Blacksmith Medicines Announces Upcoming Presentation at AACR Annual Meeting 2024

SAN DIEGO, California, March 6, 2024 – Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing medicines targeting metalloenzymes, today announced the company will present data on its oncology program targeting flap endonuclease 1 (FEN1), a structure-specific metallonuclease that cleaves 5’ DNA flaps during replication and repair, at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place April 5-10 at the San Diego Convention Center, San Diego CA.

Details of the poster presentation are as follows:

Abstract Number: 7148

Title: “Small molecule inhibitor of FEN1 nuclease utilizing a novel metal binding pharmacophore synergizes with inhibitors of USP1, PARP, PARG and ATR”

Session Category: Experimental and Molecular Therapeutics

Session Title: Novel Antitumor Agents 6

Session Date and Time: Wednesday April 10, 2024 9:00 AM – 12:30 PM

Location: Poster Section 23

Poster Board Number: 10

The abstract is now available on the conference website at AACR Annual Meeting 2024.

About FEN1

Flap endonuclease 1 (FEN1) is a structure-specific di-magnesium metallonuclease that cleaves 5’ DNA flaps during replication and repair. FEN1 is an attractive target for development of anticancer therapeutics because it is overexpressed in many tumor types and has a large number of synthetic lethality partners including genes in Homologous Recombination (HR) pathway.

About metalloenzymes and the Blacksmith platform

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.

About Blacksmith 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.

Blacksmith has executed strategic drug discovery collaborations with Basilea Pharmaceutica International Ltd., Cyteir Therapeutics Inc., Eli Lilly and Company (Lilly), Hoffmann-La Roche Ltd., and Zoetis LLC., and has been awarded non-dilutive Federal funding agreements with CARB-X and NIH/NIAID.  Blacksmith investors include Lilly, Evotec A.G., MP Healthcare Partners, MagnaSci Ventures, and Alexandria Venture Investments.