Crispr Therapeutics Ag · NASDAQ:CRSP
Crispr Therapeutics — Investor Presentation (2021)
35 slides from Crispr Therapeutics's investor presentation, 2021
Slide 1: Creating transformative gene-based medicines for serious diseases
® Creating transformative gene-based medicines for serious diseases Corporate Overview | Q4 2021 © 2021 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 focused on translating revolutionary CRISPR/Cas9 technology into transformative therapies Achieving functional cures with CTX001™ in β-thalassemia and sickle cell disease Next-generation immuno-oncology platform underlying wholly-owned, pot
Slide 4: The CRISPR/Cas9 Revolution
The CRISPR/Cas9 Revolution A SPECIFIC, EFFICIENT and VERSATILE tool for editing genes Disrupt Delete Correct or Insert “If scientists can dream of a genetic manipulation, CRISPR can now make it happen” © 2021 CRISPR Therapeutics 4
Slide 5: Our Pipeline
Our Pipeline PROGRAM RESEARCH IND-ENABLING CLINICAL MARKETED STATUS PARTNER STRUCTURE Hemoglobinopathies CTX001™: β-thalassemia Enrolling Collaboration CTX001™: Sickle cell disease (SCD) Enrolling Collaboration Immuno-oncology CTX110™: Anti-CD19 allogeneic CAR-T Enrolling Wholly-owned CTX120™: Anti-
Slide 6: Recent Collaborations to Combine Leading Capabilities
Recent Collaborations to Combine Leading Capabilities Gene editing + Natural Killer Gene + Novel AAV and T cells (NK) cells editing vectors Focus on co-developing and co-commercializing three Focus on advancing gene-edited therapies for familial gene-edited, donor-derived NK therapies: amyotrophic l
Slide 7: Hemoglobinopathies – Devastating Blood Diseases
Hemoglobinopathies – Devastating Blood Diseases Sickle Cell Disease (SCD) and β-Thalassemia Blood disorders caused by mutations Significant worldwide burden in the β-globin gene ANNUAL BIRTHS 300K 60K SCD β-thalassemia Sickled Normal Cell Thalassemic High morbidity and mortality Heavy burden of pati
Slide 8: Our Approach – Upregulating Fetal Hemoglobin
Our Approach – Upregulating Fetal Hemoglobin Symptoms in SCD and β-Thalassemia Decrease as HbF Level Increases Stroke 8 8 Aseptic necrosis 7 Hospitalization 7 Number of Morbidities Cumulative Risk Ratio 6 Chest syndrome 6 Sickle cell crisis 5 5 Meningitis 4 4 3 3 2 2 1 1 R2 = 0.933 0 0 5 10 15 20 25
Slide 9: Pioneering CRISPR Trials
Pioneering CRISPR Trials Phase 1/2, international, multi-center, open-label, single arm studies to assess the safety and efficacy Design of CTX001 in patients with transfusion-dependent β-thalassemia (TDT) and SCD, respectively 45 patients aged 12 - 35 years with TDT, including 45 patients aged 12 -
Slide 10: TDT: Patient Baseline and Treatment Characteristics
TDT: Patient Baseline and Treatment Characteristics Patients with ≥3-month follow-up (n=15) Patient baseline n Treatment characteristics Median (range) β0 / β0 2 Drug product cell dose 6.5 (3.5-16.6) β0 / IVS-I-1101 2 CD34+ cells x 106/kg IVS-I-110 / IVS-I-1101 2 Genotype β0 / βE 2 β0 / β+ 4 β+ / β+
Slide 11: TDT: Summary of Adverse Events
TDT: Summary of Adverse Events Patients with ≥3-month follow-up (n=15) Safety profile generally consistent with myeloablation and autologous stem cell transplant Patients with Patients with ▪ 3 patients experienced SAEs assessed as related or non-serious AEs, SAEs, possibly related to busulfan only:
Slide 12: TDT: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained
