Aridis Pharmaceuticals, Inc. announced positive feedback from the European Medicines Agency (EMA) on the Company?s proposed single confirmatory Phase 3 study of investigational monoclonal antibody candidate AR-301, which is being developed as an adjunctive therapy in combination with standard of care (SOC) antibiotics for the treatment of pneumonia caused by Gram-positive bacteria Staphylococcus aureus (S. aureus) in mechanically ventilated hospitalized patients. Key agreements by the EMA were similar to those agreed by the US FDA, which include: Agreement on the design of the single confirmatory Phase 3 superiority study required to support the submission of a Marketing Authorization Application (MAA) with the primary efficacy endpoint in older adults (=65 yrs). In the first Phase 3 study ?AR-301-002?, the magnitude of absolute efficacy was higher in older adults, i.e., +34% improvement on Day 21 (p= 0.057) and by +38% on Day 28 (p= 0.025) in older adults versus +11% improvement (p=0.24) in the overall population.

Agreement to the proposed expansion of the confirmatory Phase 3 study in S. aureus ventilator associated pneumonia (VAP) patients to include S. aureus pneumonia in ventilated hospital acquired pneumonia (HAP) and ventilated community acquired pneumonia (CAP) patients. Agreement on Clinical Cure of pneumonia on Day 21 as the primary efficacy endpoint, as in the first Phase 3 study ?AR-301-002?. AR-301-003 will be the second and final of two planned Phase 3 superiority studies evaluating the efficacy and safety of AR-301 for adjunctive therapy of pneumonia caused by S. aureus in critically ill hospitalized patients.

The study is a randomized, double-blind, superiority trial with the primary efficacy endpoint of Clinical Cure of pneumonia in adults 65+ years old at Day 21 post-treatment. The secondary endpoints will include Clinical Cure rates of pneumonia in study subjects =65 and <65 years of age, safety including all-cause mortality, and healthcare utilization. Approximately 200 clinical sites in 20+ countries are expected to participate in the study, including US, Latin and S. America, Europe, and Asia Pacific.

AR-301 is a fully human IgG1 monoclonal antibody that specifically targets S. aureus alpha-toxin, an important virulence factor that is secreted by both methicillin-resistant S aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). AR-301 is designed to protect against alpha-toxin mediated destruction of host cells, preserving a functional host immune response. AR-301?s mode of action is independent of the antibiotic resistance profile of S. aureus and it is active against infections caused by both MRSA and MSSA.

Previously in the AR-301-002 Phase 3 superiority study, an improvement trend in absolute efficacy in Clinical Cure rate at Day 21 of 11.2%, [p= 0.24] was observed in treated patients as compared to placebo. An improvement in Clinical Cure rate (or absolute efficacy) =10% is considered a clinically meaningful improvement by many key opinion leaders. In the prespecified older adult population of 65+ years, the absolute efficacy on Day 21 was increased to 33.6% (p= 0.057), and to 37.9% (p= 0.025) on Day 28.

The increase in absolute efficacy was particularly remarkable given the lower efficacy of SOC antibiotics in older adults 65+ years old compared to adults =65 years old (30% vs. 75%, respectively). In the patients with MRSA, the Day 21 absolute efficacy trend was 28% higher than SOC alone (p=0.831).

The increase in absolute efficacy was also driven primarily by the lower efficacy of SOC antibiotics in MRSA patients compared MSSA patients (38% vs. 63%, respectively). Furthermore, treatment with AR-301 was associated with reduction trends in key secondary outcome measures of duration of hospitalization (median 19 vs.

28 days, difference: 9 days), time in ICU (median 13 vs. 20 days, difference: 7 days) and mechanical ventilation days (median 6 vs. 8 days, difference: 2 days).

Consistent positive efficacy trends were observed in favor of AR-301 treatment in other key secondary efficacy outcomes (e.g., Clinical Cure rates at days 7, 14, 28). Primary outcome measures of safety and tolerability of AR-301 were achieved. AR-301 intravenous (IV) infusion was well tolerated.

No meaningful differences were observed in adverse Events (AEs) and Serious Adverse Events (SAEs) reported between the active and placebo treatment groups over the 28-day study period, with no SAEs deemed drug-related. Staphylococcus aureus Ventilator Associated Pneumonia (VAP), Hospital Acquired Pneumonia (HAP), and Community Acquired Pneumonia (CAP): VAP, ventilated HAP, and ventilated CAP caused by S. aureus poses serious challenges in the hospital setting, as standard of care antibiotics are becoming inadequate in treating infected patients. These patients are typically at high risk of mortality, which is compounded by other life-threatening co-morbidities and the rise in antibiotic resistance.

Epidemiology studies estimate that the probability of death attributed to S. aureus ranges from 29% to 55%. In addition, pneumonia infections can prolong patient stays in ICUs (intensive care units) and the use of mechanical ventilation, creating a major economic burden on patients, hospital systems and payors.