Debio 1453
A first-in-class antibiotic for the treatment of Neisseria gonorrhoeae infections
Debiopharm is developing an antibiotic with a novel mechanism action against Neisseria gonorrhoeae, the causative bacteria of the sexually transmitted disease gonorrhea. Debio 1453 specifically targets FabI, an essential enzyme for the growth of N. gonorrhoeae. Debio 1453 is being developed with the support of the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X). The drug candidate shows very potent activity against N. gonorrhoeae, while reducing selective pressure on other bacteria that constitute the “healthy microbiota”. The potential benefits of Debiopharm’s FabI inhibitors for gonorrhea include:
– high efficacy
– a favorable resistance profile
– no cross-resistance to existing antibiotics
– encouragement of stewardship
– appropriate antibiotic prescribing, due to targeted spectrum
– suitability for both intramuscular and oral administration
Product Snapshot
FabI Inhibitor
Inhibition of bacterial fatty acid synthesis
Being researched in:
- Pharyngeal infections
- Rectal infections
- Genital infections
In short
Debio 1453 produces rapid bactericidal activity against N. gonorrhoeae providing potential for the treatment of hard-to-treat N. gonorrhoeae infections. In addition, Debio 1453 demonstrates promising activity against Chlamydia trachomatis, the cause of the sexually transmitted infection (STI) chlamydia, which is often co-associated with N. gonorrhoeae.
Highly potent FabI inhibitor with bactericidal activity against N. gonorrhoeae in both oral and intramuscular formulations currently in pre-clinical research.
Focus on the Mode of Action
Inhibition of bacterial fatty acid synthesis
The active moiety of Debio 1453 inhibits the fatty acid synthesis (FASII) pathway in N. gonorrhoeae by interfering with FabI, an enoyl-acyl carrier protein (ACP) reductase. FabI catalyzes the final and rate-determining step in the fatty acid chain elongation by reducing enoyl-ACP to acyl-ACP, enabling bacterial growth and survival. This novel antibacterial has the potential to address the challenges of antibacterial resistance.
Focus on gonococcal infections
Gonorrhea is the second most common sexually transmitted infection (STI). Gonococcal infections may present as urogenital, anorectal, conjunctival, and pharyngeal infections. WHO estimates that 82.4 million people were newly infected with gonorrhoeae in 2020.[1] In 2021, in the US, there were 696,764 cases of gonorrhea reported.[2] However, the actual number of cases is likely much higher due to under-reporting and asymptomatic infections. Untreated gonorrhea can lead to epididymitis in males and pelvic inflammatory disease (PID) in females, which can lead to serious sequelae such as infertility, ectopic pregnancy, and chronic pelvic pain [3]. Infrequently, gonococcal infections can become invasive, and for some strains resistant to several antibiotic classes, leading to disseminated gonococcal infections, which may result in gonococcal arthritis-dermatitis syndrome, suppurative arthritis, endocarditis, and meningitis.
Sources:
[1] World Health Organization. Multi-drug resistant gohorrhoea. 2022.
[2] BMJ. Syphilis and gonorrhoea cases soar in US. 2022;378:o2355
[3] World Health Organization. Sexually Transmitted Infections (STIs). Available at: https://www.who.int/news-room/fact-sheets/detail/sexually-transmitted-infections-(stis)
