Forge Therapeutics and Evotec have announced that the companies have expanded their existing strategic alliance and launched the BLACKSMITH platform to discover a broader range of therapeutics targeting metalloenzymes.
“Over the last two years, we have experienced the power of Forge’s discovery capabilities with the discovery of the first novel antibiotic class targeting LpxC and we are pleased to have expanded our strategic alliance with the launch of the BLACKSMITH platform,” said Mario Polywka, chief operating officer of Evotec. “Evotec is focused on investing in companies and technologies that can truly advance the field of drug development – our continued relationship with Forge opens many opportunities to rapidly develop new therapies in almost any therapeutic indication where metalloenzymes are critical to disease advancement.”
“All six major enzyme classes contain a significant amount of metalloenzymes and, in fact, over 30 percent of all known enzymes across all species are metalloenzymes,” Prof. Seth Cohen, UCSD and co-founder of Forge. “Despite the rich target space for drug development there are, however, only a few examples of clinically approved metalloenzyme inhibitors as medicines which we believe is due to a shortcoming in the chemical space employed to bind the active site metal ion.”
David Puerta, COO of Forge, added, “Distinct from traditional approaches for ‘hit’ discovery using high throughput screens, the Forge approach starts with metal-ligand interactions to identify selective metal-binding fragment pharmacophores, or MBPs, from a proprietary library of greater than 500 MBPs. Intelligently selected fragments result in greater and more effective chemical diversity to rapidly identify key interactions between a fragment and the metalloenzyme active site. 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.”
Zachary A. Zimmerman, Ph.D., chief executive officer of Forge, commented, “The time for collaborative work in our industry is now and we are pleased to expand our relationship with Evotec to discover additional, novel metalloenzyme inhibitors against a wide range of diseases with our proprietary technology. Through this expanded relationship, we gain valuable resources that will accelerate our discovery engine to advance multiple therapeutic candidates toward the clinic.”
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.