Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Investor Presentation (May 2022)
30 slides from Precision Biosciences's investor presentation, May 2022
Slide 1: Precision BioSciences: A Gene Editing Company Dedicated to Improving Life
PRECISION BIOSCIENCES: A Gene Editing Company Dedicated to Improving Life (DTIL) May 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements,
Slide 3: Precision BioSciences: A Clinical Stage Gene Editing Company
Precision BioSciences: A Clinical Stage Gene Editing Company • Built on wholly owned ARCUS® Genome Editing Platform for precision and versatility • ARCUS is based on a natural homing endonuclease which allows us to replicate precise gene editing as it evolved in nature for gene knock-out, insertion
Slide 4: Two Applications for Delivering on the Promise of Therapeutic Genome Editing
Two Applications for Delivering on the Promise of Therapeutic Genome Editing ARCUS® Genome Editing Derived from natural homing endonuclease for ex vivo and in vivo applications Ex Vivo ARCUS Editing for In Vivo ARCUS Editing for Allogeneic CAR T Genetic Diseases Immunotherapy Potentially curative, S
Slide 5: ARCUS: Advanced Genome Editing Platform for ex vivo and in vivo Editing
ARCUS: Advanced Genome Editing Platform for ex vivo and in vivo Editing PRECISION • Safety VERSATILITY • Specificity • Small Size Allows Tailored Tissue Delivery (via LNP and AAV delivery) • Performs Complex Edits (Gene Insertion & Gene Repair) 5
Slide 6: ARCUS: Custom Engineered for Genome Editing with ex vivo and in vivo Applications
ARCUS: Custom Engineered for Genome Editing with ex vivo and in vivo Applications Zinc Finger CRISPR BASE ARCUS Nuclease or Sa/SpCAS9 EDITOR TALENS Eukaryotic homing Bacterial Versatility Precision Bacterial endonuclease, restriction restriction Derived Origin evolved for gene enzyme, evolved enzyme
Slide 7: The Promise of ex vivo Gene Editing for Allogeneic CAR T Therapy
The Promise of ex vivo Gene Editing for Allogeneic CAR T Therapy • Auto-CAR T potentially curing 3.5 out of 10 patients ‒ ~4 weeks required to manufacture auto-CAR T cells ‒ Up to 20% of intended auto-CAR T patients never receive treatment • Precision’s off-the-shelf allogeneic CAR T reduces complex
Slide 8: Precision BioSciences ex vivo CAR T Pipeline
Precision BioSciences ex vivo CAR T Pipeline Next Program Indication Target Preclinical Clinical Milestone Post-auto CAR T PBCAR0191 CD19 Mid-2022 relapse NHL PBCAR19B NHL CD19 Mid-2022 PBCAR269A1 in Multiple Myeloma BCMA Mid-2022 combination with GSI CD19 combination 2022 IND with foralumab2 TBD CD
Slide 9: ex vivo CAR T Pipeline Focused on First-in-Class and Best-in-Class Approaches
Precision BioSciences ex vivo CAR T Pipeline Focused on First-in-Class and Best-in-Class Approaches PBCAR0191 in Potentially: Post-Auto CAR T First approved allo-CAR T therapy Relapse First approved gene-edited therapy First-in-Class Precision Allogeneic CAR T Platform Best-in-Class PBCAR in Multipl
Slide 10: Allogeneic CAR T Portfolio Going Forward: Our Focused Path to First-in-Class
Precision BioSciences Allogeneic CAR T Portfolio Going Forward: Our Focused Path to First-in-Class • Population with highest unmet need • No clear standard-of-care • Potential rapid path to market • Potential for first allogeneic CAR T to reach the market 10
Slide 11: PBCAR0191 with Enhanced Lymphodepletion in R/R CD19+ B-Cell Malignancies
