Celyad Oncology SA · EURONEXT:CYAD
Celyad Oncology SA — Technical Presentation (June 2020)
30 slides from Celyad Oncology SA's technical presentation, June 2020
Slide 1: Remissions in Relapse/Refractory AML Patients Following NKG2D CAR-T Therapy
Remissions in Relapse/Refractory Acute Myeloid Leukemia Patients Following Treatment with NKG2D CAR-T Therapy Without a Prior Preconditioning Chemotherapy (Abstract # 902) David A. Sallman, Tessa Kerre, Xavier Poiré, Violaine Havelange, Philippe Lewalle, Eunice S. Wang, Doreen Dekker, Peggy Sotiropo
Slide 2: CYAD-01: NKG2D CAR-T
CYAD-01: NKG2D CAR-T ● NKG2D is an activating receptor on NK cells Tumor cell and some T cell subsets (CD8+ T cells NKT, γδT cells) Ligands ● Killing activity is dependent on NKG2D ligand expression & NKG2D independent of inhibitory signaling Physiological ● CYAD-01: DAP10 o Full length human NKG2D
Slide 3: NKG2D Human Ligands Expression in Cancer
NKG2D HUMAN LIGANDS EXPRESSION IN CANCER Tumor type NKG2D ligand expression prevalence Acute Myeloid Leukemia 100% expressing at least 1 NKG2D ligand ● NKG2D ligands: MICA, MICB, ULBPs 1-6 Acute Lymphoblastic Leukemia 28-67% MICA/B, 9-20% ULBP1-3 Chronic Lymphocytic Leukemia 0-85% MICA/B, 10-20% ULB
Slide 4: CYAD-01 Multiple Injections Increase Tumor Killing
CYAD-01 MULTIPLE INJECTIONS INCREASE TUMOR KILLING ● Preclinical model: Multiple injections of CYAD-01 increased tumor killing through various mode of action THP-1 (AML) cells established i.v. in NSG mice (7 per group). Animals received 107 total CYAD-01 T cells per injection (Unpublished data) ● Fi
Slide 5: CYAD-01: THINK Phase I Study
CYAD-01: THINK PHASE I STUDY THerapeutic Immunotherapy with NKG2D-based therapy ● Open-label Phase I study (3+3 design) (NCT03018405) Study endpoints ● 3 dose levels: 3x108,1x109 and 3x109 CYAD-01/injection ● Primary: - Safety ● 3 administrations (2 weeks intervals) ● Secondary: - Clinical activity
Slide 6: Patient Demographics
PATIENT DEMOGRAPHICS All patients DL-1 DL-2 DL-3 3x108 1x109 3x109 N = 14 N=6 N=3 N=5 Age (years): Mean (Range) 62,9 (29-83) 64.8 (52-79) 74.0 (60-83) 53.8 (29-68) Gender: Male/Female 11 / 3 5/1 2/1 4/1 ECOG performance score (Grade 0/1/2) 5/7/2 2/4/0 1/1/1 2/2/1 LVEF (%): Mean (Range) 60.6 (48-79)
Slide 7: Treatment-Related Adverse Events
TREATMENT-RELATED ADVERSE EVENTS All patients DL-1 DL-2 DL-3 3x10 8 1x10 9 3x109 N=14 (38 injections) N=6 (15 injections) N=3 (12 injections) N=5 (11 injections) All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 Adverse Event (AE) Prefered Te
Slide 8: Cytokine Release Syndrome Events
CYTOKINE RELEASE SYNDROME EVENTS DOSE-LEVEL 1 DOSE-LEVEL 2 DOSE-LEVEL 3 CYAD-01 injections CYAD-01 injections CYAD-01 injections ● CRS in 6/14 (43%) pts (9/39 CYAD-01 injections), 202-501 (AML) 101-502 (AML) 102-505 (AML) with 3 pts (21%) with Grade 3 or 4 101-501 (AML) 202-506 (AML) T T 102-506 (AM
Slide 9: Promising Clinical Data in R/R AML
PROMISING CLINICAL DATA IN R/R AML 14 patients (6/3/5 pts at DL-1/2/3) 3 MM and 1 MDS patients (DL1) no clinical response 2 r/r AML pts non-evaluable (DL-3) 10 r/r AML patients (2/3/5 pts at DL-1/2/3) (only one CYAD-01 injection) ● 1 pt (adverse) rapidly progressing ● 1 pt (adverse) – DLT – Reductio
Slide 10: AML Anti-Leukemic Activity
