Uvadex/Therakos Photopheresis (methoxsalen/ECP) / Mallinckrodt - LARVOL DELTA

Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's | Trial primary completion date: Dec 2026 ➔ Jul 2026

Trial primary completion date • Immunology • Scleroderma • Systemic Sclerosis

EPIC- Extracorporeal Photopheresis (ECP) for Immune-related Colitis (clinicaltrials.gov) - P2 | N=30 | Suspended | Sponsor: Therakos LLC | Initiation date: Jan 2025 ➔ Dec 2025 | Not yet recruiting ➔ Suspended

Checkpoint inhibition • Trial initiation date • Trial suspension • Gastroenterology • Gastrointestinal Disorder • Immunology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Extracorporeal Photopheresis, a Therapeutic Alternative for T cell-mediated Rejection in Renal Transplantation. (PubMed, Transplant Proc) - "The THERAKOS CELLEX system was used for patient 1, and the OPTIA system was used for patient 2, both with methoxsalen. ECP is highlighted as a viable option for TCMR in renal transplantation when conventional treatments are unsuitable."

Journal • Immunology • Nephrology • Transplantation

EPIC- Extracorporeal Photopheresis (ECP) for Immune-related Colitis (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Therakos, LLC, a Mallinckrodt Company

Checkpoint inhibition • New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Cancelled: Minimal Effect of Eltrombopag Related Plasma Discoloration on Extracorporeal Photopheresis Efficiency (AABB 2024) - "Background/Case Studies: Extracorporeal photopheresis (ECP) uses ultraviolet radiation of 320 to 400 nm wavelength (UVA) to covalently bind methoxsalen to the DNA of white blood cells collected for processing and eventual return to a patient's circulation. Instrument-calculated irradiation times vary according to the volume and hematocrit of the treatment bag contents, and the age of the UVA source. Our findings suggest that the serum chromogens associated with ELT and its metabolites should not interfere with substrate penetration by the high-energy UVA photons delivered during ECP nor the resultant immunomodulatory actions. Indeed, with no adjustments to the instrument calculated irradiation time our patient responded well, and no longer required oxygen supplementation well before his course of ECP was concluded."

Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

EXTRACORPORAL PHOTOPHERESIS (ECP) – IMPACT ON EX-VIVO APOPTOSIS AND PROLIFERATION (EHA 2024) - "After leukapheresis the MNC undergo the incubation with 8-Methoxy Psoralen (8-MOP) followedby exposure to ultraviolet (UV) irradiation, which induces covalent bonds of 8-MOP with DNA, proteins, andcell membranes leading to a selective apoptosis and other forms of (programmed) cell death...5 ml Uvadex (340 ng/ml) in a Macogenic Set(Macopharma) the cells were exposed to UVA irradiation (2 J/cm2) using a MacoGenic G2 and then isolatedusing Ficoll/PaqueTM density gradient (PANBiotech) centrifugation and subsequently washed and cultured asdescribed above... In our pilot set of experiments, ex-vivo ECP treatment induced apoptosis and inhibited T-lymphocyteproliferation in both LC and PB of healthy individuals confirming the mode of action. These novel findingshighlight the high potential for application of ECP in other indications, such as complications after modernimmune therapies."

Preclinical • Cutaneous T-cell Lymphoma • Graft versus Host Disease • Immunology • Scleroderma • Sezary Syndrome • Solid Organ Transplantation • Systemic Sclerosis • Transplantation • ANXA5

Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK). (PubMed, BMJ Open Respir Res) - "E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit...Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings. EudraCT number 2022-002659-20; ISRCTN 10615985."

Clinical • Clinical protocol • Journal • Respiratory Diseases • Transplantation

Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Lawson Health Research Institute | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

IRON DEFICIENCY IN PATIENTS UNDERGOING EXTRACORPOREAL PHOTOPHERESIS (ECP) (EBMT 2024) - "Secondly, a photosensitizing drug called 8- methoxypsoralen (UVADEXTM) is injected to the collected mononuclear cells. Iron deficiency can occur with ECP treatment. Therefore, this risk factor should be monitored. Moosavi et al."

Clinical • Acute Graft versus Host Disease • Anemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

COPAVEHDI: Steroids Versus ECP and Steroids as First-line Treatment of Grade II Acute GVHD (clinicaltrials.gov) - P2 | N=42 | Not yet recruiting | Sponsor: Central Hospital, Nancy, France

Trial completion date • Trial initiation date • Trial primary completion date • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

A Retrospective Study of Extracorporeal Photopheresis (ECP) in Treatment of Cutaneous T-Cell Lymphoma (CTCL) Evaluating Global, Skin and Blood Responses (ASH 2023) - "Besides, ECP techniques including the administration of methoxsalen have changed...At 3 months 28 pts were on ECP alone and 11 were on concurrent systemic therapy including: Interferon (4), retinoid acid (3), romidepsin (3), and pralatrexate (1). At 6 months 20 pts were on ECP alone and 19 were on concurrent systemic therapy including interferon (7), retinoid acid (4), Romidepsin (4), and 1 patient for each of mogamulizumab, vorinostat, methotrexate and interferon + retinoid acid... A total of 39 pts were included. 23 (59%) were male; 31 (82%) were Caucasian, 4 (11%) were African-American. When starting ECP, 33 (89%) had stage III/IV disease; 30 (77%) had erythroderma; 10.3%, 33.3% and 56.4% of pts had B0, B1 and B2 disease, respectively (Table 1)."

