Cellectis (Nasdaq: CLLS), a clinical-stage biotechnology company employing its pioneering TALEN® gene-editing platform to develop innovative therapeutics for the treatment of serious diseases, announced today preliminary results from the BALLI-01 Phase 1 study of UCART22, its allogeneic CAR-T cell therapy candidate targetCellectis (NASDAQ:CLLS), a clinical-stage biotechnology company employing its pioneering TALEN® gene-editing platform to develop innovative therapeutics for the treatment of serious diseases, announced today preliminary results from the BALLI-01 Phase 1 study of UCART22, its allogeneic CAR-T cell therapy candidate targeting CD22, in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), and preclinical data on TALGlobin01, its autologous cell therapy product candidate for homozygous SCD patients (HbSS) at the 63rd Annual Meeting of the American Society of Hematology (ASH) in Atlanta, Georgia.
“We are excited by the encouraging preliminary results obtained from patients administered UCART22 after fludarabine, cyclophosphamide and alemtuzumab (FCA) lymphodepletion in the BALLI-01 study. The addition of alemtuzumab to fludarabine and cyclophosphamide (FC) was demonstrated to be safe, improve host-lymphocyte suppression, and promote UCART22 expansion, which was associated with anti-leukemic activity,” said Carrie Brownstein, MD, Chief Medical Officer. “We believe these initial data support our mission to develop UCART22 for patients with r/r B-ALL, who remain in dire need of additional treatment options, particularly those who have failed CD19 therapy.”
BALLI-01 investigating UCART22 product candidate in R/R B-ALL
BALLI-01, a phase 1 open-label dose-escalation study, is designed to assess the safety, maximum tolerated dose (MTD), and preliminary anti-leukemia activity of UCART22 in patients with r/r B-ALL. Additional endpoints include characterization of the expansion, trafficking, and persistence of UCART22 cells.
The poster presentation includes preliminary data from patients who received UCART22 at dose level 2 (DL2) and intermediate dose level 2 (DL2i) after lymphodepletion with FCA. Alemtuzumab was added to FC to deepen and sustain host lymphocyte suppression and thereby promote UCART22 expansion and persistence.
As of the clinical cut-off date of October 1, 2021, 12 patients received lymphodepletion; 11 were administered UCART22, of which 6 received UCART22 and FCA. Enrolled patients were predominantly male [n=7], young (median age 30 [range 20-61]), and most had recurrent genetic abnormalities including the CRFL2 (cytokine receptor-like factor 2) rearrangement. Additionally, enrolled patients were heavily pretreated with a median of 3 prior lines of therapy [range 2-6]. Three-fourths of patients had received prior blinatumomab, approximately half had received prior inotuzumab, and 3 had received prior CD19 autologous CAR-T therapy.
Safety Data
The FCA lymphodepletion regimen was well tolerated, and most treatment-emergent adverse events (TEAEs) were mild to moderate in intensity and manageable. Importantly, no patients experienced protocol-defined dose limiting toxicities (DLTs), immune effector cell-associated neurotoxicity syndrome (ICANS), nor UCART22-related severe (grade ≥3) TEAEs. Three patients experienced mild to moderate cytokine release syndrome (CRS), and one patient reported grade II GvHD with skin involvement only, that required hospitalization.
Activity Data
Encouraging anti-leukemic activity was observed in two (2/6) patients in the FCA cohorts. Both patients, one at DL2 and one at DL2i, achieved blast reductions to < 5% (0.4% and 0%, respectively) by day 28, accompanied by measurable UCART22 expansion and changes in relevant inflammatory cytokines.
Overall, UCART22 after FCA lymphodepletion regimen demonstrated promising signs of anti-leukemic activity at DL2 and DL2i, without unexpected or significant treatment-related toxicity. The addition of alemtuzumab to the FC lymphodepletion regimen was safe and promoted sustained host T-cell suppression and expansion of UCART22. These data are encouraging and support the further development of UCART22 for patients with r/r B- ALL. BALLI-01 is currently enrolling patients at dose level 3 with FCA lymphodepletion.
TALGlobin01; an autologous ex vivo TALEN®-edited hematopoietic stem and progenitor cell gene therapy for the treatment of Sickle Cell Disease
Initial pre-clinical data from Cellectis' .HEAL platform's product candidate, TALGlobin01 demonstrates that TALEN® is specific and efficient in correcting the mutated beta-globin gene, the underlying cause of sickle cell disease.
The data, presented in a poster, demonstrate that TALEN®-based engineering could be used to correct the beta-globin gene mutation in HbSS patient-derived hematopoietic stem and progenitor cells. The data show up to 70% of HBB allelic correction, with only 9% of HBB biallelic inactivation and a low level of TALEN® off-target cleavage. Genetic correction of HBB translates into high level of hemoglobin A expression (up to 47% HbA detected among total hemoglobin) and reversion of the sickling phenotype in differentiated red blood cells. Preclinical data show the capacity of TALGlobin01 edited cells to engraft in vivo using an NSG mouse model.
Collectively, the preclinical data demonstrate high efficiency and safety of TALEN® treatment in HbSS patient-derived hematopoietic stem and progenitor cells.
A copy of each poster presentation is available on Cellectis' website, linked here.
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