Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — 2021 ASH (American Society of Hematology) Annual Meeting
36 slides from Precision Biosciences's conference presentation, Dec 11, 2021
Slide 1: 2021 ASH: Allogeneic CAR T Pipeline Update
2021 ASH: Allogeneic CAR T Pipeline Update American Society of Hematology December 11, 2021
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 the Promise of Therapeutic Genome Editing Ex vivo editing for In Vivo Editing for Allogeneic CAR T ARCUS® Genetic Diseases immunotherapy Gene edited, donor derived Genome Editing Potentially curative, one-time treatment CAR T cells Derived from natural homing endonuclease for in vivo a
Slide 4: ARCUS: Advanced Genome Editing Platform for in vivo and ex vivo Editing
ARCUS: Advanced Genome Editing Platform for in vivo and ex vivo Editing PRECISION • Safety VERSATILITY • Specificity • ARCUS is Easy to Deliver • ARCUS Performs Complex Edits (Gene Insertion & Gene Repair) 4
Slide 5: CEO Takeaways from First 50 Days at Precision BioSciences
• Exceptional scientific team created ARCUS • PBCAR0191 - potential First-in-Class allogeneic CAR T program CEO Takeaways from • PBCAR19B (stealth cell) - potential Best-in- First 50 Days at Class CD19 targeting allogeneic CAR T Precision BioSciences • Disciplined, data driven decisions • in vivo ge
Slide 6: Today's Topics
Today’s Topics • Review of clinical data - PBCAR0191 with eLD - CD19 - PBCAR269A - BCMA • Allogeneic CAR T portfolio going forward - First-in-Class approach - Best-in-Class approach • Expected 2022 CAR T program updates 6
Slide 7: First-in-Class: Allogeneic PBCAR0191 for Relapsed/Refractory B-Cell Malignancies
First-in-Class: Allogeneic PBCAR0191 for Relapsed/Refractory B-Cell Malignancies 7
Slide 8: 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 9: 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 10: Heavily Pre-Treated and Aggressive Lymphoma Population
Heavily Pre-Treated and Aggressive Lymphoma Population NHL B-ALL (n=18)2 (n=5) Age (y), median (range) 57 (34-76) 50 (26-56) Refractory to Prior Line of Therapy 6 (33%) 1 (20%) Aggressive histology,1 n (%) 14 (78%) - DLBCL 11 (61%) - CLL with Richter’s 2 (11%) - High grade 1 (6%) - Number of prior t
Slide 11: Predictable AESI Profile with Enhanced Lymphodepletion
Predictable AESI Profile with Enhanced Lymphodepletion1 `Data cutoff as of Nov 16, 2021 NHL B-ALL Number (%) of subjects experiencing events with max grade (n=18)2 (n=5) AE of special CRS Grade 1 or Grade 2 12 (67%) 4 (80%) interest Grade 3 or higher 0 0 Time to onset (Days) Median (range) 6.5 (3-19
Slide 12: 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 13: High Response Rates to PBCAR0191 with eLD on Par with Autologous CAR T
High Response Rates to PBCAR0191 with eLD on Par with Autologous CAR T NHL B-ALL n (%) (n=17)1 (n=5) Overall Response Rate (ORR) 12 (71%) 4 (80%) ≥Day 28 Complete Response (CR) 9 (53%) 4 (80%) ≥Day 28 1 One subject non-evaluable for efficacy at Day 28 assessment due to death related to cardiac arres
Slide 14: PBCAR0191 Response Duration by Subject in NHL
PBCAR01911 Response Duration by Subject in NHL Subject 1 Prior to 1st evaluation Subject 2 CR Subject 3 PR Subject 4 SD Subject 5 PD Death on study in Subject 6 ongoing response Enhanced LD2 Subject 7 Death on study prior Subject 8 to assessment Subject 9 Allo-transplant Subject 10 Prior aHCT • 4 of
Slide 15: PBCAR0191 Response Duration in B-ALL Subjects
