Crispr Therapeutics Ag · NASDAQ:CRSP
Crispr Therapeutics — 25th Congress of the European Hematology Association (Virtual Edition) (June 2020)
21 slides from Crispr Therapeutics's conference presentation, Jun 12, 2020
Slide 1: 25th Congress of the European Hematology Association Virtual Edition
Exhibitea.2 BA fp ~e__- _. VIRTUAL EDITION 25th Congress of the European Hematology Association
Slide 2: Initial Safety and Efficacy Results with a Single Dose of CRISPR-Cas9-Modified CD34+ Cells in TDT and SCD
Initial Safety and Efficacy Results with a Single Dose of Autologous CRISPR-Cas9-Modified CD34+ Hematopoietic Stem and Progenitor Cells in Transfusion-Dependent β-Thalassemia and Sickle Cell Disease Selim Corbacioglu1, Maria Domenica Cappellini2, John Chapin3, Nicole Chu-Osier4, Christine Marie Fern
Slide 3: Disclosures
Disclosures This study was sponsored by Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics AG JC is a shareholder of CRISPR Therapeutics and was an employee of CRISPR Therapeutics at the time this research was conducted. NC-O, JL-H, YL, and NS are employees of Vertex Pharmaceuticals Incorpo
Slide 4: TDT and SCD Cause Significant Morbidity and Mortality
Severe anaemia, frequent transfusions, complications related to iron overload 60,000 ANNUAL BIRTHSa TDT Loss-of-function mutations reduce the level of β-globin, lowering total Hb 300,000 ANNUAL BIRTHS Pain, anaemia, frequent hospitalizations, end-organ damage, early death SCD Single-point mutation c
Slide 5: Fetal Hemoglobin Levels and Disease Severity
CSSCD, Cooperative Study of Sickle Cell Disease 1. Musallam et al. Blood. 2012;119:364-367; 2. Ngo et al. Brit J Haematol. 2012;156:259-264; 3. Akinsheye et al. Blood. 2011;118:19-27; 4. Alsultan et al. Am J Hematol. 2012;87:824-826; 5. Nevitt et al. Cochrane Database Syst Rev. 2017;4:CD002202; 6. F
Slide 6: Disruption of BCL11A Expression Increases HbF Levels
Disruption of BCL11A Expression Increases HbF Levels Modified from Canver, Orkin. Blood. 2016;127:2536-2545 BCL11A suppresses expression of the γ-globin subunit of HbF Naturally occurring genetic polymorphisms in BCL11A are associated with elevated HbF CTX001: CD34+ cells gene edited with CRISPR-Cas
Slide 7: Phase 1/2 Studies in Patients with TDT and SCD
Phase 1 / 2 Studies in Patients with TDT and SCD Target enrollment 45 patients aged between 18 and 35 years with TDT, including β0 / β0 genotypes, defined as a history of at least 100 mL/kg/year or 10 units/year of packed RBC transfusions in the previous 2 years 45 patients aged between 18 and 35 ye
Slide 8: CTX001 Infusion Process
CTX001 Infusion Process aPatients enrolled in CLIMB THAL-111 received a combination of plerixafor and filgrastim for mobilization, while patients enrolled in CLIMB SCD-121 received plerixafor only; bPatients will be followed for 24 months after CTX001 infusion with physical exams, laboratory and ima
Slide 9: TDT Patient Baseline and Treatment Characteristics
TDT Patient Baseline and Treatment Characteristics aAnnualized number during the 2 years before consenting to study participation; bDefined as the first day of 3 measurements of absolute neutrophil count ≥500 cells/µL on 3 consecutive days; cDefined as the first day of 3 consecutive measurements of
Slide 10: TDT: Adverse Events