AML ANTI-LEUKEMIC ACTIVITY Change in BM Blast Count from Baseline (%) 102-506 (A) 100% ● 5/8 pts (62%) with relevant BM blast decrease in r/r AML pts evaluable per 80% protocol (at least one CYAD-01 cycle) 60% 202-505 (A) with 3 objective responses (CR/CRi) ● 1 pt with SD with no BM blast decrease C
Slide 11: AML Anti-Leukemic Activity
AML ANTI-LEUKEMIC ACTIVITY Change in BM Blast Count from Baseline (%) 102-506 (A) 100% ● 5/8 pts (62%) with relevant BM blast decrease in r/r AML pts evaluable per 80% protocol (at least one CYAD-01 cycle) 60% 202-505 (A) with 3 objective responses (CR/CRi) ● 1 pt with SD with no BM blast decrease C
Slide 12: CYAD-01 Phenotype in AML at Time of Injection
CYAD-01 PHENOTYPE IN AML AT TIME OF INJECTION ● Infused CYAD-01 included all four of T cells subsets, with a substantial fraction of Central Memory (CM) and Effector (EM) phenotype T cells ● Central Memory CYAD-01 T cells provide better outcome (early observation) – Median of 86,5% (range: 72,1% to
Slide 13: CYAD-01 Phenotype in AML at Time of Injection
CYAD-01 PHENOTYPE IN AML AT TIME OF INJECTION ● Infused CYAD-01 included all four of T cells subsets, with a substantial fraction of Central Memory (CM) and Effector (EM) phenotype T cells ● Central Memory CYAD-01 T cells provide better outcome (early observation) CR(i) – Median of 86,5% (range: 72,
Slide 14: Case Report: Patient 202-501
CASE REPORT: PATIENT 202-501 Male 52y AML (ELN 2017- Intermediate) DL-1 Blast percentage and hematological parameters High level of NKG2D ligands expression on bone post CYAD-01 administration marrow blast cells at baseline 100 percentage of positive CRh CRMRD- 100% donor chimerism 80 60 cells 40 20
Slide 15: Case Report: Patient 202-501
CASE REPORT: PATIENT 202-501 Male 52y AML (ELN 2017- Intermediate) DL-1 Blast percentage and hematological parameters High level of NKG2D ligands expression on bone post CYAD-01 administration marrow blast cells at baseline 100 percentage of positive CRh CRMRD- 100% donor chimerism 80 60 cells 40 20
Slide 16: Case Report: Patient 202-506
CASE REPORT: PATIENT 202-506 Male 83y AML (ELN 2017- Adverse) DL-2 RATIONALE FOR SCHEDULE OPTIMIZATION ● Anti-leukemic activity after 1st CYAD-01 cycle ● 7 weeks between last injection cycle 1 and first injection cycle 2 ● New reinduction of relevant BM blast decrease with 2nd CYAD-01 cycle ● CYAD-0
Slide 17: CYAD-01 Detection (No Preconditioning)
CYAD-01 DETECTION (NO PRECONDITIONING) DL-1 (3x108 CYAD-01/inj.) DL-2 (1x109 CYAD-01/inj.) DL-3 (3x109 CYAD-01/inj.) 12000 CYAD-01/mL 17000 CYAD-01/mL Detection CYAD-01 in BM Detection CYAD-01 in BM Detection CYAD-01 in BM 202-501 - - 101-502 - + ongoing 202-505 - - 202-506 - + Interim analysis 17
Slide 18: Conclusions & Perspectives
CONCLUSIONS & PERSPECTIVES ● CYAD-01 is a potent NKG2D CAR-T therapy that kills NKG2D ligands positive AML blasts, in vitro and in vivo ● THINK hematological arm (NCT03018405): in relapse/refractory AML patients, multiple injections of CYAD-01 without preconditioning chemotherapy showed: o An encour
Slide 19: Acknowledgements
ACKNOWLEDGEMENTS ● Patients and their families ● Investigators, coordinators and clinical trial team from the following institutions: o Moffitt Cancer Center, Tampa, Florida, USA o Gent University Hospital, Ghent, Belgium o Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brusse
Slide 20: Backup
BACKUP 20
Slide 21: Promising Clinical Data in R/R AML
