRD2 • Early Clearance of Circulating Tumor DNA (MRD-) measured by ClonoSEQ is Predictive MRD- for Relapse Free Interval After CAR T Treatment (per ZUMA-1)1 • PFS is Strongly Correlated with MRD Negative Status • Molecular
Slide 26: MRD Negativity Correlated With Durability
Azer-cel Update Since ASCO 2022: MRD Negativity Correlated With Durability Data Update First MRD Status1 Subject Assessment D28 CR Neg A CR, post SCT n/a B PR Neg C Prior to first response DL3a3 /eLD n/a D Gr5 event in ongoing response Pos E Disease progression n/a F Stem cell transplant Neg G Neg H
Slide 27: Latest Azer-cel Cohort
First-In-Class Opportunity Latest Azer-cel Cohort Additional Safety and Efficacy Data Supports Potential Phase 2 Recommended Dose 500M CAR T Cells (DL4b) + FluCy750 FluCy750 = 30 mg/m2 Flu × 3 days + 750 mg/m2 Cy × 3 days
Slide 28: Azer-cel + FluCy750 Preliminary Evidence of Efficacy
Azer-cel Azer-cel + FluCy750 Preliminary Evidence of Efficacy: Data Update Overall Response Rate with Molecular Remissions in CAR T Relapse Setting Patient MRD D28 Cell Dose1 LD Type1 Durability ID Status2 Response3 O 500M FluCy750 Neg CR PD (D90) Antigen Escape P 500M FluCy750 Neg PR D90+ 60% ORR Q
Slide 29: Established Endpoints for Single Arm Hematologic Oncology Trials
Azer-cel Established Endpoints of Key Significance for Single Arm Hematologic Oncology Trials Proposed Endpoints For Azer-cel (500M cells + FluCy750) CAR T Relapse Patients Interim Product Profile 1º Overall Response Rate (ORR) > 50% 2º Not yet fully evaluable Duration of Response (DoR) > 50% @ 3 mo
Slide 30: Azer-cel Potential First-In-Class Allogeneic Therapy
Azer-cel Azer-cel Potential First-In-Class Allogeneic Therapy for CAR T Relapsed Patients In latest cohort, Azer-cel safety profile ameliorated with 0% > Grade 3 Allogeneic CAR T related AEs in fragile CAR T relapse patient population Azer-cel highly active across CAR T relapsed patients (N=18), dem
Slide 31: PBCAR19B Stealth Cell: Anti-CD19 Allogeneic CAR T
Best-In-Class Opportunity PBCAR19B Stealth Cell: Anti-CD19 Allogeneic CAR T Cloaked Design to Evade Immune Rejection and Potentially Displace 2nd Line Auto CAR T in CD19+ CAR T Naïve Patients
Slide 32: PBCAR19B Stealth Cell Cloaked to Evade Immune Rejection
Azer-cel PBCAR19B Stealth Cell: Anti-CD19 Allogeneic CAR T Cloaked to Evade Immune Rejection Tx Goal/ Patient Population Anti-CD19 CAR TCR is knocked-out to prevent GvHD Displace 2nd Line Auto CAR T in CD19+ CAR T Naïve Patients 1 Anti-beta-2 microglobulin (β2m) shRNA Key Feature Reduces MHC I expre
Slide 33: Delayed Immune Response Demonstrates Proof of Principle
Ex Vivo Delayed Immune Response By T Cells and NK Cells Demonstrates Data Update Proof of Principle For Stealth Construct in DLBCL CD3+ cell recovery CD56+ (NK) cell recovery T Cells (relative Recovery to pre-LD baseline) NK Cell (relative Recovery to pre-LD baseline) 250 Azer-cel CD3+ recovery (n=5
Slide 34: Allogeneic CAR T Related AE Profile in PBCAR19B Subjects
Azer-cel Allogeneic CAR T Related AE Profile in PBCAR19B Stealth Cell Treated Subjects Data Update 540M Cells + 540M Cells + sLD FluCy750 Number (%) of subjects experiencing events with max grade Cohort Cohort (n=3) (n=4) AE of special CRS Grade 1 or Grade 2 1 (33%) 1 (25%) interest Grade 3 or highe
Slide 35: PBCAR19B Dosed at 540M Cells Achieved 71% ORR
Azer-cel PBCAR19B Stealth Cell Dosed at 540M Cells Achieved 71% ORR with Data Update No Grade ≥3 Allogeneic CAR T Related Adverse Events Patient ID Disease LD Type1 MRD Status2 D28 Response Durability 1 DLBCL sLD Pos PR PD (D60) 2 DLBCL sLD Neg CR D150+ 3 DLBCL sLD Pos PD n/a 4 DLBCL FluCy750 Neg CR
Slide 36: PBCAR19B Potential Best-In-Class Allogeneic Therapy
Azer-cel PBCAR19B Stealth Cell Potential Best-In-Class Allogeneic Therapy For CAR T Naïve Patients 〉 Stealth Cell Proof of Concept Achieved: Through immune cloaking, preliminary efficacy in DLBCL patients enabling expansion and persistence by delayed immune rejection Total Experience at 540M Cells:
