Safety and Efficacy of AON-D21 in Severe Community-Acquired Pneumonia.

Inclusion Criteria:

• Community-acquired pneumonia, confirmed or suspected of bacterial or viral origin.

• Admitted to an ICU (or similar unit).

• Requiring respiratory support by HFO ≥ 30 L/min with FiO2 ≥ 30% or NIV or IMV orECMO.

• CRP ≥ 50 mg/L.

• PaO2/FiO2 ratio ≤ 150 mmHg.

• Treatment initiation no more than 48 h after initiation of respiratory support (HFO ≥ 30 L/min with FiO2 ≥ 30%, NIV, IMV or ECMO).

• Written informed consent.

• Age ≥ 18 years to ≤ 85 years.

• Body mass index ≥ 17.5 kg/m² and ≤ 40 kg/m².

• For female participants of childbearing potential, agreement to use dual methods ofcontraception until Day 60.

• For male participants with female partners of childbearing potential, agreement touse barrier method of contraception until Day 60 and to refrain from donating spermduring the study and for 3 months after the last infusion.

Exclusion Criteria:

• Refractory septic shock.

• Not expected to survive 72 hours.

• Hospital-acquired or ventilator-associated pneumonia or known or suspected pneumoniadue to aspiration or other physical injury or trauma or tuberculosis.

• Known or suspected hypersensitivity to AON-D21 or any components of the formulationused (e.g., PEG, mannitol or EDTA) or a history of clinically relevant allergyrequiring continuous treatment, or of anaphylaxis.

• Known fibrotic lung disease, bronchiectasis or any other known severe chronicrespiratory disease.

• Active malignant disease.

• Factors other than a pathogen suspected or confirmed to be causative for therespiratory insufficiency.

• Hepatocellular injury defined by an ALT or AST value ≥ 3 times the ULN. Known acuteor chronic liver disease with Child-Pugh C (See Appendix 13.6.2).

• Any medical disease or condition that, in the opinion of the investigator(s),compromises the participant's safety or compromises the interpretation of theresults.

• Receiving chronic immunosuppressive therapy in relevant doses.

• Known immunodeficiency disease/condition.

• Nursing and pregnant women (defined as the state after conception until thetermination of gestation, screened in all women of child-bearing potential with achorionic gonadotrophin (hCG) blood test (local laboratory).

• Current or recent participation in an investigational trial.

• Systemic treatment with any complement inhibitor.

• Known complement deficiency.

• Unlikely to remain at the investigational site beyond 96 h.