Slide 1: Safety and Efficacy of UCART22 in Heavily Pretreated R/R CD22+ B-ALL: Phase 1 BALLI-01
UCART22 in B-ALL I EHA 2026 I N. Jain Safety and Efficacy of UCART22 in Heavily Pretreated Patients with Relapsed or Refractory CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL): Results from the Phase 1 BALLI-01 Trial Nitin Jain1, Jose Carlos2, Richard Larson3, Gary Schiller4, Aravind Ramakrishnan5
Slide 2: Disclosure
Disclosure Research Funding (N. Jain) Cellectis, Pharmacyclics, AbbVie, Genentech, AstraZeneca, BeOne, Eli Lilly, BMS, ADC Therapeutics, Adaptive Biotechnologies, Kite/Gilead, Takeda, Newave, Carna Biosciences, Bioheng Therapeutics, Ubix Therapeutics, Ascentage Advisory Board / Honoraria (N. Jain) C
Slide 3: Background: 3L and Beyond B-ALL
Background: 3L and Beyond B-ALL • B-cell Acute Lymphoblastic Leukemia (B-ALL) in the third-line (3L) setting and beyond represents an area of significant unmet clinical need • Highly aggressive disease biology • Enriched for resistance mutations • Lack of standard-of-care treatments • Few patients i
Slide 4: UCART22: Allogeneic CD22 CAR T
UCART22: Allogeneic CD22 CAR T • CD22 CAR expression to redirect T-cells to tumor antigens Lentiviral vector • Rituximab mimotope (RQR8) • TRAC disruption using TALEN® to eliminate TCR from the cell surface and avoid GvHD mRNA electroporation • CD52 disruption using TALEN® to eliminate sensitivity t
Slide 5: BALLI-01 Study Design
BALLI-01 Study Design N=19 N=26 Process 1 (P1): manufactured by external CDMO Process 2 (P2): manufactured by Cellectis Process 1 vs Process 2 UCART22 Dose Level: 2 lymphodepletion schedules were assessed DL 3 DL 3 DL1: 1×105 cells/kg n=6 n=15** • FC: Fludarabine (F), 30 mg/m²/d for 4 days DL2: 1×10
Slide 6: BALLI-01 Phase 1 Study Design
BALLI-01 Phase Study Design Key Inclusion Criteria • Age 15-70 years, adequate organ function (for sub study age ≤ 50) • ECOG PS ≤1 • Measurable or evaluable disease in the BM of at least 0.01% blasts or non-CNS extramedullary disease (for alemtuzumab weight-based sub study ≥5% marrow blasts) • % of
Slide 7: Baseline Demographic and Clinical Characteristics (N=45)
Baseline Demographic and Clinical Characteristics (N=45) P1 P2 TOTAL Summary n=19 n=26 N=45 Age (yrs), median (range) 28.5 (17-61) 28 (16-68) 28 (16-68) Sex Male, n (%) 11 (55) 14 (56) 25 (55.6) Female, n (%) 8 (42) 12 (46) 20 (44.4) ECOG ECOG 0, n (%) 6 (30) 8 (32) 14 (31.1) ECOG 1, n (%) 13 (68) 1
Slide 8: Baseline Characteristics DL3 Cohort (P2), n=15
Baseline Demographic and Clinical Characteristics DL3 Cohort (P2), n=15 DL3 P2 Target Phase 2 population, (age ≤50) n=15 (%) n=12 (%) Sub-Study Main study Alemtuzumab weight-based dosing n=7 (%) n=5 (%) Age (yrs), median (range) 28 (16-66) 23 (16-30) 39 (23-45) Sex Male, n (%) 7 (46.7) 3 (42.9) 2 (4
Slide 9: Low Incidence of Grade ≥3 CRS and ICANS
Low Incidence of Grade ≥3 CRS and ICANS CRS and ICANS Total Population n=45 CRS and ICANS DL3 P2 n=15 100 100 13 80 80 Percentage % 4 Percentage % 60 60 31 53 40 40 13 20 36 4 20 13 9 27 4 13 0 0 CRS ICANS CRS ICANS Grade 1 Grade 2 Grade 3 Grade 1 Grade 2 Grade 3 ▪ No grade 4 or 5 CRS or ICANS ▪ Med
Slide 10: UCART22 | Related SAEs
UCART22 | Related SAEs SAE Cohort Grade # of events DL3 3 2 Cytokine release syndrome DL2 2 1 Graft versus host disease in skin DL2i 2 1 Hemophagocytic lymphohistiocytosis DL3 4 1 Hydrocephalus DL2 3 1 Immune effector cell-associated neurotoxicity syndrome DL3 3 2 Multiple organ dysfunction syndrome
Slide 11: Infections & Viral reactivations
Infections & Viral reactivations Bacterial infections Grade ≥ 3 N of patients Related to LD Related to UCART22 Total 9 4 - Local infections (cystitis, cellulitis, perineal, orbital) 5 3 - Bacteremia 4 - 1 Fungal infections Grade ≥ 3 Total (aspergillosis, tracheitis, sinusitis) 6 2 - Grade 5 5 1 (asp
Slide 12: Higher Response Rates in P2
