Crispr Therapeutics Ag · NASDAQ:CRSP
Crispr Therapeutics — 62nd Annual American Society of Hematology Meeting (December 2020)
18 slides from Crispr Therapeutics's conference presentation, Dec 7, 2020
Slide 1: Safety and Efficacy of CTX001 in TDT or SCD: Early Results From CLIMB THAL-111 and CLIMB SCD-121
Safety and Efficacy of CTX001™ in Patients With Transfusion-Dependent β-Thalassemia or Sickle Cell Disease: Early Results From the CLIMB THAL-111 and CLIMB SCD-121 Studies of Autologous CRISPR-CAS9-Modified CD34+ Hematopoietic Stem and Progenitor Cells Haydar Frangoul, Yael Bobruff, Maria Domenica C
Slide 2: Studies in Patients With TDT and SCD Are Ongoing
Studies in Patients With Transfusion-dependent β-Thalassemia (TDT) and Sickle Cell Disease (SCD) Are Ongoing Target enrollment 45 patients aged 12 to 35 years with TDT, including β0 / β0 genotypes, defined as a history of at least 100 mL/kg/year or 10 units/year of pRBC transfusions in the previous
Slide 3: CRISPR-Cas9-Mediated Editing of BCL11A Increases HbF Levels
CRISPR-Cas9-Mediated Editing of BCL11A Increases HbF Levels1 Naturally occurring genetic polymorphisms in BCL11A are associated with elevated HbF and decreased severity of TDT and SCD2-4 BCL11A suppresses expression of HbF Editing of BCL11A results in reactivation of γ-globin expression and formatio
Slide 4: CTX001 Infusion Process
CTX001 Infusion Process F-cell: HbF-containing cell; HbF: fetal hemoglobin; pRBC: packed red blood cell; SCD: sickle cell disease; TDT: transfusion-dependent β-thalassemia; QC: quality control; VOCs: vaso-occlusive crises. aPatients enrolled in CLIMB THAL-111 received a combination of plerixafor and
Slide 5: TDT: Patient Baseline and Treatment Characteristics
TDT: Patient Baseline and Treatment Characteristics Patients with ≥3-month follow-up (n=7) pRBC: packed red blood cell; TDT: transfusion-dependent β-thalassemia. aIVS-I-110 phenotype is severe and similar to β0 / β0; bAnnualized number during the 2 years before consenting to study participation; cDe
Slide 6: TDT: Summary of Adverse Events
TDT: Summary of Adverse Events Patients with ≥3-month follow-up (n=7) Months of follow-up, median (range) 8.9 (3.8–21.5) Patients with non-serious AEs, n Patients with SAEs, n Relationshipa Related to plerixafor and/or G-CSF 6 0 Related to busulfan only 7 2 Related to CTX001 only 1b 1 Related to bus
Slide 7: TDT: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained
Months after CTX001 infusion TDT: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained CTX001 infusion Hb: hemoglobin; HbA: adult hemoglobin; HbF: fetal hemoglobin; TDT: transfusion-dependent β-thalassemia. aHb adducts and other variants. b With respect to Patient 2, Total Hb fro
Slide 8: TDT: Early, Sustained Increases in Total Hb & HbF Across Genotypes
TDT: Early, Sustained Increases in Total Hb & HbF Across Genotypes B 3 2 6 9 18 1 15 12 4 5 Months after CTX001 infusion B 3 2 6 1 4 5 Months after CTX001 infusion c Patient 1: β0 / β+ (IVS-I-110)a Patient 2: β0 / β+ Patient 4: β0 / β+ Patient 5: β+ / β+ Patient 3: β+ / β+ Patient 6: β0 / β+ (IVS-I-
Slide 9: TDT: Pancellular Expression of HbF Is Maintained
TDT: Pancellular Expression of HbF Is Maintained Months after CTX001 infusion Median % peripheral F-cells (range), % circulating RBCs expressing HbF CTX001 infusion n = 1 7 5 7 7 5 7 5 1 2 1 F-cells: HbF-containing cells; HbF: fetal hemoglobin; RBCs: red blood cells; TDT: transfusion-dependent β-tha
Slide 10: TDT: Duration of Transfusion Independence After CTX001
aIVS-I-110 phenotype is severe and similar to β0 / β0. Hb: hemoglobin; pRBC: packed red blood cell; RBC: red blood cell; TDT: transfusion-dependent β-thalassemia. Patient receiving pRBC transfusions Patient not receiving pRBC transfusions Months after CTX001 infusion Pre-study RBC transfusions (unit
Slide 11: SCD: Patient Baseline and Treatment Characteristics
SCD: Patient Baseline and Treatment Characteristics Patients with ≥3-month follow-up (n=3) SCD: sickle cell disease; VOCs: vaso-occlusive crises. aAnnualized rate during the 2 years before consenting to study participation; bAcross multiple drug product lots per patient; cDefined as the first day of
Slide 12: SCD: Summary of Adverse Events
SCD: Summary of Adverse Events Patients with ≥3-month follow-up (n=3) AEs: adverse events; SAEs: serious adverse events. aIncludes related and possibly related AEs. b2 patients experienced non-serious AEs related or possibly related to busulfan and CTX001: lymphopenia and dermatitis. AEs were genera
Slide 13: SCD: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained
SCD: Clinically Meaningful HbF and Total Hb Are Achieved Early and Maintained Hb: hemoglobin; HbA: adult hemoglobin; HbF: fetal hemoglobin; HbS: sickle hemoglobin; SCD: sickle cell disease. aHb adducts and other variants. CTX001 infusion Months after CTX001 infusion 12 42.4% 53.1% 15 89.7% 33.7% 46.
Slide 14: SCD: Pancellular HbF Expression is Maintained
CTX001 infusion SCD: Pancellular HbF Expression is Maintained % peripheral F-cells, % circulating RBCs expressing HbF Months after CTX001 infusion 12 15 F-cells: HbF-containing cells; HbF: fetal hemoglobin; RBCs: red blood cells; SCD: sickle cell disease. Patient 1 Patient 2 Patient 3
Slide 15: SCD: Duration VOC-free After CTX001
SCD: Duration VOC-free After CTX001 SCD: sickle cell disease; VOCs: vaso-occlusive crises. 7.0 7.5 4.0 Months after CTX001 infusion Pre-study VOC burden Average number per year over the previous 2 years g/dL g/dL g/dL Total Hb at last visit All patients have detectable haptoglobin and improved LDH,
Slide 16: Durable BCL11A Editing Observed in Bone Marrow CD34+ Cells
SCD: sickle cell disease; TDT: transfusion-dependent β-thalassemia. aBone marrow editing assessments performed starting at 6 months, 12 months, and 24 months of follow-up. 1 2 3 4 5 1 2 12-month visit 76.1 80.4 6-month visit 78.1 41.8 72.6 76.6 88.1 81.4 87.3 Total follow-up, months 21.5 11.7 9.1 8.
Slide 17: Conclusions
Conclusions HbF: fetal hemoglobin; SCD: sickle cell disease; TDT: transfusion-dependent β-thalassemia; VOCs: vaso-occlusive crises. The first 10 patients treated with CTX001 have been followed for 3.8 to 21.5 months and have stopped transfusions (TDT) and are VOC-free (SCD) Overall safety profile is
Slide 18: Thank You to Study Participants and Their Families
Thank You to Study Participants and Their Families CLIMB THAL-111 and CLIMB SCD-121 sites Lucille Packard Children’s Hospital of Stanford University, Palo Alto Columbia University Medical Center, New York The Children’s Hospital at TriStar Centennial Medical Center / Sarah Cannon Center for Blood Ca
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