The goal of this clinical trial is to compare the safety and efficacy of AON-D21 versus placebo, both on top of standard of care, in patients with severe community acquired pneumonia admitted to ICU (or similar unit). The main questions to answer are:

• The safety and tolerability of AON-D21 vs placebo.
• The efficacy of AON-D21vs placebo.
• The pharmacokinetics of AON-D21.
• The pharmacodynamics of AON D21.
• To identify biomarkers for patient stratification and analyses in future trials.

This clinical trial will enroll 100 participants, randomized 2:1 (AON-D21:placebo).

Participants diagnosed with severe community-acquired pneumonia of bacterial or viral origin requiring admission to an intensive care unit or similar setting, will receive either AON-D21 or placebo intravenous infusions for up to 10 days.

In addition, participants will receive standard of care as per local guidelines.

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 or ECMO.
• 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 of contraception until Day 60.
• For male participants with female partners of childbearing potential, agreement to use barrier method of contraception until Day 60 and to refrain from donating sperm during 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 pneumonia due to aspiration or other physical injury or trauma or tuberculosis.
• Known or suspected hypersensitivity to AON-D21 or any components of the formulation used (e.g., PEG, mannitol or EDTA) or a history of clinically relevant allergy requiring continuous treatment, or of anaphylaxis.
• Known fibrotic lung disease, bronchiectasis or any other known severe chronic respiratory disease.
• Active malignant disease.
• Factors other than a pathogen suspected or confirmed to be causative for the respiratory insufficiency.
• Hepatocellular injury defined by an ALT or AST value ≥ 3 times the ULN. Known acute or 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 the results.
• Receiving chronic immunosuppressive therapy in relevant doses.
• Known immunodeficiency disease/condition.
• Nursing and pregnant women (defined as the state after conception until the termination of gestation, screened in all women of child-bearing potential with a chorionic 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.

Placebo-controlled