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

PHOENIX-ECP- Extracorporeal Photopheresis for Immune-related Colitis and/or Hepatitis in Advanced Melanoma With Inadequate Response to Steroid Exposure (clinicaltrials.gov) - P2 | N=112 | Not yet recruiting | Sponsor: Therakos LLC

Checkpoint inhibition • New P2 trial • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Melanoma • Oncology • Skin Cancer • Solid Tumor

Photopheresis in Early-stage Mycosis Fungoides (clinicaltrials.gov) - P2 | N=74 | Recruiting | Sponsor: Columbia University | Trial completion date: Jul 2027 ➔ Jul 2028 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

PHASE 2 STUDY OF EXTRACORPOREAL PHOTOPHERESIS WITH UVADEXTM PLUS STANDARD STEROID TREATMENT FOR HIGH-RISK ACUTE GRAFT-VERSUS-HOST DISEASE (EBMT 2026) - P2 | "The addition of ECP to standard corticosteroid first-line treatment in patients with GVHD that is high risk by biomarker score was feasible. Although the sample size was relatively small the excellent short-term patient outcomes such as Day 28 response rate translated into significantly improved long-term outcomes such as one-year NRM and survival when compared to a contemporary matched cohort as well as published NRM rates. A larger randomized controlled trial is warranted."

P2 data • Acute Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

EXTRACORPOREAL PHOTOPHERESIS FOR DELAYED NEUROTOXICITY SYNDROME AFTER BCMA CAR T-CELL THERAPY (EBMT 2026) - " We treated a previously neurologically unremarkable 44 yr old male patient with cilta-cel in 4th line for high-risk MM without acute complications despite of CRS °II that was readily controlled with tocilizumab...However, neither CART hyperexpansion nor the clinical course were durably affected by high-dose steroids, intravenous immunoglobulins, cyclophosphamide, and dasatinib. Repeated therapy with etoposide (150-200 mg/m²) led to a transient decline of CART numbers with consecutive symptomatic improvement but rapid relapse and subsequent refractoriness...Methoxysalen (Uvadex) was used as UV radiosensitizer...Already after 4 sessions the patient showed an improvement of symptoms and declining CART in pB despite discontinuation of ruxolitinib.The patient retained complete remission of MM evidenced by ongoing suppression of free light chains and absence of extramedullary disease on PET/CT scan... This preliminary data indicates that ECP might represent a..."

CAR T-Cell Therapy • IO biomarker • CNS Disorders • Dystonia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Parkinson's Disease • Transplant Rejection • CD69 • IL2RA

PHASE 2 STUDY OF EXTRACORPOREAL PHOTOPHERESIS WITH UVADEXTM PLUS STANDARD STEROID TREATMENT FOR HIGH-RISK ACUTE GRAFT-VERSUS-HOST DISEASE (EBMT 2026) - P2 | "The addition of ECP to standard corticosteroid first-line treatment in patients with GVHD that is high risk by biomarker score was feasible. Although the sample size was relatively small the excellent short-term patient outcomes such as Day 28 response rate translated into significantly improved long-term outcomes such as one-year NRM and survival when compared to a contemporary matched cohort as well as published NRM rates. A larger randomized controlled trial is warranted."

P2 data • Acute Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

EXTRACORPOREAL PHOTOPHERESIS FOR DELAYED NEUROTOXICITY SYNDROME AFTER BCMA CAR T-CELL THERAPY (EBMT 2026) - " We treated a previously neurologically unremarkable 44 yr old male patient with cilta-cel in 4th line for high-risk MM without acute complications despite of CRS °II that was readily controlled with tocilizumab...However, neither CART hyperexpansion nor the clinical course were durably affected by high-dose steroids, intravenous immunoglobulins, cyclophosphamide, and dasatinib. Repeated therapy with etoposide (150-200 mg/m²) led to a transient decline of CART numbers with consecutive symptomatic improvement but rapid relapse and subsequent refractoriness...Methoxysalen (Uvadex) was used as UV radiosensitizer...Already after 4 sessions the patient showed an improvement of symptoms and declining CART in pB despite discontinuation of ruxolitinib.The patient retained complete remission of MM evidenced by ongoing suppression of free light chains and absence of extramedullary disease on PET/CT scan... This preliminary data indicates that ECP might represent a..."

CAR T-Cell Therapy • IO biomarker • CNS Disorders • Dystonia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Parkinson's Disease • Transplant Rejection • CD69 • IL2RA

Extracorporeal Photopheresis in Pediatric and Adolescent Gvhd: Clinical Outcomes in Low-Weight HCT Recipients from a MENA Center (TCT-ASTCT-CIBMTR 2026) - " This retrospective observational study was conducted at King Hussein Cancer Center, Jordan (2017 to 2024), and included pediatric patients (<18 years) who received ECP and methoxsalen using the Therakos CellEx device, for acute and chronic SR-GvHD following HCT, identified through medical record review... The study included 42 patients: 21 with acute SR-GvHD (SR-aGvHD, 50%) and 21 with chronic SR- GvHD (SR-cGvHD, 50%). Median age was 9 years in SR-aGvHD, (52·4% male) and 14 years in SR-cGvHD (66·7% male). Most had malignant conditions (76·2% SR-aGvHD, 66·7% SR-cGvHD), predominantly leukemia, and received haploidentical HCT (57·1% SR-aGvHD, 38·1% SR-cGvHD)."

Clinical • Clinical data • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Pediatrics

Extracorporeal Photopheresis in Sezary Syndrome (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: Oleg E. Akilov, MD, PhD | N=15 ➔ 20 | Trial completion date: Dec 2026 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2028

Enrollment change • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

EPIC- Extracorporeal Photopheresis (ECP) for Immune-related Colitis (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Therakos LLC | N=30 ➔ 0 | Suspended ➔ Withdrawn

Checkpoint inhibition • Enrollment change • Trial withdrawal • Gastroenterology • Gastrointestinal Disorder • Immunology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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

Photopheresis in Early-stage Mycosis Fungoides (clinicaltrials.gov) - P2 | N=74 | Recruiting | Sponsor: Columbia University | Trial completion date: Jul 2026 ➔ Jul 2027

Trial completion date • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

IMMUNE MODULATION IN LEUKEMIA PATIENTS AFTER HEMATOPOETIC STEM CELL TRANSPLANTATION WITH ACUTE OR CHRONIC GRAFT VS HOST DISEASE (A/CGVHD): 12-WEEK EXTRACORPOREAL PHOTOPHERESIS (ECP) REDUCES INFLAMMATORY AND ENHANCES INHIBITORY IMMUNE REACTIVE CELLS (EHA 2025) - "ECP was conducted at four medical centers (Department of Hematology, University Hospital of Augsburg, Munich, Ulm, Bochum) using the Therakos CELLEX photopheresis system and treating 1500ml blood using Methoxsalen (Uvadex) as photosensitizing agent 5-8 times in 3 months... 1.Patients with (vs without) a/c GvHD are characterized with "overshooting'" special adaptive, innate, and checkpoint marker expressing immune cells.2. ECP treatment modulates the immune landscape in GvHD patients, promoting a shifting cell towards immune tolerance by increasing frequences of inhibitory marker (TIGIT and TIM-3) expressing T/NK cells, decreasing frequencies of stimulatory/inflammatory marker (2B4/ KLRG1) expressing T/NK cells and Cytotoxic-, Cytokine producing- or ADCC mediating NK-cells. 3."

Clinical • IO biomarker • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Leukemia • Oncology • Transplantation • B3GAT1 • HAVCR2 • KLRG1 • TIGIT

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

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