UCART123 / UT MD Anderson Cancer Center, Cellectis - LARVOL DELTA

Understanding the proteomics and serum factors influencing expansion of re-dosed allogenic UCART123 cells in Acute Myeloid Leukemia (AML) patients [WITHDRAWN] (ESMO 2025) - No abstract available

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

AMELI-01: Study Evaluating Safety and Efficacy of UCART123v1.2 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: Cellectis S.A. | Recruiting ➔ Active, not recruiting | N=65 ➔ 29 | Trial completion date: Dec 2024 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

Cellectis Provides Business Updates and Financial Results for Third Quarter 2024 (GlobeNewswire) - "Cellectis continues to focus on the enrollment of patients in the BALLI-01 study, evaluating UCART22 in relapsed or refractory B-cell acute lymphoblastic leukemia. We expect to present the Phase 1 dataset and late-stage development strategy in 2025; Cellectis continues to focus on the enrollment of patients in the NATHALI-01 study, evaluating UCART20x22 in relapsed or refractory B-cell non-Hodgkin lymphoma. We expect to present the Phase 1 dataset and late-stage development strategy in 2025; The Company decided to focus its current development efforts on the BALLI-01 and NATHALI-01 studies and therefore to deprioritize the development of UCART123, currently evaluated in relapsed or refractory acute myeloid leukemia."

Pipeline update • Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

AMELI-01: Study Evaluating Safety and Efficacy of UCART123v1.2 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: Cellectis S.A. | Trial completion date: Mar 2023 ➔ Dec 2024 | Trial primary completion date: Mar 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

Cellectis announces the drawdown of the second tranche of €15 million under the credit facility agreement entered with the European Investment Bank (EIB) (GlobeNewswire) - "The Company plans to use the proceeds of Tranche B towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, and UCART123."

Financing • Hematological Malignancies • Oncology

Cellectis Presents Clinical Data on AMELI-01 and Preclinical Data on Multiplex Engineering for Superior Generation of CAR T-cells at ASGCT 2023 (GlobeNewswire) - P1 | N=65 | AMELI-01 (NCT03190278) | Sponsor: Cellectis S.A. | "Cellectis...presents clinical data on its Phase 1 AMELI-01 clinical trial (evaluating UCART123) that were unveiled in an oral presentation at the 64th American Society of Hematology (ASH) annual meeting, as well as preclinical data on multiplex engineering for superior generation of CAR T-cells, at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting....Two out of eight patients (25%) at DL2 in the FCA arm achieved meaningful response: A patient who failed five prior lines of therapy experienced a durable minimal residual disease (MRD) negative complete response (CR) with full count recovery at Day 56 that continues beyond one year. A patient with stable disease achieved greater than 90% bone marrow blast reduction (60% to 5%) at Day 28."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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 (AML) (ASH 2022) - P1 | "AMELI-01 (NCT04106076) is a phase 1, open-label, dose-escalation trial evaluating the safety, tolerability, expansion, and persistence of UCART123v1.2 given at escalating dose levels after LD with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients (pts) with R/R CD123+ AML...Pts must have received ≥2 cycles of chemotherapy (one with standard dose cytarabine), ≥ 1 cycle of a high/intermediate dose cytarabine containing regimen, ≥ 2 cycles of an HMA combination regimen, or prior allogeneic HSCT... Adding alemtuzumab to the FC regimen was associated with improved LD and significantly higher UCART123v1.2 cell expansion and persistence, which correlated with improved activity and safety, including one pt in the DL2 FCA arm who achieved a durable MRD-negative CR. Overall, these data support the safety and activity of UCART123v1.2 after FCA LD in pts with CD123+ R/R AML."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Leukemia • Oncology • CD123 • IFNG • IL10 • IL15 • IL2 • IL6 • TNFA

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 (AML) (ASGCT 2023) - P1 | "AMELI-01 (NCT04106076) is a phase 1 trial evaluating the safety, tolerability, expansion, and persistence of UCART123 given at escalating dose levels after LD with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients (pts) with R/R AML.Key eligibility criteria include pts 18-65 yrs, adequate organ function, ECOG PS ≤ 1, and blasts positive for CD123 by flow cytometry. Pts must have received ≥2 cycles of chemotherapy, ≥ 1 cycle of a high/intermediate dose cytarabine containing regimen, ≥ 2 cycles of an HMA combination regimen, or prior allogeneic HSCT...Overall, these data support the safety and activity of UCART123 after FCA LD in pts with CD123+ R/R AML. Based on observed UCART123 expansion patterns and cytokine profiles, the study was amended to include a UCART123 2-dose regimen with FCA LD, and enrollment is ongoing into this arm​."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Leukemia • Oncology • CD123

Cellectis Announces Oral Presentation on AMELI-01 and Poster Presentation on Multiplex Engineering for Superior Generation of CAR T-cells at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting (GlobeNewswire) - "Cellectis...announced that it will present clinical data on its Phase 1 AMELI-01 clinical trial (evaluating UCART123) that were presented in an oral presentation at the 64th American Society of Hematology (ASH) annual meeting, as well as preclinical data on multiplex engineering for superior generation of CAR T-cells, at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting....The presentation includes preliminary clinical data from the Phase 1, open-label, dose-escalation trial, AMELI-01, in patients with r/r AML administered UCART123 following lymphodepletion (LD) with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA). The data show that adding alemtuzumab to the FC regimen was associated with improved LD and significantly higher UCART123 cell expansion, which correlated with improved activity."

