Crispr Therapeutics Ag · NASDAQ:CRSP
Crispr Therapeutics — Investor Presentation (2022)
42 slides from Crispr Therapeutics's investor presentation, 2022
Slide 1: Creating transformative gene-based medicines for serious diseases
Creating transformative gene-based medicines for serious diseases Corporate Overview | Q3 2022 © 2022 CRISPR Therapeutics 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements The presentation and other related materials may contain a number of “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding CRISPR Therapeutics’ expectations about any or all of th
Slide 3: CRISPR Therapeutics Highlights
CRISPR Therapeutics Highlights Leading gene editing company | Broad pipeline | Best-in-class platform and capabilities Broad pipeline of ex vivo and in vivo programs across four franchises: hemoglobinopathies, immuno-oncology, regenerative medicine, and in vivo approaches In position for first BLA/M
Slide 4: Transforming Medicine Across Four Core Franchises
Transforming Medicine Across Four Core Franchises Hemoglobinopathies Immuno-oncology Potential BLA/MAA filing for Smart-edited allogeneic immune exa-cel in Q4 2022 cells for cancer Regenerative Medicine In vivo Edited, stem cell-derived beta >10 programs using both AAV cells for diabetes and LNP app
Slide 5: Potential for First Approved CRISPR-Based Medicine
Potential for First Approved CRISPR-Based Medicine Potential functional cure with exa-cel – Vertex and CRISPR jointly working towards BLA/MAA filing in Q4 2022 Exa-cel could address >30K patients in the U.S. and EU with severe SCD and β-thalassemia if approved Opportunity to expand the market
Slide 6: Exa-cel has a Functionally Curative Profile in SCD & TDT
Exa-cel has a Functionally Curative Profile in SCD & TDT β-thalassemia Sickle cell disease Plan to file BLA/MAA in Q4 2022 42/44 patients with transfusion- dependent thalassemia (TDT) stopped RBC transfusions (duration from 0.8 to 36.2 months) - 2 patients had not yet stopped transfusions, but hav
Slide 7: Exa-cel has a Large Addressable Market
Exa-cel has a Large Addressable Market Opportunity to broaden market via innovation in conditioning and delivery β-thalassemia Sickle Cell Disease Exa-cel addressable market with 7,000 standard of care conditioning 25,000 Exa-cel potential market with 16,000 targeted conditioning 150,000 Potential m
Slide 8: Robust Early and Late Stage I/O Pipeline
Robust Early and Late Stage I/O Pipeline Allogenic platform allows immediate “off-the-shelf” dosing, alleviating the Next-generation products advancing with complex supply barriers associated with approved autologous cell therapies potency edits to improve tumor killing capacity and resistance t
Slide 9: Executing on Our Immuno-Oncology Strategy
Executing on Our Immuno-Oncology Strategy Validate Expand Unlock Our allogeneic From hematologic The full potential of I/O platform with cancers into cell therapy with next-gen proven targets solid tumors edits and targets Proof of concept with Promising data with 2nd-generation programs CTX11
Slide 10: CTX110: Differentiated CRISPR-Edited Allogeneic CAR-T Design
CTX110: Differentiated CRISPR-Edited Allogeneic CAR-T Design Multiplex CRISPR gene editing in one step designed to: Anti-CD19 CAR • Improve persistence MHC I TCR • Prevent GvHD via TCR in the allo setting via disruption disruption disruption β2M knock-out to eliminate MHC I • Improve consistency exp
Slide 11: CARBON: Trial Design
CARBON: Trial Design CARBON: Single-arm study evaluating the safety and efficacy of CTX110 Allogeneic CAR-T enables Short screening timeframe No bridging chemotherapy simplified trial design: No apheresis On-site availability of CAR-T cell product Median time from enrollment Option for 2nd C
