ORBCEL-C (human umbilical cord derived CD362 enriched MSCs) / Orbsen - LARVOL DELTA

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST) (clinicaltrials.gov) - P1/2 | N=129 | Active, not recruiting | Sponsor: Belfast Health and Social Care Trust | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Sep 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST) (clinicaltrials.gov) - P1/2 | N=129 | Active, not recruiting | Sponsor: Belfast Health and Social Care Trust | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Mar 2024 ➔ Sep 2024

Enrollment closed • Stroma • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Merlin: Selected Mesenchymal Stromal Cells to Reduce Inflammation in Patients With PSC and AIH (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: University of Birmingham | Recruiting ➔ Active, not recruiting | Phase classification: P2a ➔ P1/2 | Trial completion date: Dec 2023 ➔ Oct 2025 | Trial primary completion date: Mar 2023 ➔ Nov 2023

Enrollment closed • Phase classification • Stroma • Trial completion date • Trial primary completion date • Autoimmune Hepatitis • Hepatology • Immunology • Inflammation • CRP

Development and usability testing of an electronic patient-reported outcome (ePRO) solution for patients with inflammatory diseases in an Advanced Therapy Medicinal Product (ATMP) basket trial. (PubMed, J Patient Rep Outcomes) - "By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmics), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmics ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development."

Journal • Metastases • Pan tumor • Patient reported outcomes • Fatigue • Inflammation • SDC2

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicentre, Randomised, Controlled Trial. (PubMed, Am J Respir Crit Care Med) - P1/2 | "ORBCEL-C MSCs were safe in moderate-to-severe COVID-related ARDS, but did not improve surrogates of pulmonary organ dysfunction. Clinical trial registration available at www."

Journal • Stroma • Acute Respiratory Distress Syndrome • Critical care • Infectious Disease • Inflammation • Interstitial Lung Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • SDC2

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST) (clinicaltrials.gov) - P1/2 | N=129 | Recruiting | Sponsor: Belfast Health and Social Care Trust | Trial primary completion date: Mar 2023 ➔ Mar 2024

Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Repair of acute respiratory distress syndrome in COVID-19 by stromal cells (REALIST-COVID trial): 1 year follow up for safety and pulmonary dysfunction (BTS WM 2022) - "Introduction and Objectives REALIST-COVID was a UK multicentre, double-blind randomised, allocation concealed, placebo-controlled phase 2 trial, investigating a novel mesenchymal stromal cell (MSC) product (ORBCEL-C cryopreserved, allogeneic, umbilical cord-derived CD362 enriched MSCs) in patients with ARDS due to COVID-19...A similar incidence of pulmonary dysfunction is reported in both groups at long term follow up.Please refer to page A?? for declarations of interest related to this ."

Clinical • Acute Respiratory Distress Syndrome • Infectious Disease • Interstitial Lung Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • SDC2

Merlin: Selected Mesenchymal Stromal Cells to Reduce Inflammation in Patients With PSC and AIH (clinicaltrials.gov) - P2a | N=18 | Recruiting | Sponsor: University of Birmingham | Unknown status ➔ Recruiting | N=56 ➔ 18 | Trial completion date: Dec 2021 ➔ Dec 2023 | Trial primary completion date: Dec 2021 ➔ Mar 2023

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Hepatology • Immunology • Inflammation

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST) (clinicaltrials.gov) - P1/2 | N=129 | Recruiting | Sponsor: Belfast Health and Social Care Trust | Active, not recruiting ➔ Recruiting | Trial completion date: Mar 2024 ➔ Jun 2025 | Trial primary completion date: Jul 2022 ➔ Mar 2023

Enrollment open • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cell Administration (REALIST-COVID) Phase 2 Randomised Controlled Trial (ATS 2022) - P1/2 | "The REALIST phase 1 study demonstrated safety of ORBCEL-C MSCs in patients with ARDS.1 The REALIST COVID phase 2 study investigated the safety and efficacy of ORBCEL-C MSCs in patients with ARDS due to COVID-19.METHODSThis was a multicentre, randomised, double-blind, allocation concealed, placebo-controlled trial in mechanically ventilated patients with moderate to severe ARDS, due to COVID-19...Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial. EClinicalMedicine 2021; 41: 101167."

Clinical • P2 data • Acute Respiratory Distress Syndrome • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • SDC2

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial. (PubMed, Trials) - P1/2 | "The development and manufacture of an advanced therapy medicinal product to Good Manufacturing Practice standards within NHS infrastructure are discussed, including challenges encountered during the early stages of trial set up. The rationale to include a separate cohort of patients with ARDS due to COVID-19 in phase 2 of the trial is outlined."

Journal • P1 data • P2 data • Acute Respiratory Distress Syndrome • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • SDC2

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial. (PubMed, EClinicalMedicine) - P1/2 | "A single intravenous infusion of ORBCEL-C was well tolerated in patients with moderate to severe ARDS. No dose limiting toxicity was reported up to 400 × 10 cells."

