Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Investor Presentation (October 2019)
46 slides from Precision Biosciences's investor presentation, Oct 2, 2019
Slide 1: Precision BioSciences: Dedicated to Improving Life
Exhibit 99.1 BIOSCIENCES < PRECISION Dedicated to Improving Life. Cure genetic disease. Feed the planet.
Slide 2: Forward Looking Statement
Forward Looking Statement This presentation (together with any other statements or information that we may make in connection herewith) may copuain forward-looking statements. All statements other than statements of present and historical facts contained in this prospectus, including without Krrtati
Slide 3: Dedicated To Improving Life: Overcome Cancer. Cure Genetic Disease. Feed the Planet.
Dedicated To Improving Life Overcome Cancer. Cure Genetic Disease. Feed the Planet.
Slide 4: Delivering on the Promise of Genome Editing to Address Core Challenges of Human Health
Delivering on the Promise of Genome Editing to Address Core Challenges of Human Health Proprietary ARCUS genome editing platform built for translation with full freedom to operate Industry leading in vivo gene correction platform first to publish in non-human primates Wholly integrated food editing
Slide 5: Our Near-Term Development Strategy
Our Near-Term Development Strategy Indication: Hepatitis B Target: cccDNA and integrated DNA IND 2020 Indication: NHL and ALL Target: CD19 (PBCAR0191) Clinical Phase 1/2a Indication: NHL, CLL, SLL Target: CD20 (PBCAR20A) IND accepted, trial start Q4 2019 Orphan designation (MCL) Product: Ultra-low s
Slide 6: Nature's Genome Editing System ARCUS
Nature’s Genome Editing System ARCUS
Slide 7: Our Objective: Therapeutic-Grade Genome Editing
Our Objective: Therapeutic-Grade Genome Editing Industry’s Approach to Genome Editing Ease of design Speed of manufacture Density of targeting Open source Precision BioSciences' Approach to Genome Editing Safety Delivery Control of edits Proprietary ü ü ü ü
Slide 8: ARCUS: Engineering Nature's Genome Editing System
ARCUS: Engineering Nature’s Genome Editing System ARCUS is derived from I-CreI, a homing endonuclease naturally evolved for highly precise genome editing Safety: Self-inactivates to prevent off-target editing Delivery: Small size (364 amino acids) maximizes delivery Control of edits: 3’ ”sticky ends
Slide 9: Overcoming Cancer: Off-the-shelf CAR T
Overcoming Cancer Off-the-shelf CAR T
Slide 10: Off-the-shelf CAR T Immunotherapy Pipeline
NHL and ALL - Ph1/2a initiated Q2 2019, Interim Data Q1 2020 NHL, CLL, SLL - IND accepted, Ph1/2a start Q4 2019 MM - IND 2020 AML - IND 2020 Off-the-shelf CAR T Immunotherapy Pipeline Product Candidates Program Area Discovery Pre-clinical Clinical Rights PBCAR0191 (CD19) PBCAR20A (CD20) PBCAR269A (B
Slide 11: An Allogeneic CAR T Platform Designed to Overcome Cancer
Highly consistent product Available on demand Minimize complexity of administration Expand flexibility in dosing Maximize use of the treatment & simplify prescriber adoption Result Precision BioSciences’ Approach Single-step cell engineering Proprietary process optimization Rigorous donor selection
Slide 12: Precision BioSciences' Proprietary Single Step CAR T Process
Precision BioSciences’ Proprietary Single Step CAR T Process Reduces heterogeneity in cell formulation Streamlines manufacturing Claimed in 9 issued US patents Single-step CAR T CAR knocked IN at targeted locus Endogenous TCR disrupted by ARCUS cutting at Exon 1 Exon 1 ARCUS CAR AAV
Slide 13: Novel Costimulatory Domain Preserves Cell Phenotype
