This is a pilot, multi-centre, open-label randomised controlled study to assess the early efficacy of intravenous (IV) administration of CYP-001 in adults admitted to an intensive care unit (ICU) with respiratory failure

After enrolment upon meeting eligibility criteria (D0), participants baseline data will be collected and participants will be randomised to receive either standard of care treatment only, or standard of care plus CYP-001. On D1 and D3, each participant randomised to receive CYP-001 will receive an IV infusion of 2 million Cymerus mesenchymal stem cells (MSCs)/kg of body weight (up to a maximum of 200 million cells). Participants will have further data collection throughout their ICU and hospital stay and follow up to 28 days.

Inclusion Criteria:

• Male or female, 18 years of age or older

• Respiratory failure with the following signs and symptoms:

  1. P/F ratio <300 mmHg
  2. Onset within one week of a known insult or new or worsening respiratory symptoms.
  3. Chest imaging shows bilateral opacities, which are not fully explained by effusions, lobar/lung collapse, or nodules.

• Respiratory failure which is not fully explained by cardiac failure or fluid overload.

• Onset of respiratory failure within the past 48 hours (as defined in inclusion criterion 2

Exclusion Criteria:

• <18 years of age
• Patient is known to be pregnant
• Known active malignancy that required treatment in the last year
• WHO Class III or IV pulmonary hypertension
• Venous thromboembolism currently receiving anti-coagulation or within the past 3 months
• Currently receiving extracorporeal life support
• Severe chronic liver disease (Child-Pugh score >12)
• "Do Not Attempt Resuscitation" order in place
• Treatment withdrawal imminent within 24 hours
• BMI > 45 kg/m2.
• Received any investigational research agent within 60 days or within five half-lives of the last treatment (if the half-life of the investigational agent is known to be longer than 12 days) prior to the planned administration of study treatment.
• Known positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus, Hepatitis C virus or any other infection which the opinion of the Investigator is likely to impact on the ability of the patient to participate in the study.
• Known sensitivity to dimethylsulfoxide (DMSO) or any other component of the study treatment.

IPD relating to efficacy of MSCs in COVID-19 may be shared, subject to permission from Sponsor and ethics approval if required. All de-identified data collected during this study may be shared confidentially to contribute to meta-analysis of mesenchymal stem cell treatments for COVID-19. Request for IPD from this trial for other purposes will be considered by the Sponsor.

Data requests will be considered after the completion of the study. There is no specified end date.

All reasonable requests for raw and analysed data that are not included in primary publications from this study may be available upon request and discretion from the Sponsor from the beginning to the trial. Data may be made available to active collaborators in the COVID-19 Stem Cell Treatment (CSCT) Group, subject to permission from the Sponsor and ethics approval if required. All other reasonable requests for raw and analysed data will be considered by the Sponsor. Data may be obtained upon permission from the Sponsor.