Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Investor Presentation (July 2021)
31 slides from Precision Biosciences's investor presentation, July 2021
Slide 1: Cure Genetic Disease. Corporate Deck
Cure Genetic Disease. Corporate Deck July 2021 © 2021 Precision BioSciences, Inc.
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation (together with any other statements or information that we may make in connection herewith) contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation (toge
Slide 3: Delivering on the Promise of Therapeutic Genome Editing
Delivering on ARCUS® Genome Editing Platform the Promise of built for translation with full freedom to operate Therapeutic Allogeneic CAR T platform validated with clinical response and safety data Genome Editing In Vivo Gene Correction pipeline seeking to cure genetic and infectious diseases Pionee
Slide 4: Focused on Overcoming Cancer and Curing Genetic Disease
Focused on Overcoming Cancer and Curing Genetic Disease Unlocking the full potential of proprietary ARCUS platform to address serious diseases ARCUS Permanently Optimize allogeneic correct genetic CAR T cells for deep diseases with and durable in vivo gene editing responses © 2021 Precision BioScien
Slide 5: Focused on Overcoming Cancer and Curing Genetic Disease
Focused on Overcoming Cancer and Curing Genetic Disease Pre-clinical Clinical Allogeneic CAR T Cell Therapy Programs PBCAR0191 (NHL and B-ALL) PBCAR19B immune evading stealth cell (NHL) PBCAR20A (NHL, CLL, SLL) PBCAR269A (MM) PBCAR269A in combination with GSI1 PBCAR269B immune evading stealth cell (
Slide 6: Advanced In-House Manufacturing Capabilities
Advanced In-House Manufacturing Capabilities Ability to produce ARCUS-based CAR T and in vivo therapies MCAT: Manufacturing Center for Advanced Therapeutics • Completed tech transfer of PBCAR0191 and PBCAR20A to MCAT • Manufactured first batch and clinical trial material for PBCAR269A • 100% on time
Slide 7: Allogeneic CAR T Candidates Created with Proprietary Gene Editing
Allogeneic CAR T Candidates Created with Proprietary Gene Editing Antigen-specific scFv (CD19, CD20, or BCMA) Patented N6 co-stimulatory domain • 1-step ARCUS gene editing process and efficient, scaled manufacturing process - High yield - Consistent, predominantly naïve T cell phenotype • CD19 clini
Slide 8: PBCAR0191 Phase 1/2a Clinical Design in R/R NHL and R/R B-ALL
PBCAR0191 Phase 1/2a Clinical Design in R/R NHL and R/R B-ALL Long-Term Screening Follow-up Follow-Up Standard LD (sLD)1 or PBCAR0191 Enhanced LD (eLD)2 • Objectives - Mitigate host immune rejection to improve CAR T cell expansion and persistence - Increase frequency and durability of Complete Respo
Slide 9: Subjects Enrolled with Advanced and Aggressive R/R NHL
Subjects Enrolled with Advanced and Aggressive R/R NHL • Over 80% of subjects had eLD (n=12) aggressive lymphomas Age (y) median (min-max) 57 (34-76) Diffuse Large B-Cell 7 (58%) • Median and mean of ~7 Subtype n (%) CLL/Richter’s Trans. 2 (17%) lines of prior NHL therapy High grade Lymphoma 1 (8%)
Slide 10: AESI Profile with eLD vs. Standard Lymphodepletion
AESI* Profile with eLD vs. Standard Lymphodepletion Data cutoff of May 21, 2021 for R/R NHL subjects treated at DL3 with Day 28 evaluation (N=18) sLD eLD Adverse Event Max Grade (n=6) (n=12) CRS Grade 1 or Grade 2 3 (50%) 7 (58%) (Cytokine release syndrome) Grade 3 or higher 0 0 ICANS Grade 1 or Gra
Slide 11: Response to PBCAR0191 in R/R NHL eLD Subjects
