M. ABSCESSUS
M. abscessus: chronic lung disease with no approved drugs
Progressive, irreversible lung damage
Persistent infection drives ongoing inflammation, declining lung function, and structural destruction
No FDA-approved drugs
Off-label, 2 to 3 IV-only regimens with significant toxicities
20% 5-year mortality
Creates urgency to treat individual patients and an imperative to develop efficacious and tolerable anti-bacterials
A serious, difficult-to-treat, and chronic lung infection with a high mortality rate and no FDA-approved treatments
Current standard of care involves multi-drug regimens (inhaled and/or IV) given for ≥12 months after culture conversion. Treatment success rates are <50%, and there is significant toxicity risk from prolonged antibiotic exposure.
Epetraborole (EBO) has a novel mechanism of action in that it inhibits leucyl-tRNA synthetase (LeuRS; leucyl tRNA synthetase is an essential enzyme in protein synthesis). This mechanism has the potential to avoid existing resistance pathways seen with current therapies.
Preclinical highlights
Potent in vitro activity against M. abscessus clinical isolates, including macrolide-resistant strains.
Favorable pharmacokinetic properties supporting potential for oral dosing.
Low drug-to-drug interaction potential may be favorable in multi-drug regimens.
Bactericidal activity in preclinical pulmonary infection models.
