The story so far
2010
In 2010 we focused on a putative new antimicrobial target; the c-di-GMP signaling system, which controls the biofilm life cycle in Gram negative bacteria. It is now well-accepted that c-di-GMP serves as the central biofilm (sessile) – planktonic (free-living) decision maker in Gram-negative bacteria. As such, the c-di-GMP signaling system is a “non-lethal” drug target that is fundamentally different from the classic antibiotic targets and modes of action. c-di-GMP is not produced by humans suggesting that c-di-GMP signaling could be a biofilm-specific drug target with reduced risk of off-target effects.
2013-2014
In 2013 we created “Proof of Concept” by plummeting bacterial c-di-GMP levels with a genetic construct, in which a PDE (c-di-GMP degrading enzyme) could be over-expressed by addition of arabinose. This was found to subsequently dismantle P. aeruginosa biofilms and eradicate P. aeruginosa biofilm infections in mice.
2015
One of the molecules identified in the screening campaign appeared particularly promising because it fulfilled our expectations with respect to mode of action.
2016-2020
In 2016, Dr Michael Graz joined the team. His role is commercial development and funding and ensuring that the research is performed in a manner to allow for clinical development. He holds a track record of mentoring biopharmaceutical start-ups, and leading and turning around both scale-up and mature life sciences companies in the UK, South Africa and South America.
From 2017 we demonstrated that the H6-P1 mode of action worked well in concert with direct acting agents to kill biofilm bacteria and eradicate a biofilm infection. During 2019 and 2020, we found the likely drug target to be a phosphodiestrase, that affects c-di-GMP concentrations in P. aeruginosa.
2021-2025
The team developed a model for P.aeruginosa biofilms on catheters and demonstrated biofilm dismantling efficacy of our first generation compound within an hour after oral administration. Furthermore, we have shown that our first generation compound works synergistically with direct acting agents to eradicate a biofilm infection. All results suggest that our first generation compound and closest variants are safe and can be considered as drug-able independent of administration route.
2026
In January 2026, Disperazol Pharma partnered with Biophys Limited in Cardiff, Wales (UK) to support its development of a asset based on compounds developed on our behalf by CC4CARB in the USA.
