CTL123 / SignalRx - LARVOL DELTA

Treating Relapsed / Refractory (RR) AML with Biodegradable Anti-CD123 CAR Modified T Cells (ASH 2017) - P; "...Patients in cohort 1 were to receive up to three doses of CART123 cells (each dose being 4x106 cells/kg), and Cohort 2 patients were to receive up to six doses, with optional lymphodepleting chemotherapy (single dose of cyclophosphamide, 1g/m2) given 4 days prior to the first CART123 cell infusion...Severe CRS was treated with tocilizumab on 3 occasions in 2 patients, and all CRS episodes resolved within 1 day...In this pilot study, RNA CART123 cells had a biological effect as manifested by fever or CRS of varying severity in all patients. There was no clinically apparent vascular, neurological or hematological toxicity. However, no anti-tumor effect could be demonstrated."

CAR T-Cell Therapy • Acute Myelogenous Leukemia • Biosimilar

[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

CD123 Redirected T Cells for AML in Pediatric Subjects (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: University of Pennsylvania; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

AML123: 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: Nov 2021 ➔ Oct 2022; Trial primary completion date: Nov 2021 ➔ Oct 2022

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

CD123 Redirected T Cells for AML in Pediatric Subjects (clinicaltrials.gov) - P1; N=12; Not yet recruiting; Sponsor: University of Pennsylvania

Clinical • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Lentivirally Redirected CD123 Autologous T Cells in AML (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: University of Pennsylvania; Recruiting ➔ Active, not recruiting

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

Prediction of immunotherapy outcome by multimodal assessment of minimal residual disease and persistence of allogeneic anti-CD123 CAR T-cells (UCART123) in pre-clinical models of acute myeloid leukemia (AACR 2018) - "Importantly, when mutated NPM1 levels became elevated with simultaneous loss of UCART123, relapse was evident by MFC in PB in subsequent time-points (2 out 20 mice, all at 1x106 dose, ~180 days) re-infusion of UCART123 cells resulted in effective elimination of AML.Taken together, we have demonstrated that simultaneous monitoring of disease and UCART123 cells provides valuable insight into the kinetics and effectiveness of UCART123 cells. Currently, we have implemented the ddPCR assay in the phase I clinical trial of UCART123 in AML allowing to simultaneously detect UCART123 cells and blasts in peripheral blood of NPM1 mutant AML patients."

CAR T-Cell Therapy • IO Biomarker • Residual disease • Acute Myelogenous Leukemia

[VIRTUAL] ASH Poster Walk on Clinical Trials in Progress: Live Q&A (ASH 2020) - "The following abstracts will be featured during this session: Adore: A Randomized, Open-Label, Phase 1/2 Open-Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Patients with Myelofibrosis, Andrew Perkins First-in-Human Phase 1/2 Clinical Trial of SIG-001, an Innovative Shielded Cell Therapy Platform, for Hemophilia Α, Pasi An Adaptive, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE), Kenneth Wood Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study, Nichola Coper Phase 1 and Dose Expansion Study of APR-246 in Combination with Ibrutinib or Venetoclax-Based Therapy in Subjects with TP53-Mutant Relapsed and/or Refractory Non-Hodgkin Lymphomas (NHL) Including Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), Meghan..."

Clinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Hemophilia • Leukemia • Lymphoma • Mantle Cell Lymphoma • Myelofibrosis • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Sickle Cell Disease • CD123 • TP53

"Many thanks for the follow-up. Did you hear something about Cellectis UCART123 ?" (@SchmittJeanPhi1)

"Upcoming Data: $AMGN Ph1/2 AMG-592 in GvHD $CLLS Ph1 UCART123 in AML $SAGE Ph2a PARADIGM in PD $BNTX Ph1 BNT111 in melanoma $RGNX Ph1/2 RGX-121 in MPS II (Cohort I & II) missing the ones from #ASH20" (@BursatilBiotech)

P2a data • Graft versus Host Disease • Immunology • Melanoma • Oncology • Solid Tumor

