Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Corporate Update (June 2022)
33 slides from Precision Biosciences's corporate update, Jun 8, 2022
Slide 1: Mid-Year 2022 Allogeneic CAR T Pipeline Update
Mid-Year 2022 Allogeneic CAR T Pipeline Update June 8, 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 is Delivering on the Promise of Therapeutic Genome Editing
Precision Biosciences is Delivering on the Promise of Therapeutic Genome Editing to Change the Future of Medicine ARCUS® Genome Editing Derived from natural homing endonuclease for ex vivo and in vivo applications Ex Vivo single-gene edit for In Vivo Editing for Allogeneic CAR T immunotherapy Geneti
Slide 4: Ex Vivo CAR T Pipeline Development Focused on First-in-Class and Best-in-Class Approaches
Ex Vivo CAR T Pipeline Development Focused on Potential First-in-Class and Best-in-Class Approaches in Distinct Patient Populations Potential First-in-Class Potential Best-in-Class PBCAR19B “Stealth Cell” PBCAR0191 2nd/3rd Line NHL in CAR T Precision Relapsed DLBCL Allogeneic CAR T Platform PBCAR269
Slide 5: Ex Vivo CAR T Pipeline Development Focused on First-in-Class and Best-in-Class Approaches
Ex Vivo CAR T Pipeline Development Focused on Potential First-in-Class and Best-in-Class Approaches in Distinct Patient Populations Data presentation for today Potential First-in-Class PotentialBest-in-Class Potential Best-in-Class Potential First-in-Class PBCAR19B“Stealth PBCAR19B “StealthCell” Cel
Slide 6: Executive Summary: PBCAR0191 potential first in class allogeneic therapy
PBCAR0191 Executive Summary PBCAR0191 potential first in class allogeneic therapy for CAR T relapsed patients (median 5+ prior lines) with highest unmet need • Efficacy1: • 100% Response Rate, 73% Complete Response in first 11 evaluable CAR T relapsed subjects • 50% ≥ 6-month Duration-of-Response in
Slide 7: Deliberate, Multi-Faceted Approach to Allogeneic CAR T Treatments
Precision is Pursuing a Deliberate, Multi-Faceted Approach to Allogeneic CAR T Treatments for Patients Our approach for Allo CAR T is to overcome host immune rejection while accomplishing an acceptable safety profile 5 levers to overcome host immune rejection 1 2 3 4 5 Construct Product Single Dose
Slide 8: PBCAR0191: Refining Optimal Therapeutic Index For Patients
PBCAR0191: Refining Optimal Therapeutic Index For Patients 1 2 3 4 5 Construct Product Single Dose Lymphodepletion Patient Selection Attributes Single-gene edit Improved DL1 = 3 × 105 cells/kg eLD = 30 mg/m2 Flu × 4 days + • R/R NHL with novel N6 manufacturing to DL2 = 1 × 106 cells/kg 1000 mg/m2 Cy
Slide 9: Peak Expansion is the Strongest Determinant of Durable CAR T Response
Peak Expansion is the Strongest Determinant of Durable CAR T Response Product Attributes “In this study, the strongest correlate of durable response was peak CAR T-cell levels in blood normalized to pre-treatment tumor burden.” “The number of CAR T-cells in peripheral blood early (within 2 weeks) af
Slide 10: Optimized Manufacturing Product Attributes Impact CAR T Efficacy & Safety
Optimized Manufacturing Product Attributes Impact CAR T Efficacy & Safety Product Attributes TOOLS: ARCUS Single-Gene Edit “ We found that optimizing the product composition towards the juvenile T-cell phenotype to find a • Puts less stress on cells vs multiplex edit CCR7+, CD45RA+, CD27+, and CD28+
Slide 11: CAR T Relapsed Market Expected to Grow ~4-5x by 2025
CAR T Relapsed Market Expected to Grow ~4-5x by 2025 Driven by Auto CAR T Becoming 2nd line DLBCL Standard-of-Care (SoC) Patient Selection CAR T Relapsed Eligible Patients in US 2022 | 3rd line+ DLBCL Patients By 2025, the Auto CAR T ~1,7001 Total available 3rd Line + CAR T patient relapsed patient
