New drugs to prevent organ inflammation and acute kidney injury

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 lungs, kidneys and liver 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

• 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 PONTIAC trial targeting drug toxin-related AKI. The PONTIAC investigators are planning to begin patient recruitment in late 2024.