PBCAR0191 with Enhanced Lymphodepletion in R/R CD19+ B-Cell Malignancies Long-Term Screening Follow-up Follow-Up Enhanced LD PBCAR0191 CAR T Cells1 Fludarabine 30 mg/m2/day × 4 days + Cyclophosphamide 1000 mg/m2/day × 3 days Objectives • Mitigate host immune rejection to improve PBCAR0191 expansion
Slide 12: eLD Markedly Increased PBCAR0191 Peak Expansion vs. sLD
eLD1 Markedly Increased PBCAR0191 Peak Expansion vs. sLD2 1000000 DL3a/4, sLD n = 12 PBCAR0191 Expansion DL3a/4, eLD n = 22 by PCR 100000 Mean Peak ~21X Copies/ ug DNA 10000 Mean Area Under ~47X the Curve (AUC) 1000 100 10 Screen Day 0 Day 1 Day 3 Day 7 Day 10 Day 14 Day 21 Day 28 Sample day (post-C
Slide 13: Best Response to PBCAR0191 with eLD Comparable Between Auto-CAR T Relapsed & Naïve
Best Response to PBCAR0191 with eLD Comparable Between Auto-CAR T Relapsed & Auto-CAR T Naïve Subjects All evaluable CAR T CAR T subjects naïve experienced n (%) (N=22)1 (n=16)2 (n=6) Overall Response Rate (ORR) 16 (73%) 10 (63%) 6 (100%) ≥Day 28 Complete Response (CR) 13 (59%) 9 (56%) 4 (66%) ≥Day
Slide 14: Depth & Duration of Response to PBCAR0191 in Auto-CAR T Relapsed Subjects
Depth & Duration of Response to PBCAR0191 in CD19 Auto-CAR T Relapsed Subjects Subject Auto CD19 CAR T • 100% ORR in subjects who A PBCAR0191 received prior auto-CAR T • PBCAR0191 response Subject Auto CD19 CAR T B duration exceeded PBCAR0191 original response to auto- CAR T in 3 of 5 evaluable Subj
Slide 15: Evidence for PBCAR0191 + eLD in Auto-CAR T Relapsed
Evidence for PBCAR0191 + eLD in Auto-CAR T Relapsed • Auto-CAR T has changed the landscape for 3rd line lymphoma; ~65% of patients relapse1 • As auto-CAR T moves to second line, the number of patients requiring salvage increases • No FDA approved therapeutics for patients who progress following auto
Slide 16: Best-in-Class: Allogeneic PBCAR T Cell Products for B-Cell Malignancies
Best-in-Class: Allogeneic PBCAR T Cell Products for Subjects with Relapsed/Refractory B-Cell Malignancies • Single dose • ARCUS single-gene edit minimizing translocation safety concerns • Therapeutic index as good as, or better than, approved auto-CAR T product profiles • Overcome rejection of allog
Slide 17: PBCAR19B Stealth Cell Progress in Clinic
PBCAR19B Stealth Cell Progress in Clinic Accomplished with a single-step gene edit to minimize risk of chromosome abnormalities Anti-CD19 CAR 1 TCR is knocked-out to prevent GvHD • Five clinical trial sites activated Anti-beta-2 microglobulin • Subjects receive increasing flat dose levels 2 shRNA (2
Slide 18: Foralumab is an Anti-CD3 Antibody for Selective Depletion of Patient T Cells
Foralumab1 is an Anti-CD3 Antibody for Selective Depletion of Patient T Cells • Foralumab may prevent CAR T cell rejection TCR by eliminating the anti-CAR T response Foralumab binds to CD3 on the surface • PBCAR T cells are resistant to foralumab of patient T cells because foralumab cannot bind allo
Slide 19: in vivo Application for Delivering on the Promise of Therapeutic Genome Editing
in vivo Application for Delivering on the Promise of Therapeutic Genome Editing ARCUS® Genome Editing Derived from natural homing endonuclease for ex vivo and in vivo applications Ex Vivo ARCUS Editing for In Vivo ARCUS Editing for Allogeneic CAR T Genetic Diseases Immunotherapy Potentially curative
Slide 20: in vivo Gene Editing Pipeline: Three INDs/CTAs in Next Three Years
