Slide 1: The COBALT-LYM Study of CTX130 in R/R T-Cell Malignancies
THE COBALT-LYM STUDY OF CTX130: A PHASE 1 DOSE ESCALATION STUDY OF CD70-TARGETED ALLOGENEIC CRISPR-CAS9–ENGINEERED CAR T CELLS IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) T-CELL MALIGNANCIES Swaminathan P. Iyer1, R. Alejandro Sica2, P. Joy Ho3, Boyu Hu4, Jasmine Zain5, Anca Prica6, Wen-Kai Weng7, You
Slide 2: Disclosures
Disclosures The COBALT™ – LYM study of CTX130TM is sponsored by CRISPR Therapeutics Dr. Swaminathan P. Iyer is a Professor, Lead of the T Cell Lymphoma Program, Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center Dr. Iyer receives research
Slide 3: Overview
Overview PTCL and CTCL are complex diseases with significant unmet need and limited approved systemic therapies. Few therapies effectively treat all disease compartments (lymph nodes, skin, blood) or achieve meaningful CR rates. For patients with R/R PTCL and transformed CTCL, median OS is 1-2.5 and
Slide 4: Role of CD70 in Immune Response and Cancer
Role of CD70 in Immune Response and Cancer CD70+ malignant cell CD70 Physiological role of CD701 Transient CD70 expression on activated lymphocytes Controls naïve and memory T-cell activation via interaction with CD27 Role of CD70 in cancer1 Increased CD70 expression has been detected in certain can
Slide 5: CTX130
CTX130 Autologous approaches continue to be challenging due to the poor function of donor T cells, potential for fratricide, and risk of infusing transduced malignant CAR T cells into patients CTX130 is an investigational allogeneic, CRISPR/Cas9 gene-edited, anti-CD70 CAR T cell therapy with TRAC, β
Slide 6: CTX130 – Preclinical Data
CTX130 – Preclinical Data Reference: Karnik S, et al.. Poster presented at American Association for Cancer Research 2020. Presented at the European Hematology Association Annual Meeting. 11 June 2022 High Moderate Low CD70 surface expression on clinical samples of TCL as measured by immunohistochemi
Slide 7: CTX130 – Preclinical Data
CTX130 – Preclinical Data IHC, immunohistochemistry; RCC, renal cell carcinoma; TCL, T-cell lymphoma Reference: Karnik S, et al.. Poster presented at American Association for Cancer Research 2020. Presented at the European Hematology Association Annual Meeting. 11 June 2022 Consistent with the IHC d
Slide 8: COBALT-LYM (NCT04502446) Clinical Trial Design
COBALT-LYM (NCT04502446) Clinical Trial Design Phase 1, open-label, multicenter, international, single-arm study (NCT04502446) evaluating the safety and efficacy of CTX130, an investigational, allogeneic CAR-T cell targeting CD70 *As assessed by Lugano response criteria for PTCL, International Socie
Slide 9: Patient Demographics and Pharmacokinetics
Time to peak expansion (Tmax)†, median days (range) 8.5 (5 – 14) * For summary statistics of Cmax, values below the limit of detection (LOD) were imputed as half the LOD and values below the limit of quantification (LOQ) were imputed as (LOQ+LOD)/2. † From Screening to D28 post infusion. 1 Includes
Slide 10: Safety
Safety All events listed in table are treatment-emergent adverse events. CRS, cytokine release syndrome; DLT, dose-limiting toxicity; EBV, Epstein-Barr virus; Gr, grade; GvHD, graft versus host disease; HLH, hemophagocytic lymphohistiocytosis; ICANS, immune effector cell associated neurotoxicity syn
Slide 11: Efficacy
Efficacy Cell dose (CAR+ T cells) DL1 3x107 N=4 DL2 1x108 N=4 DL3 3x108 N=5 DL4 9x108 N=5 DL≥3 N=10 Overall Response Rate (ORR) 2 (50) 0 3 (60) 4 (80) 7 (70) CR 1 (25) 0 2 (40)* 1 (20) 3 (30) PR 1 (25) 0 1 (20) 3 (60) 4 (40) Disease Control Rate (DCR = CR + PR + SD) 3 (75) 1 (25) 5 (100) 4 (80) 9 (9
Slide 12: CTCL Responses Observed Across All Compartments
† CTCL Responses Observed 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; PR, partial response; SD, stable disease. Dose Level / Best Overall Response 111 100 -
Slide 13: Efficacy (continued)
Efficacy (continued) Presented at the European Hematology Association Annual Meeting. 11 June 2022 Time from first CTX130 infusion (months) CR SD PD PR Re-Infusion Death Stem cell transplant Anticancer therapy AITL, angioimmunoblastic T cell lymphoma; ALCL, anaplastic large cell lymphoma; ATLL, adul
Slide 14: Case Study: Complete Response with Single-Infusion of CTX130
Case Study Complete Response with Single-Infusion of CTX130 Subject Overview Response AE, adverse event; CAR, chimeric antigen receptor; CR, complete response; D, day; DL, dose level; Gr, grade; mSWAT; modified severity weight assessment tool. Patient profile 47-year-old male with stage IVA2 transfo
Slide 15: Case Study: Complete Response at D28 After Re-Infusion
Case Study Complete Response at D28 After Re-Infusion AE, adverse event; ATLL, adult T-cell leukemia/lymphoma; CAR, chimeric antigen receptor; CR, complete response; D, day; DL, dose level; Gr, grade; IFN, interferon; mSWAT; modified severity weight assessment tool; PR, partial response; SD, stable
Slide 16: Acknowledgments
Acknowledgments Thank you to all the patients, families and investigators involved with the COBALT-LYM Study This study was sponsored by CRISPR Therapeutics COBALT-LYM (NCT04502446) Study Sites Presented at the European Hematology Association Annual Meeting. 11 June 2022