Forge Therapeutics and Evotec have strengthened their partnership on a discovery platform targeting metalloenzymes. The companies initially came together to create innovative antibiotics against drug-resistant diseases less than a year ago.
The platform begins with metal-ligand interactions to classify metal-binding pharmacophore (MBP) fragments based on Forge’s library of over 500 MBPs. David Puerta, Forge’s COO, explained that, “Using bioinorganic and medicinal chemistry principles, Forge transforms these MBP fragments into therapeutic leads using a novel fragment growth strategy incorporating our computational chemistry and structural biology”.
Last December the two companies joined forces to develop an antibiotic program to target LpxC, a zinc metalloenzyme wanted by many to use against possblebacterial infection treatments. Forge utilized its MBP library to recognize potent druggable inhibitors of LpxC, while Evotec contributed knowledge different areas such as biochemistry, medicinal chemistry, structural biology and program management.
The duo presented data for their inhibitor first in a mouse model. It was found that the antibiotic is comparable to ciprofloxacin for the treatment urinary tract infections, with less damage on the bladder and kidneys. The inhibitor revealed in vitro potency against superbug E.coli, currently front and center in the antibiotic resistance crisis.
With the success of their prior project, Forge and Evotec decided to use a similar strategy for the new platform. The goal of the platform, Blacksmith, is to create a larger range of therapeutics that focus on metalloenzymes. The primary focus will remain on infectious diseases. The biotech reported performing more than 50 metalloenzyme screens with a success rate over 15.
In March, Forge received one of the first research awards from the Combating Antibiotic Resistant Bacteria Accelerator (CARB-X). To help advance the LpxC program, Forge recieves an initial $4.8 million over 15 months and then potentially another $4 million as landmark payments.