Crispr Therapeutics Ag · NASDAQ:CRSP

Crispr Therapeutics — Technical Presentation (November 2019)

13 slides from Crispr Therapeutics's technical presentation, Nov 19, 2019

  1. Slide 1: CTX001 Clinical Data Update

    Exhibit 99.2 CTX001 Clinical Data Update November 19, 2019 1Exhibit 99.2 CTX001 Clinical Data Update November 19, 2019 1

  2. Slide 2: Hemoglobinopathies – sickle cell disease and β-thalassemia

    Hemoglobinopathies – sickle cell disease (SCD) and β-thalassemia (β-thal) Blood disorders caused by Significant worldwide burden mutations in the β-globin gene Annual births in 300,000 SCD and β-thal, respectively 60,000 Sickle Cell Normal β-thalassemia Cell High morbidity and mortality Heavy burden

  3. Slide 3: Persistence of fetal hemoglobin alleviates symptoms

    Persistence of fetal hemoglobin alleviates symptoms REDUCED RISK OF EVENTS REDUCED SYMPTOMS 2 1 SYMPTOMS ARISE SHORTLY AFTER BIRTH WHEN HEMOGLOBIN IN β-THALASSEMIA IN SICKLE CELL DISEASE SWITCHES FROM FETAL TO ADULT 8 Aseptic necrosis 8 Stroke 7 2 R = 0.933 Hospitalization 6 Chest syndrome 6 Crisis

  4. Slide 4: CTX001 edits the BCL11A erythroid enhancer region

    CTX001 edits the BCL11A erythroid enhancer region Cas9 DNA Guide RNA BCL11A gene (Chromosome 2) Erythroid enhancer Reduced BCL11A expression in erythroid lineage β-globin locus G A d ggb (Chromosome 11) Editing of the erythroid enhancer region of BCL11A causes induction of γ-globin, a subunit of fet

  5. Slide 5: CLIMB 111 and CLIMB 121: Phase 1/2 studies in β-thal and SCD

    CLIMB 111 and CLIMB 121: Phase 1/2 studies in patients with β-thal and SCD, respectively Phase 1 / 2, international, multi-center, Phase 1 / 2, international, multi-center, open-label, single arm study open-label, single arm study Design 45 patients between 18 – 35 years of age 45 patients between 1

  6. Slide 6: Trials involve a stem cell transplant using CTX001

    Trials involve a stem cell transplant using CTX001 – an investigational treatment Stage 1 Stage 2 Stage 3 Stage 4 STUDY SITE Myeloablative conditioning Screening (busulfan) Follow-up CD34+ HSPC CTX001 mobilized and collected infusion Engraftment and discharge CRISPR-Cas9 editing CENTRAL MANUFACTURIN

  7. Slide 7: CLIMB THAL-111: Patient baseline and treatment characteristics

    CLIMB THAL-111: Patient baseline and treatment characteristics Patient baseline Treatment characteristics 1 0 ▪ Successful engraftment β /IVS-I- Genotype 110 – Neutrophil engraftment at study day 33 – Platelet engraftment at study day 37 Gender F ▪ Initial safety profile consistent with myeloablativ

  8. Slide 8: First TDT patient treated is transfusion free with sustained HbF

    First TDT patient treated is transfusion free with sustained HbF > 10 g/dL Hemoglobin fractionation over time pre and post CTX001 infusion, Hemoglobin (g/dL) 1 HbF HbA HbA2 Hb Undefined CTX001 infusion 12.3 12.1 12.0 12.0 11.9 11.6 9.0 0.3 6.5 6.6 8.4 10.1 10.4 10.2 10.1 0.1 Baseline 1 2 3 4 5 6 9 M

  9. Slide 9: HbF is highly pancellular in peripheral RBCs

    HbF is highly pancellular in peripheral RBCs Peripheral RBC F-cells % F-cells (circulating RBCs expressing fetal hemoglobin) 99.7 99.8 CTX001 infusion 97.4 95.4 83.4 59.4 10.1 3.9 Baseline 1 2 3 4 5 6 9 Months post CTX001 infusion 9HbF is highly pancellular in peripheral RBCs Peripheral RBC F-cells

  10. Slide 10: CLIMB SCD-121: Patient baseline and treatment characteristics

    CLIMB SCD-121: Patient baseline and treatment characteristics Patient baseline Treatment characteristics 1 ▪ Successful engraftment S S Genotypeβ /β – Neutrophil engraftment at study day 30 – Platelet engraftment at study day 30 Gender F ▪ Initial safety profile consistent with myeloablative busulfa

  11. Slide 11: First patient treated in CLIMB SCD-121 had 46.6% HbF at 4 months

    First patient treated in CLIMB SCD-121 had 46.6% HbF at 4 months after CTX001 infusion Hemoglobin fractionation over time pre and post CTX001 infusion, % of total g/dL hemoglobin 1 HbF HbS HbA HbA2 Hb Undefined 11.3 10.1 CTX001 infusion 8.9 8.3 46.6% 0.8% 37.2% 7.2 Patient has had 25.9% 9.1% no repo

  12. Slide 12: HbF is highly pancellular in peripheral RBCs

    HbF is highly pancellular in peripheral RBCs Peripheral RBC F-cells % F-cells (circulating RBCs expressing fetal hemoglobin) 94.7 CTX001 infusion 70.2 43.8 33.9 4.3 Baseline 1 2 3 4 Months post CTX001 infusion 12HbF is highly pancellular in peripheral RBCs Peripheral RBC F-cells % F-cells (circulati

  13. Slide 13: Conclusions

    Conclusions ▪ Initial safety profile of CTX001 is consistent with myeloablative busulfan conditioning and autologous hematopoietic stem cell transplant 0 ▪ First patient with transfusion dependent β-thalassemia and β /IVS-I-110 genotype in CLIMB THAL-111 has stopped pRBC transfusions - HbF sustained

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