Slide 12: CARBON: Baseline Patient Characteristics
CARBON: Baseline Patient Characteristics N (%) (unless otherwise noted) CARBON only enrolled patients DL1 DL2 DL3 DL3.5 DL4 with aggressive LBCL Cell dose (CAR+ T cells) 30x106 100x106 300x106 450x106 600x106 N=3 N=3 N=6 N=6 N=8 High burden of disease with significant baseline tumor volume Median
Slide 13: CARBON: Dose-Dependent Responses with CTX110
CARBON: Dose-Dependent Responses with CTX110 D28 response following first CTX110 dose per 2014 Lugano criteria1 DL1 DL2 DL3 DL3.5 DL4 DL2+ DL2+ Cell dose 30x106 100x106 300x106 450x106 600x106 mITT ITT (CAR+ T cells) N=3 N=3 N=6 N=6 N=8 N=23 N=24 Overall response 0 (0%) 1 (33%) 3 (50%) 4 (67%) 6 (75
Slide 14: CARBON: Durable Responses Observed with CTX110
CARBON: Durable Responses Observed with CTX110 DL2/DL3 DL3 DL3.5 DL3 1 DL3.5/DL4 2 DL3 DL4 All patients in DL3.5 complete response at DL4 DL4 6 months remain DL3.5 clinically well without DL3 receiving any systemic DL4 anticancer therapy DL2 DL3 other than CTX110 DL4 3 DL4 DL4 DL3 CR PR SD PD Re-dos
Slide 15: CARBON: CTX110 Was Well Tolerated Across All Dose Levels
CARBON: CTX110 Was Well Tolerated Across All Dose Levels Adverse events of interest N (%) DL1 (N=3) DL2 (N=3) DL3 (N=6) DL3.5 (N=6) DL4 (N=8) DL2+ (N=23) No CRS and only one Gr 1-2 Gr 3+ Gr 1-2 Gr 3+ Gr 1-2 Gr 3+ Gr 1-2 Gr 3+ Gr 1-2 Gr 3+ Gr 1-2 Gr 3+ case of ICANS above Grade 24 1 1 2 2 3 6 13 CR
Slide 16: CARBON: Strong Rationale for Consolidation Dose of CTX110
CARBON: Strong Rationale for Consolidation Dose of CTX110 CTX110 shows a dose response, with better responses achieved with higher “effector:target” ratios 75 1.8 1 67 Cell Dose / Baseline Tumor Volume ORR, % 50 1.2 PR rate 33 0.6 CR rate, % 50 38 64% CR 33 33 rate when 0.0 “E:T” >0.2 0 Cell dose DL
Slide 17: Unlocking the Market with CTX110
Unlocking the Market with CTX110 Opportunity to address larger share of patients with off-the-shelf CTX110: potentially best-in-class allogeneic cell therapy administration and positively differentiated safety profile Only ~23% of 3L+ R/R DLBCL patients receive autologous CAR-T Initial response ra
Slide 18: CTX130: Opportunity to Change the Paradigm in T Cell Lymphomas
CTX130: Opportunity to Change the Paradigm in T Cell Lymphomas Opportunity for CTX130 in TCL Annual U.S. + EU5 incidence of patients with CD70 expression by indication subtype PTCLs CTCLs Significant unmet need with limited treatment options in both PTCL & CTCL Advanced PTCL - NOS ALCL AITL ATLL MF
Slide 19: COBALT-LYM: Trial Design and Patient Demographics
COBALT-LYM: Trial Design and Patient Demographics Phase 1 study (NCT04502446) evaluating the safety and efficacy Patient characteristics, All Dose Levels n = 18 of CTX130 in relapsed or refractory T or B cell malignancies Age, median years (range) 65 (39 – 78) ECOG PS at screening, n (%) ICF CTX130
Slide 20: COBALT-LYM: CTX130 Safety Profile
COBALT-LYM: CTX130 Safety Profile Adverse Events of Interest, N (%) DL1 DL2 DL3 DL4 DL≥3 3x107 1x108 3x108 9x108 • Acceptable safety profile across all N=10 N=4 N=4 N=5 N=5 DLs: no DLTs or instances of TLS with LDC or CTX130 Gr 1-2 Gr ≥3 Gr 1-2 Gr ≥3 Gr 1-2 Gr ≥3 Gr 1-2 Gr ≥3 Gr 1-2 Gr ≥3 • Treatmen
Slide 21: COBALT-LYM: 70% ORR and 30% CR Rate at DL3 and Above
COBALT-LYM: 70% ORR and 30% CR Rate at DL3 and Above Best overall response, n (%) DL1 DL2 DL3 DL4 PTCL CTCL Cell dose DL≥3 3x107 1x108 3x108 9x108 DL≥3 Total DL≥3 Total (CAR+ T cells) N=10 N=4 N=4 N=5 N=5 N=5 N=8 N=5 N=10 Overall Response ORR 4 (80) 5 (63) 3 (60) 4 (40) 2 (50) 0 3 (60) 4 (80) 7 (7
Slide 22: COBALT-LYM: CTCL Responses Across All Compartments
