Precision BioSciences, Inc. · NASDAQ:DTIL
Precision BioSciences — Investor Presentation (January 2021)
35 slides from Precision BioSciences's investor presentation, January 2021
Slide 1: Cure Genetic Disease. Corporate Deck
Cure Genetic Disease. Corporate Deck January 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) may contain forward-looking statements. All statements other than statements of present and historical facts contained in this presentation, including, without lim
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 4
Slide 5: Focused on Overcoming Cancer and Curing Genetic Disease
Focused on Overcoming Cancer and Curing Genetic Disease Cell Therapy Programs Pre-clinical Clinical PBCAR01911 (NHL and B-ALL) PBCAR19B1 (NHL) PBCAR20A (NHL, CLL, SLL) PBCAR269A (MM) One cohort in combination with GSI2 2 Undisclosed Blood Cancers1 2 Undisclosed Solid Tumor Cancers1 Priority In Vivo
Slide 6: 2020 Accomplishments Set up Key Milestones in 2021
2020 Accomplishments Set up Key Milestones in 2021 Announced in vivo gene editing collaboration with Lilly to develop up to six targets, including DMD ($135M upfront + ≤$420M/target in milestones + tiered royalties) Achieved 83% Objective Response Rate with PBCAR0191 + Enhanced LD in patients (n=6
Slide 7: 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 8: Allogeneic CAR T Pipeline
Allogeneic CAR T Pipeline Program Pre-clinical Clinical PBCAR0191 (CD19)1 NHL and B-ALL PBCAR19B Stealth Cell (CD19) 1 NHL PBCAR20A (CD20) NHL, CLL, SLL PBCAR269A (BCMA) MM One cohort in combination with GSI2 Hematology1 2 Undisclosed Blood Cancers Solid Tumor1 2 Undisclosed Solid Tumor Cancers 1 In
Slide 9: 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 • 1-step gene editing process and efficient, domain scaled manufacturing process - High yield - Consistent, predominantly naïve T cell phenotype - CD4:CD8 ratio ap
Slide 10: PBCAR0191 Phase 1/2a Clinical Design in R/R NHL and R/R B-ALL
PBCAR0191 Phase 1/2a Clinical Design in R/R NHL1 and R/R B-ALL2 Long-Term Screening Follow-up Follow-Up Standard LD (sLD): PBCAR0191 Fludarabine 30mg/m2/day x 3 days plus Cyclophosphamide 500 mg/m2/day x 3 days OR Enhanced LD (eLD): Fludarabine 30mg/m2/day x 4 days plus Cyclophosphamide 1000 mg/m2/d
Slide 11: PBCAR0191: Enhanced LD Regimen Shows Promising Activity
PBCAR0191: Enhanced LD Regimen Shows Promising Activity 95X Increase in Peak Expansion >90% Decrease in Tumor Size Best % Change Tumor Area (SPPD, mm2) ~95X 1NHL patients eLD Increased Cell Expansion; Correlated with 100% ORR (75% CR)1 11
Slide 12: PBCAR0191: Enhanced LD Resulted in 100% ORR in NHL
PBCAR0191: Enhanced LD Resulted in 100% ORR in NHL NHL eLD1 Total2 (n=4) (n=16) ORR at Day ≥28 4 (100%) 11 (69%) Best Response Complete Response 3 (75%)3 6 (38%) at Day ≥28 Partial Response 1 (25%) 5 (31%) Progressive Disease 0 5 (31%) 1. Enhanced LD: Fludarabine 30mg/m2/day x 4 days + Cyclophospham
Slide 13: Acceptable Safety Profile Observed with Enhanced LD
Acceptable Safety Profile Observed with Enhanced LD Phase 1 NHL patients who received a dose of cells and have completed 28-day follow-up by November 16, 2020 (n = 16 patients) eLD Total Number (%) of patients experiencing events (n=4) (n=16) CRS Grade 1 or Grade 2 3 (75%) 9 (56%) (Cytokine Release
Slide 14: PBCAR0191 Clinical Update Expected by Mid-2021
PBCAR0191 Clinical Update Expected by Mid-2021 Increased Peak Increased Persistence Repeat Dose 1. Enhanced Lymphodepletion 3. Novel Lymphodepletion 4. Scheduled Repeat Dose with • Enrolling additional NHL Regimens Repeat Lymphodepletion and B-ALL patients with eLD • Novel LD regimens designed • Enr
Slide 15: CD19 Stealth Cell Designed to Prevent Rejection by T Cells and NKs
CD19 Stealth Cell Designed to Prevent Rejection by T Cells and NKs IND accepted by FDA for PBCAR19B Phase 1 study of patients with R/R NHL will evaluate the safety and clinical 1 Anti-CD19 TCR is knocked out activity of PBCAR19B at increasing flat dose levels CAR to prevent GvHD (2.7 x 108 - 8.1 x 1