P1 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

"on another note, I saw $CLLS $ALCLS the data of UCART123 in their abstract for #ASGCT23 and was surprised to see a 2nd death (Gr5 CRS at DL2i) in FCA arm, as itwas not in the #ASH22 abstract (July'22 cutoff), but was only unveiled in the final prez in december." (@BertrandBio)

Cellectis Implements CLLS52 for the First Time in the Clinic with Sanofi’s Alemtuzumab (GlobeNewswire) - "Cellectis...announced it has implemented the use of alemtuzumab as a Cellectis Investigational Medicinal Product (IMP), coded as CLLS52, as part of the lymphodepletion regimen for UCART22 in the BALLI-01 clinical trial in relapsed/refractory B-cell ALL, for UCART123 in the AMELI-01 clinical trial in relapsed/refractory AML, and for UCART20x22 in the NatHaLi-01 clinical trial in relapsed/refractory B-cell NHL....Under the agreements, Sanofi is supplying alemtuzumab to support Cellectis’ clinical trials and the parties agreed to enter into discussions to execute a commercial supply of alemtuzumab under pre-agreed financial conditions."

Clinical protocol • Commercial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellectis enters into warrant agreement with the European Investment Bank related to credit facility agreement and announces the drawdown of the first tranche of €20 million (GlobeNewswire) - "The Company plans to use the proceeds of Tranche A towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, UCART123 and UCARTCS1."

Commercial • Oncology

[VIRTUAL] Ameli-01: Phase I, Open Label Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of UCART123 (allogeneic engineered T-cells expressing anti-CD123 chimeric antigen receptor), Administered in Patients with Relapsed/Refractory Acute Myeloid Leukemia (ASH 2020) - P1 | "Also, the CAR is co-expressed with a suicide mechanism (RQR8), which can be activated by using rituximab...Pts receive a lymphodepletion (LD) regimen of either fludarabine and cyclophosphamide (FC) or fludarabine, cyclophosphamide plus alemtuzumab (FCA) starting on Day -5, followed by an infusion of UCART123 at one of 5 dose levels on Day 0...DL1 has cleared safety without DLT, and enrollment at the next dose levels are proceeding. ClinicalTrials.gov Identifier: NCT03190278"

Clinical • Acute Myelogenous Leukemia • CNS Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD123 • CD52

Pre-Clinical Studies of Allogeneic Anti-CD123 CAR T-Cells for the Therapy of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) (ASH 2017) - P1; "...UCART123 product candidate is based on genetically modified allogeneic T-cells (derived from healthy donors, so-called “off the shelf”) containing an anti-CD123 CAR (CD123 scFv-41BB-CD3z) and a RQR8 depletion ligand that confers susceptibility to rituximab...These results demonstrate pre-clinical proof-of principle of high anti-BPDCN activity of allogeneic UCART123 cells. A phase I trial of UCART123 in BPDCN is opened for enrollment (NCT03203369)."

CAR T-Cell Therapy • Biosimilar • Graft versus Host Disease • Leukemia

Preclinical efficacy of allogeneic anti-CD123 CAR T-cells for the therapy of blastic plasmacytoid dendritic cell neoplasm (BPDCN) (AACR 2018) - P1; "Nearly 100% of patients with BPDCN overexpress CD123, and targeting CD123 emerged as an attractive therapeutic target given its differential expression on BPDCN cell surface.UCART123 product (Cellectis) uses genetically modified allogeneic T-cells (derived from healthy donors, so-called off the shelf) containing an anti-CD123 CAR and a RQR8 depletion ligand that confers susceptibility to rituximab. However, loss of CD123 through diverse genetic mechanisms could lead to escape from UCART123 therapy and cause relapses. A phase I trial of UCART123 in BPDCN is opened for enrollment."

CAR T-Cell Therapy • IO Biomarker • Preclinical • Leukemia

Cellectis Announces Closing of Global Offering and Exercise of Underwriters’ Option to Purchase Additional Shares (GlobeNewswire) - "The Company plans to use (i) approximately $17.0 million (€15.6 million) of the net proceeds of the Global Offering to fund the continued clinical development of UCART 123, UCART22, UCART20x22, and UCARTCS1, and (ii) any remainder for working capital and other general corporate purposes."