Slide 12: Current Treatment Options Offer Poor Outcomes for CAR T Relapsed Patients
Current Treatment Options Offer Poor Outcomes for CAR T Relapsed Patients with Progression Free Survival (PFS) only 1-2 Months Patient Selection Real world data for patients following treatment with Yescarta (Auto CAR T)1 Therapy ORR CR PR PFS (mos.) OS (mos.) Overall (n = 136) 29% 17% NA/NR 1.8 5.9
Slide 13: Minimal Acceptable Target Product Profile for CAR T Relapsed Patient Population
Minimal Acceptable Target Product Profile for CAR T Relapsed Patient Population Patient Selection CAR T Relapse Median 5+ prior lines 3rd line NHL Progression Free Survival (mPFS) > 3 months > 6-7 months ~35% CR at 6 months; Duration of Response (DoR) > 50% @ 3 months ~32% CR at 1 year plus Overall
Slide 14: Potential First-in-Class: Allogeneic PBCAR0191 for CAR T Relapsed Patients
Potential First-in-Class: Allogeneic PBCAR0191 for CAR T Relapsed Patients 14
Slide 15: PBCAR0191 Path to Best Therapeutic Index for CAR T Relapsed Patients
PBCAR0191 Path to Best Therapeutic Index for CAR T Relapsed Patients Step 7 PIVOTAL: Enrolling for pivotal phase Step 6 REGULATORY: Request FDA meeting to discuss path forward Step 5 ENROLLMENT: Treat next cohort with optimized PBCAR0191 treatment and standard lymphodepletion (sLD) Step 4 “New Cohor
Slide 16: CAR T Relapsed Subjects Enrolled Had Aggressive Disease and Poor Prognosis
CAR T Relapsed Subjects Enrolled Had Aggressive Disease and Poor Prognosis Patient Selection ASH Cohort New Cohort DL31,3,4 DL4b2 (n=63) (n=6) Age (y), median (range) 50.5 (38-67) 72.5 (45-77) Primary Refractory 2 (33%) 2 (33%) Aggressive histology, n (%) 5 (100%) 5 (83%) DLBCL 5 (100%) 4 (67%) FL t
Slide 17: Since ASH'21: Efficacy Results in CAR T Relapsed Population
Since ASH’21: Efficacy Results in CAR T Relapsed Population 100% Overall Response Rate (ORR), 73% CR with 50% Durable Responses at > 6 Months ORR ≥ Day 28 n (%) 11 (100%) CR ≥ Day 28 8 (73%) n (%) CAR T Relapsed > 6 mo. DoR n (%)3 3 (50%) of evaluable Median 5+ prior lines (n = 11 evaluable)1, 2 Ong
Slide 18: PBCAR0191 Response Rate and Duration Exceeds Current Standard-of-Care
PCAR0191 Response Rate and Duration Exceeds Current Standard-of-Care for CAR T Relapsed Subjects Subject A CR/CRi (MRD-) CR B PR C PD ASH Death in ongoing response Cohort D duration update E CNS PD • 100% ORR among 11 evaluable subjects F • 73% CR (8/11) G • 3/6 evaluable subjects with response dura
Slide 19: New Cohort: Optimized PBCAR0191 at DL4b with Lower Dose LD
New Cohort: Optimized PBCAR0191 at Dose Level DL4b with Lower Dose LD Drove Optimal Response and Duration1 in CAR T Relapsed Subjects Subject CR PR L2 ONGOING PD Death on study in K2 ONGOING ongoing response G ONGOING • 100% ORR in 5/5 evaluable subjects H • 100% 5/5 CR • Subject J non-evaluable for
Slide 20: Optimized PBCAR0191 Achieved Desired Peak Expansion Threshold with DL4b
Since ASH’21, Optimized PBCAR0191 Achieved Desired Peak Expansion Threshold with DL4b and Lower Dose LD Cell Dose Product Attributes 250000 NHL, DL3 (eLD), Auto-CAR-experienced (n=6) 200000 NHL, DL4b (mLD), Auto-CAR-experienced (n=4) 150000 In DL4b/mLD group CAR T cells/ml 100000 Mean peak 3X greate
Slide 21: PBCAR0191 Peak Expansion Equivalent to Auto CAR T Levels in Durable Responders
PBCAR0191 Peak Expansion Equivalent to Auto CAR T Levels in Long Term Durable Responders from ZUMA-1 Auto CAR T Durable Responders (Locke et al, 2020) PBCAR0191 NHL DL3 vs. DL4b subjects CAR-T c/uL - Peak CAR-T PBCAR0191 10 5 exceeds ZUMA-1 Durable 10 4 Median Responders1 CAR T cells in blood (cells
Slide 22: Safety: Allogeneic PBCAR0191 for CAR T Relapsed Patients
Safety: Allogeneic PBCAR0191 for CAR T Relapsed Patients 22
Slide 23: PBCAR0191 AESI Observed in CAR T Relapsed Subjects
