During IDWeek 2025 in Atlanta, Georgia, Loren G. Miller, MD, MPH, investigator at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, presented landmark findings from the Phase 2a diSArm study. Conducted in collaboration with Armata Pharmaceuticals, Inc., the study demonstrated for the first time in a randomized clinical trial the efficacy of an intravenous bacteriophage therapy in treating complicated Staphylococcus aureus bacteremia (“SAB”).
Bacteriophages are virus-like particles that infect bacteria. Bacteriophages may have advantages over traditional antibiotics in that they address the problem of increasing antibiotic resistance among bacteria by attacking with a novel mechanism. Additionally, bacteriophages target a single pathogenic bacteria and thus have minimal or no disruption of the healthy human microbiome.
The diSArm study evaluated AP-SA02, a high-purity, pathogen-specific bacteriophage cocktail developed by Armata Pharmaceuticals, in combination with best available antibiotic therapy (BAT) compared to placebo plus BAT. Results showed that AP-SA02 was safe and demonstrated encouraging efficacy in patients with complicated S. aureus bacteremia, one of the most serious and difficult-to-treat bacterial infections. At each multiple time points after treatment, patients receiving the AP-SA02 had higher clinical success than those who received placebo.
Dr. Miller played a pivotal role in the execution of the diSArm trial and presented results of the trial at IDWeek 2025 in Atlanta as a late breaker oral abstract. IDWeek 2025 only accepts highly competitive, novel, and timely abstracts as late breakers, highlighting the importance of the trial’s findings.
“The results of the diSArm study confirm, for the first time, the efficacy of intravenous phage therapy for S. aureus bacteremia,” said Dr. Miller. “These findings provide strong rationale for a Phase 3 study and signal a potential paradigm shift in how we treat antibiotic-resistant infections. High-purity, phage-based therapeutics like AP-SA02 may one day become a new standard of care for patients facing this life-threatening condition.”
Armata Pharmaceuticals’ CEO, Dr. Deborah Birx, recognized Dr. Miller and the clinical team for their contributions: “The positive results from the diSArm study represent another significant achievement as we advance AP-SA02 toward a pivotal Phase 3 trial,” said Dr. Birx. “We extend our gratitude to Dr. Miller and the other investigators for their leadership and commitment to bringing innovative therapies to patients with severe bacterial infections.”
The diSArm study was conducted with support from the U.S. Department of Defense and Innoviva, Armata’s major shareholder, both of whom have played critical roles in enabling the development of phage-based therapeutics as a potential solution to the global challenge of antimicrobial resistance.
Data Highlights
The Phase 2a study enrolled and dosed 42 patients, with 29 randomized to AP-SA02 in addition to BAT and 13 to placebo (BAT alone). Methicillin-resistant S. aureus (“MRSA”) was the causative pathogen in ~38% of both the AP-SA02 and placebo groups.
Clinical response was assessed in the intent-to-treat (ITT) population at Test of Cure (“TOC”) on day 12, one week post-BAT, and End of Study (“EOS”) four weeks after BAT completion. Safety analysis also included data from the Phase 1b portion of the trial (n=8).
Day 12 clinical response rates were higher in the AP-SA02 group — 88% (21/24) versus 58% (7/12) in the placebo group as assessed by blinded site investigators (“PI”) (p = 0.047), and 83% (20/24) in the AP-SA02 group versus 58% (7/12) in the placebo group as assessed by the blinded Adjudication Committee (“AC”).
Non-response/relapse rates were evaluated at the two later timepoints — one week post-BAT and EOS. No patients in the AP-SA02 group experienced non-response or relapse (0%) by either PI or AC assessment. In contrast, the placebo group showed 25% non-response/relapse at both timepoints reported by the PI (p = 0.017) and 22% non-response/relapse at one week post-BAT (p = 0.025) and 25% at EOS (p = 0.02) by the AC.
Patients treated with AP-SA02 showed trends toward rapid normalization of C-reactive protein, shorter time to negative blood culture, quicker time to resolution of signs and symptoms at the infection site, shorter intensive care unit and hospital utilization.
AP-SA02 was well-tolerated with no serious adverse events related to the study drug. Treatment-emergent adverse events occurred in 6% (2/35) and 0% (0/15) in the AP-SA02 and placebo groups, respectively: one patient with transient liver enzyme elevation and one patient with hypersensitivity that resolved with discontinuation of vancomycin.
New findings demonstrate that the defined and reproducible genomic variants present in AP-SA02 Drug Product may provide an immediate advantage, enabling rapid, strain-specific response to each patient’s S. aureus isolate. These characterized variants can expand from as little as 2% to dominance when infecting certain patient isolates in vitro, highlighting that these variants are favored for their enhanced ability to infect those strains and the importance of integrating this diversity into Armata’s phage cocktail from the outset. This inherent flexibility may be central to achieving optimal therapeutic efficacy.
Conclusions
AP-SA02, combined with BAT, had a higher and earlier cure rate compared to placebo in patients with complicated SAB at day 12 as assessed by both blinded site investigators and independent adjudicators.
No patients who received AP-SA02 demonstrated non-response or relapse at one week post-BAT or at EOS, as assessed by both blinded site investigators and the independent adjudication committee, compared with approximately 25% in the placebo group.
AP-SA02 appears safe with clinical efficacy against both MRSA and methicillin-sensitive S. aureus (“MSSA”) and trends toward earlier resolution and shorter hospitalization, with no evidence of relapse four weeks post-therapy.
Defined phage variants in AP-SA02 Drug Product ensure an intrinsic adaptive mechanism — a flexibility that may be key to achieving effective phage therapy from patient to patient.
These results strongly support advancement into a pivotal Phase 3 trial that Armata plans to initiate in 2026, subject to review and feedback from the U.S. Food and Drug Administration (the “FDA”). The Company is engaged with the FDA regarding a potential superiority trial design.
About AP-SA02 and diSArm Study
Armata is developing AP-SA02, a fixed multi-phage phage cocktail, for the treatment of complicated bacteremia caused by Staphylococcus aureus (S. aureus), including methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains.
The diSArm study (NCT05184764) was a Phase 1b/2a, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose escalation study of the safety, tolerability, and efficacy of intravenous AP-SA02 in addition to best available antibiotic therapy (BAT) compared to BAT alone (placebo) for the treatment of adults with complicated S. aureus bacteremia. The results from the diSArm study are an important step forward in Armata’s effort to confirm the potent antimicrobial activity of phage therapy and the completion of the study represents a significant milestone in the development of AP-SA02, moving Armata one step closer to introducing an effective new treatment option to patients suffering from complicated S. aureus bacteremia.
The Phase 1b/2a clinical development of AP-SA02 was partially supported by a $26.2 million Department of Defense (DoD) award, 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.
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