TDT: Adverse Events Patient 1 Patient 2 Screening to CTX001 infusion AEs 12 8 Serious AEs 0 0 Post-CTX001 infusion AEs 32 34 Serious AEs 2a 2b Weeks of follow-up 66.6 24.7 AE relationshipc Related to filgrastim only 4d 2 Related to plerixafor and filgrastim 0 2 Related to busulfan only 8e 15f Relate
Slide 11: TDT: Clinically Meaningful HbF and Total Hb Achieved Early and Maintained
Months post-CTX001 infusion TDT: Clinically Meaningful HbF and Total Hb are Achieved Early and Maintained aTotal Hb from local laboratory and Hb fraction from central laboratory; bHb adducts and other variants Hb fractionation, Hb (g/dL) CTX001 infusion Patient 1 Patient 2 a Hb, otherb 0.3 0.1 0.1 0
Slide 12: TDT: Pancellular Expression of HbF is Maintained
TDT: Pancellular Expression of HbF is Maintained % peripheral F-cells (% circulating RBCs expressing HbF) Months post-CTX001 infusion CTX001 infusion
Slide 13: Both TDT Patients Have Stopped pRBC Transfusions
Both TDT Patients Have Stopped pRBC Transfusions aIn the 15 months after CTX001 infusion, phlebotomy for iron reduction occurred on Study Days 98, 147, 170, and 191. Iron chelation therapy received from Study Day 205 to Study Day 316 Patient receiving pRBC transfusions Patient not receiving pRBC tra
Slide 14: SCD Patient Baseline and Treatment Characteristics
SCD Patient Baseline and Treatment Characteristics aPatient had received hydroxyurea treatment from 2016 to November 22, 2018 (Study Day −222); bAnnualized rate during the 2 years before consenting to study participation; cDefined as the first day of 3 measurements of absolute neutrophil count ≥500
Slide 15: SCD: Adverse Events
SCD: Adverse Events SCD Patient Screening to CTX001 infusion AEs 35 Serious AEs 11 Post-CTX001 infusion AEs 91a Serious AEs 3b Weeks of follow-up 45.1 AE relationshipc Related to plerixafor only 6 Related to busulfan only 21d Related to CTX001 only 0 Related to busulfan and CTX001 5e Not related to
Slide 16: SCD: Clinically Meaningful HbF is Achieved Early and Maintained
CTX001 infusion Months post-CTX001 infusion Hb fractionation, Hb (g/dL) HbS HbA 2 Hb, othera SCD: Clinically Meaningful HbF is Achieved Early and Maintained HbS, sickle hemoglobin aHb adducts and other variants 9.1% 0.8%
Slide 17: SCD: Pancellular HbF Expression is Maintained
CTX001 infusion SCD: Pancellular HbF Expression is Maintained % peripheral F-cells (% circulating RBCs expressing HbF) Months post-CTX001 infusion 33.9 4.3 43.8 70.2 94.7 99.9 99.6 99.7
Slide 18: SCD: No VOCs Post-CTX001 Infusion
Screening CTX001 infusion 6.5 months 9 months On-study / pre-CTX001a Treatment period 2 years Prior to screening Total Hb at last visit 11.8 g/dL No VOC in the 9 months of follow-up No pRBC transfusions have occurred since Study Day 19 VOCs Transfusions VOCs Transfusions related to SCD Transfusions
Slide 19: Durable BCL11A Editing Observed in Bone Marrow CD34+ Cells
CTX001 infusion Durable BCL11A Editing Observed in Bone Marrow CD34+ Cells Months post-CTX001 infusion TDT Patient 1 SCD Patient 0 3 Allelic editing in CD34+ bone marrow cellsa TDT Patient 2 aAllelic editing in CD34+ bone marrow cells assessed every 6 months 78.1% 81.4% 76.1%
Slide 20: Conclusions
Conclusions These studies are the first demonstration of the clinical impact of CRISPR-Cas9-based gene editing for hemoglobinopathies and establish proof of concept for TDT Overall safety is consistent with myeloablative conditioning and autologous transplant Clinically meaningful HbF and total Hb l
Slide 21: 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