Virulence factors are the weapon systems that bacteria use to establish infection, damage host tissue, evade the immune system, and tolerate antibiotics. Targeting virulence factors disarms bacteria, having a disease-modifying effect on pathogenicity that supports immune clearance.

Swarming is a population-level motility that is a key driver of acute virulence, as swarming populations increase their expression of virulence factors and have greater antibiotic resistance1.

Our novel small molecule targets a phosphodiesterase (PDE) regulating c-di-GMP signalling in P. aeruginosa and other Gram-negative bacteria. C-di-GMP is a bacterial-specific second messenger controlling virulence, motility, and antibiotic tolerance2. VEI-001 prevents swarming and suppresses multiple key virulence factors.

This “upstream blocker” approach has synergy with antibiotics, potentiating their activity and preventing resistance. This is a key differentiator between VEI-001 and other virulence factor therapies, which target downstream effectors.

Virulence Factor Targeting

Veirulence mechanism of action Three stages: bacteria swarm and adopt a virulent lifestyle, the VEI-001 PDE inhibitor acts as an upstream blocker, and the bacteria are disarmed. Bacteria swarm Flagella-driven motility Bacteria adopt a highly virulent lifestyle VEI-100 inhibitor Our first-in-class PDE mechanism acts as an upstream blocker against swarming and a virulent lifestyle Bacteria disarmed Virulence suppressed, infection treated
Veirulence pipeline Pipeline showing program VEI-001, a c-di-GMP pathway inhibitor for P. aeruginosa, progressing through discovery into lead optimisation. Pipeline DISCOVERY LEAD OPT. PRECLINICAL IND-ENABLING CLINICAL VEI-100 c-di-GMP pathway P. aeruginosa

References:

  1. Overhage J, Bains M, Brazas MD, Hancock RE. Swarming of Pseudomonas aeruginosa is a complex adaptation leading to increased production of virulence factors and antibiotic resistance. J Bacteriol. 2008

  2. Jenal, U., Reinders, A. & Lori, C. Cyclic di-GMP: second messenger extraordinaire. Nat Rev Microbiol