Cellectis S.a. · EURONEXT:ALCLS
Cellectis — Technical Presentation (2023)
16 slides from Cellectis's technical presentation, Nov 7, 2023
Slide 1: AMELI-01: A Phase I Trial of UCART123v1.2 in R/R CD123+ AML
AMELI-01: A Phase I Trial of UCART123v1.2, an Anti- CD123 Allogeneic CAR-T Cell Product, in Adult Patients with Relapsed or Refractory (R/R) CD123+ Acute Myeloid Leukemia David A. Sallman1, Daniel J. DeAngelo2, Naveen Pemmaraju3, Shira Dinner4, Saar Gill5, Rebecca L. Olin6, Eunice S. Wang7, Eileen S
Slide 2: Background and Introduction
Background and Introduction ▪ It is estimated that 20,050 new cases and 11,540 deaths related to AML will occur in the US in 2022 ▪ Outcomes for patients with R/R AML remain poor, with response rates <30% and an expected 5-year overall survival of <15% ▪ AMELI-01 (NCT03190278) is a phase I, open-lab
Slide 3: UCART123v1.2: Allogeneic Off-the-Shelf T-cell Product
UCART123v1.2: Allogeneic “Off-the-Shelf” T-cell Product UCART123v1.2 (anti-CD123 scFv- 41BB-CD3ζ): ▪ CD123 is a validated therapeutic target in AML ▪ Genetically modified allogeneic T- cell product manufactured from non-HLA–matched healthy donor cells ▪ TRAC disrupted using TALEN® to eliminate TCRαβ
Slide 4: AMELI-01 Study Design
AMELI-01 Study Design Key inclusion criteria Dose-Escalation UCART123v1.2 mTPI design ● 2-4 pts/cohort ▪ Relapsed or primary refractory AML (>5% bone marrow blasts) FC Arm FCA Arm ▪ Blasts expressing CD123 ▪ PS of ≤1 and adequate organ function UCART123v1.2 UCART123v1.2 (single dose) (single dose) P
Slide 5: Baseline Characteristics
Baseline Characteristics Characteristic Total (N = 18*) Age, median (range), years 57 (18-64) Female, n (%) 8 (44) ECOG PS 1, n (%) 17 (94) ELN 2017 Classification, n (%) Adverse risk 14 (78) Intermediate risk 3 (17) Median baseline bone marrow blasts % (range) 37 (0-88) Number of prior treatments,
Slide 6: UCART123v1.2 - Related TEAEs (FC + FCA)
UCART123v1.2 - Related TEAEs (FC + FCA) FC FCA FC + FCA FC Total [n=8] FCA Total [n=9] All patients DL1=2; DL2=3; DL2i=2; DL3=1 DL2=8; DL2i=1 N=17* TEAE, n Any grade Gr ≥3 Any grade Gr ≥3 Any grade Gr ≥3 CRS 8 2 9 2 17 4 HLH 1 1 1 0 2 1 ICANS 1 1 1 0 2 1 ALT increased 4 1 1 1 5 2 AST increased 4 1 1
Slide 7: UCART123v1.2 - Serious TEAEs (All Cause – FC + FCA)
UCART123v1.2 - Serious TEAEs (All Cause – FC + FCA) FC FCA FC + FCA FC Total [n=8] FCA Total [n=9] Total patients DL1=2; DL2=3; DL2i=2; DL3=1 DL2=8; DL2i=1 N=17* Serious TEAE, n (%) Any grade Gr ≥3 Any grade Gr ≥3 Any grade Gr ≥3 CRS 3 2 2 2 5 4 ICANS 1 1 0 0 1 1 Pneumonia 1 1 1 1 2 2 Pneumonia fung
Slide 8: Anti-Leukemic Activity Observed in 4/17 Patients at DL2 and Above
Anti-Leukemic Activity Observed in 4/17 Patients at DL2 and Above 100 FC Arm ▪ FC arm 90 102-201 80 104-204 DL1 • Patient 101-219 (DL2i): SD % of Blasts in BM 70 60 101-209 • Patient 103-223 (DL2i): MLFS 50 102-208 DL2 40 30 103-207 20 101-219 10 0 103-223 DL2i -10 103-211 DL3 Screening D14 D28 FCA
