| Phase 2 Clinical Trials Evaluating Multi-phage Candidates for the Treatment of Adults with Bacteremia due to Staphylococcus aureus (diSArm) and Chronic Respiratory Infections due to Pseudomonas aeruginosa (SWARM-P.a. & Tailwind) Mina Pastagia, MD, Stacey Kolar, PhD, Pierre Kyme, PhD, Thomas Feinberg, MS, Deborah Birx, MD Armata Pharmaceuticals, Inc., Los Angeles, California INTRODUCTION METHODS RESULTS* Novel therapeutics such as bacteriophage may be of clinical benefit in the treatment of challenging infections and respond to the need to combat antimicrobial resistance (AMR). Phages boast several potential advantages over conventional broad-spectrum antibiotics. As bactericidal agents with a narrow spectrum of activity, phages exert minimal disruption to normal flora, thereby exhibiting inherently lower toxicity profiles. Their efficacy extends to both antibiotic-sensitive and -resistant bacteria, rendering phage activity independent of prevailing antibiotic resistance patterns. Furthermore, phages demonstrate efficacy in disrupting bacterial biofilms, a feat poorly accomplished by antibiotics. Although phage therapy has enjoyed widespread utilization and success in human medicine, often serving as a last-resort salvage therapy, its safety and efficacy await conclusive validation through randomized, placebo-controlled clinical trials.1-3 Armata’s goal with the support of the U.S. Department of Defense is to prove the role of phage therapy through definitive pivotal trials addressing: • Phage therapy as an alternative or augmentation to antibiotics to prevent or delay resistance • Evidence that phage is non-inferior to standard-of-care antibiotics Advantages of phage therapy: • Targeted therapy while preserving the microbiome resulting in decreased patient morbidity • Ability to constantly update the phage cocktail based on evolution of bacteria at the population level • Antibiotic use eliminated or decreased OBJECTIVES 1. Administration of high doses of intravenous and inhaled phage for multiple days is well-tolerated in human clinical trial subjects 2. Systemic and local phage remain active in the blood and lungs, respectively when administered to human clinical trial subjects 3. Inhaled phage monotherapy may have similar bacterial load reduction as compared with antibiotics in human trial subjects diSArm is a Phase 1b/2a, placebo-controlled, multiple ascending dose escalation study of intravenous AP-SA02 as an adjunct to best available antibiotic therapy (BAT) compared to BAT alone. The trial has evaluated the safety and tolerability of AP-SA02 via IV bolus infusion every 6 hours for a period of 5 days in addition to BAT at 2 dose levels: 2 × 10⁹ PFU (Ph1b, Cohort 1) and 2 x 10¹⁰ PFU (Phase 1b, Cohort 2). The trial is actively enrolling subjects with complicated Staphylococcus aureus (S. aureus) bacteremia. Subjects in diSArm Phase 1b were dosed at 2 dose levels, for a total of 8 subjects. The dose was further increased in the enrolling Phase 2a. The study remains blinded. There have been no deaths or significant AEs precluding dose escalation. There is retention of phage activity from blood samples collected after dosing. Detection of phage despite 48 hours of antibiotics is observed in a subgroup of subjects (~50%), indicating that these subjects may have persistent S. aureus that the phage are potentially able to find and kill and is evidence of in vivo amplification. CONCLUSIONS* Multiple-dose administration of intravenous AP-SA02 and inhaled AP-PA02 have been well tolerated to date. Early pharmacokinetic data suggests intravenous AP-SA02 is active in all subjects, with longer phage persistence in a significant subset of subjects. This may garner increased clinical benefit for patients with difficult to treat S. aureus infections. Early evidence supports inhaled AP-PA02 monotherapy as a viable alternative to inhaled antibiotics in P. aeruginosa bronchiectasis. Promising data for both phage candidates is expected to be utilized for planning pivotal Phase 3 clinical trials in 2025. REFERENCES 1. Principi N, Silvestri E, Esposito S. Advantages and Limitations of Bacteriophages for the Treatment of Bacterial Infections. Front Pharmacol. 2019;10:513. 2. Chen Q, Dharmaraj T, Cai PC, et al. Bacteriophage and Bacterial Susceptibility, Resistance, and Tolerance to Antibiotics. Pharmaceutics. 2022;14(7). 3. Lin DM, Koskella B, Lin HC. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther. 2017;8(3):162-173. CONTACT Armata Pharmaceuticals, Inc. 5005 McConnell Ave, Los Angeles, CA 90066 Tel: +1 (310) 665-2928 Fax: +1 (310) 665-2963 Email: bd@armatapharma.com diSArm Clinical Trial Data *Preliminary findings are subject to change pending complete data that will be presented in the future Early Evidence of AP-SA02 Amplification in Subjects with Active S. aureus Bacteremia Early Timepoints Post 1st Dose Extended Timepoints Post 1st Dose Early Timepoints Post 1st Dose Extended Timepoints Post 1st Dose Subjects with Longer AP-SA02 Persistence in the Blood Subjects with Shorter AP-SA02 Persistence in the Blood Patient population: 48 non-cystic fibrosis bronchiectasis subjects across 23 U.S. sites. Status: Enrollment completed 2024. Blinded data: Comparable to better P. aeruginosa reduction with AP-PA02 monotherapy compared to AP-PA02 in combination with antibiotics: topline data available in September 2024. Patient population: ~50 subjects across ~30 U.S. and Australian sites. Status: ~75% enrolled => Completion projected Q4 2024. Early blinded data: AP-SA02 activity and persistence in a subset of subjects. Supported by: Armata has a $21.6 million Department of Defense grant, received through the Medical Technology Enterprise Consortium (MTEC) and managed by the Naval Medical Research Command (NMRC) – Naval Advanced Medical Development (NAMD) with funding from the Defense Health Agency and Joint Warfighter Medical Research Program. The grant was awarded to Armata to support clinical development of its optimized phage candidate, AP-SA02, as a potential treatment for complicated Staphylococcus aureus bacteremia. Patient population: 29 cystic fibrosis subjects across 25 U.S. sites. Status: Completed 2023. Data Results: Pseudomonas aeruginosa (P. aeruginosa) reduction with higher AP-PA02 exposures. Armata is committed to double-blind, placebo-controlled clinical trials and has completed or is enrolling 3 distinct Phase 2 trials over the past 2 years Time Viable Phage Concentration Subject G Subject H Subject J Subject U Subject V Subject L Time Viable Phage Concentration Time Viable Phage Concentration Subject I Subject N Subject R Subject M Subject P Time Viable Phage Concentration |