Ruxolitinib Prevents Cytokine Release Syndrome after CART Cell Therapy without Impairing the Anti-Tumor Effect in a Xenograft Model (ASH 2016) - "NSG-S mice bearing primary AML were treated with CART123 and randomized to receive different doses of ruxolitinib (30, 60, or 90 mg/kg) or vehicle by oral gavage twice a day. While the use of the anti-IL6 receptor antibody tocilizumab with or without steroids can usually reverse this syndrome, there is concern that the early introduction of immunosuppressive medications could impair the anti-tumor activity and therefore most investigators currently reserve tocilizumab as therapy for severe (grade 3-4) CRS. These findings provide a useful platform for the future study of CRS prevention and treatment modalities. These experiments indicate that ruxolitinib could also be combined with CART cell therapy for the prevention of CRS in patients identified to be at high risk for the development of CRS."

Acute Myelogenous Leukemia • Biosimilar • Fibrosis • Gene Therapies • Hematological Malignancies • Immunology • Leukemia • Obesity • Oncology

"No, not really. #UCART19 https://t.co/pGNxWVxYKJ is further along than #UCART123 and 1st pt was treated over 1y ago. $CLLS $ALCLS" (@portefeuillefun)

Biosimilar

AML123: Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=59; Recruiting; Sponsor: Cellectis S.A.; Trial completion date: Jun 2021 ➔ Nov 2021; Trial primary completion date: Jun 2021 ➔ Nov 2021

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

ABC123: Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN (clinicaltrials.gov) - P1; N=72; Recruiting; Sponsor: Cellectis S.A.

New P1 trial • Biosimilar • Oncology

AML123: Study Evaluating Safety and Efficacy of UCART123 in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=156; Recruiting; Sponsor: Cellectis S.A.; Suspended ➔ Recruiting

Clinical • Enrollment open • Acute Myelogenous Leukemia • Biosimilar • Graft versus Host Disease

"Goooooooood morning, Biotwitter! Hope u had a good night sleep. ICYMI, $CLLS is trading +9,2% PM after FDA lifted hold in UCART123 trial" (@BursatilBiotech)

Biosimilar

"BREAKING $CLLS UCART123 hold removed by FDA h/t @shaneblackmon" (@BursatilBiotech)

Biosimilar

"$CLLS started enrolling A Ph 1Study to Evaluate the Safety & Clinical Activity of UCART123 in Patients With BPDCN https://t.co/zzzhXlUVrw" (@DrPaulyDeSantis)

Clinical • Biosimilar

Efficacy Proof of Concept for Allogeneic CD123 Targeting CAR T-Cells Against Primary Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Efficient Control of Tumor Progression in PDX Model and Potential Loss of CD123 Expression in Relapsed Disease (ASH 2019) - "UCART123v1 is an allogeneic “off the shelf” product composed of genetically modified T-cells expressing an anti-CD123 CAR and a RQR8 depletion ligand, which confers susceptibility to rituximab. However, CD123 loss was observed in one PDX model harboring a TP53 deletion. These results provide preclinical proof-of-principle that UCART123v1 cells have potent anti-BPDCN activity, and indicate potential mechanisms leading to antigen loss and disease relapse."

CAR T-Cell Therapy • Clinical • IO Biomarker • CD123 • IFNG • IL13 • IL2 • IL5 • IL6 • NCAM1 • TP53

Phase I Study of UCART123 in Patient With Adverse Genetic Risk Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: Cellectis S.A.; N=18 ➔ 0; Trial completion date: Mar 2023 ➔ Dec 2019; Recruiting ➔ Withdrawn; Trial primary completion date: Mar 2023 ➔ Dec 2019

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal

AML123: Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=59; Recruiting; Sponsor: Cellectis S.A.; N=162 ➔ 59; Trial completion date: Dec 2021 ➔ Jun 2021

Clinical • Enrollment change • Trial completion date

Phase I Dose-Escalation Study of UCART123 in Patient With Adverse Genetic Risk Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Cellectis S.A.

Clinical • New P1 trial

IFN-γ and TNF-α aggravate endothelial damage caused by CD123-targeted CAR T cell. (PubMed, Onco Targets Ther) - " In summary, this study identified that the expression of CD123 on endothelial cells could be upregulated when co-cultured with CART123. Furthermore, IFN-γ and TNF-α could aggravate endothelial damage caused by CART123 in vitro."

CAR T-Cell Therapy • Journal