PBCAR0191 AESI1 Observed in CAR T Relapsed Subjects ASH New Cohort Number (%) of subjects experiencing events with max grade Cohort DL4b (n=6) (n=6) Grade 1 or Grade 2 5 (83%) 4 (67%) CRS Grade 3 or higher 0 0 Time to onset (Days) Median (range) 4 (4-14) 8 (7-9) Grade 1 or Grade 2 2 (33%) 1 (17%) AE
Slide 24: Median Hematologic Recovery Achieved Earlier by Lowering LD Dose
Improving Upon ASH’21: Median Hematologic Recovery Achieved Earlier by Lowering LD Dose Lymphodepletion Neutrophil Median AbsoluteCount Neutrophil Count (ANC) Recovery 6 NHL, DL3 (eLD), CAR Auto-CAR-experienced T-relapsed (n=5) NHL, DL4b (mLD), (mLD), CAR Auto/Allo-CAR-experienced T-relapsed (n=6) N
Slide 25: PBCAR0191 Efficacy Results Exceed Current Standard-of-Care
PBCAR0191 Efficacy Results in CAR T Relapsed Subjects Exceeds Current Standard-of-Care with Improved Hematologic Recovery in Lower LD Subjects Interim Results1 • Overall response, CR rate and duration of response validates ASH’21 signal in CAR T relapsed subjects − 100% ORR and 73% CR among 11 evalu
Slide 26: In Conclusion, PBCAR0191 Path to Desired Product Profile Nears Finish Line
In Conclusion, PBCAR0191 Path to Desired Product Profile for CAR T Relapsed Patients Nears Finish Line Step 7 PIVOTAL: Enrolling for pivotal phase Step 6 REGULATORY: Request FDA meeting to discuss path forward Step 5 ENROLLMENT: Treat next cohort with optimized PBCAR0191 treatment and standard lymph
Slide 27: In Conclusion, PBCAR0191 Path to Desired Product Profile Nears Finish Line
In Conclusion, PBCAR0191 Path to Desired Product Profile for CAR T Relapsed Patients Nears Finish Line Step 7 Work to be completed in H2 2022 PIVOTAL: Enrolling for pivotal phase Step 6 REGULATORY: Request FDA meeting to discuss path forward Step 5 ENROLLMENT: Treat next cohort with optimized PBCAR0
Slide 28: Ex Vivo CAR T Pipeline Focused on First-in-Class and Best-in-Class Approaches
Ex Vivo CAR T Pipeline Focused on Potential First-in-Class and Best-in-Class Approaches Data presentation for today Operational program updates First-in-Class Potential First-in-Class Potential Best-in-Class Best-in-Class PBCAR19B “Stealth Cell” PBCAR0191 2nd/3rd Line NHL in Auto CAR in CAR T T Prec
Slide 29: PBCAR19B is an Anti-CD19 Stealth Cell CAR T
PBCAR19B is an Anti-CD19 “Stealth Cell” CAR T Winning Best-in-Class is not a race – It’s about replacing Auto CAR T 3rd line+ NHL TPP to Replace Auto CAR T Anti-CD19 CAR TCR is knocked-out to prevent GvHD Median Overall Survival ~26 months3 (mOS) 1 Anti-beta-2 microglobulin (β2m) shRNA Overall Respo
Slide 30: PBCAR19B Program Update: Potential Auto CAR T Displacement
PBCAR19B Program Update: Potential Auto CAR T Displacement PBCAR19B “Stealth Cell” Next Steps • Three patients dosed at DL1 (270M Cells) + sLD 3Q 2022 End 2022 • Due to prioritization of PBCAR0191 as potential first-in-class, PBCAR19B strategically paused in DL2 (540M Cells) Next program Q1 to imple
Slide 31: Update on PBCAR269A with Nirogacestat in R/R Multiple Myeloma
Update on PBCAR269A with Nirogacestat1 in R/R Multiple Myeloma PBCAR269A Combination with gamma secretase inhibitor (GSI) for Multiple Myeloma • Completed Dose Level 2 (2.0×106 cells/kg) + GSI (nirogacestat) in six patients ⁻ Peak expansion equivalent to Dose Level 4 (960×106 cells flat dose) monoth
Slide 32: What to Expect in 2H 2022
What to Expect in 2H 2022: Disciplined Focus on Executing Remaining Steps on Path to Pivotal PBCAR0191 Step 7 Work to be completed in H2 2022 PIVOTAL: Continue enrolling for pivotal phase Step 6 REGULATORY: Request FDA meeting to review data Step 5 ENROLLMENT: Treat next cohort with optimized PBCAR0
Slide 33: Mid-Year 2022 Allogeneic CAR T Pipeline Update
Mid-Year 2022 Allogeneic CAR T Pipeline Update June 8, 2022