Novel Costimulatory Domain Preserves Cell Phenotype N6 maintains a greater percentage of naïve cells 4-1BB: N6: KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL KASRKKAAAAAKSPFASPASSAQEEDASSCRAPSEEEGSCEL CD8 N6 CD3ζ Light Heavy Precision CARs incorporate a novel proprietary costimulatory domain called “N6
Slide 14: First In-House cGMP Manufacturing Facility for Genome Edited Allogeneic CAR T
First In-House cGMP Manufacturing Facility for Genome Edited Allogeneic CAR T in the U.S. Precision’s Manufacturing Center for Advanced Therapeutics (MCAT) is a 17,300 square foot cGMP clinical manufacturing facility Allogeneic CAR T Cells, mRNA (10g scale) and rAAV (400L scale) vectors for in-vivo
Slide 15: Scaled CAR T Manufacturing: Optimizes Yield and Quality
Scaled CAR T Manufacturing: Optimizes Yield and Quality Final Yield CD19 Drug Product (64M CAR T cells/vial) CD3- >99% CAR+ 65% - 75% TN/SCM & TCM >50% 1.25 CD4:1 CD8 (Batch2) Batch Vial Count 1 130 2 114 3 100 cold storage -1 0 3 8 10 Activation Expansion 1 Expansion 2 Cell Number Ship Receive Harv
Slide 16: PBCAR0191 Phenotype Optimized for In Vivo Expansion
PBCAR0191 has a high proportion of Naïve and Central Memory CAR T cells. CAR T Cell Phenotype Optimized for In Vivo Expansion Naïve and Central Memory CAR T cells are understood to be responsible for robust in vivo CAR T expansion Donor selection and proprietary, streamlined manufacturing maximizes
Slide 17: Unique Approach to Allogeneic CAR T Positions for Potential Best-in-Class Profile
Unique Approach to Allogeneic CAR T Positions for Potential Best-in-Class Product Profile Manufacturing process preserves optimal phenotype Optimal phenotype permits milder lymphodepletion Enhanced proliferation limits need for aggressive lymphodepletion N6 domain augments benefits of low-touch manu
Slide 18: PBCAR0191 (CD19): Phase 1/2a Clinical Plan
-14 -7 -5 -4 -3 0 28 60 90 180 360 Screening Follow-Up Day LTFU Study Treatment Period PBCAR0191 Infusion x1 Enrollment Safety & Response Assessment End of Study Lymphodepletion Fludarabine 90 mg/m2 + Cyclophosphamide 1500 mg/m2 Safety Assessment Objectives Primary: safety and tolerability Secondary
Slide 19: PBCAR20A (CD20): Phase 1/2a Clinical Plan
Objectives Primary: safety and tolerability Secondary: clinical (anti-tumor) activity Exploratory: expansion, trafficking, and persistence Dose Escalation (standard 3+3) DL1 = 3 ×105/kg DL2 = 1 ×106/kg DL3 = 3 ×106/kg Eligibility Adult patients with R/R NHL (including MCL) or R/R CLL or SLL Projecte
Slide 20: PBCAR269A (BCMA): Phase 1/2a Clinical Plan
Objectives Primary: safety and tolerability Secondary: clinical (anti-tumor) activity Exploratory: expansion, trafficking, and persistence Dose Escalation (standard 3+3) DL1 = 6 ×105/kg DL2 = 2 ×106/kg DL3 = 6 ×106/kg Eligibility Adult patients with r/r Multiple Myeloma PBCAR269A (BCMA): Phase 1/2a
Slide 21: Curing Genetic Disease: In Vivo Gene Correction
Curing Genetic Disease In Vivo Gene Correction
Slide 22: In Vivo Gene Correction Pipeline
Product Candidate Program Area Discovery Pre-clinical Clinical Rights HBV Transthyretin HAO1 FVIII (Intron 22 inversion) P23H RHO ApoC3 PCSK9 Familial amyloid polyneuropathy Chronic Hepatitis B – IND 2020 Primary hyperoxaluria Hemophilia A Retinitis pigmentosa Lipoprotein lipase deficiency Familial
Slide 23: An In Vivo Gene Correction Platform to Cure Genetic Disease
