F2001: MODULATING MACROPHAGES' FUNCTION IN ACUTE RESPIRATORY DISTRESS SYNDROME

 

"There is no specific treatment for the cytokine storm of ARDS"

  • The cytokine storm is a type of immune reaction overpassing its goal, observed in ARDS of any cause, such as sepsis, infectious pneumonia (viral, bacterial or fungal), aspiration pneumonitis, pulmonary contusions, burns and smoke inhalation, lung graft reperfusion syndrome and primary dysfunction, lung injury from massive transfusions, hematopoietic stem cell transplant, Car-T cell treatment, pancreatitis, drowning, thoracic surgery, chemotherapy and radiotherapy, amiodarone…

 

  • Macrophages are immune cells responsible for the production of inflammatory cytokines that mobilize other immune cells responsible for the destruction of lung tissue.

  • F2001 modulates an immune check point to reprogram pro-inflammatory alveolar macrophages toward an anti-inflammatory phenotype, in the deep areas of the affected lung.

  • ARDS accounts for 10.4% of patients admitted in ICU, and for 23.4% of patients under invasive mechanical ventilation  (Bellani et al., JAMA 2016).

  • Hospital mortality is 40% (Bellani et al., JAMA 2016; Li et al., Am J Respir Crit Care Med. 2011; Villar et al, Intensive Care Med. 2011). It increases with the severity of ARDS.

  • Significant physical, psychological and cognitive sequelae with significant impairment of quality of life have been reported up to 5 years after ARDS (Herridge et al. N Engl J Med. 2011).

 

  • In children, the annual incidence of ARDS is 2.2-5.7/100,000, representing 2.3-3% of admissions to Pediatric Intensive Care Units with a mortality rate of 17-33%. These studies mainly concern children under 5 years of age.

  • The average length of hospital stay ranges from a few days to several weeks depending on the degree of severity.

  • Given the high costs of hospitalization in intensive care, the burden in terms of Public Health is heavy due to:

    • the large number of patients concerned, which can, in an outbreak of respiratory viral infections such as COVID-19, greatly exceed hospital capacity,
    • the high mortality rate, which can reach 35 to 46% depending on the stage of severity at admission (Pham et al., Am J Respir Crit Care Med (2017)).

  • The efficacy of steroids in the treatment of ARDS is known and widely used. It is confirmed for patients with COVID-19 by a meta-analysis published in September 2020 in JAMA. These steroid family drugs - used in many indications for their potent anti-inflammatory effect - decrease the risk of mortality in patients with Covid-19.

  • However, the reduction in mortality risk observed with these drugs is modest. In addition, nosocomial secondary infections represent a dreaded risk with steroids during a viral infection. It is recognized that mortality in intensive care patients is also often linked to bacterial superinfections.

  • Macrophages' modulation strategy is indicated for patients suffering from an ARDS induced by various causes, in its most severe forms, i.e. those associated with a cytokine storm, a critical life-threatening situation with high unmet medical need.