Precision Biosciences, Inc. · NASDAQ:DTIL
Precision Biosciences — Investor Presentation (August 2022)
40 slides from Precision Biosciences's investor presentation, August 2022
Slide 1: ARCUS Genome Editing for Transformative Cell & Gene Therapeutics
Corporate Presentation | August 2022 ARCUS Genome Editing for Transformative Cell & Gene Therapeutics
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements, as may any related presentations, within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this herein and in any related presentation that do not relate to matters of his
Slide 3: Precision BioSciences: A clinical stage gene editing company built on wholly owned ARCUS platform
Precision BioSciences: A clinical stage gene editing company built on wholly owned ARCUS genome editing platform ARCUS® platform for therapeutic drug development Diversified Pipeline Scalable in-house manufacturing capabilities ARCUS platform and nucleases are unencumbered by third-party IP; control
Slide 4: ARCUS: Well-differentiated genome editing platform to address high unmet needs
ARCUS: Well-differentiated genome editing platform to address high unmet needs in oncology and genetic diseases THREE DISTINCT ADVANTAGES OF ARCUS EDITING ARCUS® Platform for Therapeutic Drug Development Precision Versatility Delivery (Safety & Specificity) • Gene insertion, deletion • ARCUS nucleas
Slide 5: Precision: Safety and Specificity
Precision: Safety and Specificity ARCUS is inactive ARCUS can be expressed for extended periods of time without until it binds to its accumulating off-target gene edits target DNA site > 80 years of event-free in life safety testing in non-human primates Inactive form of ARCUS Active form of ARCUS C
Slide 6: ARCUS promotes HDR
Versatility ARCUS performs complex The 3’ overhangs produced by ARCUS potently stimulate DNA edits (including gene repair by either homology directed repair (HDR) or non- insertion) homologous end joining (NHEJ). 20.7% Indel ARCUS promotes HDR Cuts made by ARCUS have 3’ overhangs and are repaired pr
Slide 7: Delivery: ARCUS is small and easy to deliver
Delivery ARCUS is ARCUS is 364 amino acids. This enables delivery to tissues small and and cells using a variety of viral and non-viral delivery easy to deliver technologies, including AAV and LNP. ARCUS DNA AAV Adeno-Associated Virus: ARCUS mRNA LNP Lipid Nanoparticle: Delivery to many tissues Effi
Slide 8: Ex vivo allogeneic CAR T clinical pipeline
Ex Vivo Ex vivo allogeneic CAR T clinical pipeline focused on potential first-in-class and best-in-class approaches Potential First-in-Class Potential Best-in-Class Azercabtagene Precision PBCAR19B “Stealth Cell” Zapreleucel Allogeneic CAR T targeting CD19 for non-Hodgkin lymphoma (azer-cel; PBCAR01
Slide 9: Blood cancers remain a major unmet need
Ex Vivo Blood cancers, or hematologic cancers remain a major unmet need Diffuse large B-cell lymphoma (DLBCL) Multiple myeloma DLBCL is the most common form of non-Hodgkin’s lymphoma A type of cancer that affects plasma cells in the blood, causing (NHL), comprising more than 25% of all lymphomas rep
Slide 10: CAR T relapsed market for DLBCL expected to grow ~4-5x by 2025
Ex Vivo CAR T relapsed market for DLBCL expected to grow ~4-5x by 2025 Driven by auto CAR T becoming 2nd line standard-of-care (SoC) 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 population is
Slide 11: Pursuing a deliberate, multi-faceted approach to allogeneic CAR T treatments
Ex Vivo 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 Single cell dose Product
Slide 12: Refining optimal therapeutic index for patients
Ex Vivo Azer-cel (PBCAR0191) Refining optimal therapeutic index for patients 1 2 3 4 5 Construct Single cell dose Product attributes Lymphodepletion Patient selection Single gene edit DL1 = 3 × 105 cells/kg Improved eLD = 30 mg/m2 Flu × 4 days + • R/R NHL with novel N6 DL2 = 1 × 106 cells/kg manufac
Slide 13: Minimal acceptable target product profile for CAR T relapsed patients
Ex Vivo Azer-cel (PBCAR0191) Minimal acceptable target product profile for CAR T relapsed patient population CAR T relapse median 5+ 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 Ove
Slide 14: CAR T relapsed subjects had aggressive disease and poor prognosis
Ex Vivo Azer-cel (PBCAR0191) CAR T relapsed subjects had aggressive disease and poor prognosis YE 2021 Mid-2022 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 tran