Journal • P1 data • Acute Respiratory Distress Syndrome • Cardiovascular • Immune Modulation • Inflammation • Pulmonary Disease • Respiratory Diseases • Ventricular Tachycardia • SDC2

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST) (COVID-19) (clinicaltrials.gov) - P1/2; N=120; Active, not recruiting; Sponsor: Belfast Health and Social Care Trust; Recruiting ➔ Active, not recruiting; N=75 ➔ 120; Trial completion date: Oct 2022 ➔ Mar 2024; Trial primary completion date: Sep 2020 ➔ Jul 2022

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] NEW, LN2-FREE SOLUTION FOR CRYOGENIC TRANSPORT OF CELL THERAPIES (EBMT 2021) - "After thawing, samples were re-cultured and viable cell numbers and metabolic activity were measured after 24, 48 and 72h, to also evaluate cell proliferation ability post-thaw.The real-life LN2-free cryogenic shipping test in the VIA Capsule™ involved the ORBCEL cell therapy product, embarked on an 8-leg journey across 2 manufacturing sites and 3 clinical sites in Great Britain via air and road... Molecular mobility is greatly slowed down in frozen samples, but still exists above Tg’, which may lead to cellular damages over time, observable post-thaw. The extent of these damages depend on the time and temperature gap to Tg’. The VIA Capsule™ is a safe and predictable LN2-free, cryogenic shipping solution which ensures a 5-day fully passive shipping window below -120°C."

[VIRTUAL] NEW, LN2-FREE SOLUTION FOR CRYOGENIC TRANSPORT OF CELL THERAPIES (EBMT 2021) - "After thawing, samples were re-cultured and viable cell numbers and metabolic activity were measured after 24, 48 and 72h, to also evaluate cell proliferation ability post-thaw.The real-life LN2-free cryogenic shipping test in the VIA Capsule™ involved the ORBCEL cell therapy product, embarked on an 8-leg journey across 2 manufacturing sites and 3 clinical sites in Great Britain via air and road... Molecular mobility is greatly slowed down in frozen samples, but still exists above Tg’, which may lead to cellular damages over time, observable post-thaw. The extent of these damages depend on the time and temperature gap to Tg’. The VIA Capsule™ is a safe and predictable LN2-free, cryogenic shipping solution which ensures a 5-day fully passive shipping window below -120°C."

[VIRTUAL] NEW, LN2-FREE SOLUTION FOR CRYOGENIC TRANSPORT OF CELL THERAPIES (EBMT 2021) - "After thawing, samples were re-cultured and viable cell numbers and metabolic activity were measured after 24, 48 and 72h, to also evaluate cell proliferation ability post-thaw.The real-life LN2-free cryogenic shipping test in the VIA Capsule™ involved the ORBCEL cell therapy product, embarked on an 8-leg journey across 2 manufacturing sites and 3 clinical sites in Great Britain via air and road... Molecular mobility is greatly slowed down in frozen samples, but still exists above Tg’, which may lead to cellular damages over time, observable post-thaw. The extent of these damages depend on the time and temperature gap to Tg’. The VIA Capsule™ is a safe and predictable LN2-free, cryogenic shipping solution which ensures a 5-day fully passive shipping window below -120°C."

[VIRTUAL] NEW, LN2-FREE SOLUTION FOR CRYOGENIC TRANSPORT OF CELL THERAPIES (EBMT 2021) - "After thawing, samples were re-cultured and viable cell numbers and metabolic activity were measured after 24, 48 and 72h, to also evaluate cell proliferation ability post-thaw.The real-life LN2-free cryogenic shipping test in the VIA Capsule™ involved the ORBCEL cell therapy product, embarked on an 8-leg journey across 2 manufacturing sites and 3 clinical sites in Great Britain via air and road... Molecular mobility is greatly slowed down in frozen samples, but still exists above Tg’, which may lead to cellular damages over time, observable post-thaw. The extent of these damages depend on the time and temperature gap to Tg’. The VIA Capsule™ is a safe and predictable LN2-free, cryogenic shipping solution which ensures a 5-day fully passive shipping window below -120°C."

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial. (PubMed, Trials) - P1/2 | "Intervention: Allogeneic donor CD362 enriched human umbilical cord derived mesenchymal stromal cells (REALIST ORBCEL-C) supplied as sterile, single-use cryopreserved cell suspension of a fixed dose of 400 x10 cells in 40ml volume, to be diluted in Plasma-Lyte 148 to a total volume of 200mls for administration...In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2)."

Clinical • Journal • Acute Respiratory Distress Syndrome • Cardiovascular • Genetic Disorders • Hepatology • Infectious Disease • Mood Disorders • Novel Coronavirus Disease • Oncology • Pulmonary Arterial Hypertension • Respiratory Diseases • Solid Tumor • Venous Thromboembolism

Merlin: A Single-arm,Phase IIa,Safety and Efficacy Trial of Selected MSCs in the Treatment of Patients With PSC & AiH (clinicaltrials.gov) - P2a; N=56; Not yet recruiting; Sponsor: University of Birmingham; Trial completion date: Dec 2019 ➔ Dec 2021; Trial primary completion date: Jun 2019 ➔ Dec 2021

Trial completion date • Trial primary completion date • Biosimilar • Immunology

Merlin: A Single-arm,Phase IIa,Safety and Efficacy Trial of Selected MSCs in the Treatment of Patients With PSC & AiH (clinicaltrials.gov) - P2a; N=56; Recruiting; Sponsor: University of Birmingham; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open