New drugs to prevent acute kidney injury
Explore Arch Biopartners science, teams and publications
A new mechanism of action
A drug platform to inhibit DPEP1
In March 2024 Arch lead scientists published an article in the British Medical Journal Open (BMJ Open). The Phase II findings in the article support DPEP1 as a relevant therapeutic target in humans for acute injury in the kidneys, liver and lungs where inflammation plays a major role.
Biomarker data included in the publication provided further scientific rationale for Arch to advance the company’s lead drug candidate, LSALT peptide to prevent leukocyte recruitment and organ inflammation for other indications, including the larger ongoing international Phase II trial targeting cardiac surgery-associated AKI.
LSALT peptide
Click to WATCH LSALT peptide At work
Video data behind Arch lead scientists publication in Cell shows the real-time effects of LSALT peptide when used to prevent inflammation in pre-clinical models of AKI, similar to the inflammation found in CS-AKI – click to watch the videos and learn more about LSALT peptide.
Arch Biopartners lead scientists discovered that dipeptidase-1 (DPEP1) mediates the recruitment of white blood cells and inflammation injury in the kidneys, lungs and liver. Published in Cell, 2019 the same team showed that LSALT peptide specifically targets DPEP1.
- Organ inflammation injury is an unmet problem with no effective therapeutics currently in the market.
- There is no treatment for AKI. In cases that lead to kidney failure, patients will require dialysis or a kidney transplant to survive.
- In 2024 the company is conducting an international Phase II trial – dosing cardiac surgery patients with LSALT peptide to prevent CS-AKI, which occurs in approximately 30% of bypass surgery patients
- Drug approval for treating CS-AKI may enable off-label use for other indications such as lung or liver inflammation injury, other AKI indications and septic shock.
Cilastatin
In early 2024, the company announced its plans to repurpose and commercialize cilastatin, a second drug in its platform of DPEP1 inhibitors. The announcement included details from a pre-investigational new drug application (PIND) meeting with the U.S. Food and Drug Administration (FDA) Division of Cardiovascular and Renal Products (DCRP).
Originally developed in the 1980´s by Merck Sharp & Dohme Research Laboratories (MSDRL), cilastatin was shown to protect the drug imipenem from being destroyed by DPEP1. Whereas LSALT peptide specifically blocks DPEP1 mediated inflammation in the kidney, lungs and liver, cilastatin also has off target-effects that prevent toxin uptake in the kidneys.
- Arch has completed manufacturing of cilastatin and is working with research and clinical collaborators to repurpose the drug as a new treatment to prevent toxin-related AKI.
- The company will be providing cilastatin drug product to the PONTiAK trial targeting drug toxin-related AKI. The PONTiAK investigators are planning to begin patient recruitment in early 2025.
An experienced team of scientists with an executive, board and advisors bringing deep scientific, pharmaceutical, biotechnology and corporate financial experience.
Science and Research Teams
- Current work on LSALT Peptide is directed by Arch’s Treatments for Inflammation Team, led by Dr. Daniel Muruve, Dr. Justin Macdonald Ph. D. and Dr. Arthur Lau Ph. D, who are primarily based at the University of Calgary. David Luke, BScPhm, PharmD, is a Strategic Advisor and Senior Clinical Lead working to support the Board of Directors and the company’s ongoing clinical trials with LSALT peptide.
- The DPEP1 Inflammation Pathway and LSALT Peptide (Metablok) were discovered by the Metablok team – Dr. Stephen Robbins Ph. D., Dr. Donna Senger Ph. D. and Jennifer Rahn B Sc., M Sc. at the University of Calgary.
The company’s lead scientists have all participated and authored key papers and journal publications as a core part of their ongoing scientific research and development.
- Treatments for Inflammation publications surrounding the development of LSALT Peptide (Metablok) as a treatment for inflammation with broad application to prevent organ and tissue injury
- BMJ Open, March 2024 – Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of
- LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)
- Science Advances, February 2022 – Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury
- Cell, August 2019 – Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver
