Following its phase II stumble of AR-105, Aridis Pharmaceuticals Inc. is dropping its development of the IgG1 monoclonal antibody. The study failed to meet its primary endpoint of showing superiority in clinical cure rates compared to placebo for treating ventilator-associated pneumonia caused by gram-negative Pseudomonas aeruginosa.
The study also found a statistically significant imbalance in all-cause mortality and serious adverse events rates between treatment groups that favored placebo. The study's data monitoring committee noted that no serious adverse events or mortality in the study was found to be drug-related.
Vu Truong, Aridis CEO, said Aridis will focus on its existing pipeline, AR-301 and AR-501, both of which are in clinical studies. That pipeline could well be why the stock remained relatively sturdy Tuesday. Before the market opened, shares (NASDAQ:ARDS) had plummeted by as much as 31%. However, as trading began and the hours passed, the flow of red ink slowed and the stock recovered enough to close down only 6.6%.
The failed AR-105 phase II was a double-blind, randomized, placebo-controlled study whose 158 subjects were treated with either standard-of-care antibiotics plus placebo or standard-of-care antibiotics plus AR-105. The trial began in March 2017 and was conducted at 100 sites in 17 countries. The primary outcome measure was a clinical cure in the 21 days following dosing.
AR-105 had successfully completed a phase I trial in 16 healthy volunteers by demonstrating safety up to doses of 20 mg/kg. In January 2016, Aridis reported phase I results for the drug, also known as Aerucin, for treating hospital-acquired and ventilator-associated pneumonia caused by gram negative bacteria Pseudomonas aeruginosa. The completed first-in-human study demonstrated AR-105's safety at all dose levels tested, showing no serious adverse events and only low-grade adverse events that were not deemed to be drug-related. Patients were assigned to one of three cohorts, each receiving an increasing dose of AR-105 up to 20 mg/kg. Participants were observed for a period of 84 days.
In August 2017, the company began its phase III of Aerucin, the fully human monoclonal antibody for treating acute pneumonia caused by gram negative bacteria Pseudomonas aeruginosa. Aerucin has proved effective in promoting phagocytic killing of a wide range of both mucoid and non-mucoid P. aeruginosa clinical isolates, including antibiotic-resistant strains from pneumonia and cystic fibrosis patients. In an animal model of acute pneumonia, the compound protected mice from lethal P. aeruginosa challenges at doses as low as 0.004 mg/kg, and protected animals against eye infections in a keratitis model as well as sepsis in a systemic infection model. (See BioWorld, Aug. 3, 2017.)
Pseudomonas aeruginosa is a bacterium that causes hospital-acquired pneumonia and is responsible for about 10% of all hospital-acquired infections in the U.S.
Meanwhile, Aridis is advancing lead candidate AR-301, which targets the alpha-toxin produced by gram-positive bacteria Staphylococcus aureus. The company also has AR-501, an inhaled formulation of gallium citrate being developed as a non-antibiotic anti-infective to treat lung infections in cystic fibrosis patients, with top-line data expected from its phase I/IIa trial in healthy subjects and cystic fibrosis patients. The data from the healthy subjects are expected by the end of the first quarter of 2020 and from cystic fibrosis patients in the second quarter of 2021.
The company was founded in 2005 by Truong along with Eric Patzer, now the board chair. Two years later, Aridis entered a formulation development agreement with the nonprofit global health organization PATH for a rotavirus vaccine formulation licensed from the NIH. The agreement covered a three-year period, with Aridis reimbursed for expenses totaling up to $1.9 million through an NIH biodefense grant. The company was able to stabilize the vaccine at room temperature for up to a year. As part of the demonstration project, the company also incorporated the vaccine into a thin oral film that could be placed on a baby's tongue to provide protection against the rotavirus. But the company eventually came to focus on antibiotic resistance, which would become an ever more urgent problem.
In August 2018, the San Jose-based company priced an IPO of 2 million shares of its common stock at $13 apiece to raise $26 million.