Arch Biopartners Inc. is making strides in its clinical programs targeting acute kidney injury (AKI), with significant developments for both its lead drug candidate, LSALT peptide, and its repurposed drug, cilastatin. These advancements underscore the company's focus on addressing critical unmet needs in preventing and treating AKI, a condition associated with high morbidity and mortality.
LSALT Peptide: Ethics Approval for CS-AKI Trial
The University Health Network Research Ethics Board in Ontario has granted ethics approval for Arch Biopartners' Phase II trial of LSALT peptide in preventing and treating cardiac surgery-associated acute kidney injury (CS-AKI). This approval allows clinical teams at Toronto General Hospital and St. Michael's Hospital in Toronto to finalize preparations and begin patient recruitment in the first quarter of 2025. The trial is already recruiting patients at the University of Calgary Hospital and five clinical sites in Turkey.
The CS-AKI Phase II trial is an international, multi-center, randomized, double-blind, placebo-controlled study with a recruitment target of 240 patients. The primary objective is to evaluate the percentage of subjects with AKI within seven days following on-pump cardiac surgery, as defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria.
Richard Muruve, CEO of Arch Biopartners, expressed gratitude to the University Health Network team for their smooth navigation of the ethics board approval process. He emphasized that this milestone is an important step forward for the Phase II CS-AKI trial, as preparations continue at the Toronto clinical sites to begin enrolling patients.
CS-AKI is a common complication following coronary artery bypass grafting (CABG) and other cardiac surgeries, particularly on-pump procedures, significantly elevating the risk of AKI. The reported prevalence of CS-AKI is up to 30% and is independently associated with increased morbidity and mortality.
LSALT peptide targets the dipeptidase-1 (DPEP1) pathway and has demonstrated the ability to prevent ischemia-reperfusion injury (IRI) to the kidneys in pre-clinical models. These findings were published in Science Advances, titled "Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury" by Lau et al., providing the scientific rationale for using LSALT peptide in the current CS-AKI trial.
Cilastatin: Health Canada NOL for PONTiAK Trial
Arch Biopartners also announced that the clinical team leading the investigator-led trial, titled “Prevention Of NephroToxin Induced Acute Kidney Injury with Cilastatin” (PONTiAK), has received a No Objection Letter (NOL) from Health Canada to proceed with the trial. PONTiAK is a 700-patient Phase II trial evaluating the efficacy of cilastatin in preventing AKI caused by several drugs, including certain antibiotics, chemotherapeutic agents, and radiographic contrast.
The PONTiAK clinical team, based at the Universities of Calgary and Alberta, was awarded $1,500,000 by the Canadian Institutes of Health Research (CIHR) to fund the trial. The team also received $400,000 as part of the Accelerating Clinical Trials (ACT) call for proposals to “Evaluate Canadian Biotechnologies with Randomized Controlled Trials” (October 2023). Funds from both grants will be used by the clinical team to conduct the PONTiAK trial at up to five hospital sites in Alberta.
Arch Biopartners is acting as a study partner, providing cilastatin drug product to support the trial. While the PONTiAK team prepares the hospital sites and seeks approvals from local Research Ethics Boards (REB) and Alberta Health Services (AHS), Arch will evaluate opportunities to sponsor a new arm of the PONTiAK study in another jurisdiction, such as the United States or Europe.
Richard Muruve congratulated the PONTiAK team for receiving the No Objection Letter from Health Canada, calling it an important step forward for the Phase II trial using cilastatin to target drug-toxin-related AKI.
Drug toxins cause approximately 30% of AKI cases in hospitalized patients and include a wide range of pharmaceutical drugs such as antibiotics (vancomycin, aminoglycosides), chemotherapeutic agents, and radiographic contrast. Additionally, AKI related to cardiac surgery (CS-AKI) accounts for up to 20% of in-hospital AKI cases.
Cilastatin was originally developed by Merck Sharp & Dohme Research Laboratories to limit the role of dipeptidase-1 (DPEP1) in the breakdown of imipenem. Arch Biopartners owns and has exclusively licensed method-of-use patents to repurpose cilastatin as a new treatment targeting AKI.
While LSALT peptide specifically blocks DPEP1-mediated inflammation in the kidney, lungs, and liver, cilastatin has off-target effects that prevent toxin uptake in the kidneys. As such, cilastatin is particularly effective for toxin-related AKI.
With these advancements, Arch Biopartners is solidifying its position as a key player in the development of novel therapies for acute kidney injury, addressing significant unmet medical needs through its targeted approaches.