Commercial • Oncology

Cellectis Announces Pricing of Follow-On Offering (Cellectis Press Release) - "Cellectis plans to use (i) approximately $17.0 million (€15.6 million) of the net proceeds of the Global Offering to fund the continued clinical development of UCART 123, UCART22, UCART20x22, and UCARTCS1, and (ii) any remainder for working capital and other general corporate purposes."

Commercial • Oncology

Cellectis secures a €40 million credit facility from the European Investment Bank to support its Research, Development and Innovation activities (GlobeNewswire) - "The credit facility will enable Cellectis to support the development of its UCART product candidates pipeline. The credit facility consists of three tranches of €20 million, €15 million, and €5 million respectively, each redeemable in fine in 6 years. The credit facility is part of the European Investment Bank’s strategy to support biotech companies developing a high-level of expertise in various therapeutic areas with significant unmet medical need. Cellectis...announced that it has entered into a €40 million credit facility agreement with the European Investment Bank ('EIB') (the 'Finance Contract'). The Company plans to use the facility toward the development of its pipeline in the field of allogeneic CAR T-cell product candidates, UCART22, UCART20x22, UCART123 and UCARTCS1."

Financing • Oncology

Cellectis Announces Positive Preliminary Clinical Data for UCART22 in ALL and UCART123 in AML (GlobeNewswire) - P1 | N=65 | AMELI-01 (NCT03190278) | Sponsor: Cellectis S.A | "Evidence of UCART123 anti-tumor activity was observed in four patients out of fifteen at DL2 or above with best overall responses in the FCA arm. Two out of eight patients (25%) at DL2 with FCA arm achieved meaningful response: A patient who failed five prior lines of therapy experienced a durable minimal residual disease (MRD) negative complete response (CR) with full count recovery at Day 56 that continues beyond one year. A patient with stable disease achieved greater than 90% bone marrow blast reduction (60% to 5%) at Day 28...Overall, these preliminary data support the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Cellectis Provides Business Update and Reports Financial Results for Third Quarter and First Nine Months 2022 (GlobeNewswire) - "AMELI-01 (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML):...Cellectis announced the release of an abstract, which was accepted for oral presentation at the American Society of Hematology (ASH) 2022 Annual Meeting. The abstract includes preliminary clinical data from the Phase I, open-label, dose-escalation AMELI-01 study in patients with r/r AML, showing that adding alemtuzumab to the fludarabine and cyclophosphamide lymphodepletion regimen was associated with improved lymphodepletion and significantly higher UCART123 cell expansion, which correlated with improved activity. These encouraging data support the continued enrollment into the study. Oral presentation will occur on December 12 at 5:00PM..."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

CD123-directed allogeneic chimeric-antigen receptor T-cell therapy (CAR-T) in blastic plasmacytoid dendritic cell neoplasm (BPDCN): Clinicopathological insights. (PubMed, Leuk Res) - "No definitive cause of death was determined, but we hypothesized that the patient may have succumbed to CAR-T-mediated cardiopulmonary toxicity. UCART123 cells displayed low overall distribution, with predominance in immune organs and tissues. Mechanism of CRS development is still poorly understood in patients receiving CAR-T therapy. Future directions in the field developing CD123-targeted agents in BPDCN are discussed."

CAR T-Cell Therapy • IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Inflammation • Oncology • CD123

AMELI-01: Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: Cellectis S.A. | Trial completion date: Oct 2022 ➔ Mar 2023 | Trial primary completion date: Oct 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Targeting CD123 in blastic plasmacytoid dendritic cell neoplasm using allogeneic anti-CD123 CAR T cells. (PubMed, Nat Commun) - "One potential challenge of CD123 targeting therapies is the loss of CD123 antigen through diverse genetic mechanisms, an event observed in one of three BPDCN PDX studied. In summary, these results provide a preclinical proof-of-principle that allogeneic UCART123 cells have potent anti-BPDCN activity."

CAR T-Cell Therapy • Journal • Hematological Disorders • Hematological Malignancies • Oncology • CD123 • IFNG

Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia. (PubMed, Nat Commun) - "As safety feature, cells express RQR8 to allow elimination with Rituximab. Furthermore, UCART123 preferentially target AML over normal cells with modest toxicity to normal hematopoietic stem/progenitor cells. Together these results suggest that UCART123 represents an off-the shelf therapeutic approach for AML."

CAR T-Cell Therapy • Journal • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • CD123

Cellectis Publishes Two Articles in Nature Communications Providing Strong Preclinical Validation of UCART123 to Treat AML and BPDCN (GlobeNewswire) - "Cellectis...announced the publication of two manuscripts in Nature Communications on its product candidate UCART123, currently being evaluated in the Phase 1 dose-escalation trial AMELI-01 in patients with relapsed or refractory acute myeloid leukemia (r/r AML)....UCART123 targets AML cells in vivo and results in improved overall survival in patient-derived xenografts (PDX) models....UCART123 cells result in specific killing of BPDCN primary samples in vitro and in xenograft (PDX) experiments in vivo."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology