Forge Therapeutics, Inc., (Forge), a biotechnology company discovering first-in-class antibiotics using a breakthrough drug discovery platform, presented the first efficacy data for an LpxC inhibitor in a urinary tract infection (UTI) mouse model at ASM Microbe 2017 in New Orleans. In these preclinical studies, including the UTI data announced, Forge’s LpxC inhibitors have demonstrated:
- Comparable efficacy to ciprofloxacin, a current standard of care antibiotic to treat UTI infections, with the demonstration of significant burden reductions in both the bladder and kidney;
- Favorable pharmacokinetics profile, stability in the blood, orally bioavailable;
- In vitro potency against wildtype and ‘superbug’ E.coli, not affected by resistance mechanisms.
“Over the last 20 years, other LpxC inhibitors have been discovered and evaluated by biopharma, but chemistry limitations have yielded unsuitable compounds that suffer from poor drug-like properties. Given that, there still are no approved therapeutics targeting LpxC,” said Dr Peter Warn, SVP Antibiotic Discovery of Evotec. “Forge, using its chemistry platform, has developed novel, non-hydroxamate inhibitors of LpxC that are effective in multiple animal models of Gram-negative infection, such as UTI, and are able to kill Gram-negative superbugs where other antibiotics are ineffective. In the global landscape of deadly infections, urinary tract infections represent a large patient population and high unmet medical need because of resistance to the approved antibiotics.”
Zachary A. Zimmerman, Ph.D., CEO of Forge, commented, “These preclinical data represent an advancement in the Forge LpxC program, and to our knowledge, this is the first time a non-hydroxamate inhibitor of LpxC has demonstrated efficacy in a UTI model. We are very encouraged and excited by these results to realize the potential of our novel, non-hydroxamate chemistry.”
About LpxC and the ‘Superbug’ Epidemic
Millions of people around the globe have become infected with bacteria that are resistant to current antibiotic treatments, or ‘superbugs’, creating a global health epidemic. An estimated 700,000 worldwide deaths occur each year from these drug-resistant infections, and in the U.S. alone, an estimated 23,000 people die each year from antibiotic resistant infections. The biotechnology industry, leading government agencies and world leaders agree that the need for new antibiotics is urgent.
LpxC is an attractive and highly sought after antibiotic target – it is conserved across Gram-negative bacteria and not found in Gram-positive bacteria or human cells. Other LpxC inhibitors have been evaluated by biopharma in the past but chemistry limitations (e.g. hydroxamic acid) have yielded unsuitable compounds that suffer from poor drug-like properties. There are no approved therapeutics targeting LpxC.