Blacksmith Medicines Announces Publication in Journal of Medicinal Chemistry Highlighting Discovery of a Non-Hydroxamate LpxC Inhibitor

SAN DIEGO, Aug. 5, 2026 /PRNewswire/ -- Blacksmith Medicines, Inc. (Blacksmith), a leading biopharmaceutical company dedicated to discovering and developing therapeutics that target metalloenzymes, today announced the publication of research in the Journal of Medicinal Chemistry titled "Discovery and Optimization of Novel Non-Hydroxamate LpxC Inhibitors for the Treatment of Multidrug-Resistant Gram-Negative Infections."

"This peer-reviewed data demonstrates the capability of Blacksmith's chemistry platform to advance novel small-molecule inhibitors against challenging metalloenzyme targets," said Zachary Zimmerman, Ph.D., CEO and co-founder of Blacksmith. "LpxC has been studied for decades across the biopharmaceutical industry, with an overwhelming reliance on problematic hydroxamic acid to bind and inhibit the catalytic metal in the enzyme active site. The Blacksmith platform offers a differentiated solution by leveraging a proprietary metal-binding pharmacophore library to identify novel non-hydroxamate starting points for elaboration through rational drug design."

Blacksmith's lead antibacterial candidate targeting LpxC, FG-2101, is being advanced for both intravenous and oral administration for the treatment of susceptible and multidrug-resistant Gram-negative pathogens.

The FG-2101 program is currently supported under a contract with NIAID and was previously supported by CARB-X (see below for contract details).

About LpxC
LpxC is a zinc-dependent hydrolase and an attractive antibiotic target that is conserved across Gram-negative bacteria but absent from Gram-positive species and human cells. Inhibition of LpxC results in potent, selective killing of Gram-negative bacteria. Previous LpxC inhibitors, primarily based on hydroxamic acid chemistry, have exhibited poor drug-like properties, and no LpxC-targeted therapies have been approved to date. Leveraging its proprietary chemistry platform, Blacksmith has developed novel non-hydroxamate LpxC inhibitors that demonstrate differentiated safety profiles and are efficacious in animal models against multidrug-resistant Gram-negative pathogens.

About Metalloenzymes and the Blacksmith Platform
Metalloenzymes use metal ion cofactors in their active sites to carry out essential biological functions. Historically, these targets have been difficult to drug because conventional small-molecule chemistry has had limited ability to engage metal-dependent active sites with the precision needed for safe and effective therapeutics. The Blacksmith platform is designed to overcome these challenges through:

• A proprietary fragment library of metal-binding pharmacophores;
• A comprehensive database that maps metalloenzyme functions, metal cofactors, and disease associations;
• A proprietary metallo-CRISPR library of custom single-guide RNAs;
• An advanced computational toolkit for docking, modeling, and structure-based drug design; and
• A robust intellectual property portfolio spanning bioinorganic, medicinal, and computational chemistry for metalloenzyme-targeted therapeutics.

About Blacksmith Medicines
Blacksmith Medicines is pioneering the development of therapeutics that target metal-dependent enzymes, a large and important class representing more than 30% of all known enzymes across major categories, including oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. These enzymes rely on essential metal ions—such as magnesium, zinc, iron, manganese, and copper—for catalytic activity. Blacksmith's purpose-built platform integrates a proprietary library of metal-binding pharmacophores with advanced computational modeling to design small-molecule inhibitors that precisely engage metal ions within enzyme active sites. This approach enables the rapid and predictable development of potent, selective inhibitors.

The company has established strategic collaborations with Basilea Pharmaceutica International Ltd., Cyteir Therapeutics Inc., Eli Lilly and Company, Hoffmann-La Roche Ltd., and Zoetis LLC, and has secured non-dilutive funding from CARB-X and NIH/NIAID. Blacksmith's investors include Eli Lilly, Evotec A.G., MP Healthcare Partners, MagnaSci Ventures, and Alexandria Venture Investments.

For more information, visit www.BlacksmithMedicines.com or follow Blacksmith Medicines on LinkedIn.

Media Contact:
Amy Conrad
Juniper Point
[email protected]
858-366-3243

This program has been supported by CARB-X (4500002736) and is currently supported under a contract with NIAID (75N93022C00060). Funding for CARB-X has been provided by federal funds from the U.S. Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) under agreement number 75A50122C00028 and by awards from Wellcome (WT224842), the UK Department of Health and Social Care's Global Antimicrobial Resistance Innovation Fund (GAMRIF), the Gates Foundation, Germany's Federal Ministry of Research, Technology and Space (BMFTR), the Novo Nordisk Foundation, The Public Health Agency of Canada, Italy's Ministry of Economy and Finance (MEF), Japan's Ministry of Health, the European Commission's DG Health Emergency Preparedness and Response Authority (DG HERA), and KfW Development Bank. The U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) in HHS, provides support in the form of in-kind services through access to a suite of preclinical services for product development. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any CARB-X funders.

SOURCE Blacksmith Medicines