The Potentiator program is designed to disrupt the cell membrane of Gram-negative bacteria, allowing access for Gram-positive antibiotics.
The outer membrane of Gram-negative bacteria is comprised of highly polar and negatively charged lipopolysaccharide (LPS), which represents a persistent barrier for many antibiotics. As such, the LPS constitutes one of the greatest impediments to the discovery of Gram-negative antimicrobials.
Spero is developing a series of novel chemical entities—potentiators— that specifically interact with the outer membrane of Gram-negative bacteria to increase the membrane’s permeability. This increase in permeability allows Gram-positive antibiotics to enter and kill the cell.
Using potentiator molecules in combination with existing antimicrobial drugs has the potential to offer patients in critical need superior therapeutic options. Spero has initiated first-in-human studies for SPR741.