Aridis Announces a Key Milestone of Closing of Patient Enrollment in the Phase 2a Study of AR-501 in Cystic Fibrosis Patients

Aridis Pharmaceuticals, Inc. recently announced the closing of patient enrollment in the multiple ascending dose (MAD) and dose-ranging cohorts in the Phase 2a clinical trial of AR-501 in cystic fibrosis (CF) patients. The Company is on track to complete database lock, data analyses, and disclose top-line data in the first quarter of 2023.

The Phase 2a study enrolled 39 CF patients from 24 clinical centers in the US. The CF patients were randomized and treated in 4 cohorts; 3 cohorts received three weekly multiple ascending doses of active drug at 6.4 mg, 20 mg and 40 mg or placebo, while the 4th Cohort being dose-ranging with subjects randomized to three weekly doses of AR-501 6.4 mg, 20 mg, or 40 mg, or placebo. CF subjects were followed for 28 days after last study dose for safety and pharmacokinetics (PK) of inhaled AR-501. Aridis previously reported positive Phase 1 safety data in June 2020 in healthy adults who were exposed to either a single ascending dose (SAD) regimen or a multiple ascending dose (MAD) regimen.

“We worked diligently through the pandemic to enroll patients and are very pleased to reach this key milestone for our Phase 2a study of AR-501 in CF patients,” said Aridis’ Chief Medical Officer Hasan Jafri, MD. “Our focus is now on data gathering from the clinical trial centers. We anticipate reporting top-line results in the first quarter of 2023.”

AR-501 is being developed in collaboration with the Cystic Fibrosis Foundation (CFF) and has been granted Orphan Drug Designation (ODD), Fast Track, and Qualified Infectious Disease Product (QIDP) designations by the US FDA. In addition, the European Medicines Agency (EMA) granted ODD to AR-501.

AR-501 is an inhalable broad-spectrum anti-infective currently under development for controlling debilitating chronic lung infections in CF patients. AR-501 functions as an iron analog, which is a mechanism of action that is distinct from antibiotics, and has broad antimicrobial activity against several common bacterial, fungal, and mycobacterial species are sometimes found to colonize the lungs of CF patients. The current study is a randomized, double-blind, placebo-controlled Phase 2a trial investigating the safety and pharmacokinetics of multiple ascending doses of inhaled AR-501 in CF patients with chronic bacterial lung infections. Based on available blinded safety data of the on-going Phase 2a study, FDA concurred with the company’s proposal to include an optional higher dose cohort after enrollment of the current dose cohorts.

Cystic Fibrosis (CF) is a genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) protein. This leads to numerous medical problems, including abnormal airway secretions, mucus accumulation, and opportunistic bacterial infections. Pseudomonas aeruginosa is the most significant pathogen, with > 80% of CF patients becoming chronically infected with P. aeruginosa by 18 years of age. Also of increasing prevalence in CF patients are infections caused by Staphylococcus aureus and non-tuberculosis mycobacterium (NTM). Extensive antibiotic treatment has led to selection of resistant strains, which are less responsive to drug treatment and exacerbate disease progression.

Aridis Pharmaceuticals, Inc. discovers and develops novel anti-infective therapies to treat life-threatening infections, including anti-infectives to be used as add-on treatments to standard-of-care antibiotics. The company is utilizing its proprietary ʎPEX and MabIgX technology platforms to rapidly identify rare, potent antibody-producing B-cells from patients who have successfully overcome an infection, and to rapidly manufacture monoclonal antibodies (mAbs) for therapeutic treatment of critical infections. These mAbs are already of human origin and functionally optimized for high potency by the donor’s immune system; hence, they typically do not require genetic engineering or further optimization to achieve full functionality.

The company is advancing multiple clinical stage mAbs targeting bacteria that cause life-threatening infections such as ventilator associated pneumonia (VAP) and hospital acquired pneumonia (HAP), in addition to preclinical stage antiviral mAbs. The use of mAbs as anti-infective treatments represents an innovative therapeutic approach that harnesses the human immune system to fight infections and is designed to overcome the deficiencies associated with the current standard of care which is broad spectrum antibiotics. Such deficiencies include, but are not limited to, increasing drug resistance, short duration of efficacy, disruption of the normal flora of the human microbiome and lack of differentiation among current treatments. The mAb portfolio is complemented by a non-antibiotic novel mechanism small molecule anti-infective candidate being developed to treat lung infections in cystic fibrosis patients. The Company’s pipeline is highlighted below:

Aridis’ Pipeline

AR-301 (VAP). AR-301 is a fully human IgG1 mAb targeting gram-positive Staphylococcus aureus (S. aureus) alpha-toxin and is being evaluated in a global Phase 3 superiority clinical study as an adjunctive treatment of S. aureus ventilator associated pneumonia (VAP).

AR-320 (VAP). AR-320 is a fully human IgG1 mAb targeting S. aureus alpha-toxin that is being evaluated in a Phase 3 clinical study as a preventative treatment of S. aureus colonized mechanically ventilated patients who do not yet have VAP.

AR-501 (cystic fibrosis). AR-501 is an inhaled formulation of gallium citrate with broad-spectrum anti-infective activity being developed to treat chronic lung infections in cystic fibrosis (CF) patients. This program is currently in Phase 2a clinical development in CF patients.

AR-701 (COVID-19). AR-701 is a cocktail of fully human mAbs discovered from convalescent COVID-19 patients that are directed at multiple protein epitopes on the SARS-CoV-2 virus. It is formulated for delivery via intramuscular injection or inhalation using a nebulizer.

AR-401 (blood stream infections). AR-401 is a fully human mAb preclinical program aimed at treating infections caused by gram-negative Acinetobacter baumannii.

AR-101 (HAP). AR-101 is a fully human immunoglobulin M, or IgM, mAb in Phase 2 clinical development targeting Pseudomonas aeruginosa (P. aeruginosa) liposaccharides serotype O11, which accounts for approximately 22% of all P. aeruginosa hospital acquired pneumonia cases worldwide.

AR-201 (RSV infection). AR-201 is a fully human IgG1 mAb out-licensed preclinical program aimed at neutralizing diverse clinical isolates of respiratory syncytial virus (RSV).

For more information, visit https://aridispharma.com/.