Indication

Cause

• Aspiration of toxic substances, sepsis, trauma, massive blood transfusion, aspiration pneumonia, etc.
• Abnormal increase in permeability between alveoli and capillaries causes pulmonary edema and hypoxic respiratory failure due to severe inflammation.

Incidence, Mortality

• Incidence: 78.9 per 100,000 person-years
• Mortality: 34 to 58% (acute respiratory distress syndrome

Symptoms

• Shortness of breath, fast breathing, fast heart rate, taking lots of rapid, shallow breaths, fatigue, fever, cracklings found in the lungs

Unmet Needs

Glucocorticoids, inhaled nitric oxide, and activated protein C (APC) have been tried as therapeutic agents, but they have low clinical efficacy and side effects.

Mechanism of Action

• Inhibits hyper-permeability of the alveolar-capillary barrier and the occurrence of pulmonary edema by suppressing osmotic fluid escaping into the alveoli.
• Fundamentally blocks hyper-permeability by stabilizing endothelial cell junctions by modifying the actin structure of vascular endothelial cells.
• Blocks NF-kB inflammatory signaling system in vascular endothelial cells.
• Enhances survival rate and protective effect of vascular endothelial cells.

Pathogenesis of ALI

CU102: principle of action

Lungs in COVID-19 patients: vascular endothelial dysfunction observed as a key finding

CU102 blocks

• Endothelial cell death
• Destruction of endothelial cell barrier and modification of cell membrane
• Platelet adhesion and thrombus formation due to endothelial barrier loss
• Expression of endothelial inflammatory cell adhesion factor
• Cytokine secretion

The function of CU102 to inhibit endothelial cell-specific apoptosis, block blood vessel leakage and inflammation is noted as a novel treatment for ALI

▶ Proven excellent efficacy in ALI animal models

Efficacy

Improvement of survival rate & inhibition of pulmonary edema

Oral administration of CU102 (10mg/kg) showed comparable survival rate to dexamethasone (steroid) and also relieved pulmonary edema

Inhibition of inflammation in lung tissue

Reduces the influx of inflammatory cells into the lung tissue and tissue damage caused by LPS

• In the LPS-induced ALI model, we were able to confirm CU102 improved the survival rate and immune cell penetration and reduced pulmonary edema.
• CU102 demonstrated similar efficacy to dexamethasone in animal studies. Corticosteroids have significant side effect which is dependent on capacity and duration of treatment.
• Recent ALI (ARDS: Acute Respiratory Distress Syndrome) study stemming from COVID-19 results: In the case of dexamethasone, it is only efficacious in patients with more than moderate to severe patients requiring mechanical ventilation, and it may worsen symptoms in mild cases.

Electron microscope data of alveoli and pulmonary blood vessels

CU102 improves the alveolar-capillary barrier thickened by edema after LPS administration and significantly inhibits the adhesion of inflammatory cells to the inside of the pulmonary blood vessels

• CU102 approaches treating ALI by targeting vascular endothelial cells and normalizing pulmonary blood vessels. Thereby strengthening the alveolar-capillary barrier and blocking vascular leakage and inflammatory responses.
• Through normalization of blood vessels, rather than simple symptom relief, a fundamental therapeutic effect can be expected.

Additional Research

• It was confirmed that the neutrophil infiltration in lung tissue was reduced by reducing MPO activity.
• The reduction of cytokine was confirmed in BALF and serum.

Additional Research

Verified CU102’s suppression of NF-ĸB expression and activation using immunohistochemical staining and Western blot.