PBCAR01911 Response Duration in B-ALL Subjects Subject 18 Enhanced LD2 Subject 19 • 3 of 5 subjects secured adequate window for allo-HCT Subject 20 ‒ 1 subject with response ongoing >9 months (deemed ineligible) Subject 21 ‒ 1 subject refused allo-HCT ‒ 1 subject transplanted Subject 22 0 50 100 150
Slide 16: PBCAR0191 with eLD Experience
PBCAR0191 with eLD Experience • Enhanced LD mitigated PBCAR0191 rejection to markedly improve peak cell expansion and persistence • Predictable toxicity without ≥ Grade 3 CRS, one Grade 3 self-limited ICANS. Prolonged cytopenias with ≥ Grade 3 infections required careful management • In heavily pre-
Slide 17: Precision BioSciences Allogeneic CAR T Portfolio Going Forward
Precision BioSciences Allogeneic CAR T Portfolio Going Forward: Our Focused Path to First-in-Class 17
Slide 18: CD19-Directed Auto-CAR T Failure: A Growing and Underserved Population
CD19-Directed Auto-CAR T Failure: A Growing and Underserved Population with High Unmet Need • Auto-CAR T has changed the landscape for 3rd line lymphoma patients and created an emerging group of patients with highest unmet need • ~40% of auto-CAR T treated patients do not respond AND ~60% of respond
Slide 19: Depth & Duration of Response to PBCAR0191 in CD19 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 duration exceeded original B PBCAR0191 response to auto-CAR T in 3 of 5 evaluable subj
Slide 20: Auto-CAR T Relapsed Subjects Have Deeper Nadir & Delayed CD3 Cell Recovery
Auto-CAR T Relapsed Subjects Have Deeper Nadir & Delayed CD3 Cell Recovery that May Delay Allo-CAR T Rejection 2500000 CD19 Auto-CAR T Relapsed 2000000 CD19 Auto-CAR T Naive •Lymphoma treatment reduces 1500000 early-lineage T cells necessary 1000000 for auto-CAR T cell expansion1 CD3+ cells/ml 50000
Slide 21: PBCAR0191 with eLD: Earlier Expansion, Higher Peak & Prolonged Persistence
PBCAR0191 with eLD: Earlier Expansion, Higher Peak & Prolonged Persistence in Relapsed Auto-CAR T Setting 80000 CD19 Auto-CAR T Relapsed PBCAR0191 Expansion by Flow CD19 Auto-CAR T Naive •CD19 auto-CAR T relapsed subjects 60000 have 3.2x higher PBCAR0191 AUC vs. CD19 auto-CAR T naïve subjects CAR T
Slide 22: Evidence for PBCAR0191 + eLD in Auto CAR T Relapsed
Evidence for PBCAR0191 + eLD in Auto CAR T Relapsed PBCAR0191 + eLD may offer effective salvage for relapsed auto-CAR T patients whose progression results from sub-optimal product fitness • PBCAR0191 CAR T cells from healthy donor using single gene edit optimizes expansion & cytotoxicity • Impaired
Slide 23: Study Update on PBCAR269A - BCMA
Study Update on PBCAR269A - BCMA 23
Slide 24: PBCAR269A with or without Nirogacestat in R/R Multiple Myeloma
PBCAR269A with or without Nirogacestat1 in R/R Multiple Myeloma Long-Term Screening Follow-up Follow-Up Nirogacestat Day -3 to Day 60* Standard LD: Day -5 to Day-3: PBCAR269A CAR T Cells on Day 0 fludarabine 30 mg/m2/day × 3 days + cyclophosphamide 500 mg/m2/day × 3 days End of Day 28 DLT assessment
Slide 25: Dose-dependent Increase in CAR T Expansion with PBCAR269A Monotherapy
Dose-dependent Increase in CAR T Expansion with PBCAR269A Monotherapy Response to PBCAR269A at ≥Day 28 10000 (n=14) DL4 n = 3 8000 Overall Response DL3 n = 6 4 (29%) 6000 Rate (ORR)1 4000 DL2 n = 3 DL1 n = 3 Complete Response 2000 0 (CR) CAR T cells/ml 2000 PBCAR269A Expansion 1500 Very Good Partial
Slide 26: Nirogacestat Profoundly Increases PBCAR269A CAR T Expansion
