# Development of synergistic clofazimine-amikacin inhalable powders for the treatment of pulmonary Mycobacterium abscessus infections

> **NIH NIH R43** · VIA THERAPEUTICS, LLC · 2021 · $256,350

## Abstract

PROJECT SUMMARY
Mycobacterium abscessus (Mab) lung infections are extremely resistant to drug therapy and are growing in
prevalence, particularly in the cystic fibrosis community where they are associated with decreased lung
function and a high mortality rate. Current treatment guidelines recommend a two-year regimen of a
combination of four antibiotics that are associated with numerous systemic toxicities that require regular
monitoring, and treatments are successful in only 30% of cases. The noted virulence of Mab and recalcitrance
to antibiotic therapy may be related to its ability to persist both extracellularly in biofilms and abscesses and
intracellularly in macrophages. Delivery of antibiotics by the inhalation route is promising alternative for the
treatment of Mab, as it would enable high drug concentrations at both sites of infection while minimizing
systemic drug exposure. However, two promising inhaled antibiotics, clofazimine (CFZ) and liposomal
amikacin (AMK), have resulted in little to no efficacy when utilized in vivo to treat chronic Mab lung infections,
despite notable in vitro activity against Mab and in vivo activity against other mycobacterial species. Based
upon the premise that inhaled monotherapy is ineffective, we have developed a patentable inhaled co-
formulation of CFZ and AMK which will enable simultaneous delivery of these antibiotics to the site of Mab lung
infection, thereby enabling the transition of the noted in vitro synergistic activity of the antibiotics to an in vivo
environment. The proposed research seeks to optimize the mechanism of formulation engineering and
composition CFZ-AMK powder through the in vitro and in vivo evaluation of composite spray dried CFZ-AMK
particles and physically blended CFZ and AMK micronized powders prepared at varying mass ratios. The
relationship between powder composition and properties will be determined through evaluation of powder
aerosol performance using commercially available devices, modeling of in vitro dissolution rate, assessing
extracellular and intracellular antimicrobial activity and determining in vivo pharmacokinetic parameters and
efficacy in a chronic Mab infection model. The significance of this study is that it utilizes existing, already-
proven-safe drugs and repurposes them in a patentable manner for simultaneous lung delivery and at-site
synergistic activity, which will improve therapeutic outcomes in this extremely difficult to treat infection. The
expected outcome is that inhaled CFZ-AMK fixed dose combination powders will successfully treat multiple
facets of Mab lung disease, which will de-risk the transition from the pre-clinical to clinical stages.

## Key facts

- **NIH application ID:** 10256328
- **Project number:** 1R43AI162348-01
- **Recipient organization:** VIA THERAPEUTICS, LLC
- **Principal Investigator:** Zachary N Warnken
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $256,350
- **Award type:** 1
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10256328

## Citation

> US National Institutes of Health, RePORTER application 10256328, Development of synergistic clofazimine-amikacin inhalable powders for the treatment of pulmonary Mycobacterium abscessus infections (1R43AI162348-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10256328. Licensed CC0.

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