Retrospective data • Cutaneous T-cell Lymphoma • Dermatology • Dermatopathology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Pruritus • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

COPAVEHDI: Steroids Versus ECP and Steroids as First-line Treatment of Grade II Acute GVHD (clinicaltrials.gov) - P2 | N=42 | Not yet recruiting | Sponsor: Central Hospital, Nancy, France

New P2 trial • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

Mallinckrodt Announces Reimbursement Approval in Japan for the CELLEX Extracorporeal Photopheresis (ECP) System for the Treatment of Chronic Graft Versus Host Disease (cGvHD) (Mallinckrodt Press Release) - "Mallinckrodt...today announced that Japan's National Health Insurance (NHI) system has approved reimbursement for the CELLEX® extracorporeal photopheresis (ECP) system for the treatment of steroid-resistant or -intolerant chronic graft versus host disease (cGvHD). 'We are very pleased that we have received approval for reimbursement in Japan for the CELLEX ECP System. As a pharmaceutical company focused on improving outcomes for under-served patients with severe and critical conditions, we strive to develop treatment options that address unmet medical needs,'..."

Reimbursement • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Efficacy of Methoxsalen Sterile Solution in Conjunction with the Therakos® Cellex® Photopheresis System in Pediatric Patients with Steroid-Refractory Acute GvHD: Interim Analysis (ASH 2019) - P3; "After 4 weeks of ECP using methoxsalen sterile solution and the Therakos Cellex Photopheresis System, the OR rate was 61%. These encouraging data warrant further investigation in pediatric/young adult patients with SR-aGvHD."

Clinical

Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Lawson Health Research Institute | Trial completion date: Jun 2024 ➔ Jun 2026 | Trial primary completion date: Sep 2023 ➔ Dec 2025

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • CRP

Photopheresis in Early-stage Mycosis Fungoides (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Columbia University

New P2 trial • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CORIN

Extracorporeal Photopheresis in Sezary Syndrome (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Oleg E. Akilov, MD, PhD | Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous T-cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

Extracorporeal Photopheresis in Sezary Syndrome (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Oleg E. Akilov, MD, PhD | Initiation date: Jan 2022 ➔ Jun 2022

Trial initiation date • Cutaneous T-cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Lawson Health Research Institute | Initiation date: Mar 2022 ➔ Sep 2022 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Trial initiation date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • CRP

[VIRTUAL] EXTRACORPOREAL PHOTOPHERESIS - FIRST PROCEDURE PERFORMED IN THE APHERESIS SERVICE OF THE BLOOD BANK OF HOSPITAL SANTA MARCELINA - CASE REPORT (HEMO 2021) - "Introduction Extracorporeal Photopheresis (FEC) is based on the manipulation of T lymphocytes with photosensitizing substances that, when exposed to ultraviolet (UV) light, undergo apoptosis and, when returned to the patient, trigger a series of immunomodulatory effects. Few services have the equipment and we report the first experience of the Apheresis sector at Hospital Santa Marcelina in the use of FEC.Case report A 55-year-old male patient with Cutaneous T-Cell Lymphoma since 2017, previously treated with corticoids and CHOEP, no response ; from Dec/2017 to Jan/2018 he took methotrexate, partial response; changed to GVD from Feb/2018 to May/2018 and again partial response. New treatment with Cladribine in Jun/2018 with complete response. Oct/2018 again presents erythema and biopsy showed relapse. Interferon was prescribed and sent in Aug/2019 to our Bone Marrow Transplant Service (BMT), disease activity was found and FEC was indicated..."

Clinical • Bone Marrow Transplantation • Bullous Pemphigoid • Cutaneous T-cell Lymphoma • Dermatology • Dermatopathology • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • Transplantation

ECP: Extracorporeal Photopheresis in Sezary Syndrome (clinicaltrials.gov) - P2; N=15; Not yet recruiting; Sponsor: Oleg E. Akilov, MD, PhD

Clinical • New P2 trial • Cutaneous T-cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2; N=15; Not yet recruiting; Sponsor: Lawson Health Research Institute; Trial completion date: Mar 2024 ➔ Jun 2024; Initiation date: Sep 2021 ➔ Mar 2022; Trial primary completion date: Sep 2023 ➔ Mar 2023

Trial completion date • Trial initiation date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • CRP

Mallinckrodt and Terumo Blood and Cell Technologies Announce Positive Recommendations in Australia for Public Funding of UVADEX (methoxsalen) for ECP Administration with the THERAKOS CELLEX Photopheresis System for Chronic Graft Versus Host Disease (cGvHD) in Adults (Mallinckrodt Press Release) - "Mallinckrodt...announced today that both the Medical Services Advisory Committee (MSAC) and the Pharmaceutical Benefits Advisory Committee (PBAC) recently recommended that UVADEX® (methoxsalen) for extracorporeal administration with the THERAKOS® CELLEX® Photopheresis System be listed on the Pharmaceutical Benefits Scheme (PBS) in Australia for the treatment of steroid dependent, intolerant or resistant chronic graft versus host disease (cGvHD) in adults....'The positive reimbursement recommendation is an important step to help ensure that UVADEX with the THERAKOS ECP system is broadly available to patients who may benefit from this treatment.'"

Reimbursement • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

PROMPT: Study of Photopheresis in the Treatment of Erythrodermic MF and SS (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: European Organisation for Research and Treatment of Cancer - EORTC; N=46 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2; N=15; Not yet recruiting; Sponsor: Lawson Health Research Institute

New P2 trial • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • CRP