FG-2101 is Blacksmith’s non-hydroxamate small molecule inhibitor of LpxC for treating Gram-negative bacteria infections including drug-resistant strains
Presentation highlights Blacksmith’s novel chemistry platform for targeting metalloenzymes
SAN DIEGO, CA, USA I March 26, 2025 I Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing therapeutics targeting metalloenzymes, today disclosed the discovery and structure of FG-2101 at the American Chemical Society Spring 2025 meeting in San Diego, CA. FG-2101 is a non-hydroxamate small molecule antibiotic candidate discovered at Blacksmith that is designed to selectively inhibit LpxC, a zinc-dependent metalloenzyme found only in Gram-negative bacteria. FG-2101 is being developed for intravenous and oral routes of administration to treat Gram-negative bacteria infections, including drug-resistant strains. FG-2101 has advanced through IND enabling studies and is poised to enter human trials later this year.
“Today’s presentation at the ACS meeting showcases Blacksmith’s innovative small molecule chemistry platform that combines fragment-based drug design (FBDD) and structure-based drug design (SBDD) with proprietary computational approaches for metalloenzymes,” said Zachary Zimmerman, Ph.D., CEO and co-founder of Blacksmith. “In addition to representing an important milestone for FG-2101 as a potential treatment for serious bacterial infections, today’s presentation further validates the Blacksmith chemistry platform as a solution for novel small molecule inhibitors of disease-causing metalloenzymes that have been problematic to drug development.”
TITLE: First disclosure of FG-2101: A novel non-hydroxamate inhibitor of LpxC for treating Gram-negative bacteria infections including drug-resistant strains
SESSION: First Time Disclosures
DAY & TIME OF PRESENTATION: Wednesday, March 26, 2025, from 9:05 AM – 9:35 AM
ROOM & LOCATION: Room 28A/B – San Diego Convention Center
PRESENTER: Seth Cohen, Ph.D., co-founder of Blacksmith Medicines and Distinguished Professor of Chemistry and Biochemistry, U.C. San Diego
“For the past 23 years, my lab at U.C. San Diego has been working on developing a novel fragment-based drug discovery approach for inhibitors of medically relevant metalloenzymes. This unique platform has been leveraged by Blacksmith to create first-in-class and best-in-class medicines,” said Seth Cohen, Ph.D., co-founder of Blacksmith Medicines and Distinguished Professor of Chemistry and Biochemistry, U.C. San Diego. “As a scientific co-founder of Blacksmith, a chemistry-based platform company based in San Diego with technology from U.C. San Diego, I am proud to present Blacksmith’s lead program FG-2101 at ACS First Time Disclosures session being held in our hometown of San Diego.”
The FG-2101 program is currently supported under a contract with NIAID (75N93022C00060).
About LpxC
LpxC, a zinc-dependent hydrolase, is an attractive and highly sought-after antibiotic target – it is conserved across Gram-negative bacteria and not found in Gram-positive bacteria or human cells. Inhibiting LpxC results in potent killing of Gram-negative bacteria with the expected benefit of sparing protective Gram-positive bacteria, such as those residing in the microbiome of the gut which help to deter opportunistic C. difficile infections.
Other LpxC inhibitors have been evaluated by biopharma in the past, but chemistry limitations (e.g., use of hydroxamic acid-based warheads) have yielded ineffective compounds that suffer from poor drug-like properties. Thus, there are no approved therapeutics targeting LpxC. Blacksmith, using its proprietary chemistry platform, has developed novel non-hydroxamate inhibitors of LpxC that are safe and effective in animal models of Gram-negative infection and are able to kill Gram-negative ‘superbugs’ where other antibiotics are ineffective.
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.
For further information, please visit the company’s website www.BlacksmithMedicines.com and LinkedIn
SOURCE: Blacksmith Medicines
Post Views: 770
FG-2101 is Blacksmith’s non-hydroxamate small molecule inhibitor of LpxC for treating Gram-negative bacteria infections including drug-resistant strains
Presentation highlights Blacksmith’s novel chemistry platform for targeting metalloenzymes
SAN DIEGO, CA, USA I March 26, 2025 I Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing therapeutics targeting metalloenzymes, today disclosed the discovery and structure of FG-2101 at the American Chemical Society Spring 2025 meeting in San Diego, CA. FG-2101 is a non-hydroxamate small molecule antibiotic candidate discovered at Blacksmith that is designed to selectively inhibit LpxC, a zinc-dependent metalloenzyme found only in Gram-negative bacteria. FG-2101 is being developed for intravenous and oral routes of administration to treat Gram-negative bacteria infections, including drug-resistant strains. FG-2101 has advanced through IND enabling studies and is poised to enter human trials later this year.
“Today’s presentation at the ACS meeting showcases Blacksmith’s innovative small molecule chemistry platform that combines fragment-based drug design (FBDD) and structure-based drug design (SBDD) with proprietary computational approaches for metalloenzymes,” said Zachary Zimmerman, Ph.D., CEO and co-founder of Blacksmith. “In addition to representing an important milestone for FG-2101 as a potential treatment for serious bacterial infections, today’s presentation further validates the Blacksmith chemistry platform as a solution for novel small molecule inhibitors of disease-causing metalloenzymes that have been problematic to drug development.”
TITLE: First disclosure of FG-2101: A novel non-hydroxamate inhibitor of LpxC for treating Gram-negative bacteria infections including drug-resistant strains
SESSION: First Time Disclosures
DAY & TIME OF PRESENTATION: Wednesday, March 26, 2025, from 9:05 AM – 9:35 AM
ROOM & LOCATION: Room 28A/B – San Diego Convention Center
PRESENTER: Seth Cohen, Ph.D., co-founder of Blacksmith Medicines and Distinguished Professor of Chemistry and Biochemistry, U.C. San Diego
“For the past 23 years, my lab at U.C. San Diego has been working on developing a novel fragment-based drug discovery approach for inhibitors of medically relevant metalloenzymes. This unique platform has been leveraged by Blacksmith to create first-in-class and best-in-class medicines,” said Seth Cohen, Ph.D., co-founder of Blacksmith Medicines and Distinguished Professor of Chemistry and Biochemistry, U.C. San Diego. “As a scientific co-founder of Blacksmith, a chemistry-based platform company based in San Diego with technology from U.C. San Diego, I am proud to present Blacksmith’s lead program FG-2101 at ACS First Time Disclosures session being held in our hometown of San Diego.”
The FG-2101 program is currently supported under a contract with NIAID (75N93022C00060).
About LpxC
LpxC, a zinc-dependent hydrolase, is an attractive and highly sought-after antibiotic target – it is conserved across Gram-negative bacteria and not found in Gram-positive bacteria or human cells. Inhibiting LpxC results in potent killing of Gram-negative bacteria with the expected benefit of sparing protective Gram-positive bacteria, such as those residing in the microbiome of the gut which help to deter opportunistic C. difficile infections.
Other LpxC inhibitors have been evaluated by biopharma in the past, but chemistry limitations (e.g., use of hydroxamic acid-based warheads) have yielded ineffective compounds that suffer from poor drug-like properties. Thus, there are no approved therapeutics targeting LpxC. Blacksmith, using its proprietary chemistry platform, has developed novel non-hydroxamate inhibitors of LpxC that are safe and effective in animal models of Gram-negative infection and are able to kill Gram-negative ‘superbugs’ where other antibiotics are ineffective.
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.
For further information, please visit the company’s website www.BlacksmithMedicines.com and LinkedIn
SOURCE: Blacksmith Medicines
Post Views: 770
