Technology
AMPs are different from conventional antibiotics
The development of conventional antibiotics heavily relies on the concept of each antibiotic having a single primary target and a single mode of action. Traditional antibiotics typically are intended stop an essential biological functions of the bacteria like multiplication or growth.
Madam Therapeutics has developed her SAAPs inspired by examples from our own body and other organisms to fight infections. Nature appears to have chosen a very different concept for the evolution of host defense using anti-microbial peptides (AMPs), favoring the design of rather ‘a specific’ drugs that disturb many biological functions of the bacteria simultaneously rather than blocking a specific high-affinity target. As a result, AMPs have been effective for billions of years, and therefore new therapeutic approaches using AMPs might represent a method of extending the half-life of these antimicrobials, beyond the 1–2 decades enjoyed by most conventional antibiotics.
In contrast to traditional antibiotics, SAAPs kill bacteria from the outside. As soon as they come into contact with the bacterial cell membrane, the cell membrane gets punctured and the bacteria will start leaking their contents. The bacteria will die within a few minutes in contrast to traditional antibiotics which take hours or even days to kill the bacteria.
Our SAAPs have therefore are excellent candidate agents that subvert a number of microbial antibiotic resistance mechanisms (AMR), and thus are attractive agents to address and overcome AMR.
What makes SAAPs attractive as antibacterial agents?
BioWorld Today, a leading news source for the biotech industry from Thomson Reuters, has recently described AMPs such as our SAAPs as the most exciting developments in the anti-microbial development. In the O’Neill report of 2016 on solutions to fight AMR, AMPs and their derivatives are ranked amongst the most promising alternatives to traditional antibiotics. In a commentary in Science Translational Medicine, following a publication on our human peptides, several unique characteristics were highlighted. The commentary mentioned that our SAAPs represents “the first published demonstration of the killing of persisters bacteria”. Comments are provided by Bob Hancock, a renowned microbiologist at the University of British Columbia in Vancouver, Canada: “The environment of the human body inhibits the activity of many such molecules because they stick to proteins and lipids in the blood. SAAPs looks to be one of the few known peptides that kill bacteria efficiently without also binding to these circulating obstacles in serum”, he notes. We are currently developing our SAAPs for testing in PoC trials in humans together with leading scientists at the Leiden University Medical Center (LUMC) and Amsterdam UMC.
Advances in Antimicrobial Treatment
provided by our SAAP and p10 Platforms
- They kill a wide spectrum of bacteria, including (multi-, and PAN-) resistant bacteria.
- They kill bacteria from the outside
- They have antibiofilm properties – killing persister cells
- They lower the chance of AMR to emerge as our SAAPs are more robust against resistance development.
- They kill bacteria within minutes rather than days or weeks
- They have a very favorable tolerance profile, as SAAP are inspired by a human-derived molecule
An animation of how our peptides work
How we use Artificial Intelligence to identify the most suitable SAAPs
Our patented peptide library contains billions of variants, all having the potential to fight many different infectious diseases. Traditional methods of identifying antibiotics by screening natural or synthetic compounds continue to come up short. As our peptides cannot simply all be produced and screened in the lab, we take a smarter and more state-of-the-art approach. Fortunately, computers and artificial intelligence assist us finding an answer.
Artificial Intelligence computational design of peptides with desired biological activities is an emerging/trending research topic. The Gent based company BioLizard (closely related to University of Ghent) has helped us with the development and practical application of AI techniques that bring the concepts of machine-learning to SAAP identification. Artificial Intelligence has helped us to discover new pearls with in our SAAP peptide library dedicated for specific infections and design improved “resistance-proof” and safe antibiotics.