Precision BioSciences in vivo Gene Editing Pipeline: Three INDs/CTAs in Next Three Years Candidate IND- Expected Program Indication Tissue Target Delivery Research Partner Selection Enabling IND/CTA PBGENE- Familial PCSK91 Hypercholesterolemia Liver PCSK9 AAV 2022 PBGENE- Primary PH1 Hyperoxaluria T
Slide 21: in vivo Gene Editing Strategy
Precision BioSciences: in vivo Gene Editing Strategy Pipeline Validation & 22 Expansion Creates Value Pipeline Expansion Complex Edits & 1 Multiple Tissues Clinical Validation Knock-out Genes in Liver PBGENE-DMD PBGENE-LLY21 AAV PBGENE-PCSK9 PBGENE-LLY31 LNP PBGENE-PH1 PBGENE-HBV IND/CTA 2022 2023 2
Slide 22: ARCUS for Familial Hypercholesterolemia (FH)
ARCUS for Familial Hypercholesterolemia (FH) • One of the most common genetic diseases with pattern of severe hypercholesterolemia, cholesterol deposition and high risk of early onset coronary artery disease. Disorders all share decreased LDL clearance Heterozygous FH (HeFH) Homozygous FH (HoFH) LDL
Slide 23: PBGENE-PCSK9: Single-Dose AAV8-ARCUS Reduced PCSK9 & LDL-C in NHPs
PBGENE-PCSK9: Single-Dose of AAV8-ARCUS Significantly Reduced Serum PCSK9 Levels & LDL-C Levels in NHPs for 3yr1 PCSK9 LDL-C PCSK9 (% reduction from baseline) LDL-C (% reduction from baseline) 0 0 -20 -20 -40 42-62% Reduction -40 60-82% Reduction -60 -60 -80 -80 1. Wang, et al. (2021) Mol. Ther. 29(
Slide 24: 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 • HAO1 encodes glycolate oxidase acts upstream of the formation of oxalate 40% of patients ha
Slide 25: PBGENE-PH1 Decreased HAO1 mRNA by 98% and Increased Serum Glycolate in NHPs
PBGENE-PH1 Decreased HAO1 mRNA by 98% and Increased Serum Glycolate in NHPs ARCUS Reduced HAO1 mRNA Levels ARCUS Increased Serum Glycolate Levels 1.2 100 ARCUS (M1HAO1) 98% Normalized HAO1 mRNA (n=3) 1.0 single dose reduction 80 µM 0.8 Glycolate 60 Maximum with siRNA Glycolate, 4mg/kg monthly 0.6 Al
Slide 26: PBGENE-HBV Novel Approach to Chronic HBV
PBGENE-HBV Novel Approach to Chronic HBV (cHBV) ARCUS-mediated inactivation of cccDNA HBV Infected Hepatocyte ARCUS LNP and integrated HBV could result in a functional cure Chronic HBV unmet need is massive inactivate cccDNA US >860,000 cHBV infections Globally >200 million cHBV infections • >90% of
Slide 27: Transformative Gene Editing Partnership for Precision
Transformative Gene Editing Partnership for Precision Research collaboration and license agreement aimed at treating challenging genetic diseases 3+ Initial collaboration for 3 programs, including DMD Precision: Pre-IND R&D; Lilly: IND to commercial Upfront payment of $135 million including 3 Lilly
Slide 28: ARCUS for Therapeutic Treatment of DMD
ARCUS for Therapeutic Treatment of DMD ARCUS 1 ARCUS 2 Goal: Restore Exons 45–55 dystrophin expression Exon 44 Exon 56 Exon 57 by deleting exons 45-55 using a pair of ARCUS Exons 45–55 deletion nucleases intended to Exon 44 Exon 56 Exon 57 remove a mutation hotspot responsible for genome repair via
Slide 29: Focused Execution in 2022 to Clinically Validate ARCUS
Precision BioSciences Focused Execution in 2022 to Clinically Validate ARCUS ex vivo CAR T Pipeline: • PBCAR0191 with eLD: Potential first-in-class allogeneic CAR T – update in June 2022 • PBCAR19B stealth cell: Potential best-in-class – update in June 2022 • PBCAR269A combination with nirogacestat
Slide 30: Overcome cancer. Cure genetic disease.
Overcome cancer. Cure genetic disease.
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