More than twenty million UTIs occur each year in the US alone with gram-negative uropathogenic Escherichia coli being the primary cause. Options for treating UTIs and other gram-negative bacterial infections have become increasingly limited due to the increase in antibiotic resistance. The new therapy is an orally bioavailable, mannose-containing small molecule drug, GSK3882347, that targets an adhesive protein in bacteria called FimH. This FimH antagonist represents a new strategy for treating bacterial infections by preventing the bacteria that cause UTIs from sticking to the walls of the bladder, thus allowing the body to naturally eliminate the infection. Since GSK3882347 has an alternative mechanism of action, it could potentially treat and prevent UTIs with minimal disturbance to the microbiome.
“We are very excited that GSK3882347, which we co-developed with our industry partner GSK, has entered into human clinical trials for the treatment and prevention of recurrent UTI,” Dr. Thomas Hannan, Chief Scientific Officer of Fimbrion Therapeutics, said. “This moves us one step closer towards providing relief for the millions of patients suffering from recurrent UTI.”
Fimbrion’s mission is to discover, develop, and commercialize antimicrobial-sparing and -enabling drugs for the prevention and treatment of infectious diseases caused by bacteria, including drug-resistant strains. “The decision by CARB-X to financially support GSK’s early clinical development efforts is a resounding validation of Fimbrion’s approach to target bacterial virulence, rather than viability,” added Dr. Hannan. Fimbrion will continue to develop its pipeline with additional narrow-spectrum antimicrobial strategies to combat UTIs and other bacterial infections.
The mannoside technology originated in the laboratories of Fimbrion co-founders and Washington University in St. Louis School of Medicine scientists Dr. Scott Hultgren, a microbiologist and expert in UTIs, and Dr. James Janetka, a medicinal chemist. They teamed together to develop new classes of mannosides, obtaining an American Recovery and Reinvestment Act of 2009 National Institutes of Health (NIH) Challenge Grant in Health and Science to fund their initial discovery efforts. Together with infectious disease specialist, Dr. Thomas Hooton, they founded Fimbrion Therapeutics in 2012 and licensed the intellectual property from Washington University in St. Louis with the help of the university’s Office of Technology Management.
Fimbrion Therapeutics continued the preclinical development of the mannosides for the treatment and prevention of UTIs with grant support from the NIH in the form of Small Business Innovation Research awards as well as business development support from Biogenerator, the investor arm of BioSTL. In 2016, these efforts led to the formation of a collaboration with GSK, a science-led global healthcare company, to accelerate lead optimization efforts. The joint project between Fimbrion and the Discovery Partnerships with Academia (DPAc) team at GSK proceeded rapidly, leading to the selection of GSK3882347 as a clinical candidate drug in 2018. Fimbrion continues to actively support the clinical development of GSK3882347 with ongoing preclinical research studies.
“This project demonstrates the true power of interdisciplinary research and collaboration in the face of the imminent antibiotic resistance crisis,” Dr. Hultgren, principal investigator for the collaboration with GSK and member of the National Academies of Sciences and Medicine, said. “We dissected the molecular details of how UPEC bacteria stick to the bladder walls and designed new classes of orally bioavailable mannosides to potently disrupt this interaction. We then leveraged this great science from academic research, the energy of an entrepreneurial start-up, and the expertise and resources of a world leading global healthcare company to deliver a new antimicrobial therapy."
Fimbrion Therapeutics research reported in this blog was partially supported by the NIH under award numbers RC1DK086378 and R43/44AI106112. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