An In Vivo Gene Correction Platform to Cure Genetic Disease In vivo gene corrections are permanent and require a therapeutic-grade genome editing approach Self-inactivating system Protein/DNA interaction Sticky-end off-targeting assay Safety Delivery Control Elimination of random off-targeting Enabl
Slide 24: Precision's In Vivo Gene Correction Strategy
Precision’s In Vivo Gene Correction Strategy Difficulty of Edit Difficulty of Delivery Initial focus is primarily on gene deletions in the liver and eye In vivo gene corrections are complicated by the type of edit and the need to deliver efficiently to specific tissues More technically challenging e
Slide 25: Hepatitis B: Targeted Elimination of Virus DNA
Hepatitis B: Targeted Elimination of Virus DNA ARCUS can target and destroy HBV cccDNA Development of a potential cure We are working with Gilead to develop a drug formulation for curing chronic HBV infection mRNA-based drug Lipid nanoparticle (LNP) delivery Large-scale in-house mRNA manufacturing p
Slide 26: Rhesus Macaques Show Reductions in PCSK9 and LDL Levels
Rhesus macaques treated with ARCUS show reductions in PCSK9 and LDL levels, sustained since 2017 First peer-reviewed data demonstrating in vivo gene correction in a non-human primate model Animals tolerated treatment, no obvious AEs and appear healthy two years after dosing Similar results obtained
Slide 27: Autosomal Dominant Retinitis Pigmentosa: Restore Vision
Autosomal Dominant Retinitis Pigmentosa: Restore Vision ARCUS can be used to selectively eliminate the P23H RHO gene associated with adRP >RHO C68A (P23H) mutant ACGGGTGTGGTACGCAGCCACT >wild-type rhodopsin ACGGGTGTGGTACGCAGCCCCT leave WT allele intact eliminate mutant allele AAV5 ARCUS-P23H Electror
Slide 28: Feed the Planet: Elo Life Systems
Feed the Planet Elo Life Systems
Slide 29: Food Pipeline
Product Discovery Greenhouse Field Program Lead Ultra-low Saturate Canola Oil Scaled, Zero Calorie Watermelon Sweetener Self-Breeding Stevia High Protein Chickpea Food Pipeline
Slide 30: A Food Editing Platform Built to Deliver Healthy Nutrition
Elo Life Systems, a subsidiary of Precision BioSciences, seeks to improve human health through food Cross-species information transfer Multi-omic target discovery Massively parallel computing Data Tech Partner Rapid response to climate change Answer demand for healthier foods Improved sustainability
Slide 31: Ultra-Low Saturate Canola Oil
Source: US patent 2017/0034541 W; TSFA: C18:0/C20:0/C22:0/C24:0; TSFA = Total Saturated Fatty Acid Ultra-Low Saturate Canola Oil Fatty Acid Biosynthesis Pathway in Canola Cargill is one of the world’s largest producers of cooking oil. We are collaborating with Cargill to develop ultra-low saturate “
Slide 32: Mogroside V: Scaled Zero Calorie Sweetener
Mogroside V: Scaled Zero Calorie Sweetener Mogroside V is an all-natural zero calorie sweetener from Monk Fruit + ARCUS Mogroside V pathway activity Scalable ü û û ü ü ü Mogroside V is difficult to source because monk fruit is not scalable Grown regionally, long life cycle, small, difficult to culti
Slide 33: Cash Runway Takes Us Into 2021
Cash Runway Takes Us Into 2021 Initial Public Offering (Ticker: DTIL) - Q2 2019 ü Clinical dosing of allogeneic CD19 CAR T - Q2 2019 Open cGMP manufacturing facility: CAR T, mRNA, AAV – Q3 2019 CD20 CAR T enters clinic Q4 2019 Interim data from Ph1/2a CD19 CAR T – no later than Q1 2020 IND for lead
Slide 34: Key Takeaways
Key Takeaways Highly experienced team of over 180 Precisioneers includes the pioneers in editing Proprietary ARCUS genome editing platform with full freedom to operate Independent cGMP manufacturing capabilities by YE 2019 Multiple allogeneic CAR T programs expected to be in clinical trials by YE 20
