SAN DIEGO, CA, USA I September 7, 2017 I Forge Therapeutics, Inc., (Forge) and its strategic alliance partner Evotec AG (Evotec), announced new preclinical data today on Forge’s LpxC antibiotic program at the 2017 ASM/ESCMID Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance.  In these preclinical studies, Forge’s LpxC inhibitors have demonstrated efficacy in four different infection models via clinically relevant routes of administration against multiple strains of Gram-negative bacteria including extensively drug resistant (XDR) strains. Efficacy data presented include:

  • Urinary Tract Infection Model:  Intravenous and oral routes of administration against uropathogenic E. coli showing comparable bacterial burden reductions in the kidney, bladder, and urine to that of ciprofloxacin, a current standard of care antibiotic to treat UTI infections;
  • Lung and Thigh Infection Models: Intravenous administration against clinical XDR E. coli harboring multiple resistance genes including multiple ESBLs such as CTX-M with comparable efficacy to tigecycline, an antibiotic of last resort;
  • Intra-abdominal Sepsis Infection Model: Intravenous administration demonstrating near clearance of XDR E. coli harboring multiple resistance genes including NDM-1 and resistant to fluoroquinolones and aminoglycosides; comparable efficacy to tigecycline, an antibiotic of last resort.

“Forge continues to build a strong data set demonstrating LpxC in vivo target engagement and bacterial cidality in multiple sites of infection against difficult-to-treat organisms. This program opens exciting opportunities to develop much needed new classes of antibiotics,” said Dr Peter Warn, SVP Antibiotic Discovery of Evotec. 

Zachary A. Zimmerman, Ph.D., CEO of Forge, commented, “Using our novel chemistry platform for targeting metalloenzymes, we are developing novel classes of antibiotics that are differentiated from other approaches that are simply derivatizing existing classes.  The LpxC program is one of our examples of applying Forge’s innovative chemistry platform to target novel mechanisms of action.” 

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. 

About Forge Therapeutics

Forge Therapeutics is a privately-held biopharmaceutical company developing novel antibiotics to treat multi-drug resistant bacteria, or ‘superbugs,’ that have ignited a global health epidemic. With its proprietary chemistry approach, Forge develops small molecule inhibitors targeting metalloenzymes.  Forge’s lead effort is focused on LpxC, a zinc metalloenzyme found only in Gram-negative bacteria and which is essential for bacteria to grow. Forge has discovered novel small molecule inhibitors of LpxC that are potent in vitro, efficacious in vivo, and effective against drug resistant Gram-negative bacteria ‘superbugs.’ To complement its innovative approach to drug discovery, Forge has an efficient business model that utilizes a mix of non-dilutive and traditional funding sources to advance its programs, including LpxC. Forge has formed a strategic alliance with leading drug discovery alliance and development partnership company Evotec AG and has been awarded multiple government awards to address the global ‘superbug’ epidemic.  In addition, Forge has amassed a rich intellectual property estate on metalloprotein inhibitors to protect its technology and pipeline.  For further information, please visit the company’s website www.ForgeTherapeutics.com and follow us on Twitter @ForgeThera.

SOURCE: Forge Therapeutics