Fimbrion Therapeutics Pioneers Anti-Virulence Solutions to Treat UTIs

ST. LOUIS – Fimbrion Therapeutics, Inc. is a Washington University startup biopharmaceutical company focused on innovative, antibiotic-sparing drugs for the prevention and treatment of bacterial diseases with an emphasis on urinary tract infections (UTIs).

Working closely with the Office of Technology Management (OTM), Fimbrion recently obtained an exclusive license to patented technology from Washington University to develop small molecule drugs, known as mannosides, for the treatment and prevention of UTIs.  Fimbrion has also worked with OTM while entering into a strategic partnership with GlaxoSmithKline (GSK), a science-led global healthcare company, to accelerate the pre-clinical development and commercialization of the mannosides towards their eventual use in the clinic.

Founded in 2012 by Drs. Scott Hultgren and James Janetka at the Washington University School of Medicine, along with Dr. Thomas Hooton at the University of Miami, Fimbrion is taking an unconventional approach of treating bacterial infections.  The company targets key virulence mechanisms utilized by bacteria, such as adherence to, and invasion of, host cells.

Dr. Hultgren, a member of the National Academy of Sciences, has been a key contributor in the understanding of molecular pathogenesis of UTIs caused by uropathogenic E. coli (UPEC).  This work has demonstrated the mechanistic and structural basis of the bacterial adhesion protein, FimH, as a key virulence factor for UTIs.

From this discovery, mannosides were rationally developed to tightly bind to FimH, blocking their ability to bind mannose-bearing receptors on the bladder, and thus preventing UPEC attachment.

Early in its development, Fimbrion participated in Washington University’s “Bear Cub” program, which provided key resources that resulted in SBIR funding from the National Institute of Health (NIH).

“We are fortunate to be at an institution like Washington University, where the OTM has been instrumental in negotiating license agreements to help us advance Fimbrion,” Dr. Hultgren said.  “It is particularly rewarding to know that this technology was originally made possible by an NIH Challenge Grant, as part of the American Recovery and Reinvestment Act of 2009.”

The development of antibiotics has led to significant improvements in human health and these drugs have markedly increased the longevity of the human population. However, escalating bacterial resistance to traditional antibiotics coupled with the lack of significant effort to develop new antibiotics, especially those with a different mechanism of action, threatens to reverse these trends.

In contrast to traditional antibiotics that target bacterial viability, Fimbrion’s research aims to target the specific adhesive mechanisms used by pathogens to colonize the host and its niches of infection.  This novel drug mechanism is narrow-spectrum and is predicted to limit resistance, thus sparing beneficial bacteria within the host microbiota.

“We are all excited about the possibility that this work may finally come to fruition and make a significant contribution to the worldwide battle against antimicrobial resistance,” Dr. Hooton said.

The Fimbrion team is confident they are taking the necessary steps to continue making substantial advancements toward the clinical development of their first-in-class FimH mannoside antagonist in the near future.  In addition, the company is looking to strengthen its pipeline of other anti-virulence drugs to treat infectious diseases, including small molecules and biologics.

“We are not that far from selecting pre-clinical candidates for toxicology studies,” said Dr. Janetka, the medicinal chemist who designed the mannosides.  “Within the next year, we hope to have selected one or two compounds as pre-clinical candidates to profile for toxicology.  If we’re successful, we would be less than two years away from being in the clinic.”

For more information on Fimbrion Therapeutics, visit their website: www.fimbrion.com.