Slide 35: Precision BioSciences
PRECISION BIOSCIENCES rc ria Y aul Overcome Cancer. Feed the Planet. Dedicated To Improving Life
Slide 36: Appendix
¢ 2 Appendix
Slide 37: ARCUS Intellectual Property
Precision controls more than 45 issued US and foreign patents related to the ARCUS platform and ARCUS nuclease products Two core US patents (‘867 & ‘015) have undergone reexamination and were confirmed with no changes Each new ARCUS nuclease that generates a novel mutation is a non-obvious entity an
Slide 38: ARCUS: Engineered I-CreI Nucleases
ARCUS: Engineered I-CreI Nucleases ARCUS platform – an iterative protein engineering process involving changes to the specificity, affinity, and cleavage efficiency of I-CreI
Slide 39: Highly Sensitive Off-Target Detection
Highly Sensitive Off-Target Detection Clinical Candidate Step 1: Transfect cells with first generation ARCUS and a DNA “tag” Step 3: Genomic DNA is isolated from cells and evaluated on a next-gen sequencer 1st Generation ARCUS Optimized clinical candidate nuclease has zero detected off-target editin
Slide 40: I-CreI: A Natural Genome Editing Enzyme
I-CreI: A Natural Genome Editing Enzyme ARCUS is derived from I-CreI, a genome editing “homing” endonuclease (HE) from the algae Chlamydomonas reinhardtii Intron-encoded enzyme in the 23S ribosomal RNA gene Member of the LAGLIDADG homing endonuclease family and among the best biochemically understoo
Slide 41: Example: Creating an ARCUS Nuclease from I-CreI
Wang et al. Nat. Biotech, 2018.36:717-725 Example: Creating an ARCUS Nuclease from I-CreI Alter the amino acids at these positions so the nuclease now specifically binds to PCSK9 gene Amino acids responsible for recognizing specific target sequence Goal: Create an ARCUS nuclease to knockout the PCSK
Slide 42: ARCUS: Engineered I-CreI Endonucleases
CAAAACGTCGTGAGACAGTTTG wild-type I-CreI target site in Chlamydomonas TGGACCTCTTTGCCCCAGGGGA M1PCSK9 target site in human PCSK9 Exon 7 Linker ARCUS: Engineered I-CreI Endonucleases
Slide 43: ARCUS Example: PCSK9
TGGACCTCTTTGCCCCAGGGGA M3PCSK9 (generation 3) H40 K28 V40 I68 C44/H48/G50 W71/ C73 TGGACCTCTTTGCCCCAGGGGA TGGACCTCTTTGCCCCAGGGGA target site in human PCSK9 M2PCSK9 (generation 2) M1PCSK9 (generation 1) specificity improved at these positions specificity improved at these positions K28 H40 V40 ARCUS
Slide 44: ARCUS Example: PCSK9 Off-Target Editing
M3PCSK9 (generation 3) M2PCSK9 (generation 2) M1PCSK9 (generation 1) # off-target sites # off-target sites # off-target sites ARCUS Example: PCSK9 Three generations of a PCSK9 ARCUS nuclease were assayed for off-target editing in human cells and NHP liver biopsies using an advanced method called “Ol
Slide 45: Roadmap for CAR T Clinical Development
*Novel cell masking strategy that does not require additional editing Intensified Lymphodepletion (fludarabine + cyclophosphamide) 2 Biologic Lymphodepletion (F/C + biologic) 3 “Stealth Cell” Vector* 2 Roadmap for CAR T Clinical Development Maximization of naïve and central memory T cells allows for
Slide 46: "Stealth Cell" β2M Knockdown to Extend Cell Persistence
“Stealth Cell” “Stealth Cell” B2M B2M B2M Expression (normalized mean MFI) B2M Expression (normalized mean MFI) % CAR T Cell Lysis % CAR T Cell Lysis Rejection by T Cells Rejection by NK Cells “Stealth Cell” β2M Knockdown to Extend Cell Persistence Completely eliminating MHC-I (knocking out β2M) res
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