(507) PHASE 1/2a RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY: SAFETY, PK, AND EFFICACY OUTCOME MEASURES OF INHALED GALLIUM CITRATE (AR-501) IN CYSTIC FIBROSIS PATIENTS

Background: AR-501, inhaled gallium citrate, a novel iron analog disrupts microbial iron-dependent metabolic pathways, resulting in antimicrobial activity against bacteria, non-tuberculous mycobacterium (NTM), and fungi, and a low potential to induce antimicrobial resistance (AMR). A Phase 1/2a study evaluating the safety and pharmacokinetics (PK) of inhaled AR-501 in healthy volunteers (HV) and preliminary efficacy in P. aeruginosa infected cystic fibrosis (CF) subjects is scheduled to be completed with data readout by August 2022 (www.clinicaltrials.gov NCT03669614). As previously reported, inhaled AR-501 in HV’s was generally well tolerated once weekly for 5 weeks. In this PLACEHOLDER ABSTRACT, we report the safety, PK, and exploratory efficacy outcome results in adult CF subjects receiving a once-weekly inhaled dose of AR-501 x3 doses over four weeks. Full results are anticipated before the 2022 NACFC. The abstract will be updated with these results for the NACFC 2022 meeting.

Methods: In this randomized, double-blind, placebo-controlled study, Phase 1 in 50 healthy volunteers has been completed, while the Phase 2a study is currently being conducted in 39 CF adult subjects dosed in 3 sentinel cohorts. Each cohort will receive a once-weekly, 3-dose regimen of an escalating inhaled active drug (6.4, 20 and 40 mg Ga) or placebo, in a 3:1 ratio. Subjects are followed for 28 days after the 3rd study dose. Outcome measures include safety, PK, pulmonary function (FEV₁), respiratory microbiology, CFQ-R, and systemic inflammatory biomarkers.

Results: In Phase 2a, all CF sentinel subjects have completed all 3 doses across the Low (6.4mg), Medium (20 mg), and High (40 mg) dose cohorts in a blinded fashion, and the safety data have been reviewed by an independent unblinded Data and Safety Monitoring Board (DSMB). AR-501 administered via nebulization has been well tolerated, with no serious adverse events (SAEs) reported during the study. The unblinded DSMB expressed no safety concerns and recommended proceeding to the expanded phase of dosing. The expanded dose cohort entails 30 subjects to be randomized in a 2:3:3:2 ratio across Low Dose (n=6), Medium Dose (n=9), High Dose (n=9), and Placebo (n=6). The DSMB will review the cumulative data from the expanded cohort, prior to full database lock and unblinding of safety, PK, efficacy and biomarker data.

Conclusions: AR-501 is being developed as a once-a-week aerosolized antimicrobial with low potential for inducing AMR. Inhaled AR-501 in chronically P aeruginosa infected CF subjects has been well tolerated when administered once weekly x 3 weeks. The Phase 2a safety, efficacy and biomarker data readout is expected prior to the 2022 NACFC meeting and will be added to the current placeholder abstract prior to the meeting.

Acknowledgements: Alan H. Cohen¹, Noah Lechtzin², Kimberly McBennett³, Peter Murphy⁴, Edmund Sears⁵, Lucas Hoffman⁶, Milene Saavedra⁷, Katherine B. Hisert⁷, Michelle Stevens-Brogan¹, Clara Plascencia¹, Lynne Deans¹, Andrew Kelson¹, Phillip Lovalenti¹, Jennifer Woo¹, Vu Truong¹ and Hasan S. Jafri¹.

Aridis Pharmaceuticals, Inc. Los Gatos, CA. John Hopkins University², University of Cleveland Medical Center³, University of Nebraska medical Center⁴, Maine Medical Center⁵, University of Washington⁶, and National Jewish Health^7.

This study is supported by the Cystic Fibrosis Foundation.

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