Forge Therapeutics secures license for intellectual property on metalloprotein inhibitors

Forge Therapeutics CEO Zachary Zimmerman said: "We are pleased to obtain exclusive worldwide rights to this intellectual property, which adds to our expanding and dominant patent portfolio protecting the development and commercialization of metalloprotein inhibitors.

"In addition to strengthening our patent portfolio, we continue to apply our expertise in bioinorganic chemistry to discover and develop novel inhibitors against validated targets, potentially overcoming previous chemistry limitations in the industry."

The licensed technology relates to the discovery of novel metal-binding pharmacophores toward LpxC, a zinc metalloenzyme found only in Gram-negative bacteria, and uses of these pharmacophores to inhibit LpxC for therapeutic benefit in treating Gram-negative bacteria infections.

The Centers for Disease Control and Prevention estimates that drug resistant bacteria cause 23,000 deaths and 2 million illnesses each year in the US.

Among all of the bacteria resistance problems, Gram-negative bacteria are particularly worrisome because they are becoming resistant to nearly all drugs that would be considered for treatment. Gram-negative bacteria cause infections including pneumonia, bloodstream infections, wound or surgical site infections. The high priority Gram-negative organisms include Klebsiella, Acinetobacter, Pseudomonas aeruginosa, and E. coli.

LpxC is a zinc-dependent metalloenzyme required for the outer membrane of Gram-negative bacteria, and inhibition of LpxC has antimicrobial activity. LpxC is an attractive antibacterial target as there is no human homologue and it is highly conserved in Gram-negative bacteria.

As inhibitors of LpxC are not among the approved antibiotics currently prescribed for the treatment of bacterial infections, compounds targeting LpxC would likely overcome pre-existing drug-resistance mechanisms.

Various small molecule LpxC inhibitors have been reported, however, the majority of the highly potent compounds rely on hydroxamate chemistry to bind zinc in the enzyme catalytic site. Unfortunately, hydroxamates suffer from liabilities including high clearance, low bioavailability, and metabolism that leads to toxic byproducts. Forge Therapeutics has developed a non-hydroxamate LpxC inhibitor that is potent, on-target, well-tolerated, and efficacious in an animal infection model.

The Forge Therapeutics patent estate covers over 300 distinct metal binding pharmacophores and their uses for the inhibition of metalloprotein targets. In addition, Forge has patent protection related to select targets including LpxC. This layered approach protects the Forge platform technology as well as methods of inhibition for any metalloprotein.