Slide 9: Addition of Alemtuzumab Results in Prolonged Lymphodepletion
Addition of Alemtuzumab Results in Prolonged Lymphodepletion Absolute Lymphocyte Counts FC Arm FCA Arm 10 10 102-201 102-222 5 DL1 5 104-204 103-225 2.0 2.0 ALC (K/mL) ALC (K/mL) 101-209 103-231 1.5 102-208 DL2 1.5 104-218 DL2 1.0 103-207 1.0 104-224 101-219 104-226 0.5 DL2i 0.5 103-223 114-229 0.0
Slide 10: Addition of Alemtuzumab Results in Increased UCART123v1.2 Expansion
Addition of Alemtuzumab Results in Increased UCART123v1.2 Expansion UCART123 Cell Expansion in WB by VCN VCN AUC(0-28days) 1000000 FC Arm 102-201 DL1 Psi copies/mg DNA 100000 104-204 100 101-209 10000 (days x copies/ug of DNA) 102-208 DL2 1000 103-207 80 100 101-219 VCN - AUC LLOQ DL2i 10 103-223 60
Slide 11: Cytokine Secretion and Ferritin Levels Correlated with Cell Expansion
Cytokine Secretion and Ferritin Levels Correlated with UCART123v1.2 Cell Expansion Cytokine Profile of All Patients from FCA Arm IL-2 IL-6 IFN-g TNF-a 10 10000 1000 10 102-222 102-222 102-222 102-222 1000 103-225 103-225 103-225 103-225 Fold change (log) Fold change (log) Fold change (log) 100 Fold
Slide 12: Patient 104-226 Achieved a Durable MRD Negative CR
Patient 104-226 Achieved a Durable MRD Negative CR Clinical Characteristics Age, Race, Sex 64 year old white female ECOG 1 ELN 2017 Classification; WHO Classification Adverse risk; AML with myelodysplasia-related changes Cytogenetic and Molecular Abnormalities 45,XX,-7,t(10;12)(q24;p13)[5]; IDH1, EZ
Slide 13: Translational Data Supports Use of a Two-Dose Regimen
Translational Data From Patient 104-226 and Others Supports Use of a Two-Dose Regimen of UCART123v1.2 ▪ UCART123v1.2 expansion correlates with reduction in tumor burden at DL2 (6.25 x 105 cells/kg) but at this dose, UCART123v1.2 cell function is not sufficient for sustained anti- leukemic activity i
Slide 14: AMELI-01 Amended Protocol with Two-Dose Regimen Design
AMELI-01 Amended Protocol with Two-Dose Regimen Design Dose-Escalation UCART123.1.2 mTPI design; 2-4 pts/cohort FC Arm FCA Arm UCART123v1.2 UCART123v1.2 UCART123v1.2 (single dose) (single dose) (2-dose regimen) DL 3 DL 3 DL 3 x 2 DL 2i DL 2i DL 2i x 2 DL 2 DL 2 DL 2 x 2 UCART123.v1.2 DL-1 1.25×105 c
Slide 15: Conclusions
Conclusions ▪ Adding alemtuzumab to the FC regimen was associated with improved LD and significantly higher UCART123v1.2 cell expansion, which correlated with improved activity and cytokine profiles ➢ One patient in the DL2 FCA arm achieved >90% blast reduction at Day 28 ➢ One patient in the DL2 FCA
Slide 16: Acknowledgments
Acknowledgments ▪ We thank the patients, families, co-investigators and all study personnel who made this trial possible ▪ The AMELI-01 study is funded by Cellectis, S.A. ▪ For more information, please contact clinicaltrials@cellectis.com 16