Forge Therapeutics collaborates with CARB-X to accelerate development of its LpxC antibiotic

CARB-X is supported by its partners around the globe including BARDA, NIH, Wellcome Trust, AMRC UK, California Life Science Institute, RTI, Mass Biotech Council, and Boston University. The CARB-X goal is to move promising antibacterial candidates, like Forge’s LpxC programme, through the critical early stages of product development.

“The need for new antibiotics to solve the drug resistance epidemic is beyond urgent – resistant bacteria are clearly plentiful, but unfortunately, novel drugs are extremely rare. In partnership with Evotec, whose participation was key to our CARB-X application, we are tackling this global health issue from all sides – government, industry, charities – with the shared goal of reducing the worldwide death toll from ‘superbug’ bacterial infections,” said Zachary A. Zimmerman, Ph.D., chief executive officer of Forge. “Because of this, we at Forge feel a tremendous sense of responsibility to advance our LpxC antibiotic program into the clinic as quickly as possible and we are thankful to CARB-X for their support of our efforts.  In the next few years, we expect to advance the program to IND/Phase 1, which could yield the first novel Gram-negative antibiotic in decades.”

“Forge’s LpxC-inhibitor is an extremely important program to us,” said Dr. Mario Polywka, COO, Evotec AG, Forge’s strategic alliance partner. “The fact that CARB-X selected Forge as one of its first partners aligns with our assessment of the company’s innovative technology and capabilities to advance this program into the clinic and provide a much-needed new option against multi-drug resistant bacteria.”

In August 2016, CARB-X was launched to accelerate pre-clinical product development in the area of antibiotic-resistant infections, one of the world’s greatest health threats. CARB-X was established by BARDA and NIAID of the US Department of Health and Human Services along with Wellcome Trust, a global charitable foundation dedicated to improving health. This partnership has committed up to $450 million in new funds over the next five years to increase the number of antibacterial products in the drug-development pipeline. It reflects a new approach to how antibacterial research and drug development is identified, funded and accelerated to the clinic.

Millions of people around the globe have become infected with bacteria that are resisted 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 US 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 ineffective compounds that suffer from poor drug-like properties. Thus, there are no approved therapeutics targeting LpxC. Forge, using its proprietary chemistry platform, has developed novel non-hydroxamate inhibitors of LpxC that are safe and effective in an animal model of Gram-negative infection and are able to kill Gram-negative ‘superbugs’ where other antibiotics are ineffective.

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