PIPELINE | CV-15
Sepsis is one of the top 5 diseases leading death worldwide and widely recognized as a clinical syndrome, resulting from an overwhelming, systemic inflammatory response.
Sepsis is occurred by excessive secretion of pro-inflammatory cytokine called ‘cytokine storm’, caused by microbial infection, severe injuries or surgical stresses. The global incidence of sepsis is 30 million and its overall mortality is more than 20 %, meaning that there are 6 million of death caused by sepsis every year. Besides, sepsis treatment is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments.
Previously, a polypeptide suppressing various pro-inflammatory pathways caused by endotoxamia has been developed by synthesizing the 1’st generation hydrophobic cell-penetrating peptide (CPP), termed membrane translocating sequence (MTS) derived from the signal peptide of fibroblast growth factor 4 (FGF4), along with NF-κB-derived nuclear localization sequence (NLS).
Cell-permeable nuclear import inhibitor (CP-NI) increased survival rate of severe acute inflammatory animals by suppressing expression of pro-inflammatory cytokines such as TNF-α, IL-6 and IFN-γ. However, CP-NI was hard to manufacture mainly due to its low solubility, resulting in low clinical applicability. To address this limitation, improved cell-permeable nuclear import inhibitor (iCP-NI) has been developed by adopting advanced macromolecule transduction domain (aMTD) and demonstrated its superior stability and activity in sepsis animal models. iCP-NI successfully inhibits the activation of pro-inflammatory pathways and suppress secretion of pro-inflammatory cytokines. In addition, iCP-NI showed dramatically increased survivability in acute severe sepsis mouse models by protecting organ failure. Efficacy study with additional clinical animal models and safety study are on process to prove the powerful therapeutic applicability of iCP-NI.
As a result, this enhanced therapeutics, iCP-NI, can be developed as a novel, unique measures for severe lethal inflammatory syndromes such as septic shock.