Higher Response Rates in P2 Overall Response Rates in P1 and P2 (%) 100 P1 manufactured by external CDMO 90 P2 manufactured Internally 80 70 n=25 Percentage % 60 ▪ 36% of P2 achieved CR/CRi 50 28 • P2: 78% of CR/CRi achieved 40 n=18 30 6 8 MRD neg (flow) 20 17 28 10 11 0 P1 P2 CR/CRi (MRD -ve) CR/CR
Slide 13: Higher Response Rates at P2 Dose Level
Higher Response Rates at P2 Dose Level 3 ▪ Low weight-based dose of alemtuzumab evaluated in advance of Phase 2 dose optimization ▪ Required for Project Optimus Overall Response Rate 100 90 80 70 Percentage % 60 33 50 28 40 30 20 36 40 10 0 Total n=25 DL3 n=15 CR/CRi MLFS P13 UCART22 in B-ALL I EHA
Slide 14: Clinically meaningful CR/CRi Rates in Patients Prior Exposed to Targeted Therapies
Clinically meaningful CR/CRi Rates in P2 Patients Prior Exposed to Targeted Therapies Blinatumomab + CD19 CAR-T + Inotuzumab Response Rates (CR/CRi) in patients 100 with prior Blinatumomab + CD19 CAR-T + Inotuzumab 90 80 Patient characteristics (n=13) Percentage % 70 60 n=3/6 ▪ Age, median [range]:
Slide 15: Subjects Received Transplant post UCART22 (P2)
Subjects Received Transplant post UCART22 (P2) Subjects who received HSCT (%) ➢ Decision for transplant was at 100 the discretion of the treating 90 physician 80 ➢ Transplant was not a 70 predefined trial endpoint 60 50 100 ➢ Sub study investigated a low 40 weight-based dose of 67 alemtuzumab 30 53
Slide 16: DL3 – P2 Subjects Swimmer Plot
DL3 – P2 Subjects Swimmer Plot Age > 50 Years P16 UCART22 in B-ALL I EHA 2026 I N. Jain
Slide 17: UCART22-P1 – confirmed expansion with FCA but not FC LD regimen
UCART22-P1 – confirmed expansion with FCA but not FC LD regimen UCART22_P1 expansion with FC or FCA regimen in peripheral blood 1000000 FC_DL1 n=3 VCN (copies/µg DNA) 100000 10000 FC_DL2 n=2 1000 FCA_DL2 n=3 100 FCA_DL2i n=4 10 FCA_DL3 n=6 1 0.1 0.01 0 10 20 30 40 50 Day ▪ FC Lymphodepletion regimen
Slide 18: UCART22-P2 Expansion and Alemtuzumab Exposure by Response
UCART22-P2 Expansion and Alemtuzumab Exposure by Response UCART22-P2 expansion in peripheral blood UCART22-P2 by dose level (DL) Alemtuzumab exposure per DL 200000 100000 Responders - DL3 n=11 175000 VCN (copies/µg DNA) AUCLD-14d (ng.d/mL) 150000 Responders - DL2i n=1 80000 125000 Responders - DL2 n
Slide 19: Alemtuzumab-Exposure Response Data Guides Weight-Based Dosing Thresholds (P2)
Alemtuzumab-Exposure Response Data Guides Weight-Based Dosing Thresholds (P2) < 0.7 mg/kg 0.7-0.89 mg/kg ≥ 0.9 mg/kg CR/CRi: 25.0%* CR/CRi: 20.0% CR/CRi: 66.7%* RD/PD: 50.0%* RD/PD: 20.0% RD/PD: 11.1%* 100000 RD/PD AUCLD-14d (ng.d/mL) 80000 CR/CRi MLFS 60000 NE (non 40000 evaluable) 20000 0 D M D M
Slide 20: Pivotal Phase 2: Study Design
Pivotal Phase 2 : Study Design Key Inclusion Criteria ▪ Age 12- 50 years ▪ R/R disease after ≥2 lines ▪ BM of at least 5% blasts ▪ Prior CD19 CAR-T unless subject unable to receive Primary Endpoints 2 CR/CRi within 3 months Secondary Endpoints ▪ Transplant eligibility ▪ MRD negativity (within 3 mont
Slide 21: Conclusions from the Phase 1 Study
Conclusions from the Phase 1 Study ▪ UCART22 led to low rates of grade ≥3 CRS and ICANS ▪ One DLT occurred during Phase 1 – Dose Escalation ▪ In a very heavily pre-treated patient population with a median of 5 prior lines of therapy, clinically meaningful CR/CRi rates were achieved ▪ RP2D of UCART22
Slide 22: Pivotal Phase 2 Study Now Enrolling
Pivotal Phase 2 Study Now Enrolling 3 5 37 11 8 11 75 planned study centers in North America and Europe NCT04150497 P22 UCART22 in B-ALL I EHA 2026 I N. Jain
Slide 23: Acknowledgements
Acknowledgements • We thank the patients, families, co-investigators and all study personnel who made this trial possible • The BALLI-01 study is funded by Cellectis, S.A • For questions or comments, please contact Dr. Nitin Jain: njain@mdanderson.org • For more information, please contact clinicalt