COBALT-LYM: CTCL Responses Across All Compartments *Day 7 assessment; †Initially unconfirmed CR, later confirmed to be PR by mSWAT and biopsy. CR, complete response; CTCL, cutaneous T cell lymphoma; DL, dose level; PD, progressive disease; PR, partial response; SD, stable disease Data cutoff date: 2
Slide 23: COBALT-LYM: Clinically Meaningful Responses with CTX130
COBALT-LYM: Clinically Meaningful Responses with CTX130 AITL, angioimmunoblastic T cell lymphoma; ALCL, anaplastic large cell lymphoma; ATLL, adult T cell leukemia/lymphoma; CR, complete response; CTCL, cutaneous T cell lymphoma; DL, dose level; PD, progressive disease; PR, partial response; PTCL-NO
Slide 24: RCC: Large Unmet Need and Significant Addressable Population
RCC: Large Unmet Need and Significant Addressable Population Renal Cell Carcinoma (RCC) Significant Poor response High morbidity High potential worldwide rates to current and mortality opportunity burden therapies 50K 45K 18% 40% 80% US EU5 Annual 5-year survival Primary CD70 expression in incidence
Slide 25: COBALT-RCC: Durable Complete Response with CTX130
COBALT-RCC: Durable Complete Response with CTX130 Case Study Screening Patient profile 64-year-old male with clear cell RCC diagnosed in 2017 1 prior line of therapy with cabozantinib and atezolizumab Relapsed after PR with lesions in the lung and pleura Day 42 CD70+ expression: 100% at base
Slide 26: Next-Generation Potency Edits: Regnase-1 and TGFBR2
Next-Generation Potency Edits: Regnase-1 and TGFBR2 CTX131 eliminates three different xenograft tumor models in succession without exhaustion Tumor 1: NCI-H1975 (Lung) Tumor 2: Rechallenge 1 with ACHN (RCC) Tumor 3: Rechallenge 2 with Caki-1 (RCC) No treatment CTX131: CTX130 + Regnase-1 KO + TGFBR2
Slide 27: Collaborations with Top Cancer Centers on New Targets
Collaborations with Top Cancer Centers on New Targets Clinical trial to begin in next 12 months IND-enabling studies to begin this year First-in-human trial for autologous CAR-T Initial trial for gene-edited, autologous CAR-T therapy targeting CD83 therapy targeting GPC3 CD83: Expressed on cer
Slide 28: CRISPR Enables Regenerative Medicine 2.0
CRISPR Enables Regenerative Medicine 2.0 CRISPR gene editing and pluripotent stem cell technology enable a new class of cell replacement therapies Developing a beta-cell replacement product that aims to treat diabetes without requiring immunosuppression – gene editing key to achieve this goal
Slide 29: Multi-staged Product Strategy
Multi-staged Product Strategy Perforated Device Approach Deviceless approach Progenitor cells (stage 4) Immature β-cells (stage 6) Retrievable, enabling broader initial patient population Portal vein injection 212 211 210 Unencapsulated, stage 6 cell aggregates containing Entered clinic
Slide 30: VCTX211 – Further Optimized for Cell Fitness
VCTX211 – Further Optimized for Cell Fitness VCTX211 has 2 gene KOs and 4 insertions to improve functionality VCTX210 Immune evasion Cell fitness MHC-I KO eliminates T cell Thioredoxin interacting protein mediated rejection (TXNIP) KO protects from oxidative and ER stress PD-L1 KI reduces immu
Slide 31: Edited Cells Evade Immunity In Vitro and In Vivo
Edited Cells Evade Immunity In Vitro and In Vivo Adaptive – T cells do not respond to 211 cells in vitro Adaptive & Innate – 211 cells survive in humanized mouse model 2.5 T cell proliferation 1.5 2.0 1.5 Luminescence 1.0 1.0 0.5 0.0 Unedited 211 edits T cells alone 0.5 Innate – 211 cells resist NK
Slide 32: VCTX211 Reverses Hyperglycemia in Diabetic Rat Model
