Arch Scientists Publish Data on the Mechanism of Action & Efficacy of Lead Drug Candidate LSALT Peptide in the Prevention of Acute Kidney Injury

Arch Biopartners Inc. recently announced a scientific team led by Dr. Daniel Muruve at the University of Calgary, and their collaborators, have published a paper in the journal Science Advances describing the mechanism of action for dipeptidase-1 (DPEP-1) in acute kidney injury (AKI). Dr. Muruve is also the Chief Science Officer of Arch.

In this preclinical study, scientists demonstrated the mechanism by which DPEP-1 regulates the recruitment of leukocytes (ie, inflammation) to the kidney following ischemia reperfusion injury, which is injury that occurs after a reduction in blood flow to the kidney. Ischemia reperfusion injury is a common cause of AKI in humans undergoing cardiac surgery or kidney transplantation. Importantly, the study also confirmed the mechanism of action of two DPEP-1 inhibitors, the LSALT peptide (Metablok) and cilastatin that effectively protected the kidney during ischemia reperfusion injury. Both the LSALT peptide and cilastatin are protected by composition and method of use patents for AKI respectively and held by Arch Biopartners.

Details of these findings are reported in the journal Science Advances and provides Arch with the scientific rationale to pursue a Phase 2 trial for LSALT and/or cilastatin targeting the prevention of cardiac surgery-associated AKI. The publication, titled Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury by Lau, et al can be found at https://www.science.org/doi/10.1126/sciadv.abm0142.

In the same issue of Science Advances, a group at University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany independently identified an additional role for DPEP-1 in a form of cell death termed ferroptosis. The publication, titled Dexamethasone sensitizes to ferroptosis by glucocorticoid receptor–induced dipeptidase-1 expression and glutathione depletion by von Mässenhausen, et al can be found at https://www.science.org/doi/10.1126/sciadv.abl8920. This study further expands the potential significance for DPEP-1 in human inflammation and disease.

Acute kidney injury (AKI) represents an additional challenge for patients recovering from cardiac surgery. AKI occurs in approximately 30% of patients that undergo cardiac bypass surgery with approximately 5% of patients requiring dialysis. For patients who recover from the need for dialysis or mild AKI, there is a greater likelihood they will develop chronic kidney disease in future than those who did not have AKI.

Currently, no specific therapies exist to prevent AKI. Worldwide, there are over one million patients per year that have cardiac surgery procedures. Inflammation is known to contribute to AKI related to ischemia-reperfusion and other insults to the kidney that may occur in the course of cardiac surgery.

A scientific team led by Arch scientists Dr. Donna Senger and Dr. Stephen Robbins first described a novel mechanism of action for organ inflammation in the journal Cell in August 2019. In the publication, the enzyme DPEP-1 was identified for the first time as a major neutrophil adhesion receptor on the lung, liver and kidney endothelium. Their findings identified DPEP-1 as a novel therapeutic target for diseases of these organs where inflammation plays a major role.

LSALT peptide is a novel therapeutic agent and the lead DPEP-1 inhibitor in the Arch peptide drug pipeline and recently completed an international phase II trial to treat complications in hospitalized Covid-19 patients.

Arch also has patent protection to re-purpose the small molecule cilastatin, a known DPEP-1 inhibitor, for the prevention of acute kidney injury caused by inflammation in several different indications.

For more information about LSALT peptide, recent clinical disclosures, and related publications, visit www.archbiopartners.com.

Arch Biopartners Inc. is a clinical-stage company focused on the development of innovative technologies that have the potential to make a significant medical or commercial impact.  Arch is developing a pipeline of new drug candidates that inhibit inflammation in the lungs, liver and kidneys via the dipeptidase-1 (DPEP-1) pathway, relevant for multiple medical indications. The company has 62,002,302 common shares outstanding following the recent exercise of 40,000 stock options by a non-insider consultant for proceeds of CAD $59,200. For more information, visit www.archbiopartners.com.