BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections
- Nat Commun. 2024 Sep 18;15(1):8202. doi: 10.1038/s41467-024-52557-2.
- 1. Bugworks Research India Pvt. Ltd. Center for Cellular & Molecular Platforms, National Center for Biological Sciences, GKVK Campus, Bellary Road, Bangalore, 560 065, India.
- 2. Apconix Ltd. Alderley Park, Alderley Edge, Cheshire, SK10 4TG, UK.
- 3. RxMD, 320/1, Lloyds Road, Royapettah, Chennai, 600 014, India.
- 4. Medchemica Ltd., No. 8162245, Ebenezer House, Newcastle-under-Lyme, Staffordshire, ST5 2BE, England.
- 5. TheraIndx Lifesciences Pvt. Ltd., Sy No. 27, Deganahalli, Bangalore, 562123, India.
- 6. JMI Laboratories, 345 Beaver Kreek Center, North Liberty, IA, 52317, USA.
- 7. IHMA USA, 2122 Palmer Drive, Schaumburg, IL, 60173-3817, USA.
- 8. IHMA India, Gurugram, Haryana, 122018, India.
- 9. Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7BE, UK.
- 10. Syngene International Ltd., Biocon Park, Plot No. 2 & 3, Bommasandra Jigani Link Road, Bangalore, 560 099, India.
- 11. Narayana Health, Mazumdar Shaw Medical Center, 258/A, Bommasandra Industrial Area, Hosur Road, Bangalore, 560 099, India.
- 12. Microbiology laboratory, St. John's Hospital, Sarjapur Road, Bangalore, 560 034, India.
- 13. Highbury Regulatory Science Limited, SK10 4TG, Nether Alderley, Cheshire, SK10 4TG, UK.
- 14. Bugworks Research India Pvt. Ltd. Center for Cellular & Molecular Platforms, National Center for Biological Sciences, GKVK Campus, Bellary Road, Bangalore, 560 065, India. [email protected].
The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum Antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits Bacterial DNA replication via inhibition of DNA gyrase and Topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03-2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR Bacterial pneumonias.