VCTX211 Reverses Hyperglycemia in Diabetic Rat Model Normalization of blood glucose by 12-16 weeks Treated rats maintain glucose sensitivity 600 Insulin Treatment 1500 Blood glucose (mg/dL) 500 Serum C-peptide (pM) 400 Control (no STZ) 1000 STZ 300 200 500 100 STZ Implant 0 0 -5 0 5 10 15 20 25 12 w
Slide 33: In Vivo Platform Advancing Rapidly
In Vivo Platform Advancing Rapidly 90% of the most prevalent severe monogenic Developing a multi-modal whole gene correction platform, starting diseases only addressable with gene disruption with AAV+LNP in the liver and advancing to AAV-free, HDR-independent and/or whole gene correction methodo
Slide 34: Becoming an In Vivo Leader – Our Strategy
Becoming an In Vivo Leader – Our Strategy Focus on disruption and whole gene correction – needed to address ~90% of the most prevalent severe monogenic diseases Establish a leading platform for in vivo gene disruption, starting in the liver Disruption Advance a broad portfolio of programs across
Slide 35: Established a Leading mRNA/LNP Platform for Gene Disruption
Established a Leading mRNA/LNP Platform for Gene Disruption Dose-dependent liver editing up to 70% in NHPs 100 80 Editing in liver (%) 70+% editing in 60 whole liver typically equates to 90+% 40 hepatocyte editing and reduction in 20 serum protein levels 0 0.5 mg/kg 1.5 mg/kg 3 mg/kg Single intraven
Slide 36: ASCVD Programs – Proven Benefit in a Once-and-Done Format
ASCVD Programs – Proven Benefit in a Once-and-Done Format Proven benefit based on natural human genetics (similar to CTX310 – BCL11A) and antibody / small RNA therapeutics ANGPTL3 Paradigm shift possible with single-dose, potentially lifetime durable editing approach CTX320 – Lp(a) Development paths
Slide 37: CTX310: Potentially Transformative for Cardiovascular Disease
CTX310: Potentially Transformative for Cardiovascular Disease >50% reduction in serum triglycerides ~90% reduction in serum ANGPTL3 protein in NHPs at one month 50 0 Control 0.5 mg/kg Change from baseline (%) Change from baseline (%) -20 1.5 mg/kg 0 3 mg/kg -40 10 20 30 40 N=8 per group -60 -50 -56%
Slide 38: CTX320: Lp(a) is Emerging as an Ideal Target for ASCVD
CTX320: Lp(a) is Emerging as an Ideal Target for ASCVD Coronary artery disease risk increases >90% reduction in serum Lp(a) in NHPs with increasing Lp(a) level 50 Control (N=2) 0.5 mg/kg (N=4) Change from baseline (%) 1.5 mg/kg (N=4) 0 3 mg/kg (N=4) 20 40 60 -19% -50 -74% -92% -100 Median Lp(a) leve
Slide 39: Unlocking Whole Gene Correction and Insertion
Unlocking Whole Gene Correction and Insertion AAV + LNP Next-generation technologies Proven technologies allow whole gene correction Dedicated internal group focused on emerging via repair mechanisms at specific loci technologies to allow HDR-independent and/or AAV-free whole gene correction/ins
Slide 40: Strong U.S. and Global Foundational IP Position
Strong U.S. and Global Foundational IP Position United States Europe and Global CVC granted patents of broad scope; CVC granted foundational patents, multiple applications progressing including use in eukaryotes Patents of broad scope granted in the EU; one EP 50+ Patents of broad scope granted 2 pa
Slide 41: Building a Great Company
Building a Great Company END-TO-END COLLABORATIVE & EXPERIENCED CAPABILITIES ENTREPRENEURIAL Management Team with ~500 employees culture INTERNAL ~$2 BILLION MANUFACTURING cash balance in state-of-the-art GMP facility CRISPR Therapeutics | www.crisprtx.com © 2022 CRISPR Therapeutics 41
Slide 42: Our Pipeline
Our Pipeline Program Research IND-enabling Clinical Marketed Partner Structure Exa-cel: β-thalassemia Collaboration Hemoglobin- opathies Exa-cel: Sickle cell disease (SCD) Next-generation conditioning Wholly-owned1 In vivo editing of HSCs Anti-CD19 CTX110 Wholly owned allogeneic CAR-T CTX112 Wholly