Nirogacestat1 Profoundly Increases PBCAR269A CAR T Expansion at Dose Level 2 Versus Monotherapy 10000 8000 Cohort A, DL2 n = 3 6000 Cohort A, DL4 n = 3 4000 Cohort B, DL2 n = 5 2000 CAR T cells/ml 2000 PBCAR269A Expansion 1500 by Flow 1000 500 200 150 100 50 0 10 14 21 28 42 60 0 1 3 7 n ay ay ay ay
Slide 27: Summary of PBCAR269A in Multiple Myeloma
Summary of PBCAR269A in Multiple Myeloma Monotherapy (n=14) • Dose-dependent increase in peak expansion • No grade ≥ 3 CRS or ICANS • One subject achieved deep response (VGPR1) with monotherapy at dose level 4 • Monotherapy has favorable safety profile however, activity is below high threshold autol
Slide 28: Best-in-Class: Allogeneic PBCAR T Cell Products for R/R B-Cell Malignancies
Best-in-Class: Allogeneic PBCAR T Cell Products for Subjects with Relapsed/Refractory B-Cell Malignancies 28
Slide 29: Best in Class Allogeneic CAR T Attributes
Best in Class Allogeneic CAR T Attributes Objective • Single dose • ARCUS single-gene edit minimizing translocation safety concerns • Therapeutic index as good as or better than approved auto-CAR T product profiles Challenge • Overcome rejection of allogeneic CAR T cells by patient immune system 29
Slide 30: Second-Generation "Stealth Cell" CAR T Platform
Second-Generation “Stealth Cell” CAR T Platform • The Stealth Cell vector incorporates an anti-β2m shRNA and an HLA-E transgene • Stealth Cell CAR Ts resist rejection by T cells & NK cells in mixed-lymphocyte reactions Rejection by T cells Rejection by NK cells (n=4 mismatched donors) (n=3 mismatche
Slide 31: PBCAR19B is an Anti-CD19 Stealth Cell CAR T
PBCAR19B is an Anti-CD19 Stealth Cell CAR T *Accomplished with a single-step gene edit to minimize risk of chromosome abnormalities 1 Anti-CD19 CAR TCR is knocked-out to prevent GvHD 2 Anti-beta-2 microglobulin (β2m) shRNA Reduces MHC I expression to prevent rejection by T cells PBCAR19B 3 HLA-E tra
Slide 32: PBCAR19B Stealth Cell Progress in Clinic
• Phase 1 study initiated June 30, 2021 • Subjects receive increasing flat dose levels (2.7 x 108 - 8.1 x 108 CAR T cells) plus PBCAR19B Stealth Cell standard lymphodepletion1 Progress in Clinic • First three patients dosed at dose level 1 • Currently enrolling at multiple sites • Expect initial cli
Slide 33: 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 • Including foralumab in the lymphodepletion regimen may prevent CAR T cell rejection by eliminating the anti-CAR T response Foralumab binds to Foralumab cannot CD3 on the surface of bind allogeneic CAR T TCR patient T cel
Slide 34: Combination with Foralumab to Prevent CAR T Cell Rejection
Combination with Foralumab to Prevent CAR T Cell Rejection • Including foralumab in the LD regimen may prevent CAR T cell rejection by eliminating the anti-CAR T response • Foralumab may induce tolerance in host T-cells via CD3 internalization and homeostatic recovery to maximize CAR T persistence •
Slide 35: Precision BioSciences Focused Execution of Allogeneic CAR T Pipeline
Precision BioSciences Focused Execution of Allogeneic CAR T Pipeline First in Class approach: • PBCAR0191 with eLD: o Focus enrollment on CD19 auto-CAR T relapsed B-cell lymphoma subjects o Next data in mid-2022 Best in Class approaches: • NHL: PBCAR19B stealth cell clinical trial enrolling Dose Lev
Slide 36: Dedicated to Improving Life
Dedicated to Improving Life American Society of Hematology December 11, 2021
Precision BioSciences — 2021 ASH (American Society of Hematology) Annual Meeting on 6ix