Response to PBCAR0191 in R/R NHL eLD Subjects All eLD Subjects CD19-CAR Naïve Prior Auto CAR (n=12) (n=8) (n=4*) Overall Response 9 (75%) 6 (75%) 3 (75%) Rate (ORR), n (%) Complete Response 6 (50%) 4 (50%) 2 (50%) (CR), n (%) DL3 sLD at Day ≥ 28: ORR 3/6 (50%), CR 2/6 (33%). *3 of 4 responders had p
Slide 12: PBCAR0191 CAR T Cell Expansion in Peripheral Blood
PBCAR0191 CAR T Cell Expansion in Peripheral Blood Flow Cytometry PCR 60000 1000000 DL3 sLD DL3 sLD DL3 eLD DL3 eLD 40000 100000 PBCAR Copies/ ug DNA 20000 CAR T cells/ml 10000 1000 72X 56X Peak AUC 800 1000 600 400 100 200 0 10 Screen Day 0 Day 1 Day 3 Day 7 Day 10 Day 14 Day 21 Day 28 Screening Da
Slide 13: PBCAR19B Stealth Cell: A Differentiated Strategy for Deeper, More Durable Responses
PBCAR19B Stealth Cell: A Differentiated Strategy for Deeper, More Durable Responses PBCAR19B first patient dosed in Q2 2021 Phase 1 study of patients with R/R NHL will evaluate the safety and clinical activity of PBCAR19B at increasing flat dose 1 Anti-CD19 CAR TCR is knocked-out to prevent GvHD lev
Slide 14: Both T Cells and NKs Can Potentially Mediate CAR T Rejection
Both T Cells and NKs Can Potentially Mediate CAR T Rejection NHL DL3 (n=6) An analysis of patient samples from PBCAR0191 Dose Level 3 reveals that patient NK cells return to baseline levels within two weeks post-lymphodepletion. © 2021 Precision BioSciences, Inc. 14 14
Slide 15: PBCAR19B Incorporates an anti-β2m shRNA and an HLA-E Transgene
PBCAR19B Incorporates an anti-β2m shRNA and an HLA-E Transgene In mixed-lymphocyte reactions, stealth cell CAR Ts are highly-resistant to rejection by T cells and NK cells. Stealth Cell CAR T Vector CAR 2A HLA shRNA -E Rejection by T cells Rejection by NK cells (n=4 mismatched donors) (n=3 mismatche
Slide 16: Phase 1 Interim Data for PBCAR20A Expected in 2021
Phase 1 Interim Data for PBCAR20A Expected in 2021 Safety Assessment Screening Treatment and Follow-Up (365d) Standard LD Population Approved Dose Status Escalation Range Adult patients with: DL1 = 1.0 × 106 cells/kg1 • DL3 completed; pausing until PBCAR0191 • R/R NHL (including DL2 = 3.0 × 106 cell
Slide 17: Three Potential Shots on BCMA Target for R/R Multiple Myeloma
Three Potential Shots on BCMA Target for R/R Multiple Myeloma • DL3 began Q1/2021 PBCAR269A • Interim update planned for 2021 • Approved dose escalation range DL1 = 6.0 × 105 cells/kg; DL2 = 2.0 × 106 cells/kg; DL3 = 6.0 × 106 cells/kg PBCAR269A in combination with • Cohort with SpringWorks gamma se
Slide 18: ARCUS Genome Editing Based on I-CreI: A Natural Editing Enzyme
ARCUS Genome Editing Based on I-CreI: A Natural Editing Enzyme Attributes that make I-CreI an excellent therapeutic editing tool: • Specificity. I-CreI recognizes a large target site (22 base pairs) and rarely edits off-target sites because it self-inactivates after editing • Type of cut. 3’ “sticky
Slide 19: ARCUS: Engineered I-CreI Nucleases
ARCUS: Engineered I-CreI Nucleases Advanced protein engineering process In silico Directed involving changes to the specificity, Design Evolution affinity, and catalytic efficiency of I-CreI 1st Generation ARCUS DNA-Binding Surface of an ARCUS Nuclease Unbiased Off- Target Analysis Off-Target Confir
Slide 20: In Vivo Gene Correction Pipeline
In Vivo Gene Correction Pipeline Program Area Pre-clinical Clinical Duchenne Muscular Dystrophy1 Programs Priority 2 undisclosed targets1 Primary Hyperoxaluria Type 1 (HAO1 ) Chronic Hepatitis B Familial Amyloid Polyneuropathy (TTR ) Programs Research Familial Hypercholesterolemia (PCSK9 ) Autosomal
Slide 21: ARCUS Knock-Out of PCSK9 Gene in Liver