TDT: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained Hemoglobin fractionation, Hb (g/dL) HbF HbA HbA2 CTX001 infusion 14.7 13.2 14.1 12.1 12.1 - 14.2 13.3 12.2 12.4 12.0 10.0 - 16.9 11.6 11.1 - 12.9 11.0 9.7 - 17.2 9.9 - 13.5 11.4 Total Hb, 10.1 6.6 - 16.2 8.5 - 17.6 8.9 - 1
Slide 13: TDT: Duration of Transfusion Independence After CTX001
TDT: Duration of Transfusion Independence After CTX001 Pre-study RBC Patient transfusions Patient receiving pRBC transfusions Patient not receiving pRBC transfusions Total Hb at Genotype (units/year) last visit (g/dL) β0 / IVS-I-1101 34 1.0 25.2 14.7 β0 / β+ 61 1.9 15.4 12.1 β+ / β+ 51.5 1.5 13.2 11
Slide 14: SCD: Patient Baseline and Treatment Characteristics
SCD: Patient Baseline and Treatment Characteristics Patients with ≥3-month follow-up (n=7) Patient baseline n Treatment characteristics Median (range) Drug product cell dose Genotype βS / βS 7 3.3 (3.1-3.9) CD34+ cells x 106/kg Gender 3/4 Neutrophil engraftment2 Female/Male 25 (17-33) Study day3 Med
Slide 15: SCD: Summary of Adverse Events
SCD: Summary of Adverse Events Patients with ≥3-month follow-up (n=7) Safety profile generally consistent with myeloablation and autologous stem cell transplant Patients with Patients with non-serious AEs, SAEs, n n Relationship1 Related to plerixafor only 6 2 ▪ Post-CTX001 infusion, 1 patient exper
Slide 16: SCD: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained
SCD: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained Hemoglobin fractionation, Hb (g/dL) HbF HbS HbA HbA2 CTX001 infusion 13.5 13.2 12.5 11.3 - 15.9 12.1 11.7 - 16.1 11.2 9.7 - 14.9 11.3 10.0 - 15.4 12.0 12.0 8.9 - 13.7 10.7 - 11.8 10.7 11.4 Total Hb, 9.5 10.3 - 11.0 Mean (r
Slide 17: SCD: Duration VOC-Free After CTX001
SCD: Duration VOC-Free After CTX001 Pre-study VOC burden Average number per year Total Hb at over the previous 2 years last visit (g/dL) 1 7.0 22.4 12.0 2 7.5 13.6 11.0 3 4.0 9.6 13.7 4 2.5 7.5 15.9 5 5.5 6.3 15.2 6 9.5 5.6 11.7 7 4.0 4.9 12.5 0 2 4 6 8 10 12 14 16 18 20 22 Months after CTX001 infus
Slide 18: Pancellular HbF Expression and Durable Editing
TDT Pancellular HbF Expression and Durable Editing SCD Pancellular expression of HbF maintained Mean % peripheral F-cells (range), % circulating RBCs expressing HbF 96.9 98.7 98.6 99.7 98.5 100 97.6 100 92.6 82.0 - 100 94.7 - 100 96.5 - 100 99.1 - 100 96.9 - 100 75.4 - 98.4 CTX001 infusion 97.8 96.3
Slide 19: Allogeneic CAR-T Therapy Has Transformative Potential
Allogeneic CAR-T Therapy Has Transformative Potential Before Patient Diagnosis After Patient Diagnosis ▪ Off-the-shelf: Immediate treatment without risk of manufacturing failure, saving patients valuable time in which their disease could progress ▪ Flexible dosing (e.g., re-dosing) ▪ A more consiste
Slide 20: 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 disruption disruption disruption in the allo setting via β2M knock-out to eliminate MHC I • Improve consistency exp
Slide 21: 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 22: CARBON: Patient Flow
CARBON: Patient Flow As of the data cutoff date: Enrolled: 30 patients Modified ITT (mITT) Treated1: 29 patients nearly identical to ITT: just one patient enrolled ≥28 days of follow-up (included in data cut): 26 patients but not treated Dose Level CAR+ T cells DL2 and above: 23 patients DL4 600x106
