ON February 21, 2024 Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing medicines targeting metalloenzymes, reported the release of $3.3M from its contract with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), Department of Health and Human Services (HHS), to conduct IND-enabling and Phase 1 studies of FG-2101, its novel non-hydroxamate LpxC inhibitor, using both intravenous (IV) and oral administration for the treatment of urinary tract infections caused by multidrug-resistant Gram-negative bacteria (Press release, Blacksmith Medicines, FEB 21, 2024, View Source [SID1234643532]).
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The company’s recent successful completion of certain Base Period activities including preclinical toxicology studiestriggered the release of this award under its contract with NIAID (75N93022C00060). The total funding could be up to $17.2M over five years, depending on contract options exercised. The new funding will be used for GMP clinical material manufacturing and IND preparation/submission.
"With support from NIAID, we have successfully completed preclinical toxicology studies including 7-day and 14-day repeat dose assessments (non-GLP and GLP) and safety pharmacology evaluations including cardiovascular, respiratory and CNS assessments of our novel non-hydroxamate LpxC inhibitor FG-2101," said Andrew Tomaras, Ph.D., Senior Vice President of Blacksmith. "Next, with the achievement of these safety studies, we will initiate the preparation of an investigational new drug (IND) application as well as the manufacturing campaign of GMP material for upcoming clinical studies. We are extremely grateful to the NIAID team for their continued support for the candidacy of our potential first-in-class antibacterial agent."
About LpxC
LpxC, a zinc metalloenzyme, 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 presumed benefit of sparing Gram-positive bacteria such as those residing in the protective 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. hydroxamic acid) 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.