Phase 2 Study of Inhaled SNG001 in Mechanically Ventilated Patients With Respiratory Viral Infection

Part 1 Inclusion Criteria:

To be eligible for randomisation into Part 1 of this study, each participant must fulfil the following criteria:

• Informed consent or legal representative's consent obtained.
• Patients ≥50 years of age at the time of consent.
• Patient admitted to the ICU and requiring invasive mechanical ventilation (IMV) due to a respiratory virus infection.
• Presence of Influenza A (Flu A), Influenza B (Flu B), respiratory syncytial virus (RSV), rhinovirus (RV), adenovirus, parainfluenza, human metapneumovirus (HMPV), or coronaviruses (including SARS-COV-2 and seasonal coronaviruses) in a nose swab sample, confirmed by a positive virus test using a Sponsor approved rapid POC test (e.g., reverse transcription polymerase chain reaction [RT-PCR]).
• Time from intubation to administration of first dose of study medication ≤48 hours.
• Women of childbearing potential must have a negative pregnancy test. For this study, women of childbearing potential are defined as women <55 years old.

Part 1 Exclusion Criteria:

A participant must not be randomised into Part 1 of the study if they meet any of the following criteria:

• Expected termination of IMV within 24 hours from the time of randomisation
• Life expectancy <24 hours.
• Liver failure (Child-Pugh C).
• Severe congestive heart failure (New York Heart Association [NYHA] IV).
• Receipt of lung transplant.
• Known or suspected active tuberculosis, or infection with other mycobacteria
• Known or suspected active systemic fungal infection.
• Anticipated transfer to another hospital which would prevent the participant from continuing in the study and completing protocol assessments.
• Need for long-term mechanical ventilation prior to ICU admission.
• Use of inhaled sedation.
• Presence of tracheostomy or laryngectomy.
• Requirement for airway pressure release ventilation mode.
• History of hypersensitivity to natural or recombinant IFNβ or to any of the excipients in the drug preparation.
• Any condition, including findings in the patient's medical history or in the pre-randomisation study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
• Participation in previous clinical studies of SNG001.
• Current or previous participation in another clinical study where the participant has received a dose of an Investigational Medicinal Product (IMP) containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study.
• Known or suspected pregnancy.
• Females who are breast-feeding or lactating.
• Immunocompromising condition, including:

• Established acquired immune deficiency syndrome (AIDS) defined as a cluster of differentiation 4 (CD4) count <200 cells/microL, and/or the presence of any AIDS-defining condition;
• Haematological malignancy;
• Bone marrow transplantation; or
• Immunosuppressive therapy, including:
• Cancer therapy (e.g. chemo-, radio-, immuno-, hormone or other types of therapy), immune-cell depleting therapy, immunosuppressive therapy for autoimmune disorders, medications for prevention of organ transplantation rejection, administered within 6 months prior to randomisation; or
• Corticosteroids >20 mg of prednisone or equivalent per day administered continuously for >14 days prior to randomisation.
• Severe chronic lung disease requiring home oxygen therapy, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis.

Part 2 Inclusion Criteria:

To be eligible for randomisation into Part 2 of this study, each participant must fulfil the following criteria:

1.a Patients ≥18 and <50 years of age at the time of consent, with an immunocompromising condition, including:

• Solid tumour malignancy undergoing cancer therapy (e.g. chemo-, radio-, immuno-, hormone or other types of therapy);
• Haematological malignancy in remission, with or without maintenance therapy;
• Immunosuppressive therapy for autoimmune disease;
• Therapy for prevention of organ transplant rejection;
• Corticosteroids >20 mg of prednisone or equivalent per day, administered continuously for >14 days prior to randomisation or

• b Patients ≥50 years of age at the time of consent, with or without an immunocompromising condition (as defined above).
• Patient admitted to the ICU and requiring IMV due to a respiratory virus infection.
• Presence of Flu A, Flu B, RSV, RV, adenovirus, parainfluenza, HMPV, or coronaviruses (including SARS-COV-2 and seasonal coronaviruses) in a Lower Respiratory Tract sample, confirmed by a positive virus test using a Sponsor approved rapid POC test (e.g., RT-PCR).
• Time from intubation to administration of first dose of study medication ≤48 hours.
• Informed consent or legal representative's consent obtained.
• Women of childbearing potential must have a negative pregnancy test. For this study, women of childbearing potential are defined as women <55 years old.

Part 2 Exclusion Criteria:

A participant must not be randomised into Part 2 of the study if they meet any of the following criteria:

• Expected termination of IMV within 24 hours from the time of randomisation.
• Life expectancy <24 hours.
• Liver failure (Child-Pugh C).
• Severe congestive heart failure (NYHA IV).
• Receipt of lung transplant.
• Known or suspected active tuberculosis, or infection with other mycobacteria.
• Known or suspected systemic fungal infection.
• Immunocompromising condition, including:

• Haematological malignancy requiring induction or consolidation therapy within 3 months prior to randomisation;
• Bone marrow transplant within 6 months prior to randomisation;
• Solid organ transplant within 6 months prior to randomisation;
• Corticosteroids >75 mg of prednisone or equivalent per day, administered continuously for >7 days prior to randomisation;
• Methotrexate therapy at randomisation, if the indication is chemotherapy for cancer;
• Chimeric antigen receptor (CAR)-T cell therapy, administered within 3 months prior to randomisation;
• Ibrutinib or alemtuzumab, administered within 3 months prior to randomisation;
• Neutropenia <500/mm3 not due to sepsis;
• Clinical presentation consistent with severe bone marrow suppression or pancytopenia;pancytopenia;
• Established AIDS, defined as a CD4 count <200 cells/microL, and/or the presence of any AIDS-defining condition.
• Anticipated transfer to another hospital which would prevent the participant from continuing in the study and completing protocol assessments.
• Need for long-term mechanical ventilation prior to ICU admission.
• Use of inhaled sedation.
• Presence of tracheostomy or laryngectomy
• History of hypersensitivity to natural or recombinant IFNβ or to any of the excipients in the drug preparation.
• Any condition, including findings in the patient's medical history or in the pre-randomisation study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
• Participation in previous clinical studies of SNG001.
• Current or previous participation in another clinical study where the participant has received a dose of an IMP containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study.
• Known or suspected pregnancy.
• Females who are breast-feeding or lactating.
• Severe chronic lung disease requiring home oxygen therapy, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis