Arch Biopartners Advances LSALT Peptide Phase II Trial for Cardiac Surgery-Associated Acute Kidney Injury
Key Insights
St. Michael's Hospital (search) has commenced patient dosing in Arch Biopartners (search)' Phase II trial evaluating LSALT peptide for preventing cardiac surgery-associated acute kidney injury (CS-AKI).
The international multicenter trial targets 240 patients and represents a potential first-in-class therapeutic approach for CS-AKI, which affects up to 30% of cardiac surgery patients.
LSALT peptide works by binding to the DPEP1 (search) enzyme to inhibit organ inflammation, with previous Phase II results showing statistically significant reductions in inflammatory biomarkers.
Arch Biopartners (search) Inc. announced that St. Michael's Hospital (search), part of Unity Health Toronto, has commenced patient dosing in the company's ongoing Phase II trial evaluating LSALT peptide for the prevention and treatment of cardiac surgery-associated acute kidney injury (CS-AKI). This milestone marks the third Canadian site to successfully recruit patients in the international multicenter study.
The Phase II CS-AKI trial is a randomized, double-blind, placebo-controlled study targeting 240 patients undergoing on-pump cardiac surgery. Subjects receive either LSALT peptide (10 mg IV twice daily for five days) or placebo, with the primary objective of evaluating the percentage of subjects developing acute kidney injury within seven days following surgery, as defined by KDIGO criteria.
Expanding Clinical Network
St. Michael's Hospital (search) joins Toronto General Hospital and the University of Calgary Cumming School of Medicine as active recruiting sites, while Royal Columbian Hospital in British Columbia is completing site start-up activities. The company is progressing feasibility discussions with additional cardiac surgery centers in Canada and the United States, with three prospective U.S. sites and one additional Ontario site under consideration.
According to the company's blinded review of trial data, AKI has been consistently observed using protocol-defined criteria, supporting the trial's study design and endpoints. No adverse events or serious adverse events have been assessed as related to LSALT peptide, and no suspected unexpected serious adverse reactions (SUSARs) have been reported.
Addressing Significant Unmet Medical Need
CS-AKI represents a major clinical challenge, with studies reporting that up to 30% of patients undergoing on-pump cardiac surgery develop this condition. The injury often results from ischemia-reperfusion injury, which restricts blood flow and oxygen to the kidney, leading to cell damage. When blood flow is restored, inflammation is triggered, exacerbating kidney injury. Currently, no approved pharmacologic therapies exist to prevent this type of acute kidney injury.
LSALT peptide, Arch's lead drug candidate, targets the dipeptidase-1 (search) (DPEP1 (search)) enzyme, which is primarily expressed in the kidney, to inhibit its role in triggering organ inflammation. The mechanism was first described in Cell (2019) and further characterized in Science Advances (2022) by Lau et al., who demonstrated that LSALT reduced ischemia-reperfusion injury to kidneys in preclinical models.
Clinical Validation and Biomarker Evidence
Previous Phase II trial results evaluating LSALT peptide for acute lung inflammation, published in BMJ Open (2024), provided first-in-human evidence validating DPEP1 (search) as a therapeutic target for organ inflammation. In that study, patients receiving a 5 mg daily dose showed reductions in inflammation-related biomarkers, including a statistically significant decrease in CXCL10 (search), a protein linked to inflammation in lungs and kidneys.
Parallel Development Program
Arch is simultaneously advancing the PONTiAK Phase II trial, an investigator-led study evaluating cilastatin for preventing AKI associated with nephrotoxic pharmaceuticals. The trial, currently recruiting at Calgary and Edmonton hospital sites, plans to enroll 698 patients across five Alberta hospital sites. Published studies indicate that medications are associated with AKI in 14%-26% of adults in prospective cohort studies, with AKI occurring in up to 25% of patients exposed to nephrotoxic pharmaceuticals.
The company is working to establish a U.S. arm of the PONTiAK trial to broaden clinical awareness of cilastatin as a potential AKI prevention treatment. To date, no adverse events or serious adverse events have been assessed as related to cilastatin in the trial.
Market Impact and Future Outlook
Together, Arch's development programs target serious unmet needs in kidney care affecting more than 800 million people worldwide. AKI is associated with adverse long-term outcomes, including progression of chronic kidney disease, increased cardiovascular risk, and higher mortality. With no approved pharmacologic therapies for CS-AKI or drug-induced AKI prevention, both conditions represent areas of significant unmet medical need.
The company's integrated approach includes LSALT peptide for cardiac surgery-associated AKI, cilastatin for toxin-induced AKI, and a chronic kidney disease platform targeting next-generation therapeutics. These assets represent distinct, mechanism-based approaches to treating and preventing common causes of kidney damage across both acute and chronic indications.