Targeting inflammation with LSALT Peptide
LSALT Peptide (Metabloktm)
LSALT Peptide is the company’s lead drug candidate for treating inflammation in the lungs, liver and kidneys.
The company is focused on producing new data from additional human trials to support drug approval. Next steps include a human trial to prevent acute kidney injury (AKI) – a life-threatening injury that affects over six million people in the U.S. every year.
The drug’s clinical trial history has led to LSALT Peptide being the first novel therapeutic to join the Canadian Treatments for COVID-19 (CATCO) trial, an ongoing multi-centre adaptive, randomized, open-label, controlled Phase III trial to treat patients in fifty-five hospitals across Canada.
About LSALT Peptide
Arch believes that LSALT Peptide 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 paper, the enzyme dipeptidase-1 (DPEP1) was identified as a major neutrophil (white blood cell) adhesion receptor on the lung, liver and kidney endothelium – additionally, DPEP1 was shown to be the target of LSALT Peptide – identifying a target for neutrophil-driven inflammatory diseases of the lungs.
CELL – August 2019
Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver
“…we identified dipeptidase-1 (DPEP1) as the target and established its role as a physical adhesion receptor for neutrophil sequestration…”
Arch is pursuing clinical development of LSALT Peptide to treat acute injury in the lungs, kidneys and liver caused by inflammation
Upon completion of a Phase I trial in 2020, Arch also completed a Phase II trial conducted in Canada, Turkey and the United States. The Phase II trial was designed to investigate LSALT Peptide’s efficacy in the prevention of organ inflammation, known to trigger acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) in patients infected with SARS-CoV-2 (COVID-19).
Beyond treating inflammation in COVID-19 patients, Arch expects in future that LSALT Peptide will be developed to target organ inflammation in other applications.The company is working on multiple tasks to advance the program, including;
- dose escalation studies;
- manufacturing new drug product supply to support future non-COVID human trials;
- the non-COVID Phase II trials (such as a cardiac surgery associated acute kidney injury trial) to gather more human data to support future drug approval; and
- additional non-clinical studies to discover potential biomarkers and to further understand the mechanism of action related to LSALT peptide.
LSALT Trial Information
This Phase III study is an adaptive, randomized, open-label, controlled clinical trial, in collaboration with countries around the world through the World Health Organization.
About the CATCO PHASE III Trial
Subjects will be randomized, across one, two, three or up to four separate randomizations (including LSALT Peptide vs. Standard of care, alongside other therapies), to receive either standard-of-care products or the study medication plus standard of care, while being hospitalized for COVID-19.
The primary outcome measures for LSALT Peptide will measure patients number respiratory support free days.
The secondary outcome measures will include measures of clinical effectiveness, need for invasive mechanical ventilation, CU admission, hospital and ICU length of stay, days alive and free of vasopressors, ventilation, and renal replacement therapy (RRT), severe adverse events, and 1, 3 and 6 months mortality, laboratory (cardiac pulmonary coagulation, and renal) and clinical evaluation using standardized pre-defined COVID-19 virtual and/or in person follow-up and mortality after Randomization
Due to waning numbers of hospitalizations due to COVID-19, Arch does not have a projected end-date for the complete accumulation of data from the CATCO Trial. The Company will release updates about data as they are received and assembled in collaboration with our colleagues in the trial.
The phase II trial was an international, multi-center, randomized, double-blind, placebo-controlled, proof of concept study of LSALT peptide 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).
About the Phase II Trial
The primary composite endpoint of the Phase II trial included the prevention of acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Additional secondary endpoints included reducing coagulopathy, cardiomyopathy and acute liver injury experienced by hospitalized COVID-19 patients.
The trial dosed 61 patients in an international, multi-center, randomized, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of organ inflammation known to trigger acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) in patients infected with SARS-CoV-2 (COVID-19) or new variants of the virus.
The composite primary endpoint of the Phase II trial reflects the severe effects often experienced by hospitalized COVID-19 patients and deemed appropriate for LSALT peptide’s novel mechanism of action in blocking consequential inflammation in the lungs, kidneys, and other organs.
The Phase II results are a component of the design of the Phase III program which includes greater patient numbers, to more fully evaluate efficacy and safety in hospitalized patients at risk of inflammation in the lungs, kidneys or liver.
Beyond treatments for COVID-19 patients, Arch is targeting organ inflammation in other applications. More information about the Phase II trial can be found at:
In March 2020, Arch announced that Metablok successfully met the primary endpoints of safety and tolerability in a Phase I Human Trial involving 52 healthy, normal volunteers. The placebo controlled, double blind study was conducted in Australia.
Previously, in December 2019, Arch made an announcement that Metablok had achieved primary endpoints of safety and tolerability. Based on the initial completion of the Phase I trial, Arch announced that it had expanded the dosing in trial to increase the dose range for future Phase II studies.
About the Phase I Trial
“Metablok was well tolerated during the placebo-controlled trial and no drug-related adverse effects were observed in any of the forty-four volunteers, split into five groups. Three of the groups received either a low, medium or high single dose of Metablok and the remaining two groups received a low or medium single daily dose over three days.” (From the Arch Biopartners December 2019 press release)
PreClinical Data and Background
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.
Following publication in the peer-reviewed journal Cell in August 2019, Arch Scientists released a series of preclinical videos using Intravital Microscopy data to show the real-time effects of Metablok when used to reduce inflammation in preclinical mouse models.
The video series includes demonstrations of LSALT Peptide compared to normal and injured organs. In each video, the treated liver, kidneys and lungs are shown to have a reduction of the action of inflammation present in the organ.
From the publication in Cell, August 2019
“Using biochemical, genetic, and confocal intravital imaging approaches, we identified dipeptidase-1 (DPEP1) as the target and established its role as a physical adhesion receptor for neutrophil sequestration independent of its enzymatic activity. Importantly, genetic ablation or functional peptide blocking of DPEP1 significantly reduced neutrophil recruitment to the lungs and liver and provided improved survival in models of endotoxemia.”
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 the current standard of care, mortality rates are over 20% for sepsis and over 50% for septic shock.
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.