CEP-37248 / Teva - 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

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

[VIRTUAL] Recombinant Soluble Thrombomodulin in Prolonged Porcine Cardiac Arrest (AHA 2021) - "Our porcine CA model provides an excellent platform for evaluating antithrombotic interventions. Plasma testing after prolonged CA/CPR suggests consumptive coagulopathy, although TEG indicates a persistent hypercoagulable state. ART-123 given before no-flow or just after CPR demonstrates antithrombotic effects, although the specific modes of action depending on the timing of administration."

Preclinical • Cardiovascular • Hematological Disorders • Thrombosis

Efficacy and safety of a recombinant soluble human thrombomodulin (ART-123) in preventing oxaliplatin induced peripheral neuropathy (OIPN): results of a placebo-controlled, randomized, double-blind phase 2 study (ESMO 2018) - P2; "ART-123 showed promising efficacy in delaying and reducing OIPN without serious safety concerns."

Clinical • P2 data • Colorectal Cancer

Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET. (PubMed, Ann Intensive Care) - "Results from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART-123, a fact that should be confirmed in future studies with more restrictive inclusion criteria."

Clinical • Journal • Retrospective data • Hematological Disorders • Infectious Disease • Septic Shock

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

A Trial Measuring ART-123 Ability to Prevent Sensory Neuropathy in Unresectable mCRC Subjects w/Oxaliplatin-based Chemo (clinicaltrials.gov) - P2b; N=300; Not yet recruiting; Sponsor: Asahi Kasei Pharma America Corporation; Initiation date: Nov 2020 ➔ Jul 2021

Clinical • Trial initiation date • Colorectal Adenocarcinoma • Colorectal Cancer • Pain

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

A placebo-controlled, double-blind, randomized study of recombinant thrombomodulin (ART-123) to prevent oxaliplatin-induced peripheral neuropathy. (PubMed, Cancer Chemother Pharmacol) - P2 | "ART-123 showed a potential preventive effect against OIPN with good tolerability. A larger study with 1-day ART is warranted. NCT02792842, registration date: June 8, 2016."

Clinical • Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Pain • Solid Tumor

A Trial Measuring ART-123 Ability to Prevent Sensory Neuropathy in Unresectable mCRC Subjects w/Oxaliplatin-based Chemo (clinicaltrials.gov) - P2b; N=300; Not yet recruiting; Sponsor: Asahi Kasei Pharma America Corporation

Clinical • New P2b trial • Colorectal Adenocarcinoma • Colorectal Cancer • Pain

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

Beneficial effect modification on survival outcome of sepsis between ART-123 and polymyxin B‑immobilised haemoperfusion: a nationwide Japanese registry study. (PubMed, Ann Intensive Care) - "The main effect of the administration of ART-123 may be beneficial for survival outcome in patients with sepsis. In addition, a significant beneficial effect modification on survival outcome was observed between the administration of ART-123 and PMX-HP treatment."

Journal • Infectious Disease • Septic Shock

"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 and safety of recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy: a systematic review and meta-analysis. (PubMed, J Thromb Haemost) - "In patients with sepsis, SAC is associated with higher 28-day mortality. The administration of rhsTM reduced 28-day mortality in patients with SAC, but not in those without SAC."

Journal • Retrospective data • Review

Plasma from Patients Undergoing Liver Transplantation Is Resistant to Anticoagulant Activity of Soluble Thrombomodulin (ART-123). (PubMed, Liver Transpl) - "This study suggests that ART-123 is unlikely to provoke bleeding in patients undergoing liver transplantation as proposed clinical dosages have a virtually absent anticoagulant effect in these patients. Clinical studies are required to confirm safety of ART-123 and efficacy on alleviating I/R injury during liver transplantation."

Clinical • Journal