“We are excited to unveil the merger of Blacksmith and Forge, which we believe will be transformational for both companies. Prospects are very bright for the new Blacksmith, as we are now able to expand our metalloenzyme platform, advance our internal and partnered programs, and create increased value for our shareholders by discovering first-in-class and best-in-class medicines,” said Zachary Zimmerman, Ph.D., CEO and co-founder of Blacksmith. “Our target strategy is to focus on metalloenzymes of significant unmet need and high pharma interest, targets with validated biology that have been challenging to drug due to chemistry limitations that we can solve with our platform.”
The Blacksmith platform has been validated through multiple pharmaceutical partnerships, including deals with Roche, Eli Lilly, and Basilea, which have the potential to earn over $800M in milestone payments plus royalties. Furthermore, the company currently has earned non-dilutive federal awards of up to $25.3M to fully fund its infectious disease programs to the end of Phase 1. Blacksmith also has emerging precision oncology programs focused on novel synthetic lethality targets involved in the DNA Damage Response. Blacksmith investors include Evotec A.G., MagnaSci Ventures, MP Healthcare Partners, Alexandria Venture Investments, and Eli Lilly.
Metalloenzymes utilize a metal ion cofactor in the enzyme active site to perform essential biological functions. This diverse class of targets has historically been difficult to drug due to small molecule chemistry limitations that have plagued the industry. The Blacksmith metalloenzyme platform has solved this problem by leveraging the following:
- A large proprietary fragment library of metal-binding pharmacophores (MBPs);
- A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease;
- A first-of-its-kind metallo-CRISPR library of custom single guide RNAs;
- An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and
- A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines.
At Blacksmith Medicines, we are developing medicines targeting metal-dependent enzymes. Over 30% of known enzymes are metalloenzymes, covering all major enzyme classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Metal ions, including magnesium, zinc, iron, manganese and copper, are the essential ingredient in these metalloenzymes. We recognized a large unmet need for new chemical matter and innovative approaches to drug this important class of enzymes. Our purpose-built platform for metalloenzyme-targeted medicines combines, for the first time in industry, a focused library of metal-binding pharmacophores with proprietary computational modeling approaches to rapidly and rationally design small molecule inhibitors that interact with key metal ions in the enzyme’s active site. Our comprehensive knowledge of the metal environment and key active site interactions enables Blacksmith to rapidly build potent and selective inhibitors in a stepwise and predictable manner.
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