Slide 37: Differentiating the ARCUS platform
Differentiating the ARCUS platform Highly differentiated genome editing platform for high unmet needs in genetic diseases
Slide 38: 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 39: 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 40: ARCUS is Capable of Simple Edits and 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 41: 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 42: Effective Gene Editing Requires Both AAV and LNP Delivery
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 43: Unlocking Greater In Vivo Editing 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 44: 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 45: Broad and Deep In Vivo Pipeline
In Vivo Broad and Deep In Vivo Pipeline Showcases ARCUS for Gene Insertion and Complex Edits PROGRAM INDICATION TISSUE TARGET COMPLEX EDIT RESEARCH CANDIDATE IND- PARTNER TYPE / DELIVERY SELECTION ENABLING PBGENE-HBV Chronic hepatitis B Liver HBV Deletion/LNP Sickle cell disease/ PBGENE-HbE HSCs — I
Slide 46: 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 47: 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 48: 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 TCGA AGCT resulting from ARCUS cleavage 5’
Slide 49: ARCUS for Gene Insertion
ARCUS for Gene Insertion Wholly owned and partnered programs, including those for large gene insertions
Slide 50: Hemophilia B Gene Insertion in Newborn and Infant 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 51: OTC Clinical Candidate Shows Stable Gene Insertion at Year 1
In Vivo Ornithine Transcarbamylase Deficiency (OTC) Clinical Candidate Shows Stable Gene Insertion Gene Insertion at Year 11 for OTC > Delivery of twin AAV-based vectors carrying ARCUS nuclease Long-term stability of the edited genome vector (GTP-506A) and therapeutic donor vector (GTP- in NHPs was
Slide 52: Gene Insertion to a Safe Harbor Locus in HSCs
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 53: 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 54: Precision Approach in HBV: Excision in Two Locations
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 CU S Degradation by A R exonuclease cccDNA is a pool of minichromosomes HBV DNA break HBV that h
Slide 55: ARCUS HBV Program 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 PBS 100 nuclease via LNP showed pot
Slide 56: ARCUS to Restore Dystrophin Expression for DMD
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 57: 2023 Priorities
PRECISION BIOSCIENCES 2023 Priorities
Slide 58: 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 59: 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 60: Senior Leadership Team
Precision BioSciences: Senior Leadership Team Michael Amoroso Derek Jantz, Ph.D. Jeff Smith, Alex Kelly Cindy Atwell Since Sep 2021 Since Mar 2006 Ph.D. Since Oct 2020 Since Apr 2019 President & Chief Scientific Officer, Since Mar 2006 Chief Financial Officer Chief Business Officer Chief Executive O
Slide 61: 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 62: Appendix
PRECISION BIOSCIENCES Appendix
Slide 63: ARCUS for Chronic Hepatitis B Virus Targeting cccDNA
In Vivo ARCUS for Chronic Hepatitis B Virus (cHBV) Targeting cccDNA Gene Excision 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. AAA >
Slide 64: Novartis Collaboration Complementary to Existing Lilly Partnership
In Vivo Novartis Collaboration Complementary to Precision’s Existing In Vivo Gene Gene Excision 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 targets
Slide 65: Duchenne Muscular Dystrophy Currently Lacks a Curative Treatment
In Vivo Duchenne Muscular Dystrophy Currently Lacks a Curative Treatment Gene Excision 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 66: 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 67: 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 68: OTC is a Severe, Ultra Rare Genetic Condition
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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