Spero 2

A propargyl-linked antifolate, yellow, bound to its target, dihydrofolate reductase (DHFR) from methicillin-resistant Staphylococcus aureus. The antifolate compound inhibits the function of this essential enzyme, which results in bacterial cell death.

Spero Therapeutics, LLC, a biopharmaceutical company founded to develop novel therapies for the treatment of bacterial infections, recently announced it has entered into a sublicense agreement with Promiliad Biopharma for access to its dihydrofolate reductase (DHFR) inhibitors. Promiliad’s DHFR Program relies on technology licensed from UConn and developed in the laboratories of Drs. Amy Anderson and Dennis Wright from the School of Pharmacy.

“Promiliad’s DHFR program is a unique addition to Spero’s growing pipeline of antibacterial candidates, and pre-clinical studies with these inhibitors are already demonstrating the immense potential for the DHFR pathway to treat drug-resistant infections,” said Ankit Mahadevia, M.D., Chief Executive Officer of Spero. “We are excited to work with the world-class researchers at the University of Connecticut to identify and develop new candidate compounds.”

Spero 1

A propargyl-linked antifolate, light green, bound to its target, dihydrofolate reductase (DHFR) from a drug-resistant Klebsiella pneumoniae. The antifolate compound inhibits the function of this essential enzyme, which results in bacterial cell death.

“A big part of our mission is to make sure that innovative technologies developed at UConn have a significant impact beyond our campuses,” said UConn Vice President for Research, Dr. Jeff Seemann. “Working with industry experts like Spero and Promiliad is essential to achieving that goal.”

Through a long-standing and productive partnership, Wright and Anderson, both professors of Medicinal Chemistry, have spent several years designing new inhibitors of DHFR. Bacteria and other pathogens need DHFR to grow since it is a key enzyme for making one of the four bases required for DNA synthesis, thymidine. As a result, effective inhibition of DHFR is highly toxic to rapidly proliferating bacterial, fungal and protozoal pathogens. Since the DHFR in the bacteria and fungi is structurally different from human DHFR, targeting this enzyme for antibacterial drug development has been successful in creating highly specific antibacterial agents that are anticipated to have lower side-effects in humans.

“We are improving upon existing antibacterial drugs, since there are currently no approved antifolates targeting invasive bacterial pathogens,” said Wright. “We’re excited that this important work can continue thanks to the license agreement between Promiliad and Spero.”