Sepsis is a global health crisis that affects between 47 and 50 million people every year, at least 11 million die – one death every 2.8 seconds. Depending on the country, mortality varies between 15 and more than 50%. No sepsis drugs are available and over 30 drugs failed in late-stage clinical trials. This highlights an urgent need for new therapies.
Sepsis is associated with overwhelming production of proinflammatory cytokines ("cytokine storm") and macrophages are their main producers. In sepsis, TREM-1 expression is most pronouncedly increased on monocytes and macrophages. TREM-1 blockade blunts excessive inflammation but in contrast to many other currently explored therapeutic targets in sepsis, preserves the capacity for microbial control.
In preclinical models of sepsis, SignaBlok's ligand-independent TREM-1 inhibitor is well-tolerable and demonstrates high single agent efficacy in reducing systemic inflammation and protecting animals from the lethality of endotoxic shock. Importantly, effective and longer-lasting protection is provided when SignaBlok's TREM-1 inhibitor is administered even at a later timepoint after the toxic challenge.
Acute Respiratory Distress Syndrome (ARDS) and Coronavirus Disease 2019 (COVID-19)
Approximately, 2.2 million patients are affected each year by ARDS, an inflammatory lung condition that is associated with "cytokine storm" and may complicate severe pneumonia (including influenza and COVID-19), trauma, sepsis, cancer, and many other conditions. The mortality of ARDS is 27%, 32%, and 45% for mild, moderate, and severe disease, respectively.
"Cytokine storm" is recognized as a leading cause of severe COVID-19. The survival rate for COVID-19 patients with ARDS is about 25%.
There is neither known prevention for ARDS nor any known cure at the present time. ARDS patients are treated with supportive care, most often in the Intensive Care Unit. This highlights an urgent need for effective prevention and treatment of ARDS.
TREM-1 is involved in the pathogenesis of "cytokine storm" in ARDS and is overexpressed in patients with ARDS. In animals, TREM-1 blockade reduces “cytokine storm” and protects against lung injury.
Further expanding on its TREM-1 SCHOOL technology platform, SignaBlok has launched a program focusing on a new therapeutic modality targeting ARDS and COVID-19.