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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 drug is the first novel therapeutic to have joined the Canadian Treatments for COVID-19 trial (CATCO), a multi-centre adaptive, randomized, open-label, controlled clinical trial involving fifty-five hospitals across Canada in 2022.

Upon completion the Phase I trial Arch also completed a Phase II trial conducted in Canada, Turkey and the United States that was a 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).
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

In 2020 and 2021, Arch completed a Phase II Trial to investigate LSALT Peptide’s efficacy in the prevention of multiple organ injuries in patients with COVID-19 with patient dosing in the United States, Canada and Turkey.

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 Phase II trial was 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. 

Beyond COVID-19 patients, Arch expects in future that LSALT Peptide will be developed to target organ inflammation in other applications.

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

The Phase II trial was an international, multi-center, 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).
About the Phase II Trial

The primary composite endpoint of the Phase II trial included 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.

Additional information about the Phase II trial can be found at:

The Phase II results will be used to design the Phase III program, including greater patient numbers, to more fully evaluate efficacy and safety in hospitalized patients at risk to inflammation in the lungs, kidneys or liver.

Beyond COVID-19 patients, Arch expects in future to target organ inflammation in other applications.

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)

Pre-Clinical Data and Background
Videos & Media

Intravital Microscopy after LPS

Treating Lung Inflammation

Intravital Microscopy after LPS

Treating Liver Inflammation

Intravital Microscopy after IRI

Treating Kidney Inflammation
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 pre-clinical video data using Intravital Microscopy to observe the real-time effects of Metablok when used to reduce inflammation in pre-clinical mouse models.

From 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.

The series of videos here include demonstrations of Metablok (LSALT Peptide) shown compared to normal and injured organs. In each video series, the treated liver, kidneys and lungs are shown to have a reduction of the action of inflammation present in the organ.

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.

Intellectual Property

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.

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