MOTREM is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. The manufacturing is in compliance with the principles of good manufacturing practice (GMP). LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. Thus, LR12 inhibits the TREM-1-induced activation of leucocytes in a dose dependent manner, conferring significant protective effects during septic shock.
MOTREM in Septic Shock
TREM-1 pathway is an amplification loop of the immune response that triggers an exuberant and hyperactivated immune state which is responsible for the onset and progression of sepsis. The administration of MOTREM to treat sepsis inhibits such amplification loop, thus modulating, but without complete abrogation, the immune response. Moreover, MOTREM targets both pro- and anti-inflammatory arms of the immune response, which is linked to an increase in bacterial clearance, therefore restoring the delicate balance between effective bacterial clearing and inflammation. MOTREM administration is also able to restore the vascular tonus (vasoreactivity) that is severely impaired during shock and decrease the vasopressor need. This approach of targeting TREM-1 and the host innate immune response provides a therapeutic solution with broad-spectrum coverage and independent of pathogen type. MOTREM represents a new class of anti-sepsis drug and the perspective of a first causal treatment for sepsis.
MOTREM in Myocardial Infarction (MI)
TREM-1 pharmacological inhibition by LR12 during the acute phase of myocardial infarction dampens myocardial inflammation, limits neutrophils recruitment and monocyte chemoattractant protein-1 production, thus reducing classical monocytes mobilization to the heart. These effects during the acute phase allow to limit the reperfusion injury and the infarct size as a consequence of a limitation of the ventricular remodeling, which translates into beneficial effects 6 weeks after the event with an improved left ventricular function.
A first clinical trial to assess the safety, tolerability and pharmacokinetics of MOTREM in healthy volunteers is currently ongoing.