Aridis Receives Agreement from the European Medicines Agency (EMA) on the Clinical Study Design and a Single Confirmatory Phase 3 Study of AR-301

Rhea-AI Summary

Aridis Pharmaceuticals has received positive feedback from the European Medicines Agency (EMA) regarding its proposed Phase 3 study for AR-301, an investigational monoclonal antibody candidate. The study aims to evaluate the efficacy of AR-301 as an adjunctive therapy for pneumonia caused by Gram-positive bacteria Staphylococcus aureus in mechanically ventilated hospitalized patients. The EMA has agreed to the study design, including the primary efficacy endpoint of Clinical Cure on Day 21. The magnitude of absolute efficacy was higher in older adults, with a +34% improvement on Day 21 and +38% improvement on Day 28 compared to +11% improvement in the overall population. The EMA also approved the expansion of the study to include ventilated hospital acquired pneumonia and ventilated community acquired pneumonia patients.

Positive

• The positive feedback from the EMA on Aridis Pharmaceuticals' proposed Phase 3 study for AR-301 is a significant development for the company.
• The agreement on the study design and endpoints provides a globally harmonized clinical study and regulatory pathway for AR-301.
• The higher efficacy observed in older adults suggests that AR-301 may be particularly beneficial for this vulnerable population.
• The expansion of the study to include additional patient populations increases the potential market for AR-301.
• The positive feedback from both the EMA and the FDA indicates a favorable regulatory outlook for AR-301.

Negative

• None.

LOS GATOS, Calif., July 17, 2023 (GLOBE NEWSWIRE) -- Aridis Pharmaceuticals, Inc. (Nasdaq: ARDS) today 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’.

“We are particularly gratified to reach concurrence, first with the FDA, and now with the EMA on the overall study design, endpoints, and patient populations,” said Aridis CEO Vu Truong. “This provides for a globally harmonized clinical study and regulatory pathway to bring AR-301 to patients with high vulnerabilities to Staph. Aureus infections, particularly older adults whose immune system is in the inevitable steady decline as they age.”

About the Confirmatory AR-301-003 Phase 3 Study
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.

About AR-301
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.

About Aridis Pharmaceuticals, Inc.
Aridis Pharmaceuticals, Inc. discovers and develops anti-infectives to be used as add-on treatments to standard-of-care antibiotics.

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/HAP/CAP). AR-301 is a fully human IgG1 mAb currently in Phase 3 clinical development targeting gram-positive S. aureus alpha-toxin in ventilator associated pneumonia (VAP), ventilated hospital acquired pneumonia (HAP), and ventilated community acquired pneumonia (CAP) patients.
AR-320 (VAP). AR-320 is a fully human IgG1 mAb targeting S. aureus alpha-toxin that is being developed 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 additional information on Aridis Pharmaceuticals, please visit https://aridispharma.com/.

Forward-Looking Statements
Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. These statements may be identified by the use of words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Aridis' expectations, strategy, plans or intentions. These forward-looking statements are based on Aridis' current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, the need for additional financing, the timing of regulatory submissions, Aridis' ability to obtain and maintain regulatory approval of its existing product candidates and any other product candidates it may develop, approvals for clinical trials may be delayed or withheld by regulatory agencies, risks relating to the timing and costs of clinical trials, risks associated with obtaining funding from third parties, management and employee operations and execution risks, loss of key personnel, competition, risks related to market acceptance of products, intellectual property risks, risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses, risks associated with the uncertainty of future financial results, Aridis' ability to attract collaborators and partners and risks associated with Aridis' reliance on third party organizations. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described under the caption "Risk Factors" in Aridis' 10-K for the year ended December 31, 2022 and Aridis' other filings made with the Securities and Exchange Commission. Forward-looking statements included herein are made as of the date hereof, and Aridis does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.

Contact:
Dave Gentry
RedChip Companies, Inc.
ARDS@redchip.com
1-800-733-2447

SOURCE Aridis Pharmaceuticals, Inc.

FAQ

What is the purpose of Aridis Pharmaceuticals' Phase 3 study for AR-301?

The Phase 3 study aims to evaluate the efficacy of AR-301 as an adjunctive therapy for pneumonia caused by Staphylococcus aureus in mechanically ventilated hospitalized patients.

What is the primary efficacy endpoint of the study?

The primary efficacy endpoint is Clinical Cure of pneumonia on Day 21.

What was the magnitude of absolute efficacy observed in older adults in the first Phase 3 study?

In the first Phase 3 study, older adults showed a +34% improvement on Day 21 and a +38% improvement on Day 28 compared to +11% improvement in the overall population.

What patient populations will be included in the expanded Phase 3 study?

The expanded Phase 3 study will include ventilated hospital acquired pneumonia and ventilated community acquired pneumonia patients.

What does the positive feedback from the EMA and FDA indicate?

The positive feedback from both regulatory agencies indicates a favorable outlook for AR-301.