Arch Biopartners Announces Start of Patient Recruitment in Phase 2 Trial Targeting Drug-Toxin-Related Acute Kidney Injury

Arch Biopartners Inc. recently announced the investigator-led Phase 2 trial titled Prevention Of NephroToxin Induced Acute Kidney Injury with Cilastatin (PONTIAK) has commenced patient recruitment at its primary clinical sites in Alberta, Canada.

The Phase 2 PONTIAK study aims to evaluate the efficacy of cilastatin in preventing AKI associated with nephrotoxic pharmaceuticals, which include commonly used drugs such as antibiotics, chemotherapy agents, and imaging dyes, some of which are known to cause kidney damage as a side effect. The trial plans to enrol approximately 698 patients in five hospital sites in Alberta.

The PONTIAK clinical team, based at the Universities of Calgary and Alberta, secured $1.5 million in funding for the Phase 2 trial from the Canadian Institutes of Health Research (CIHR), along with $400,000 under the Accelerating Clinical Trials (ACT) initiative aimed at evaluating Canadian biotechnologies using randomized controlled trials.

Arch Biopartners recently manufactured the first-ever, stand-alone cilastatin drug product and has provided the drug supply for the trial. While the trial is investigator-led and independently funded, the company is also evaluating opportunities to support a complementary arm of the study in another jurisdiction, such as the US under an application to the US FDA.

“Congratulations to the PONTIAK team for achieving this milestone and beginning patient enrolment. This marks an important advancement in evaluating cilastatin as a potential first-in-class treatment to prevent AKI caused by exogenous toxins from several commonly used pharmaceutical products, said Richard Muruve, CEO, Arch Biopartners.

AKI reflects a broad spectrum of clinical presentations, ranging from mild injury to severe injury that may result in permanent and complete loss of renal function. Clinically, the causes of AKI include sepsis, ischemia-reperfusion injury, and various endogenous as well as exogenous (drug) toxins. There is no specific therapeutic treatment available on the market that prevents AKI. In the worst cases, the kidneys fail, requiring dialysis or kidney transplantation for patient survival.

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 in the early 1980s by Merck Sharp & Dohme Research Laboratories to limit the role of dipeptidase-1 (DPEP1) in the breakdown of imipenem, a β-lactam antibiotic used for the treatment of systemic infections. Cilastatin was approved for use as a fixed combination with imipenem to treat different types of bacterial infections. This fixed combination, approved by the FDA in 1985, is currently marketed under different names, including Primaxin (USA, UK, Australia, Italy), Tienam (Spain, Belgium), or Zienam (Germany). Composition of matter patents for imipenem and cilastatin have expired, and the combination drug is currently in a generic phase. There is no commercial history of cilastatin as a stand-alone drug product.

Cilastatin has a slightly different mechanism of action compared with Arch’s novel drug candidate, LSALT peptide (Metablok), a non-enzymatic DPEP1 inhibitor. Whereas 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. Arch Biopartners owns and has exclusively licensed method-of-use patents to repurpose cilastatin as a new treatment targeting AKI.

The PONTIAK Phase 2 clinical trial is registered on ClinicalTrials.gov under identifier NCT06886464.

Arch Biopartners Inc. is a late-stage clinical trial company focused on preventing acute kidney injury and organ damage caused by inflammation. The company is developing a platform of novel drugs targeting the dipeptidase-1 (DPEP1) inflammation pathway prevalent in the kidneys, lungs, and liver.

LSALT peptide and cilastatin are lead drug candidates in separate Phase 2 trials targeting acute kidney injury caused by inflammation and toxins, respectively. Both indications represent significant unmet medical needs in global kidney care. For more science details: www.archbiopartners.com/our-science. For investor materials and filings: www.archbiopartners.com/investor-hub.