-Data demonstrates broad applicability for LpxC inhibitor in Acinetobacter baumannii, a life-threatening respiratory bacteria-
LpxC antibiotic is Forge’s flagship program stemming from BLACKSMITH platform-
San Diego, California, October 31, 2017 – Forge Therapeutics, Inc. (Forge) announced new efficacy data today on Forge’s LpxC antibiotic program at the 2017 Keystone Symposia Conference “Antimicrobials and Resistance: Opportunities and Challenges” during an oral presentation and a poster session. The scientific conference is being held October 29 – November 1, 2017 at the Eldorado Hotel & Spa in Santa Fe, New Mexico.
In preclinical studies, exposure to Forge’s LpxC inhibitors rendered A. baumannii avirulent in a murine model of infection. These results build upon previously reported data demonstrating efficacy in several infection models against multiple strains of Gram-negative bacteria including extensively drug resistant strains.
“Using our BLACKSMITH platform, we are focused on developing entirely new classes of antibiotics that possess novel mechanisms of action which will be a powerful tool in treating life-threatening bacterial infections,” said Zachary A. Zimmerman, Ph.D., CEO of Forge. “This data generated from a collaboration among USC/Spellberg Lab, Evotec and Forge highlight the potential of our platform and broad applicability of our LpxC program against several Gram-negative bacteria such as E. coli, the leading cause of urinary tract infections, and now A. baumannii, a high-priority pathogen with an increasing rate of antibiotic resistance.”
Tuesday, October 31, 2017
- Presentation Track: Alternative Approaches to Tackling Resistant Infections; 8:30am-11:45am
- Oral Presentation Title: Activity of non-hydroxamate LpxC inhibitors against Acinetobacter baumannii
- Poster Session 2; 7:30pm-10:00pm
- Poster Number 2029: Activity of non-hydroxamate LpxC inhibitors against Acinetobacter baumannii
About the ‘Superbug’ Epidemic, Acinetobacter baumannii and LpxC
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.
Acinetobacter baumannii is an opportunistic bacterial pathogen primarily associated with hospital-acquired infections, which has become a major cause for concern in conflict zones, and has gained particular notoriety in the resent desert conflicts in Iraq, earning it the moniker “Iraqibacter.” The recent increase in incidence of multidrug-resistant (MDR) strains has significantly raised the profile of this emerging pathogen.
LpxC is an attractive antimicrobial target with the potential to provide a solution to this ‘superbug’ epidemic. LpxC is a zinc-dependent deacetylase responsible for the biosynthesis of lipid A, essential for many Gram-negative bacteria. Though bactericidal against many Gram-negative pathogens, LpxC inhibitors do not eliminate A. baumannii in vitro, but block LPS synthesis and reduce virulence in vivo.
BLACKSMITH Platform & Strategy
Forge’s platform called BLACKSMITH comprises a deep knowledge of metalloenzymes, bioinorganic and medicinal chemistry know-how, and a focused library of proprietary metal-binding fragment pharmacophores (MBPs) that provide selective & diverse starting points for novel inhibitors. Our strategy is to use the BLACKSMITH platform to discover new chemistry for the treatment of a broad range of diseases in areas of unmet needs with initial efforts in the area of infectious disease. To date, Forge has performed over 50 metalloenzyme screens with library hit rates of >15%, providing multiple starting points to build potent selective inhibitors of metalloenzymes across a variety of therapeutic areas.
About Forge Therapeutics
At Forge Therapeutics, we are developing medicines targeting metal-dependent enzymes found in nature. Over 30% of known enzymes are metalloenzymes covering all major enzymes classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Metal ions, including magnesium, zinc, iron, manganese, calcium, cobalt, and copper are the essential ingredient in these metalloenzymes. At Forge, we are the blacksmiths of modern medicine, providing the tools to address any metalloenzyme challenge.
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 a strategic alliance with leading drug discovery alliance and development partnership company Evotec AG and has been awarded multiple government awards including CARB-X. In addition, Forge has amassed a rich intellectual property estate on metalloprotein inhibitors to protect its BLACKSMITH platform and pipeline including technology licensed from UCSD. For further information, please visit the company’s website www.ForgeTherapeutics.com and follow us on Twitter @ForgeThera.
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