Arch Biopartners Announces Cilastatin GMP Manufacturing

TORONTO, June 27, 2024 – Arch Biopartners Inc., a clinical-stage biotechnology company, has achieved a significant milestone in the development of cilastatin, a drug aimed at preventing acute kidney injury (AKI). Dalton Pharma Services has successfully completed the good manufacturing practice (GMP) glass vial filling stage for cilastatin, the company's second drug candidate. Over the next six to eight weeks, Dalton will conduct quality control processes, culminating in the release of the first-ever standalone cilastatin drug product. This product will be used in a Phase II clinical trial targeting drug toxin-related AKI in hospitalized patients, expected to begin in late 2024.

Arch Biopartners has committed to partnering with a group of Canadian clinical researchers for this Phase II trial. The company will provide the cilastatin drug product, as well as scientific and regulatory advice. It will also act as a study partner for grant funding opportunities. Arch holds method-of-use patents for cilastatin in several jurisdictions, including North America and Europe, either proprietary or exclusively licensed to the company. This announcement marks a pivotal step forward in Arch's efforts to repurpose cilastatin as a new treatment for toxin-related AKI.

Cilastatin is a dipeptidase-1 (DPEP1) inhibitor developed in the early 1980s by Merck Sharp & Dohme Research Laboratories. Initially, it was used to limit the renal metabolism of imipenem, a β-lactam antibiotic for systemic infections. The fixed combination of cilastatin and imipenem was marketed under various names, including Primaxin®, Tienam®, and Zienam®, and was approved by the FDA in 1985. However, there has been no commercial history of cilastatin as a standalone drug product.

Cilastatin operates through a distinct mechanism of action compared to Arch's novel drug candidate, LSALT peptide (Metablok), another DPEP1 inhibitor. While LSALT peptide specifically targets DPEP1-mediated inflammation in the kidneys, lungs, and liver, cilastatin has additional off-target effects that hinder toxin uptake in the kidneys. This makes cilastatin particularly effective for treating toxin-related AKI, unlike LSALT peptide, which targets non-toxin-related AKI.

AKI encompasses a range of clinical presentations, from mild injury to severe cases that may result in permanent kidney failure. The causes of AKI include sepsis, ischemia-reperfusion injury, and various endogenous and exogenous (drug) toxins, with no specific therapeutic treatment currently available. In severe cases, patients may require kidney dialysis or a transplant for survival. About 30% of AKI cases in hospitalized patients are induced by drug toxins, such as antibiotics, chemotherapeutic agents, and radiographic contrast. Cilastatin's unique off-target effects make it particularly suited to preventing AKI caused by these drug toxins. Multiple in vitro and in vivo studies have shown that cilastatin can prevent AKI induced by various nephrotoxic drugs.

Arch Biopartners Inc. is focused on developing new drugs to prevent inflammation and acute organ injury in the kidneys, liver, and lungs, aiming to address common injuries and diseases where organ inflammation is a significant issue. The company is advancing a platform of drugs targeting the DPEP1 pathway to tackle these unmet medical needs. 

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