LpxC has been recognised as an attractive antibacterial target for more than the past 15 years; however, a lack of suitable chemical starting points has hampered its progress. Forge has been applying its proprietary metal-binding pharmacophores ("MBP") library and processes and has been able to identify potent drugable inhibitors of LpxC.
The alliance will be focused on lead optimisation of these inhibitors with the goal of identifying a development candidate in the next couple of years Evotec will, through a team of more than 10 scientists, contribute cutting-edge biochemistry, microbiology, medicinal chemistry, structural biology, computational chemistry, ADME/PK/analytical, and programme management.
Forge Therapeutics CEO Zachary A. Zimmerman, Ph.D. said: "Antibacterials that act via novel mechanisms of action are desperately needed to address untreatable infections that arise from drug-resistant Gram-negative bacteria.
"Our LpxC inhibitors have proven to be stable, potent in vitro, and have shown preliminary efficacy in vivo. We are thrilled to partner with Evotec during lead optimisation as they provide significant pre-clinical expertise and added horsepower to rapidly advance our novel antibiotic to address this growing unmet global issue."
Evotec Chief Operating Officer Dr Mario Polywka said: "The antibiotic field has been suffering from an innovation void over the last 30 years and requires significant intellectual and financial stimulus to address the issues of resistance.
"Importantly, Forge's novel LpxC programme coupled with Evotec's unrivalled drug discovery platform and expertise offers significant promise in addressing this issue. We look forward to working with our new partners at Forge."
ABOUT LPXC
LpxC 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 innovative 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.