PROMISING CLINICAL DATA IN R/R AML 14 patients (6/3/5 pts at DL-1/2/3) 3 MM and 1 MDS patients (DL1) no clinical response 2 r/r AML pts non-evaluable (DL-3) 10 r/r AML patients (2/3/5 pts at DL-1/2/3) (only one CYAD-01 injection) ● 1 pt (adverse) rapidly progressing ● 1 pt (adverse) – DLT – Reductio
Slide 22: AML Patients Clinical Evolution (Nov 28)
AML PATIENTS CLINICAL EVOLUTION (NOV 28) DL-1 202-501 (I-52y) CRh CR MRD- 16m+ 101-501 (F-73y) CRi DL-2 101-502 (F-60y) 9m 202-506 (A-83y) 202-505 (A-79y) DL-3 102-505 (I-65y) CRi CR 102-506 (A-29y) 202-510 (A-68y) DLT (peripheral blast from 14% to 4%) 202-511 (A-48y) 202-508 (A-59y) 0 1 month 2 3 4
Slide 23: Promising Clinical Data in R/R AML
PROMISING CLINICAL DATA IN R/R AML 14 patients (6/3/5 pts at DL-1/2/3) 3 MM and 1 MDS patients (DL1) no clinical response 2 r/r AML pts non-evaluable (DL-3) 10 r/r AML patients (2/3/5 pts at DL-1/2/3) (only one CYAD-01 injection) ● 1 pt (adverse) rapidly progressing ● 1 pt (adverse) – DLT – Reductio
Slide 24: AML Best Anti-Leukemic Activity
AML BEST ANTI-LEUKEMIC ACTIVITY Change in BM Blast Count from Baseline (%) 102-506 (A) 100% ● 5/8 pts (62%) with relevant BM blast decrease in r/r AML pts evaluable per 80% protocol (at least one CYAD-01 cycle) 60% 202-505 (A) with 4 objective responses (CR/CRi/PR) ● 1 pt with SD with no BM blast de
Slide 25: AML Best Anti-Leukemic Activity
AML BEST ANTI-LEUKEMIC ACTIVITY Change in BM Blast Count from Baseline (%) 102-506 (A) 100% ● 5/8 pts (62%) with relevant BM blast decrease in r/r AML pts evaluable per 80% protocol (at least one CYAD-01 cycle) 60% 202-505 (A) with 4 objective responses (CR/CRi/PR) ● 1 pt with SD with no BM blast de
Slide 26: AML Patients Clinical Evolution (Nov 28)
AML PATIENTS CLINICAL EVOLUTION (NOV 28) DL-1 202-501 (I-52y) CRh CR MRD- 16m+ 101-501 (F-73y) CRi DL-2 101-502 (F-60y) 9m 202-506 (A-83y) PRi 202-505 (A-79y) DL-3 102-505 (I-65y) CRi CR 102-506 (A-29y) 202-510 (A-68y) DLT (peripheral blast from 14% to 4%) 202-511 (A-48y) 202-508 (A-59y) 0 1 month 2
Slide 27: Case Report: Patient 202-506
CASE REPORT: PATIENT 202-506 Male 83y AML (ELN 2017- Adverse) DL-2 RATIONALE FOR SCHEDULE OPTIMIZATION ● Rapid anti-leukemic activity after 1st CYAD-01 cycle with SD with BM blasts decrease from 9.8% to 5.5% ● 7 weeks between last injection cycle 1 and first injection cycle 2 ● PR with incomplete bl
Slide 28: Conclusions & Perspectives
CONCLUSIONS & PERSPECTIVES ● CYAD-01 is a potent NKG2D CAR-T therapy that kills NKG2D ligands positive AML blasts, in vitro and in vivo ● THINK hematological arm (NCT03018405): in relapse/refractory AML patients, multiple injections of CYAD-01 without preconditioning chemotherapy showed: o An encour
Slide 29: AML Patients Clinical Evolution (Nov 28)
AML PATIENTS CLINICAL EVOLUTION (NOV 28) DL-1 202-501 (I-52y) CRh CR MRD- 16m+ 101-501 (F-73y) CRi DL-2 101-502 (F-60y) 9m 202-506 (A-83y) PRi 202-505 (A-79y) DL-3 102-505 (I-65y) CRi CR 102-506 (A-29y) 202-510 (A-68y) DLT (peripheral blast from 14% to 4%) 202-511 (A-48y) 202-508 (A-59y) 0 1 month 2
Slide 30: AML Patients Clinical Evolution (Nov 28)
AML PATIENTS CLINICAL EVOLUTION (NOV 28) DL-1 202-501 (I-52y) CRh CR MRD- 16m+ 101-501 (F-73y) CRi DL-2 101-502 (F-60y) 9m 202-506 (A-83y) 202-505 (A-79y) DL-3 102-505 (I-65y) CRi CR 102-506 (A-29y) 202-510 (A-68y) DLT (peripheral blast from 14% to 4%) 202-511 (A-48y) 202-508 (A-59y) 0 1 month 2 3 4