Breathing Hope For ARDS Patients

Scientific Foundations

• Understanding ARDS

  Acute Respiratory Distress Syndrome (ARDS) is a severe, life-threatening syndrome of acute lung injury not a single disease, but a clinical response triggered by multiple causes: viral or bacterial pneumonia, sepsis, trauma, or aspiration.

  Because ARDS can be triggered by so many different causes, clinical trials have historically enrolled highly heterogeneous populations. Classifications based on oxygenation parameters such as the Berlin criteria capture the symptom, not the biology. Major pharmacological trials (SAILS, ROSE, INTEREST) have repeatedly failed as a result, driving most large pharmaceutical companies to exit the indication entirely.

  As demonstrated by Dr. Renaud Prével (CHU Bordeaux), a shared immune mechanism drives tissue damage across all ARDS etiologies: the pathological accumulation of CXCR4⁺ neutrophils, particularly prone to NETosis — a process that amplifies inflammation and destroys lung tissue. Elevated NETosis plasma markers are directly associated with mortality in ARDS, defining a biologically distinct patient subgroup whose immune signature is independent of the underlying cause.

• Biomarkers for ARDS

  Patient heterogeneity is the core reason ARDS trials have failed — and biomarker-driven stratification is our answer. As part of our precision medicine strategy, we are identifying and validating early biomarkers that predict ARDS progression and define the subpopulation most likely to respond to CXCR4 antagonism.

  Our approach focuses on circulating NETosis biomarkers specifically citrullinated Histone H3 as a proxy for CXCR4⁺ neutrophil accumulation in the lungs. Since CXCR4⁺ neutrophils are the primary source of NETs, elevated NETosis levels at ICU admission provide a direct, actionable readout of the immune dysregulation targeted by 4P021, independent of the underlying aetiology, whether viral, bacterial, or non-infectious.

• Our Innovative Scientific Approach

  Our innovation is rooted in a fundamental repositioning of how ARDS is treated — moving away from aetiology-based, one-size-fits-all interventions toward a biology-driven, patient-centered precision medicine strategy.
  At the core of our approach: 4P021 acts upstream blocking the pathological recruitment of CXCR4⁺ neutrophils and their propensity for NETosis before irreversible lung damage occurs, regardless of ARDS aetiology. This stratification is validated through the CHOPIN study and translated into clinical practice through CX-DiagPlex, our rapid point-of-care diagnostic measuring citrullinated Histone H3 at ICU admission.
  The right treatment. The right patient. The right moment.