Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — 40th J.P. Morgan Health Care Conference (January 2022)
27 slides from Precision Biosciences's conference presentation, Jan 12, 2022
Slide 1: Precision BioSciences: A Gene Editing Company Dedicated to Improving Life
PRECISION BIOSCIENCES: A Gene Editing Company Dedicated to Improving Life (DTIL) January 12, 2022 40th J.P. Morgan Health Care Conference
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: Agenda
Agenda • ARCUS® premier gene editing platform • ex vivo applications of ARCUS focused on first-in-class and best-in-class allogeneic CAR T programs • in vivo applications of ARCUS expect to deliver 3 INDs/CTAs in 3 YEARS 3
Slide 4: Building on 2021 Progress to Further Validate ARCUS in 2022
Building on 2021 Progress to Further Validate ARCUS in 2022 2021 Accomplishments: • Closed ≤6 target in vivo gene editing deal with Lilly • Announced phase 1 data for PBCAR0191 supporting trial expansion • Advanced PBCAR19B stealth cell into the clinic • Expedited clinical PBGENE-PCSK9 development p
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: 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 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: ex vivo CAR T Pipeline
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 CD19 amendment (anti-CD3
Slide 9: ex vivo CAR T Pipeline Focused on First-in-Class and Best-in-Class Approaches
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 Multiple Potentially: PBCAR19
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: PBCAR0191 with eLD: Earlier Expansion, Higher Peak, Prolonged Persistence
PBCAR0191 with eLD: Earlier Expansion, Higher Peak, Prolonged Persistence, Delayed CD3 Recovery in Relapsed Auto-CAR T Setting PBCAR0191 expansion and CD3+ cells measured by flow cytometry 80000 2500000 CD19 Auto-CAR T Relapsed CD19 Auto-CAR T Relapsed 2000000 CD19 Auto-CAR T Naive CD19 Auto-CAR T N
Slide 16: 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 17: Best-in-Class: Allogeneic PBCAR T Cell Products for Relapsed/Refractory 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 18: 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 • Phase 1 study initiated on June 30, 2021 1 TCR is knocked-out to prevent GvHD • Subjects receive increasing flat dose levels Anti-beta-2 microglobulin 2 shR
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: 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 22: PBGENE-PCSK9: Single-Dose of 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 23: 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 24: 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 25: 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 26: 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 mid-2022 • PBCAR19B stealth cell: Potential best-in-class – update in mid-2022 • PBCAR269A combination with nirogacestat in
Slide 27: Overcome cancer. Cure genetic disease.
Overcome cancer. Cure genetic disease.
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