Slide 15: Efficacy results: 100% ORR, 73% CR
Ex Vivo Azer-cel (PBCAR0191) Efficacy results1: 100% ORR, 73% CR with 50% durable responses at > 6 mos ORR ≥ Day 28 n (%) 11 (100%) CR ≥ Day 28 8 (73%) n (%) CAR T relapsed ≥ 6 mo. DoR median 5+ prior lines 3 (50%) of evaluable n (%)2 (n = 11 evaluable)2,3 Ongoing responders 6 (55%) n (%) PFS > 2 mo
Slide 16: Response rate and duration exceeds current standard-of-care
Ex Vivo Azer-cel (PBCAR0191) Response rate and duration exceeds current standard-of-care for CAR T relapsed patients Subject CR/CRi (MRD-) A CR B PR YE ‘21 PD C update Death in ongoing response D E • 100% ORR among 11 evaluable subjects F CNS PD • 73% CR (8/11) G • 3/6 evaluable subjects with respon
Slide 17: Peak expansion equivalent to auto CAR T levels in durable responders
Ex Vivo Azer-cel (PBCAR0191) Peak expansion equivalent to auto CAR T levels in long term durable responders from ZUMA-11 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 c
Slide 18: Adverse events of special interest observed in CAR T relapsed subjects
Ex Vivo Azer-cel (PBCAR0191) Adverse events of special interest observed in CAR T relapsed subjects1 YE 2021 Mid-2022 Number (%) of subjects who experienced events with max grade update update (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
Slide 19: Path to desired target product profile nears finish line
Ex Vivo Azer-cel (PBCAR0191) Path to desired target product profile for CAR T relapsed patient population nears finish line Step 7 Work to be completed PIVOTAL: Continue enrolling for pivotal phase Step 6 REGULATORY: Request FDA meeting to review data Step 5 ENROLLMENT: Treat next cohort with optimi
Slide 20: PBCAR19B Stealth Cell
Ex Vivo PBCAR19B “Stealth Cell” Next-generation anti-CD19 allogeneic CAR T designed to evade immune rejection and displace 2nd and 3rd line 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 micr
Slide 21: PBCAR19B Stealth Cell next steps
Ex Vivo PBCAR19B “Stealth Cell” Next-generation anti-CD19 allogeneic CAR T designed to evade immune rejection and displace 2nd and 3rd line auto CAR T PBCAR19B “Stealth Cell” Next Steps • Three patients dosed at DL1 (270M cells) + sLD Q3 2022 Toward year-end • Due to prioritization of PBCAR0191, as
Slide 22: PBCAR269A: allogeneic alternative targeting BCMA for multiple myeloma
Ex Vivo PBCAR269A Pursuit of an allogenic alternative to autologous CAR T targeting BCMA for relapsed/refractory multiple myeloma PBCAR269A Combination with gamma secretase inhibitor1 (GSI) for Expected Next Steps multiple myeloma • Completed Dose Level 2 (2.0 × 106 cells/kg) + GSI Q3 2022 Toward ye
Slide 23: Broad and deep in vivo gene editing pipeline
In Vivo Broad and deep in vivo gene editing pipeline demonstrates unique attributes of ARCUS EDIT TYPE / CANDIDATE IND- EXPECTED PROGRAM INDICATION TISSUE TARGET RESEARCH PARTNER DELIVERY SELECTION ENABLING IND/CTA WHOLLY OWNED Familial PBGENE-PCSK91 hypercholesterolemia Liver PCSK9 Deletion/AAV — P
Slide 24: ARCUS for familial hypercholesterolemia (FH)
See Appendix: FH ARCUS for familial hypercholesterolemia (FH) targeting the PCSK9 gene Heterozygous FH Homozygous FH (HeFH) (HoFH) LDL-C LDL-C > 190 mg/dl > 400 mg/dl in adults in adults Prevalence Prevalence One of the most common genetic diseases that affects 1 in 250 people with pattern of 1.3 –1
Slide 25: ARCUS for primary hyperoxaluria type 1 (PH1)
See Appendix: PH1 ARCUS for primary hyperoxaluria type 1 (PH1) targeting the HAO1 gene 40% Rare genetic disease characterized by accumulation of calcium oxalate in kidneys, which leads to painful kidney stones and ultimately end-stage renal disease of patients have HAO1 encodes glycolate oxidase act
Slide 26: ARCUS for chronic hepatitis B virus (cHBV)
See Appendix: cHBV ARCUS for chronic hepatitis B virus (cHBV) targeting cccDNA ARCUS-mediated inactivation of cccDNA and integrated HBV could HBV Infected Hepatocyte ARCUS LNP result in a functional cure Chronic HBV is one of greatest racial health disparities in the U.S. Inactivate > 860,000 cccDNA
Slide 27: In vivo gene insertion collaboration with Novartis for hemoglobinopathies
In Vivo In vivo gene insertion collaboration with Novartis for hemoglobinopathies Builds on the unique gene insertion capabilities of ARCUS® and further validates ARCUS as a + premium genome editing platform Develop single Preclinical to ARCUS nuclease commercial Precision receives $75M upfront fo
