Metablok (LSALT peptide) is our lead drug candidate for treating inflammation in the lungs, liver and kidneys.
Arch believes Metablok has the potential to deliver a major breakthrough in the treatment of diseases where inflammation plays a major role. In August 2019, a scientific team led by Arch scientists Dr. Donna Senger and Dr. Stephen Robbins published a paper in the journal Cell describing a novel mechanism of action for organ inflammation. In the publication, the enzyme dipeptidase-1 was identified as a major neutrophil (white blood cell) adhesion receptor on the lung, liver and kidney endothelium. In the same publication, dipeptidase-1 was shown to be the target of Metablok.
Arch is pursuing clinical development of Metablok to treat acute injury in the lungs, kidneys and liver caused by inflammation.
Arch is currently conducting a Phase II Trial to investigate Metablok’s efficacy in the prevention of multiple organ injuries in patients with COVID-19. Arch has announced that patient dosing in the United States and Turkey has begun. The trial is designed to target the prevention of acute lung injury, acute kidney injury and other complications caused by inflammation in hospitalized patients with moderate to severe cases of COVID-19.
The Phase II trial is an international, multicenter, randomized, double-blind, placebo-controlled, proof of concept study of LSALT peptide (Metablok) as a treatment to prevent organ inflammation known to trigger acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) in patients infected with SARS-CoV-2 (COVID-19).
In the worst cases of COVID-19 infection, fatalities are often linked to severe acute lung inflammation and subsequent respiratory failure, or acute kidney injury and renal failure.
The primary composite endpoint of the Phase II trial includes prevention of acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Additional secondary endpoints include reducing coagulopathy, cardiomyopathy and acute liver injury experienced by hospitalized COVID-19 patients.
The COVID-19 pandemic has accelerated the development of the organ inflammation drugs at Arch and has also accelerated regulatory reviews by health authorities. Beyond COVID-19 patients, Arch expects in future to target organ inflammation in other applications.
The video segments presented below are produced using Intravital Microscopy to observe the real-time effects of Metablok when used to reduce inflammation in mouse models.
METABLOK Treating Lung Inflammation - Intravital Microscopy after LPS (2020)
METABLOK Treating Liver Inflammation - Intravital Microscopy after LPS (2020)
METABLOK Treating Kidney Inflammation - Intravital Microscopy after IRI (2019)
Arch scientists have demonstrated Metablok’s ability to block the inflammatory response triggered in the lung and liver with lipopolysaccharide (LPS) induced inflammation and in the kidney with ischemia/reperfusion (IRI) induced injury. Currently, there are no specific or effective treatments to prevent acute kidney injury.
MetaBlok was invented by Arch scientists Dr. Stephen Robbins, Dr. Donna Senger, Dr. Jennifer Rahn and their University of Calgary colleague, Dr. Paul Kubes. The inventors have assigned the Metablok intellectual property to the Company.
Inflammation Based Disease
Inflammation is a localized physical condition that involves the activation of the immune system in response to infection, tissue injury, or autoimmunity. Inflammation is involved in the pathogenesis of many diseases and contributes to organ dysfunction and failure.
Metablok was originally invented to prevent organ inflammation related to sepsis.
Sepsis represents a large unmet medical need in the world today. Sepsis alone occurs in 1 to 2% of all hospitalizations in the US. It affects at least 700,000 individuals per year.
Permanent organ damage can occur in patients who survive sepsis. Under current standard of care, mortality rates are over 20% for sepsis and over 50% for septic shock.