Slide 16: 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) In clinical studies, patient NK cells returned to baseline levels within 2 weeks post-lymphodepletion 16 16
Slide 17: Stealth Cell Technology Designed to Prevent Rejection
Stealth Cell Technology Designed to Prevent Rejection Pre-clinical studies showed anti-CD19 stealth cell CAR T cells resisted rejection by allo-reactive T cells and NKs in mixed-lymphocyte reactions Rejection by T cells Rejection by NK cells (n=4 mismatched donors) (n=3 mismatched donors) 70 120 60
Slide 18: Phase 1 Interim Data for PBCAR20A & PBCAR269A Expected in 2021
Phase 1 Interim Data for PBCAR20A & PBCAR269A Expected in 2021 Safety Assessment Screening Treatment and Follow-Up (365d) Standard Lymphodepletion Flu/Cy Population Approved Dose Escalation Range Status PBCAR20A Adult patients with: DL1 = 1.0 × 106 cells/kg1 • First patient dosed 04/2020 • R/R NHL (
Slide 19: I-CreI: A Natural Genome Editing Enzyme
I-CreI: A Natural Genome 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 ends” promote homology
Slide 20: 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 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 results in long-term reductions in
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: ARCUS Efficiently Targets Single-Nucleotide Polymorphisms (SNPs)
ARCUS Efficiently Targets Single-Nucleotide Polymorphisms (SNPs) Autosomal Dominant Retinitis Pigmentosa (adRP) P23H is the most common mutation causing adRP. It is a SNP that causes rhodopsin to aggregate in rod cells leading to degeneration of the retina. Pig Animal Model One-time delivery of an A
Slide 24: In Vivo Gene Correction Pipeline
In Vivo Gene Correction Pipeline Program Area Pre-clinical Clinical Duchenne Muscular Dystrophy (DMD)1 Programs Priority 2 Undisclosed Targets1 Primary Hyperoxaluria Type 1 (HAO1) Chronic Hepatitis B Familial Amyloid Polyneuropathy (TTR) Programs Research Familial Hypercholesterolemia (PCSK9) Autoso
Slide 25: 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 • Upfront payment of $135 million including $35 programs, including DMD million equity stake +
Slide 26: Duchenne Muscular Dystrophy Lacks a Curative Treatment
Duchenne Muscular Dystrophy Lacks a Curative Treatment Mutation on the X chromosome interferes with dystrophin protein production, which is needed to form and maintain healthy muscle On average, children lose Affects their ability to approximately walk by age 12 1 in 3,500 live male births Muscular
Slide 27: Goal: Restore Dystrophin Expression Using a Pair of ARCUS Nucleases
Goal: Restore 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 5
Slide 28: 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 29: 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 30: 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 31: Approach: Reduce Oxalate Levels by Editing HAO1
Approach: Reduce Oxalate Levels by Editing HAO1 PH1 patient ARCUS edited 31
Slide 32: 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 33: Each in vivo Editing Program Faces Unique Set of Technical Challenges
Each in vivo Editing Program Faces Unique Set of Technical Challenges Difficulty of Edit Repair Technical Success “Unlocks” Additional Programs As we overcome specific technical challenges, learnings can be Insertion applied to new projects Deletion Difficulty of Delivery Liver Eye Muscle Lung CNS 3
Slide 34: Precision Expects to Achieve Important Milestones in 2021
Precision Expects to Achieve Important Milestones in 2021 Primary Hyperoxaluria Type 1 program update in 1H/2021 Dose first patient with next generation PBCAR19B stealth cell in 1H/2021 Initiate clinical cohort with PBCAR269A combined with GSI in 1H/2021 Updated interim PBCAR0191 data by mid-2021 Co
Slide 35: Dedicated To Improving Life
Overcome cancer. Cure genetic disease. Dedicated To Improving Life 35
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