Slide 28: Hemoglobinopathies are a major world health problem
In Vivo Hemoglobinopathies are a major world health problem Sickle Cell Disease (SCD) Beta Thalassemia Affects the structure/function of hemoglobin, One of the most common genetic diseases caused by a disruption reducing the ability of red blood cells to transport of normal hemoglobin production oxy
Slide 29: Gene insertion to a safe harbor locus in hematopoietic stem cells
In Vivo Gene insertion to a “safe harbor” locus in hematopoietic stem cells ARCUS will be used to add an Permanent integration of an antisickling gene into a antisickling gene to hematopoietic “safe harbor” locus in HSCs is expected to prevent the stem cells (HSCs) sickle cell phenotype in mature er
Slide 30: Novartis collaboration complementary to existing partnership with Lilly
In Vivo Novartis collaboration complementary to Precision’s existing in vivo gene editing partnership with Lilly Research collaboration and license agreement aimed at treating + challenging genetic diseases Pre-IND R&D IND to Commercial 3 Initial collaboration for three targets, including Duchenne m
Slide 31: Duchenne muscular dystrophy currently lacks a curative treatment
In Vivo Duchenne muscular dystrophy currently lacks a curative treatment Mutation on the X chromosome interferes On average, with dystrophin protein production, which children lose is needed to form and maintain healthy muscle their ability to walk by Affects approximately age 12 1 in 3,500 live mal
Slide 32: ARCUS for Duchenne muscular dystrophy
In Vivo ARCUS for Duchenne muscular dystrophy Restore dystrophin Deleting exons 45-55 using a pair of ARCUS nucleases intended to expression remove a mutation hotspot responsible for >50% of DMD GOAL ARCUS 1 ARCUS 2 Exons 45–55 Exon 44 Exon 56 Exon 57 Restore dystrophin expression by deleting exons
Slide 33: Building the leading therapeutic gene editing company
Technology: ARCUS, a premier genome editing platform Building the leading People: Fortified Senior Leadership therapeutic gene editing Team with 15+ years perfecting ARCUS company focused on high protein engineering unmet needs in oncology and genetic diseases Focus & Discipline: Fiscal resources su
Slide 34: Appendix
Corporate Presentation | Appendix
Slide 35: Familial Hypercholesterolemia: PBGENE-PCSK9 NHP data
Familial Hypercholesterolemia PBGENE-PCSK9 Single-dose of AAV8-ARCUS significantly reduced serum PCSK9 levels & LDL-C levels in NHPs for 3yr 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 https://w
Slide 36: Suppressing HAO1 expression to reduce calcium oxalate
Primary hyperoxaluria type 1 PBGENE-PH1 Suppressing expression of the HAO1 gene is a compelling approach to reduce calcium oxalate ARCUS Glycolaldehyde Glycolate Glycolate excreted HAO1 Glyoxylate AGXT LDH Oxalate Calcium Oxalate Glycine https://precisionbiosciences.com/wp-content/uploads/2022/05/DT
Slide 37: PBGENE-PH1: decreased HAO1 mRNA by 98% in NHPs
Primary hyperoxaluria type 1 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 98% Normalized HAO1 mRNA (n=3) 1.0 ARCUS (M1HAO1) reduction 80 single dose µM 0.8 Glycolate 60 Glycolate, 0.6 Maximum
Slide 38: PBGENE-HBV: HBV-infected human hepatocyte results
Hepatitis B virus PBGENE-HBV: HBV-infected Human Hepatocyte Results Antiviral activity in HBV-infected human hepatocytes cccDNA Indels HBsAg ARCUS treatment resulted in significant Indel mutations were detected in the ARCUS treatment resulted in significant reductions in total HBV cccDNA remaining H
Slide 39: PBGENE-HBV: Mouse episomal model results
Hepatitis B cHBV virus PBGENE-HBV: Mouse Episomal Model Results LNP-ARCUS efficiently edited HBV sequences in an immunodeficient mouse model AAV Copy Number Indels HBsAg ARCUS treatment resulted in significant ARCUS treatment introduced a high ARCUS treatment resulted in a reductions in total AAV ge
Slide 40: PBGENE-HBV: NHP episomal model results
Hepatitis B virus PBGENE-HBV: NHP Episomal Model Results LNP-ARCUS efficiently edited HBV sequences in a NHP model AAV Copy Number Indels ARCUS treatment resulted in significant reductions ARCUS treatment introduced a high frequency of in total AAV genome copies indel mutations into the remaining AA
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