Slide 23: 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 24: Dose-Dependent Responses with CTX110
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%) 14 (6
Slide 25: Durable Responses Observed with CTX110
Durable Responses Observed with CTX110 DL2/DL3 DL3 DL3.5 1 DL3 2 DL3.5/DL4 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 3 DL4 DL4 DL4 DL3 CR PR SD PD Re-dose DL3.5
Slide 26: CTX110 Was Well Tolerated Across All Dose Levels
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 CRS - - -
Slide 27: Strong Rationale for Consolidation Dose of CTX110
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 Cell Dose / Baseline Tumor Volume 67 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 DL1 DL2 DL
Slide 28: Conclusions and Next Steps for CTX110
Conclusions and Next Steps for CTX110 CTX110 is a potentially best-in-class allogeneic cell therapy in r/r LBCL with a profile that can compete with approved autologous CAR-T therapies ▪ Initial response rates in line with approved ▪ Expand CARBON into a potentially registrational autologous CAR-T t
Slide 29: Our I/O Strategy and Allogeneic CAR-T Pipeline
Our I/O Strategy and Allogeneic CAR-T Pipeline PROGRAM RESEARCH IND-ENABLING CLINICAL MARKETED STATUS Validate CTX110 (anti-CD19) Enrolling B-cell malignancies allogeneic platform with CTX120 (anti-BCMA) Enrolling proven targets Multiple myeloma Expand CTX130 (anti-CD70) Enrolling T- and B-cell lymp
Slide 30: CRISPR Enables the Next Generation of I/O Cell Therapy
CRISPR Enables the Next Generation of I/O Cell Therapy Multiplexed, single-shot 6x knock-out plus CAR insertion performed at high efficiency CRISPR gene editing facilitates 100 consistent, multiplex editing to: 80 Editing (%) ▪ Produce allogeneic cell therapies 60 40 ▪ Enhance immune cell performanc
Slide 31: CRISPR Enables Regenerative Medicine 2.0
CRISPR Enables Regenerative Medicine 2.0 CRISPR/Cas9 Technology Opens Broader Applications for Regenerative Medicine Exemplified by our • Allow immune evasion collaboration with ViaCyte CRISPR/ • Improve cell function Cas9 • Aim to develop beta-cell replacement • Direct cell fate product to treat di
Slide 32: Unlocking In Vivo Applications of CRISPR/Cas9
Unlocking In Vivo Applications of CRISPR/Cas9 AAV Vectors for Neuromuscular Indications LNPs for Liver Indications • Adeno-associated virus (AAV) to deliver Cas9 and gRNA to muscle, • Lipid nanoparticles (LNPs) the nervous system and other containing mRNA encoding Cas9 tissues and gRNA for delivery
Slide 33: Optimizing the CRISPR/Cas9 Platform
Optimizing the CRISPR/Cas9 Platform Nuclease Engineering Guide RNA Optimization Enhance CRISPR/Cas9 system through Identify optimal guide RNA formats and protein engineering sequences for therapeutic editing PLATFORM ENHANCEMENT Advanced Editing Synthetic Biology Improve efficiency of gene correctio
Slide 34: Strong U.S. and Global Foundational IP Position
Strong U.S. and Global Foundational IP Position United States Europe and Global Charpentier / UC Berkeley / U. Vienna granted patents Charpentier / UC Berkeley / U. Vienna granted of broad scope; multiple applications progressing foundational patents, including use in eukaryotes Patents of broad sco
Slide 35: Building a Great Company
Building a Great Company EXPERIENCED END-TO-END COLLABORATIVE & Management Team CAPABILITIES ENTREPRENEURIAL With >400 Employees Culture CRISPR Therapeutics | www.crisprtx.com © 2021 CRISPR Therapeutics 35