ARCUS Knock-Out of PCSK9 Gene in Liver Familial Hypercholesterolemia (FH) Rare genetic disorder leading to high levels of serum LDL, severe cholesterol deposits, and early-onset heart disease. Non-Human Primate Animal Model One-time delivery of an AAV-ARCUS vector resulted in long-term reductions of
Slide 22: ARCUS Knock-Out of TTR Gene in Liver
ARCUS Knock-Out of TTR Gene in Liver Hereditary Transthyretin Amyloidosis (ATTR) Rare genetic disease characterized by accumulation of mutant transthyretin protein in peripheral organs, which leads to neuropathy and/or cardiomyopathy. Non-Human Primate Animal Model One-time delivery of an AAV-ARCUS
Slide 23: Precision-Lilly Partnership: Unlocking the Value of In Vivo Gene Editing
Precision-Lilly Partnership: Unlocking the Value of In Vivo Gene Editing Research collaboration and license agreement with Lilly aimed at treating challenging genetic diseases 3 Initial collaboration for 3 programs, including • Upfront payment of $135 million including $35 Duchene muscular million e
Slide 24: Restore DMD Dystrophin Expression Using a Pair of ARCUS Nucleases
Restore DMD Dystrophin Expression Using a Pair of ARCUS Nucleases N-terminal Rod Domain C-terminal Dystrophin Exons 9 - 44 Exons 45 - 55 Exons 56 - 70 Gene Deletion Hot Spot ARCUS 1 ARCUS 2 1. Two separate ARCUS nucleases target the introns flanking exons 45-55 Exons 45 – 55 Exon 44 Exon 56 Exon 57
Slide 25: Dystrophin Gene Correction in DMD Patient Myoblasts
Dystrophin Gene Correction in DMD Patient Myoblasts Corrected DNA Corrected mRNA Corrected Protein exons 45-55 deleted exon 44 spliced to Exon 56 dystrophin protein expressed 40 % Editing (“perfect ligation”) 10 kDa (normalized to ANKRD27) 30 8 Spliced DMD mRNA 6 20 Dystrophin 4 10 2 0 0 mock mock A
Slide 26: Correction of Satellite Cells for Long-Term Benefit
Correction of Satellite Cells for Long-Term Benefit Microdystrophin or Antisense ARCUS Gene Correction Direct targeting of myofiber results Goal: Targeting of satellite stem cells in transient and low-level could result in amplified and long-term dystrophin expression dystrophin expression Myofiber
Slide 27: Overview of Primary Hyperoxaluria Type 1 (PH1)
Overview of Primary Hyperoxaluria Type 1 (PH1) Rare genetic disease characterized by accumulation of calcium oxalate in kidneys, which leads to painful kidney stones and ultimately end- stage renal disease ~40% Combined patients have liver-kidney end-stage renal disease at the time of diagnosis tran
Slide 28: Approach: Reduce Oxalate Levels by Editing HAO1
Approach: Reduce Oxalate Levels by Editing HAO1 PH1 patient ARCUS edited © 2021 Precision BioSciences, Inc. 28
Slide 29: ARCUS Treatment Greatly Reduced HAO1 Gene Expression in NHPs
ARCUS Treatment Greatly Reduced HAO1 Gene Expression in NHPs HAO1 mRNA GO protein Serum glycolate ARCUS treatment reduced HAO1 mRNA ARCUS treatment reduced GO protein levels ARCUS treatment significantly increased serum levels >90% in liver of non-human primates >80% in liver of non-human primates g
Slide 30: Important Program Progress and Upcoming Milestones
Important Program Progress and Upcoming Milestones • PBCAR0191 and PBCAR19B data will be evaluated to determine the best path for overcoming rejection prior to making pivotal trial decision - PBCAR0191 highly active following eLD yielding ORR of 75% and CR of 50% at Day ≥28 with acceptable safety pr
Slide 31: Dedicated To Improving Life
Overcome cancer. Cure genetic disease. Dedicated To Improving Life 31
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